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Huang CW, Hu HM, Hsu WH, Chen CY, Huang MY, Chen CP, Wei PL, Shen BN, Chang TK, Wang JY. Results of phase Ib/II trial of PEP503 (NBTXR3, radioenhancer) with chemoradiotherapy in patients with rectal cancer. Nanomedicine (Lond) 2025; 20:929-941. [PMID: 40255171 PMCID: PMC12051569 DOI: 10.1080/17435889.2025.2487411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Accepted: 03/28/2025] [Indexed: 04/22/2025] Open
Abstract
AIM To evaluate the efficacy, recommended phase II dose (RP2D), dose-limiting toxicity (DLT), and safety profiles of PEP503 (NBTXR3) in combination with concurrent chemoradiotherapy (CCRT) in patients with locally advanced or unresectable rectal adenocarcinoma. METHODS A single administration of intratumor injection of PEP503 (NBTXR3) (multiple punctures) was applied, followed by radiotherapy in combination with capecitabine or 5-fluorouacil (5-FU). Surgery was performed 8 to 12 weeks after completion of CCRT. RESULTS Thirty-two patients were enrolled (one dropped out before CCRT), comprising 20 in phase Ib and 12 in phase II. The disease control rate was 100% (n = 31). One (3.2%) and 19 (61.3%) patients achieved clinical complete response and partial response, respectively. Twenty-five patients underwent surgery, of whom 24 (96%) had R0 resection and 5 (20%) had pathological complete response. Most of the adverse events were grade 1/2 events. CONCLUSION Intratumor injection of PEP503 (NBTXR3) in patients with locally advanced or unresectable rectal adenocarcinoma is safe and effective. Addition of PEP503 (NBTXR3) to fluoropyrimidine-based neoadjuvant CCRT does not engender increased toxicity. The strong safety profile and encouraging efficacy of PEP503 (NBTXR3) in combination with neoadjuvant CCRT in locally advanced or unresectable rectal cancer warrant further examination in clinical studies. CLINICAL TRIAL REGISTRATION This study was registered on ClinicalTrials.gov Identifier: NCT02465593.
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Affiliation(s)
- Ching-Wen Huang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Huang-Ming Hu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chiao-Yun Chen
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yii Huang
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chou-Pin Chen
- Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Po-Li Wei
- Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan
| | | | - Tsung-Kun Chang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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Sano S, Akiyoshi T, Yamamoto N, Noguchi T, Sakamoto T, Matsui S, Mukai T, Yamaguchi T, Taketomi A, Fukunaga Y, Miyazaki N, Kawachi H. Prognostic Significance of Desmoplastic Reaction After Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer. Dis Colon Rectum 2025; 68:327-337. [PMID: 39625404 DOI: 10.1097/dcr.0000000000003589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/22/2025]
Abstract
BACKGROUND Desmoplastic reaction is recognized as a prognostic factor in colorectal cancer. However, its significance in locally advanced rectal cancer after neoadjuvant chemoradiotherapy remains underexplored. OBJECTIVE To assess the prognostic value of desmoplastic reaction in specimens from patients with advanced rectal cancer after chemoradiotherapy. DESIGN This was a retrospective study. SETTINGS This study was conducted at a single comprehensive cancer center. PATIENTS The study included 255 patients with advanced rectal cancer who underwent fluoropyrimidine-based chemoradiotherapy followed by total mesorectal excision from 2005 to 2014. Desmoplastic reaction was classified into mature, intermediate, and immature categories based on histological analysis. MAIN OUTCOME MEASURES The primary outcomes were recurrence-free survival and overall survival. RESULTS Desmoplastic reaction was classified as mature (69.0%), intermediate (5.5%), or immature (25.5%). The mature group had a higher percentage of good responders (34.1%) compared with the intermediate (0%) and immature (4.6%) groups ( p < 0.0001). The mature group correlated with better outcomes, with a higher 5-year recurrence-free survival (85.4%) and overall survival (93.0%) as compared with intermediate (45.1% and 76.2%, respectively) and immature (65.8% and 88.8%, respectively) groups. In the multivariable analysis, intermediate/immature desmoplastic reaction was significantly associated with poorer recurrence-free survival ( p = 0.03). Among poor responders, intermediate/immature desmoplastic reaction was associated with poorer recurrence-free survival ( p = 0.03). Adjuvant chemotherapy did not significantly improve the 5-year recurrence-free survival rate for the mature group (adjuvant chemotherapy vs no chemotherapy, 86.4% vs 84.8%; p = 0.64), with worse trends observed in the intermediate/immature combined group (55.9% vs 69.4%, respectively, p = 0.27). LIMITATIONS The limitations include the subjective nature of the desmoplastic reaction assessment and the retrospective design of the study. CONCLUSIONS Desmoplastic reaction in surgical specimens after chemoradiotherapy is associated with responses to chemoradiotherapy and serves as a significant prognostic factor in advanced rectal cancer, particularly for those responding poorly to chemoradiotherapy. See Video Abstract . IMPORTANCIA PRONSTICA DE LA REACCIN DESMOPLSICA TRAS LA QUIMIORRADIOTERAPIA NEOADYUVANTE EN EL CNCER RECTAL AVANZADO ANTECEDENTES:La reacción desmoplásica se reconoce como un factor pronóstico en el cáncer colorrectal. Sin embargo, su importancia en el cáncer rectal localmente avanzado después de la quimiorradioterapia neoadyuvante sigue sin explorarse.OBJETIVO:Evaluar el valor pronóstico de la reacción desmoplásica en muestras de pacientes con cáncer rectal avanzado después de la quimiorradioterapia.DISEÑO:Este es un estudio retrospectivo.ESCENARIO:Este estudio se llevó a cabo en un solo centro oncológico integral.PACIENTES:El estudio incluyó a 255 pacientes con cáncer rectal avanzado que se sometieron a quimiorradioterapia basada en fluoropirimidina seguida de una escisión mesorrectal total entre 2005 y 2014. La reacción desmoplásica se clasificó en categorías madura, intermedia e inmadura según el análisis histológico.RESULTADOS PRINCIPALES:Los resultados primarios fueron la supervivencia sin recurrencia y la supervivencia general. RESULTADOS: La reacción desmoplásica se clasificó como madura (69,0%), intermedia (5,5%) o inmadura (25,5%). El grupo maduro tuvo un mayor porcentaje de buenos respondedores (34,1%) en comparación con los grupos intermedio (0%) e inmaduro (4,6%) (p < 0,0001). El grupo maduro se correlacionó con mejores resultados, con una mayor supervivencia libre de recurrencia a 5 años (85,4%) y supervivencia general (93,0%) en comparación con los grupos intermedio (45,1% y 76,2%, respectivamente) e inmaduro (65,8% y 88,8%, respectivamente). En el análisis multivariable, la reacción desmoplásica intermedia/inmadura se asoció significativamente con una peor supervivencia libre de recurrencia ( p = 0,03). Entre los malos respondedores, la reacción desmoplásica intermedia/inmadura se asoció con una peor supervivencia libre de recurrencia (p = 0,03). La quimioterapia adyuvante no mejoró significativamente la tasa de supervivencia sin recurrencia a 5 años para el grupo maduro (quimioterapia adyuvante vs. ninguna quimioterapia, 86,4% vs. 84,8%; p = 0,64), observándose tendencias peores en el grupo combinado intermedio/inmaduro (55,9% vs. 69,4%, respectivamente, p = 0,27).LIMITACIONES:Las limitaciones incluyen la naturaleza subjetiva de la evaluación de la reacción desmoplásica y el diseño retrospectivo del estudio.CONCLUSIONES:La reacción desmoplásica en muestras quirúrgicas después de la quimiorradioterapia se asocia con respuestas a la quimiorradioterapia y sirve como un factor pronóstico significativo en el cáncer rectal avanzado, particularmente para aquellos que responden mal a la quimiorradioterapia. (Traducción-Yesenia Rojas-Khalil ).
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Affiliation(s)
- Shuhei Sano
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Akiyoshi
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Noriko Yamamoto
- Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tatsuki Noguchi
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Sakamoto
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shimpei Matsui
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiki Mukai
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Yamaguchi
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Yosuke Fukunaga
- Department of Colorectal Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Miyazaki
- Division of Clinical Research Planning and Strategy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiroshi Kawachi
- Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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Zeng ZX, Wu JY, Wu JY, Zhang ZB, Wang K, Zhuang SW, Li B, Zhou JY, Lin ZT, Li SQ, Li YN, Fu YK, Yan ML. Prognostic Value of Pathological Response for Patients with Unresectable Hepatocellular Carcinoma Undergoing Conversion Surgery. Liver Cancer 2024; 13:498-508. [PMID: 39435272 PMCID: PMC11493390 DOI: 10.1159/000536376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/17/2024] [Indexed: 10/23/2024] Open
Abstract
Introduction Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.
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Affiliation(s)
- Zhen-Xin Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Jia-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jun-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Zhi-Bo Zhang
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Kai Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shao-Wu Zhuang
- Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Bin Li
- Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jian-Yin Zhou
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Zhong-Tai Lin
- Department of General Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Shu-Qun Li
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Yi-Nan Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Yang-Kai Fu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Mao-Lin Yan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
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Kohrman NM, Wlodarczyk JR, Ding L, McAndrew NP, Algaze SD, Cologne KG, Lee SW, Koller SE. Rectal Cancer Survival for Residual Carcinoma In Situ Versus Pathologic Complete Response After Neoadjuvant Therapy. Dis Colon Rectum 2024; 67:920-928. [PMID: 38498775 DOI: 10.1097/dcr.0000000000003261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/20/2024]
Abstract
BACKGROUND Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome. OBJECTIVE To compare the survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response. DESIGN Retrospective cohort study. SETTING National public database. PATIENTS A total of 4594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative ypTis or ypT0 on final pathology were included. Of these, 4321 patients (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology. MAIN OUTCOME MEASURE Overall survival. RESULTS The median age was 60 years, and 1822 patients (39.7%) were women. On initial staging, 54.5% (n = 2503) had stage II disease and 45.5% (n = 2091) had stage III disease. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42; 95% CI, 1.04-1.95; p = 0.028). Other factors associated with decreased overall survival were older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage II and stage III. LIMITATIONS Standard therapy versus total neoadjuvant therapy could not be abstracted. Overall survival was defined as the time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths. CONCLUSIONS ypTis is associated with worse overall survival than ypT0 for patients with locally advanced rectal cancer who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract . SUPERVIVENCIA DEL CNCER DE RECTO PARA EL CARCINOMA RESIDUAL IN SITU VS RESPUESTA PATOLGICA COMPLETA DESPUS DE LA TERAPIA NEOADYUVANTE ANTECEDENTESLa respuesta patológica completa después de la quimiorradioterapia neoadyuvante para el cáncer de recto se asocia con una mayor supervivencia. No está claro si el carcinoma residual in situ presagia un resultado similar.OBJETIVOComparar la supervivencia de pacientes con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante y lograron un carcinoma patológico in situ versus una respuesta patológica completa.DISEÑOEstudio de cohorte retrospectivo.ESCENARIOBase de datos pública nacional.PACIENTESSe incluyeron 4,594 pacientes de la Base de Datos Nacional de Cáncer de 2006 a 2016 con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante, fueron sometidos a cirugía y tuvieron ganglios negativos, ypTis o ypT0 en el reporte patológico final. 4.321 (94,1%) tuvieron ypT0 y 273 (5,9%) tuvieron ypTis en el reporte final.PRINCIPALES MEDIDAS DE RESULTADOSupervivencia general.RESULTADOSLa mediana de edad fue de 60 años. 1.822 pacientes (39,7%) fueron mujeres. El 54,5% (n = 2.503) tuvo la enfermedad en estadio II y el 45,5% (n = 2.091) tuvo la enfermedad en estadio III según la estadificación inicial. El grupo ypTis tuvo una supervivencia general reducida en comparación con el grupo ypT0 (HR 1,42, IC 95 % 1,04-1,95, p = 0,028). Otros factores asociados con una menor supervivencia general fueron una edad más avanzada al momento del diagnóstico, un aumento de la puntuación de Charlson-Deyo y un grado tumoral poco diferenciado. Las variables asociadas con una mejor supervivencia fueron el sexo femenino, el seguro privado y la recepción de quimioterapia neoadyuvante y adyuvante. Para la cohorte total, no hubo diferencias en la supervivencia entre el estadio clínico 2 y el estadio 3.LIMITACIONESNo se pudo resumir el tratamiento estándar versus el tratamiento neoadyuvante total. La supervivencia general se definió como el tiempo transcurrido desde la cirugía hasta la muerte por cualquier causa o último contacto, lo que permite algunas muertes erróneamente clasificadas.CONCLUSIONESypTis se asocia con una peor supervivencia general que ypT0 en pacientes con cáncer de recto localmente avanzado que reciben quimiorradioterapia neoadyuvante seguida de cirugía. Para esta cohorte, el estadio clínico no fue un predictor significativo de supervivencia. Se necesitan ensayos prospectivos que comparen la supervivencia de estos resultados patológicos. ( Traducción-Dr Osvaldo Gauto ).
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Affiliation(s)
- Nathan M Kohrman
- University of Southern California Keck School of Medicine, Los Angeles, California
| | - Jordan R Wlodarczyk
- Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, California
| | - Li Ding
- Department of Population and Public Health Sciences, University of Southern California Keck School of Medicine, Los Angeles, California
| | - Nicholas P McAndrew
- Division of Hematology/Oncology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
| | - Sandra D Algaze
- Division of Medical Oncology, University of Southern California Keck School of Medicine, Los Angeles, California
| | - Kyle G Cologne
- Division of Colorectal Surgery, University of Southern California Keck School of Medicine, Los Angeles, California
| | - Sang W Lee
- Division of Colorectal Surgery, University of Southern California Keck School of Medicine, Los Angeles, California
| | - Sarah E Koller
- Division of Colorectal Surgery, University of Southern California Keck School of Medicine, Los Angeles, California
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de Moraes FCA, Kelly FA, Souza MEC, Burbano RMR. Impact of adjuvant chemotherapy on survival after pathological complete response in rectal cancer: a meta-analysis of 31,558 patients. Int J Colorectal Dis 2024; 39:96. [PMID: 38913175 PMCID: PMC11196358 DOI: 10.1007/s00384-024-04668-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/12/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.
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Affiliation(s)
| | - Francinny Alves Kelly
- Department of Hypertension, Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil
| | | | - Rommel Mario Rodríguez Burbano
- Federal University of Pará, Rua Augusto Corrêa, nº 01, Guamá, Belém, Pará, 66073-000, Brazil
- Ophir Loyola Hospital, Belém, Pará, Brazil
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Nakao E, Honda M, Uesugi N, Osakabe M, Sato A, Todate Y, Yaegashi M, Takano Y, Sasaki A, Kono K, Sugai T. Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy. J Surg Oncol 2024; 129:1521-1533. [PMID: 38691656 DOI: 10.1002/jso.27662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/03/2024] [Accepted: 04/22/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. OBJECTIVES We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). METHODS We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. CONCLUSIONS The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.
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Affiliation(s)
- Eiichi Nakao
- Diagnostic Pathology Center, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan
- Division of Surgery, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
| | - Michitaka Honda
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan
- Division of Surgery, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
| | - Noriyuki Uesugi
- Diagnostic Pathology Center, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Yahaba, Japan
| | - Mitsumasa Osakabe
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Yahaba, Japan
| | - Ayaka Sato
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Yahaba, Japan
| | - Yukitoshi Todate
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan
- Division of Surgery, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
| | - Mizunori Yaegashi
- Department of Surgery, School of Medicine, Iwate Medical University, Yahaba, Japan
| | - Yoshinao Takano
- Division of Surgery, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
| | - Akira Sasaki
- Department of Surgery, School of Medicine, Iwate Medical University, Yahaba, Japan
| | - Koji Kono
- Department of Gastrointestinal Surgery, Fukushima Medical University, Fukushima, Japan
| | - Tamotsu Sugai
- Diagnostic Pathology Center, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Yahaba, Japan
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Cui Y, Song M, Tie J, Li S, Wang H, Zhang Y, Geng J, Liu Z, Teng H, Sui X, Zhu X, Cai Y, Li Y, Wang W. Clinicopathological factors predict residual lymph node metastasis in locally advanced rectal cancer with ypT0-2 after neoadjuvant chemoradiotherapy. J Cancer Res Clin Oncol 2024; 150:176. [PMID: 38575793 PMCID: PMC10995092 DOI: 10.1007/s00432-024-05662-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 02/21/2024] [Indexed: 04/06/2024]
Abstract
PURPOSE Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). METHODS We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50-50.6 Gy for the planning gross tumor volume and 41.8-45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610-0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. CONCLUSION The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.
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Affiliation(s)
- Yujun Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Maxiaowei Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Jian Tie
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Shuai Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Hongzhi Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yangzi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Jianhao Geng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Zhiyan Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Huajing Teng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Xin Sui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Xianggao Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yong Cai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yongheng Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
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Yang J, Deng Q, Cheng Y, Fu Z, Wu X. Effect of adjuvant chemotherapy on the oncological outcome of rectal cancer patients with pathological complete response. World J Surg Oncol 2024; 22:31. [PMID: 38273352 PMCID: PMC10809453 DOI: 10.1186/s12957-024-03300-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 01/13/2024] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Locally advanced rectal cancer is typically treated using a combination of neoadjuvant chemoradiotherapy and total mesorectal resection. While achieving pathological complete response following neoadjuvant chemoradiotherapy has been recognized as a positive prognostic factor in oncology, the necessity of adjuvant chemotherapy for locally advanced rectal cancer patients with pathological complete response after surgery remains uncertain. The objective of this meta-analysis was to examine the impact of adjuvant chemotherapy on the oncological outcomes of rectal cancer patients who attain pathological complete response after neoadjuvant chemoradiotherapy. METHODS This meta-analysis followed the guidelines outlined in the preferred reporting items for systematic review and meta-analysis (PRISMA). The Web of Science, PubMed, and Cochrane Library databases were systematically searched to identify relevant literature. RESULTS A total of 34 retrospective studies, including 9 studies from the NCBD database, involving 31,558 patients with pathological complete response rectal cancer, were included in the meta-analysis. The included studies were published between 2008 and 2023. The pooled analysis demonstrated that adjuvant chemotherapy significantly improved overall survival (HR = 0.803, 95% CI 0.678-0.952, P = 0.011), and no heterogeneity was observed (I2 = 0%). Locally advanced rectal cancer patients with pathological complete response who underwent adjuvant chemotherapy exhibited a higher 5-year overall survival rate compared to those who did not receive adjuvant chemotherapy (OR = 1.605, 95% CI 1.183-2.177, P = 0.002). However, the analysis also revealed that postoperative ACT did not lead to improvements in disease-free survival and recurrence-free survival within the same patient population. Subgroup analysis indicated that pathological complete response patients with clinical stage T3/T4, lymph node positivity, and younger than 70 years of age may benefit from adjuvant chemotherapy in terms of overall survival. CONCLUSIONS The findings of this meta-analysis suggest that adjuvant chemotherapy has a beneficial effect on improving overall survival among rectal cancer patients with pathological complete response. However, no such association was observed in terms of disease-free survival and recurrence-free survival.
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Affiliation(s)
- Jianguo Yang
- Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China
| | - Qican Deng
- Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China
| | - Yong Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Zhongxue Fu
- Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China
| | - Xin Wu
- Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China.
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Lai YH, Chang YT, Chang YJ, Tsai JT, Li MH, Lin JC. Predictive Value of the Interaction between CEA and Hemoglobin in Neoadjuvant CCRT Outcomes in Rectal Cancer Patients. J Clin Med 2023; 12:7690. [PMID: 38137759 PMCID: PMC10744245 DOI: 10.3390/jcm12247690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 12/01/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
The adoption of neoadjuvant concurrent chemoradiotherapy (CCRT) has reshaped the therapeutic landscape, but response prediction remains challenging. This study investigates the interaction between pre-CCRT carcinoembryonic antigen (CEA) and post-CCRT hemoglobin (Hb) levels in predicting the response of locally advanced rectal cancer (LARC) to CCRT. Retrospective data from 93 rectal cancer patients receiving neoadjuvant CCRT were analyzed. Univariate analyses assessed clinical factors associated with tumor regression grade (TRG) and T-stage outcomes. Machine learning identified predictive biomarkers. Interaction effects between CEA and Hb were explored through subgroup analyses. Post-CCRT Hb varied between pre-CCRT CEA groups. The interaction between pre-CCRT CEA and post-CCRT Hb influenced TRG. Males with normal pre-CCRT CEA and anemia showed better treatment responses. Females with elevated pre-CCRT CEA and post-CCRT anemia exhibited poorer responses. The interaction effect between them was significant, indicating that their relationship with TRG was not additive. Inflammatory biomarkers, WBC, neutrophil count, and post-CCRT platelet level correlated with CCRT response. Contrasting with previous findings, anemia was a predictor of better treatment response in males with normal pre-CCRT CEA. The interaction between pre-CCRT CEA and post-CCRT Hb levels predicts the response of LARC to CCRT. CEA, Hb, and sex should be considered when assessing treatment response. Inflammatory biomarkers contribute to response prediction. Understanding these complex relationships can enhance personalized treatment approaches in rectal cancer patients.
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Affiliation(s)
- Yi-Hsuan Lai
- Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, Taiwan; (Y.-H.L.); (J.-T.T.); (M.-H.L.)
| | - Yu-Tien Chang
- School of Public Health, National Defense Medical Center, Taipei 114201, Taiwan;
| | - Yu-Jia Chang
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan;
| | - Jo-Ting Tsai
- Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, Taiwan; (Y.-H.L.); (J.-T.T.); (M.-H.L.)
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan;
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
| | - Ming-Hsien Li
- Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, Taiwan; (Y.-H.L.); (J.-T.T.); (M.-H.L.)
| | - Jang-Chun Lin
- Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, Taiwan; (Y.-H.L.); (J.-T.T.); (M.-H.L.)
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
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10
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Cloos AJ, Schissel M, Batra R, Donahue SR, Wenos CD, Kumar T, Leinicke JA, Thompson JS, Langenfeld SJ. Characteristics of pathologic complete response for locally advanced rectal cancer. Am J Surg 2023; 226:873-877. [PMID: 37460372 DOI: 10.1016/j.amjsurg.2023.07.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 07/09/2023] [Accepted: 07/11/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Neoadjuvant chemoradiation (NACRT) is the standard of care for locally advanced rectal cancers. The purpose of this study was to determine patient and tumor factors associated with a pathologic complete response (pCR). METHODS The National Surgical Quality Improvement Program proctectomy-targeted database was utilized to identify all patients from 2016 to 2020 who underwent NACRT followed by proctectomy with curative intent for T3-4N0-2 rectal cancers. RESULTS A total of 1891 patients were included, of which 253 (13.4%) demonstrated a pCR. Pretreatment N0 staging was associated with a higher rate of pCR (18.9%) when compared to N1 (6.7%) and N2 (6.7%) (p < 0.0001). Patients clinically staged at T3N0 had the highest rate of pCR (19.5%). Gender, age, race, weight, smoking status, and tumor height were not associated with pCR. CONCLUSIONS Patients with cN0 disease were more likely to experience a pCR compared to cN1-2 patients. Tumor height relative to anal verge or patient demographics were not associated with pCR.
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Affiliation(s)
- Adam J Cloos
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Makayla Schissel
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA
| | - Rishi Batra
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Steven R Donahue
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Chelsea D Wenos
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Terrence Kumar
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Jennifer A Leinicke
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Jon S Thompson
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sean J Langenfeld
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA. https://twitter.com/SeanLangenfeld
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11
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Santini D, Danti G, Bicci E, Galluzzo A, Bettarini S, Busoni S, Innocenti T, Galli A, Miele V. Radiomic Features Are Predictive of Response in Rectal Cancer Undergoing Therapy. Diagnostics (Basel) 2023; 13:2573. [PMID: 37568936 PMCID: PMC10417449 DOI: 10.3390/diagnostics13152573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 07/14/2023] [Accepted: 07/19/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Rectal cancer is a major mortality cause in the United States (US), and its treatment is based on individual risk factors for recurrence in each patient. In patients with rectal cancer, accurate assessment of response to chemoradiotherapy has increased in importance as the variety of treatment options has grown. In this scenario, a controversial non-operative approach may be considered in some patients for whom complete tumor regression is believed to have occurred. The recommended treatment for locally advanced rectal cancer (LARC, T3-4 ± N+) is total mesorectal excision (TME) after neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) has become a standard technique for local staging of rectal cancer (tumor, lymph node, and circumferential resection margin [CRM] staging), in both the US and Europe, and it is getting widely used for restaging purposes. AIM In our study, we aimed to use an MRI radiomic model to identify features linked to the different responses of chemoradiotherapy of rectal cancer before surgery, and whether these features are helpful to understand the effectiveness of the treatments. METHODS We retrospectively evaluated adult patients diagnosed with LARC who were subjected to at least 2 MRI examinations in 10-12 weeks at our hospital, before and after nCRT. The MRI acquisition protocol for the 2 exams included T2 sequence and apparent diffusion coefficient (ADC) map. The patients were divided into 2 groups according to the treatment response: complete or good responders (Group 1) and incomplete or poor responders (Group 2). MRI images were segmented, and quantitative features were extracted and compared between the two groups. Features that showed significant differences (SF) were then included in a LASSO regression method to build a radiomic-based predictive model. RESULTS We included 38 patients (26 males and 12 females), who are classified from T2 and T4 stages in the rectal cancer TNM. After the nCRT, the patients were divided into Group 1 (13 patients), complete or good responders, and Group 2 (25 patients), incomplete or poor responders. Analysis at baseline generated the following significant features for the Mann-Whitney test (out of a total of 107) for each sequence. Also, the analysis at the end of the follow-up yielded a high number of significant features for the Mann-Whitney test (out of a total of 107) for each image. Features selected by the LASSO regression method for each image analyzed; ROC curves relative to each model are represented. CONCLUSION We developed an MRI-based radiomic model that is able to differentiate and predict between responders and non-responders who went through nCRT for rectal cancer. This approach might identify early lesions with high surgical potential from lesions potentially resolving after medical treatment.
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Affiliation(s)
- Diletta Santini
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Ginevra Danti
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Eleonora Bicci
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Antonio Galluzzo
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Silvia Bettarini
- Department of Health Physics, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Simone Busoni
- Department of Health Physics, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Tommaso Innocenti
- Clinical Gastroenterology Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Andrea Galli
- Clinical Gastroenterology Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Vittorio Miele
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
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12
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Cho IJ, Jeong JU, Nam TK, Kim YH, Song JY, Yoon MS, Ahn SJ, Cho SH. Efficacy of hypofractionated preoperative chemoradiotherapy in rectal cancer. Oncol Lett 2023; 25:263. [PMID: 37216168 PMCID: PMC10193375 DOI: 10.3892/ol.2023.13849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 04/04/2023] [Indexed: 05/24/2023] Open
Abstract
The efficacy and toxicity of hypofractionated preoperative chemoradiotherapy (HPCRT) combined with oral capecitabine was evaluated in patients with rectal cancer. HPCRT was delivered by intensity-modulated radiotherapy of either 33 Gy to the whole pelvis or 35 Gy in 10 fractions to the primary tumor and 33 Gy to the surrounding pelvis. Surgery was performed 4-8 weeks after HPCRT completion. Oral capecitabine was administered concurrently. A total of 76 patients were eligible for this study, and patient numbers in clinical stages I, II, III and IVA were 5, 29, 36 and 6, respectively. Tumor response, toxicity and survival were analyzed. A total of 9/76 patients (11.8%) achieved a pathological complete response. Sphincter preservation was achieved in 23/32 (71.9%) and 44/44 (100%) of patients with a distal extent from the anal verge of ≤5 and >5 cm, respectively. A total of 28/76 patients (36.8%) achieved tumor-downstaging and 25/76 (32.9%) achieved nodal (N)-downstaging. The 5-year disease-free survival (DFS) and overall survival rates were 76.5% and 90.6%, respectively. In the multivariate analysis for DFS, pathological N stage and lymphovascular space invasion were notable prognostic factors. A total of 6 patients in stage IVA underwent salvage treatments for lung or liver metastasis after HPCRT completion, and all 6 were alive at the last follow-up. Only 4 patients experienced grade 3 postoperative complications. No grade 4 toxicities were observed. HPCRT of 33 or 35 Gy in 10 fractions showed similar results to those of long-course fractionation. This fractionation scheme could be beneficial for patients with early stage disease, locally advanced rectal cancer, simultaneous distant metastasis requiring early intervention or for patients who wish to avoid multiple hospital visits.
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Affiliation(s)
- Ick Joon Cho
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
| | - Jae-Uk Jeong
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
| | - Taek-Keun Nam
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
| | - Yong-Hyub Kim
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
| | - Ju-Young Song
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
| | - Mee Sun Yoon
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
| | - Sung-Ja Ahn
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
| | - Shin Haeng Cho
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Jeollanamdo 58128, Republic of Korea
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Benlice C, Koc MA, Gulcu B, Bilgin IA, Akyol C, Baca B, Ozturk E, Guney Y, Utkan G, Er O, Agaoglu F, Yildirim I, Avci N, Elhan AH, Kuzu MA. Short-Course Radiotherapy Followed by Consolidation Chemotherapy Is Safe and Effective in Locally Advanced Rectal Cancer: Comparative Short-term Results of Multicenter Propensity Score Case-Matched Study. Dis Colon Rectum 2023; 66:681-690. [PMID: 36856669 DOI: 10.1097/dcr.0000000000002646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
BACKGROUND Consolidation chemotherapy strategies have demonstrated improved pathological complete response and tumor downstaging rates for patients diagnosed with rectal cancer. OBJECTIVE This study aimed to compare perioperative outcomes and pathological complete response rates among different neoadjuvant treatment strategies in patients undergoing total mesorectal excision for locally advanced rectal cancer. DESIGN Propensity score case-matched study. SETTING High-volume tertiary care centers. PATIENTS Consecutive patients undergoing curative total mesorectal excision between January 2014 and June 2021 were queried. INTERVENTIONS Patients were divided into 3 groups: long-course chemoradiation therapy with (N = 128) or without (N = 164) consolidation chemotherapy or short-course radiotherapy (N = 53) followed by consolidation chemotherapy. MAIN OUTCOME MEASURES Demographics, preoperative tumor characteristics, histopathologic outcomes, and postoperative complication rates were reviewed and compared. Propensity score match analysis was conducted. RESULTS A total of 345 patients (mean age: 58 ± 12 years; female: 36%) met the study inclusion criteria. Time interval from neoadjuvant treatment until surgery was longer for patients receiving consolidation chemotherapy ( p < 0.001). Pathological complete response rates were comparable among patients receiving long-course chemoradiation therapy (20.3%) and short-course radiotherapy with consolidation chemotherapy (20.8%) compared to long-course chemoradiation therapy alone (14.6%) ( p = 0.36). After the propensity score case-matched analysis, 48 patients in the long-course chemoradiation therapy with consolidation chemotherapy group were matched to 48 patients in the short-course radiotherapy with consolidation chemotherapy group. Groups were comparable with respect to age, sex, clinical stage, tumor location, type of surgical approach, and technique. Pathological complete response rate was comparable between the groups (20.8% and 18.8%, p = 0.99). LIMITATIONS Study was limited by its retrospective nature. CONCLUSIONS Among recent neoadjuvant treatment modalities, pathological complete response rates, and short-term clinical outcomes were comparable. Short-course radiotherapy with consolidation chemotherapy is safe and effective as long-course chemoradiation therapy as in a short-term period. See Video Abstract at http://links.lww.com/DCR/C174 . LA RADIOTERAPIA DE CORTA DURACIN SEGUIDA DE QUIMIOTERAPIA DE CONSOLIDACIN ES SEGURA Y EFICAZ EN EL CNCER DE RECTO LOCALMENTE AVANZADO RESULTADOS COMPARATIVOS A CORTO PLAZO DEL ESTUDIO MULTICNTRICO DE CASOS EMPAREJADOS POR PUNTAJE DE PROPENSION ANTECEDENTES: Las estrategias de quimioterapia de consolidación han demostrado una mejor respuesta patológica completa y tasas de reducción del estadio del tumor para pacientes diagnosticados con cáncer de recto.OBJETIVO: Comparar los resultados perioperatorios y las tasas de respuesta patológica completa entre diferentes estrategias de tratamiento neoadyuvante en pacientes sometidos a escisión mesorrectal total por cáncer de recto localmente avanzado.DISEÑO: Estudio de casos emparejados por puntaje de propensión.ENTORNO CLINICO: Centros de atención terciaria de alto volumen.PACIENTES: Pacientes consecutivos sometidos a escisión mesorrectal total curativa por cáncer de recto localmente avanzado entre enero de 2014 y junio de 2021.INTERVENCIONES: Los pacientes se dividieron en tres grupos según la modalidad de tratamiento neoadyuvante: quimiorradioterapia de ciclo largo con (N = 128) o sin (N = 164) quimioterapia de consolidación o radioterapia de ciclo corto (N = 53) seguida de quimioterapia de consolidación.PRINCIPALES MEDIDAS DE RESULTADO: El punto final primario fue la respuesta patológica completa. Se revisaron y compararon los datos demográficos, las características preoperatorias del tumor, los resultados histopatológicos y las tasas de complicaciones posoperatorias entre los grupos de estudio. Se realizó un análisis de casos emparejados por puntaje de propensión.RESULTADOS: Un total de 345 pacientes (edad media de 58 ± 12 años y mujeres: 36%) cumplieron los criterios de inclusión del estudio. El intervalo de tiempo desde el tratamiento neoadyuvante hasta la cirugía fue mayor para los pacientes que recibieron quimioterapia de consolidación ( p < 0,001). Las tasas de respuesta patológica completa fueron comparables entre los pacientes que recibieron quimiorradioterapia de larga duración con quimioterapia de consolidación (20,3 %) y radioterapia de corta duración con quimioterapia de consolidación (20,8%) en comparación con la quimiorradiación de larga duración sola (14,6%) ( p = 0,36). Después del análisis de casos emparejados por puntaje de propensión, 48 pacientes en el grupo de quimiorradioterapia de ciclo largo con quimioterapia de consolidación se emparejaron con 48 pacientes en el grupo de radioterapia de ciclo corto con quimioterapia de consolidación. Los grupos fueron comparables con respecto a la edad, sexo, estadio clínico, ubicación del tumor, tipo de abordaje quirúrgico y la técnica. La tasa de respuesta patológica completa fue comparable entre los grupos (20,8% y 18,8%, p = 0,99). La morbilidad postoperatoria a los 30 días y las tasas de fuga anastomótica fueron similares.LIMITACIONES: El estudio estuvo limitado por su naturaleza retrospectiva.CONCLUSIONES: Entre las modalidades de tratamiento neoadyuvante recientes, las tasas de respuesta patológica completa y los resultados clínicos a corto plazo fueron comparables. La radioterapia de corta duración con quimioterapia de consolidación es segura y eficaz como terapia de quimiorradioterapia de larga duración en un período corto. Consulte Video Resumen en http://links.lww.com/DCR/C174 . (Traducción-Dr. Fidel Ruiz Healy ).
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Affiliation(s)
- Cigdem Benlice
- Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Mehmet Ali Koc
- Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Baris Gulcu
- Department of General Surgery, Bursa Medicana Hospital, Bursa, Turkey
| | - Ismail Ahmet Bilgin
- Department of General Surgery, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
| | - Cihangir Akyol
- Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Bilgi Baca
- Department of General Surgery, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
| | - Ersin Ozturk
- Department of General Surgery, Bursa Medicana Hospital, Bursa, Turkey
| | - Yildiz Guney
- Department of Radiation Oncology, Yuksek Ihtisas University, Memorial Ankara Hospital, Ankara, Turkey
| | - Gungor Utkan
- Department of Medical Oncology, Ankara University, Ankara, Turkey
| | - Ozlem Er
- Department of Medical Oncology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
| | - Fulya Agaoglu
- Department of Radiation Oncology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
| | - Ibrahim Yildirim
- Department of Radiation Oncology, Bursa Medicana Hospital, Bursa, Turkey
| | - Nilufer Avci
- Department of Medical Oncology, Bursa Medicana Hospital, Bursa, Turkey
| | - Atilla Halil Elhan
- Department of Biostatistics; Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Mehmet Ayhan Kuzu
- Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey
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14
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Fang Z, Pu H, Chen XL, Yuan Y, Zhang F, Li H. MRI radiomics signature to predict lymph node metastasis after neoadjuvant chemoradiation therapy in locally advanced rectal cancer. Abdom Radiol (NY) 2023; 48:2270-2283. [PMID: 37085730 DOI: 10.1007/s00261-023-03910-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 04/01/2023] [Accepted: 04/05/2023] [Indexed: 04/23/2023]
Abstract
PURPOSE To investigative the performance of MRI-radiomics analysis derived from T2WI and apparent diffusion coefficients (ADC) images before and after neoadjuvant chemoradiation therapy (nCRT) separately or simultaneously for predicting post-nCRT lymph node status in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Eighty-three patients (training cohort, n = 57; validation cohort, n = 26) with LARC between June 2017 and December 2022 were retrospectively enrolled. All the radiomics features were extracted from volume of interest on T2WI and ADC images from baseline and post-nCRT MRI. Delta-radiomics features were defined as the difference between radiomics features before and after nCRT. Seven clinical-radiomics models were constructed by combining the most predictive radiomics signatures and clinical parameters selected from support vector machine. Receiver operating characteristic curve (ROC) was used to evaluate the performance of models. The optimum model-based LNM was applied to assess 5-years disease-free survival (DFS) using Kaplan-Meier analysis. The end point was clinical or radiological locoregional recurrence or distant metastasis during postoperative follow-up. RESULTS Clinical-deltaADC radiomics combined model presented good performance for predicting post-CRT LNM in the training (AUC = 0.895,95%CI:0.838-0.953) and validation cohort (AUC = 0.900,95%CI:0.771-1.000). Clinical-deltaADC radiomics-postT2WI radiomics combined model also showed good performances (AUC = 0.913,95%CI:0.838-0.953) in the training and (AUC = 0.912,95%CI:0.771-1.000) validation cohort. As for subgroup analysis, clinical-deltaADC radiomics combined model showed good performance predicting LNM in ypT0-T2 (AUC = 0.827;95%CI:0.649-1.000) and ypT3-T4 stage (AUC = 0.934;95%CI:0.864-1.000). In ypT0-T2 stage, clinical-deltaADC radiomics combined model-based LNM could assess 5-years DFS (P = 0.030). CONCLUSION Clinical-deltaADC radiomics combined model could predict post-nCRT LNM, and this combined model-based LNM was associated with 5-years DFS in ypT0-T2 stage.
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Affiliation(s)
- Zhu Fang
- Department of Radiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, 32# Second Section of First Ring Road, Qingyang District, Chengdu, 610070, Sichuan, China
| | - Hong Pu
- Department of Radiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, 32# Second Section of First Ring Road, Qingyang District, Chengdu, 610070, Sichuan, China
| | - Xiao-Li Chen
- Department of Radiology, Affiliated Cancer Hospital of Medical School, University of Electronic Science and Technology of China, Sichuan Cancer Hospital, 55#Four Section of South Renmin Road, Wuhou District, Chengdu, 610000, China
| | - Yi Yuan
- Department of Radiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, 32# Second Section of First Ring Road, Qingyang District, Chengdu, 610070, Sichuan, China
| | - Feng Zhang
- Department of Radiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, 32# Second Section of First Ring Road, Qingyang District, Chengdu, 610070, Sichuan, China
| | - Hang Li
- Department of Radiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, 32# Second Section of First Ring Road, Qingyang District, Chengdu, 610070, Sichuan, China.
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15
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Abstract
The current preferred standard of care management for patients with locally advanced rectal cancer is total neoadjuvant therapy, in which all chemotherapy and radiotherapy is delivered before surgery. Within this approach, developed in response to persistently high distant failure rates despite excellent local control with preoperative chemoradiotherapy, there remains questions regarding the optimal radiotherapy regimen (short course vs long course) and sequencing of chemotherapy (induction vs consolidation).
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Affiliation(s)
- Timothy Lin
- Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD 21287, USA
| | - Amol Narang
- Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD 21287, USA.
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16
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Grotenhuis BA, Beets GL. Watch-and-Wait is an Option in Rectal Cancer Patients: From Controversy to Common Clinical Practice. Clin Oncol (R Coll Radiol) 2023; 35:124-129. [PMID: 36481218 DOI: 10.1016/j.clon.2022.11.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 10/26/2022] [Accepted: 11/14/2022] [Indexed: 12/12/2022]
Abstract
Overview of the introduction of organ preservation in rectal cancer patients and future challenges.
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Affiliation(s)
- B A Grotenhuis
- Department of Surgical Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - G L Beets
- GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
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17
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Sakamoto K, Okabayashi K, Matsui S, Seishima R, Shigeta K, Kitagawa Y. Association of Tumor Pathological Response with the Use of Metformin During Neoadjuvant Chemoradiotherapy in Rectal and Esophageal/Gastroesophageal Cancer Patients: a Systematic Review and Meta-analysis. J Gastrointest Surg 2022; 26:2227-2236. [PMID: 35829868 DOI: 10.1007/s11605-022-05354-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/30/2022] [Indexed: 01/31/2023]
Abstract
PURPOSE Metformin has been reported to be associated with improved cancer prognosis when used in combination with chemotherapy and/or radiotherapy. In this study, we present a systematic review and meta-analyses of studies evaluating the association of tumor pathological response with the use of metformin during neoadjuvant chemoradiotherapy (NACRT) in rectal and esophageal/gastroesophageal cancer patients. METHODS We systematically searched databases for articles that compared concurrent metformin use with no metformin use in cancer patients treated with NACRT following the PRISMA 2020. The design and quality of the collected studies were reviewed, and meta-analyses were performed on the pathologic complete response (pCR) rate, tumor regression grade (TRG), T factor downstaging, and N factor downstaging. RESULTS Three databases were searched, and 220 papers were screened. Five retrospective cohort study papers were eligible for the meta-analysis, with a total of 2041 patients. The included papers contained only rectal and esophageal/gastroesophageal cancers. In the metformin group, the pCR rate was 26% [20-32%], and metformin was associated with the pCR rate (odds ratio [OR] = 0.51 [0.34-0.76], p < 0.01). Meta-regression analysis of the pCR rate showed a positive correlation with adenocarcinoma (coefficient = 0.13 [0.02-0.25], p = 0.03) and fluoropyrimidine anticancer drug use (coefficient = 0.01 [0.001-0.02], p = 0.03). CONCLUSIONS The results suggest that metformin is associated with pCR rate when used in combination with NACRT. The association of metformin and pCR rate in combination with fluoropyrimidine anticancer drugs was observed mostly for adenocarcinoma patients.
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Affiliation(s)
- Kyoko Sakamoto
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan
| | - Koji Okabayashi
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan
| | - Shimpei Matsui
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan
| | - Ryo Seishima
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan
| | - Kohei Shigeta
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan
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18
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The Effect of Continuing Chemotherapy after Chemoradiotherapy during the Time to Surgery on Tumor Response and Survival for Local Advanced Rectal Cancer. JOURNAL OF ONCOLOGY 2022; 2022:4108677. [PMID: 36157223 PMCID: PMC9499766 DOI: 10.1155/2022/4108677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022]
Abstract
Aim The current standard treatment of locally advanced rectal carcinoma is total mesorectal excision and postoperative adjuvant chemotherapy after neoadjuvant concurrent chemoradiotherapy (NCRT). Many studies have shown that pathological complete response (pCR) is an important prognostic factor for patients receiving NCRT. Many studies have therefore been conducted to increase pCR rates by changing the perioperative treatment strategies. Prolonging the chemotherapy time may be a reasonable way to increase the effectiveness of NCRT, pCR, and survival rates. We investigated whether neoadjuvant consolidation chemotherapy had an effect on tumor response and survival. Methods The data of 163 patients diagnosed with locally advanced rectal carcinoma were evaluated. The data of 107 patients (Group 1) who were radiologically T3–T4 and/or N+ and received chemotherapy after NCRT until their operations were compared with the data of 56 patients (Group 2) who were operated after NCRT. Results Group 1 patients had tumor and node downstaging. Their pCR was found significantly higher than in Group 2 (p = 0.005). In Group 1 patients with T3, pCR was significantly higher than for those with T4. The elapsed time between NCRT and surgery was significantly longer in patients with pCR (respectively, p = 0.012 and p = 0.008). Conclusion Neoadjuvant consolidation chemotherapy after NCRT is a safe approach that can lead to higher pathological complete response rates. The time until surgery with neoadjuvant consolidation chemotherapy may provide the chance to follow the patient without surgery in addition to increasing pCR.
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19
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Beypinar I, Tercan M, Tugrul F. Three perspectives: the approach to neoadjuvant treatment of rectal cancer according to medical oncologists, radiation oncologists, and surgeons. MEDICAL SCIENCE PULSE 2022. [DOI: 10.5604/01.3001.0015.9812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background: Two treatment options considered for radiotherapy are short-course radiotherapy and immediate surgery, or chemoradiation with 5-Fluorouracil based chemotherapy and delayed surgery. Aim of the study: Evaluate the real-life treatment approaches of medical, radiation, and surgical oncologists, to neoadjuvant treatment of rectal cancers. Material and methods: An online survey was established via Google Forms. The survey was taken voluntarily by medical oncologists, radiation oncologists, surgical oncologists, and general surgeons. Results: Of those who participated, 183 were medical oncologists, 36 were radiotherapists, and 36 were surgeons. Most of the study population preferred long-course radiation therapy and chemotherapy (85%). Meanwhile, two-thirds of the participants preferred chemotherapy prior to operating. The most frequent chemotherapy cycles for the pre-operative setting were ‘three’ and ‘four-or-more’ (27.8% and 25.1%, respectively). Medical oncologists had a significantly higher tendency to offer chemotherapy between radiation therapy and surgery compared to the other groups. Optimal time of surgery was different between groups, but there was no difference among groups between surgery and the ‘watch & wait’ strategy. Neoadjuvant chemotherapy regimens were significantly different between groups. Conclusions: We found that the new pre-operative chemotherapy regimen with short-course radiotherapy was slowly adopted into current practice. Also, medical oncologists tended to prefer pre-operative chemotherapy in comparison to the other groups.
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Affiliation(s)
- Ismail Beypinar
- Department of Medical Oncology, Eskisehir City Hospital, Turkey
| | - Mustafa Tercan
- Department of Surgical Oncology, Eskisehir City Hospital, Turkey
| | - Fuzuli Tugrul
- Department of Radiation Oncology, Eskisehir City Hospital, Turkey
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20
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Emons G, Auslander N, Jo P, Kitz J, Azizian A, Hu Y, Hess CF, Roedel C, Sax U, Salinas G, Stroebel P, Kramer F, Beissbarth T, Grade M, Ghadimi M, Ruppin E, Ried T, Gaedcke J. Gene-expression profiles of pretreatment biopsies predict complete response of rectal cancer patients to preoperative chemoradiotherapy. Br J Cancer 2022; 127:766-775. [PMID: 35597871 PMCID: PMC9381580 DOI: 10.1038/s41416-022-01842-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 03/19/2022] [Accepted: 05/04/2022] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Preoperative (neoadjuvant) chemoradiotherapy (CRT) and total mesorectal excision is the standard treatment for rectal cancer patients (UICC stage II/III). Up to one-third of patients treated with CRT achieve a pathological complete response (pCR). These patients could be spared from surgery and its associated morbidity and mortality, and assigned to a "watch and wait" strategy. However, reliably identifying pCR based on clinical or imaging parameters remains challenging. EXPERIMENTAL DESIGN We generated gene-expression profiles of 175 patients with locally advanced rectal cancer enrolled in the CAO/ARO/AIO-94 and -04 trials. One hundred and sixty-one samples were used for building, training and validating a predictor of pCR using a machine learning algorithm. The performance of the classifier was validated in three independent cohorts, comprising 76 patients from (i) the CAO/ARO/AIO-94 and -04 trials (n = 14), (ii) a publicly available dataset (n = 38) and (iii) in 24 prospectively collected samples from the TransValid A trial. RESULTS A 21-transcript signature yielded the best classification of pCR in 161 patients (Sensitivity: 0.31; AUC: 0.81), when not allowing misclassification of non-complete-responders (False-positive rate = 0). The classifier remained robust when applied to three independent datasets (n = 76). CONCLUSION The classifier can identify >1/3 of rectal cancer patients with a pCR while never classifying patients with an incomplete response as having pCR. Importantly, we could validate this finding in three independent datasets, including a prospectively collected cohort. Therefore, this classifier could help select rectal cancer patients for a "watch and wait" strategy. TRANSLATIONAL RELEVANCE Forgoing surgery with its associated side effects could be an option for rectal cancer patients if the prediction of a pathological complete response (pCR) after preoperative chemoradiotherapy would be possible. Based on gene-expression profiles of 161 patients a classifier was developed and validated in three independent datasets (n = 76), identifying over 1/3 of patients with pCR, while never misclassifying a non-complete-responder. Therefore, the classifier can identify patients suited for "watch and wait".
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Affiliation(s)
- Georg Emons
- Section of Cancer Genomics, Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany
| | - Noam Auslander
- Section of Cancer Genomics, Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Program in Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA
| | - Peter Jo
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany
| | - Julia Kitz
- Department of Pathology, University Medical Center, Göttingen, Germany
| | - Azadeh Azizian
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany
| | - Yue Hu
- Section of Cancer Genomics, Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Clemens F Hess
- Department of Radiotherapy and Radio-oncology, University Medical Center, Göttingen, Germany
| | - Claus Roedel
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University, Frankfurt, Germany
| | - Ulrich Sax
- Department of Medical Informatics, University Medical Center, Göttingen, Germany
| | - Gabriela Salinas
- Transcriptome and Genome Analysis Laboratory (TAL), Department of Developmental Biochemistry, University of Göttingen, Göttingen, Germany
| | - Philipp Stroebel
- Department of Pathology, University Medical Center, Göttingen, Germany
| | - Frank Kramer
- Department of Medical Statistics, University Medical Center, Göttingen, Germany
| | - Tim Beissbarth
- Department of Medical Statistics, University Medical Center, Göttingen, Germany
| | - Marian Grade
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany
| | - Michael Ghadimi
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany
| | - Eytan Ruppin
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Thomas Ried
- Section of Cancer Genomics, Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jochen Gaedcke
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, Germany.
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21
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Lorenzon L, De Luca R, Santoro G, Parini D, Rega D, Mellano A, Vigorita V, Jiménez-Rosellón R, Sandin M, Andriola V, Gallo G, Marino G, Turati L, Marsanic P, Marano L, Lucarini A, Aprile A, Sagnotta A, Biondi A. Pathologic stage of ypT0N+ rectal cancers following neo-adjuvant treatment: clinical interpretation of an orphan status. Pathol Res Pract 2022; 237:154002. [PMID: 35849868 DOI: 10.1016/j.prp.2022.154002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 11/26/2022]
Abstract
Approximately 20% of locally advanced rectal cancers treated with neoadjuvant therapy achieve a pathologic complete response, but approximately 10% of them present residual nodal metastases (ypT0N+). We aimed this research to compare the survival rates of ypT0/ypTisN+ and stage 3a rectal cancer patients. A large multicenter study recently investigated ypT0/ypTis rectal cancers treated between 2005 and 2015 in Italy and Spain. ypT0/ypTisN+ were selected and compared with stage 3a rectal cancers treated at the same institutions with upfront surgery (ySICO group). Additionally, the SEER database was searched for patients with stage 3a rectal cancers treated with surgery in the same years. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were analyzed using Kaplan-Meier curves and random survival forest analysis (RSF). The ySICO study population consisted of 19 ypT0/2ypTisN+ (mean follow-up 41.8 months) and 72 Stage 3a patients (mean follow-up 56.9 months). These subgroups were comparable, but stage 3a patients were treated more frequently with adjuvant therapy (90.5% vs 61.9%, p 0.0001). No significant differences were reported between the ySICO subgroups for the OS, DFS, and DSS curves. When the 1213 SEER patients were added to Stage 3a, the RFS model failed to differentiate OS between groups that presented identical survival. Root analysis showed that adjuvant therapy was the only variable differentiating OS and DSS in the ySICO population. These findings suggest that ypT0/ypTisN+ and stage 3a rectal cancers could be ranked together based on their similar outcomes and pathologic assessment, and they stress the importance of adjuvant therapy in patients presenting with residual nodal metastases.
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Affiliation(s)
- Laura Lorenzon
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University, Rome, Italy; Surgical and Medical Department of Translational Medicine, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Italy.
| | - Raffaele De Luca
- Department of Surgical Oncology, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Gloria Santoro
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University, Rome, Italy
| | - Dario Parini
- General Surgery Unit, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - Daniela Rega
- Colorectal Surgical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale IRCCS, Naples, Italy
| | - Alfredo Mellano
- Surgical Oncology Unit, Candiolo Cancer Institute - IRCCS - Candiolo Cancer Institute - IRCCS, Turin, Italy
| | - Vincenzo Vigorita
- Unit of Coloproctology, Department of General and Digestive Surgery, University Hospital Complex of Vigo Alvaro Conquieiro Hospital, Vigo, Spain
| | | | - Marta Sandin
- Department of Medicine, Surgery and Neurosciences - Unit of General Surgery and Surgical Oncology, University of Siena, Italy
| | | | - Gaetano Gallo
- Coloproctology Unit, Santa Rita Clinic, Vercelli, Italy
| | - Graziella Marino
- Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, Potenza, Italy
| | - Luca Turati
- Surgical Oncology Unit, Treviglio Hospital, ASST Bergamo Ovest, Italy; UOC Chirurgia Generale, Ospedale La Memoria di Garvado, ASST Garda, Italy
| | - Patrizia Marsanic
- Surgical Oncology Unit, Candiolo Cancer Institute - IRCCS - Candiolo Cancer Institute - IRCCS, Turin, Italy; Ospedale Edoardo Agnelli, Pinerolo, Turin, Italy
| | - Luigi Marano
- Department of Medicine, Surgery and Neurosciences - Unit of General Surgery and Surgical Oncology, University of Siena, Italy; Multidisciplinary Robotic Surgery Unit, "San Matteo degli Infermi Hospital" - ASL Umbria 2, Spoleto, Perugia, Italy
| | - Alessio Lucarini
- Surgical and Medical Department of Translational Medicine, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Italy
| | - Alessandra Aprile
- Oncologic Surgical Unit, Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Sagnotta
- Department of General Surgery and Surgical Oncology, San Filippo Neri Hospital, Roma, Italy
| | - Alberto Biondi
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University, Rome, Italy
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22
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Lou X, Zhou N, Feng L, Li Z, Fang Y, Fan X, Ling Y, Liu H, Zou X, Wang J, Huang J, Yun J, Yao J, Huang Y. Deep Learning Model for Predicting the Pathological Complete Response to Neoadjuvant Chemoradiotherapy of Locally Advanced Rectal Cancer. Front Oncol 2022; 12:807264. [PMID: 35756653 PMCID: PMC9214314 DOI: 10.3389/fonc.2022.807264] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 05/02/2022] [Indexed: 12/24/2022] Open
Abstract
Objective This study aimed to develop an artificial intelligence model for predicting the pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) of locally advanced rectal cancer (LARC) using digital pathological images. Background nCRT followed by total mesorectal excision (TME) is a standard treatment strategy for patients with LARC. Predicting the PCR to nCRT of LARC remine difficulty. Methods 842 LARC patients treated with standard nCRT from three medical centers were retrospectively recruited and subgrouped into the training, testing and external validation sets. Treatment response was classified as pCR and non-pCR based on the pathological diagnosis after surgery as the ground truth. The hematoxylin & eosin (H&E)-stained biopsy slides were manually annotated and used to develop a deep pathological complete response (DeepPCR) prediction model by deep learning. Results The proposed DeepPCR model achieved an AUC-ROC of 0.710 (95% CI: 0.595, 0.808) in the testing cohort. Similarly, in the external validation cohort, the DeepPCR model achieved an AUC-ROC of 0.723 (95% CI: 0.591, 0.844). The sensitivity and specificity of the DeepPCR model were 72.6% and 46.9% in the testing set and 72.5% and 62.7% in the external validation cohort, respectively. Multivariate logistic regression analysis showed that the DeepPCR model was an independent predictive factor of nCRT (P=0.008 and P=0.004 for the testing set and external validation set, respectively). Conclusions The DeepPCR model showed high accuracy in predicting pCR and served as an independent predictive factor for pCR. The model can be used to assist in clinical treatment decision making before surgery.
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Affiliation(s)
- Xiaoying Lou
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Lili Feng
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Radiation Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhenhui Li
- Department of Pathology, Yunnan Cancer Hospital, Kunming, China
| | - Yuqi Fang
- Tencent AI Lab, Shenzhen, China.,Department of Electronic Engineering, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Xinjuan Fan
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yihong Ling
- Department of Pathology, Cancer Center of Sun Yat-sen University, Guangzhou, China
| | - Hailing Liu
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuan Zou
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jing Wang
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Jingping Yun
- Department of Pathology, Cancer Center of Sun Yat-sen University, Guangzhou, China
| | | | - Yan Huang
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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23
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Value of intravoxel incoherent motion for assessment of lymph node status and tumor response after chemoradiation therapy in locally advanced rectal cancer. Eur J Radiol 2022; 146:110106. [DOI: 10.1016/j.ejrad.2021.110106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 11/12/2021] [Accepted: 12/08/2021] [Indexed: 12/23/2022]
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Ding M, Zhang J, Hu H, Cai Y, Ling J, Wu Z, Xie X, Li J, Li W, Deng Y. mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: A Propensity Score Matching Analysis. Clin Colorectal Cancer 2021; 21:e12-e20. [PMID: 34963563 DOI: 10.1016/j.clcc.2021.11.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 11/10/2021] [Accepted: 11/23/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Preoperative chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, CRT failed to impact metastatic recurrence and the risk of side effects on bowel and genitourinary remained a concern. Neoadjuvant chemotherapy alone with mFOLFOX6 or FOLFOXIRI had been investigated in LARC. Here, we tried to compare the efficacy of mFOLFOXIRI with mFOLFOX6 as neoadjuvant chemotherapy in LARC. PATIENTS AND METHODS Between January 2014 and December 2019, patients with LARC receiving neoadjuvant chemotherapy with mFOLFOXIRI or mFOLFOX6 were retrospective analyzed, including data from a prospective trial (NCT02217020). All patients underwent total mesorectal excision (TME). The propensity-score matching was preformed to adjust baseline potential confounders and to estimate differences in outcomes between patients receiving mFOLFOXIRI and mFOLFOX6. Survival analysis was done using Kaplan-Meier analysis and Cox proportional regression analysis. RESULTS The median follow-up time was 31.1 months. After propensity score matching, 156 patients were available for comparison in each group. The pathological complete response (pCR) rate was 17.9% vs. 5.1% (P< .001), the incidence rate of anastomotic fistula was 3.2% vs. 9% (P = .03), the 3 year disease-free survival (DFS) rate was 75% vs. 66.7% (P = .047) and the distant metastasis rate was 16.4% versus 26.6% (P = .013) for mFOLFOXIRI and mFOLFOX6 group, respectively. Patients receiving mFOLFOXIRI had higher incidence of grade III and/or IV nausea and/or vomiting (7.6% vs. 2.5%, P = .04). CONCLUSIONS Neoadjuvant mFOLFOXIRI regimens improved pCR rate and survival outcome, reduced the rate of distant metastasis and anastomotic fistula when comparing with propensity-score matched controls of mFOLFOX6 neoadjuvant chemotherapy. MICROABSTRACT This trial assessed the short-term and long-term effects of neoadjuvant chemotherapy with mFOLFOXIRI and mFOLFOX6 in patients with locally advanced rectal cancer. Comparing with propensity-score matched historical control of chemoradiotherapy, neoadjuvant mFOLFOXIRI chemotherapy was well tolerated and led to higher rates of 3 year disease-free survival in patients with locally advanced rectal cancer.
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Affiliation(s)
- Miaomiao Ding
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Jianwei Zhang
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Huabin Hu
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Yue Cai
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Jiayu Ling
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Zehua Wu
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Xiaoyu Xie
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Jianxia Li
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Weiwei Li
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China
| | - Yanhong Deng
- Department of Medical Oncology, Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, P.R. China.
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Kim MJ, Lee TG. Transanal minimally invasive surgery using laparoscopic instruments of the rectum: A review. World J Gastrointest Surg 2021; 13:1149-1165. [PMID: 34754384 PMCID: PMC8554714 DOI: 10.4240/wjgs.v13.i10.1149] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 07/18/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Transanal minimally invasive surgery (TAMIS) was first described in 2010 as an alternative to transanal endoscopic microsurgery (TEM). The TAMIS technique can be access to the proximal and mid-rectum for resection of benign and early-stage malignant rectal lesions and also used for noncurative intent surgery of more advanced lesions in patients who are not candidates for radical surgery. TAMIS has a shorter learning curve, reduced device setup time, flexibility in instrument use, and versatility in application than TEM. Also, TAMIS shows similar results in a view of the operation time, conversion rate, reoperation rate, and complication to TEM. For these reasons, TAMIS is an easily accessible, technically feasible, and cost-effective alternative to TEM. Overall, TAMIS has enabled the performance of high-quality local excision of rectal lesions by many colorectal surgeons. As TAMIS becomes more broadly utilized such as pelvic abscess drainage, rectal stenosis, and treatment of anastomotic dehiscence, the acquisition of appropriate training must be ensured, and the continued assessment and assurance of outcome must be maintained.
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Affiliation(s)
- Myung Jo Kim
- Department of Surgery, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju 28644, South Korea
| | - Taek-Gu Lee
- Department of Surgery, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju 28644, South Korea
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Cui CL, Luo WY, Cosman BC, Eisenstein S, Simpson D, Ramamoorthy S, Murphy J, Lopez N. Cost Effectiveness of Watch and Wait Versus Resection in Rectal Cancer Patients with Complete Clinical Response to Neoadjuvant Chemoradiation. Ann Surg Oncol 2021; 29:1894-1907. [PMID: 34529175 PMCID: PMC8810473 DOI: 10.1245/s10434-021-10576-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 06/22/2021] [Indexed: 01/04/2023]
Abstract
BACKGROUND Watch and wait (WW) protocols have gained increasing popularity for patients diagnosed with locally advanced rectal cancer and presumed complete clinical response after neoadjuvant chemoradiation. While studies have demonstrated comparable survival and recurrence rates between WW and radical surgery, the decision to undergo surgery has significant effects on patient quality of life. We sought to conduct a cost-effectiveness analysis comparing WW with abdominoperineal resection (APR) and low anterior resection (LAR) among patients with stage II/III rectal cancer. METHODS In this comparative-effectiveness study, we built Markov microsimulation models to simulate disease progression, death, costs, and quality-adjusted life-years (QALYs) for WW or APR/LAR. We assessed cost effectiveness using the incremental cost-effectiveness ratio (ICER), with ICERs under $100,000/QALY considered cost effective. Probabilities of disease progression, death, and health utilities were extracted from published, peer-reviewed literature. We assessed costs from the payer perspective. RESULTS WW dominated both LAR and APR at a willingness to pay (WTP) threshold of $100,000. Our model was most sensitive to rates of distant recurrence and regrowth after WW. Probabilistic sensitivity analysis demonstrated that WW was the dominant strategy over both APR and LAR over 100% of iterations across a range of WTP thresholds from $0-250,000. CONCLUSIONS Our study suggests WW could reduce overall costs and increase effectiveness compared with either LAR or APR. Additional clinical research is needed to confirm the clinical efficacy and cost effectiveness of WW compared with surgery in rectal cancer.
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Affiliation(s)
- Christina Liu Cui
- School of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - William Yu Luo
- School of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Bard Clifford Cosman
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, San Diego Health Systems, La Jolla, CA, 92093-0987, USA.,Veterans Affairs San Diego Medical Center, San Diego, CA, USA
| | - Samuel Eisenstein
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, San Diego Health Systems, La Jolla, CA, 92093-0987, USA
| | - Daniel Simpson
- Department of Radiation Medicine and Applied Science, University of California, San Diego, La Jolla, CA, USA
| | - Sonia Ramamoorthy
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, San Diego Health Systems, La Jolla, CA, 92093-0987, USA
| | - James Murphy
- Department of Radiation Medicine and Applied Science, University of California, San Diego, La Jolla, CA, USA
| | - Nicole Lopez
- Department of Surgery, Division of Colon and Rectal Surgery, University of California, San Diego Health Systems, La Jolla, CA, 92093-0987, USA.
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27
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Baloyiannis I, Perivoliotis K, Vederaki S, Koukoulis G, Symeonidis D, Tzovaras G. Current evidence regarding the role of adjuvant chemotherapy in rectal cancer patients with pathologic complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Int J Colorectal Dis 2021; 36:1395-1406. [PMID: 33772323 DOI: 10.1007/s00384-021-03915-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/18/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of this meta-analysis was to investigate the role of adjuvant chemotherapy (AC) in rectal cancer patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) and curative resection. METHODS This study was completed in accordance to the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The electronic scholar databases (Medline, Web of Science, Scopus) were screened for eligible articles. The level of evidence (LoE) was assessed using the GRADE methodology. RESULTS Overall, 23 non-randomized studies and 17,406 patients were included in the present meta-analysis. Pooled comparisons confirmed that AC improved overall survival (HR: 0.68, p=0.0003), but not disease-free (p=0.22) and recurrence-free survival (p=0.39). However, the LoE for all outcomes was characterized as "very low," due to the absence of RCTs. CONCLUSIONS Considering the study limitations and the lack of randomized studies, further high-quality RCTs are required to confirm the findings of our study.
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Affiliation(s)
- Ioannis Baloyiannis
- Department of Surgery, University Hospital of Larissa, Mezourlo, 41110, Larissa, Greece
| | | | - Styliani Vederaki
- Faculty of Medicine, University of Thessaly, Mezourlo, 41110, Larissa, Greece
| | - Georgios Koukoulis
- Faculty of Medicine, University of Thessaly, Mezourlo, 41110, Larissa, Greece
- Department of Surgery, Koutlimbaneio and Triantafylleio General Hospital of Larissa, Larissa, Greece
| | - Dimitrios Symeonidis
- Department of Surgery, University Hospital of Larissa, Mezourlo, 41110, Larissa, Greece
| | - George Tzovaras
- Department of Surgery, University Hospital of Larissa, Mezourlo, 41110, Larissa, Greece
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Rubio J, Cristóbal I, Santos A, Caramés C, Luque M, Sanz-Alvarez M, Zazo S, Madoz-Gúrpide J, Rojo F, García-Foncillas J. Low MicroRNA-19b Expression Shows a Promising Clinical Impact in Locally Advanced Rectal Cancer. Cancers (Basel) 2021; 13:cancers13061456. [PMID: 33810186 PMCID: PMC8005118 DOI: 10.3390/cancers13061456] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 03/08/2021] [Accepted: 03/19/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary The establishment of molecular markers to predict response to neoadjuvant chemoradiotherapy (CRT) would help to avoid unnecessary toxicities and surgery delays in the clinical management of locally advanced rectal cancer (LARC) patients. Our aim here was to in-vestigate the clinical impact of miR-19b in this disease. Interestingly, our findings highlight the potential usefulness of miR-19b as a predictor of response to neoadjuvant CRT and outcome, and suggest PPP2R5E as a relevant miR-19b target in LARC. Abstract The standard treatment for patients with locally advanced colorectal cancer (LARC) is neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy (CRT) followed by surgical mesorectal excision. However, the lack of response to this preoperative treatment strongly compromises patient outcomes and leads to surgical delays and undesired toxicities in those non-responder cases. Thus, the identification of effective and robust biomarkers to predict response to preoperative CRT represents an urgent need in the current clinical management of LARC. The oncomiR microRNA-19b (miR-19b) has been reported to functionally play oncogenic roles in colorectal cancer (CRC) cells as well as regulate 5-FU sensitivity and determine outcome in CRC patients. However, its clinical impact in LARC has not been previously investigated. Here, we show that miR-19b deregulation is a common event in this disease, and its decreased expression significantly associates with lower tumor size after CRT (p = 0.003), early pathological stage (p = 0.003), and absence of recurrence (p = 0.001) in LARC patients. Interestingly, low miR-19b expression shows a predictive value of better response to neoajuvant CRT (p < 0.001), and the subgroup of LARC patients with low miR-19b levels have a markedly longer overall (p = 0.003) and event-free survival (p = 0.023). Finally, multivariate analyses determined that miR-19b independently predicts both patient outcome and response to preoperative CRT, highlighting its potential clinical usefulness in the management of LARC patients.
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Affiliation(s)
- Jaime Rubio
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (J.R.); (A.S.); (C.C.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
- Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
| | - Ion Cristóbal
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (J.R.); (A.S.); (C.C.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
- Correspondence: (I.C.); (J.G.-F.); Tel.: +34-915504800 (I.C. & J.G-F.)
| | - Andrea Santos
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (J.R.); (A.S.); (C.C.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
| | - Cristina Caramés
- Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (J.R.); (A.S.); (C.C.)
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
- Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
| | - Melani Luque
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.L.); (M.S.-A.); (S.Z.); (J.M.-G.); (F.R.)
| | - Marta Sanz-Alvarez
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.L.); (M.S.-A.); (S.Z.); (J.M.-G.); (F.R.)
| | - Sandra Zazo
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.L.); (M.S.-A.); (S.Z.); (J.M.-G.); (F.R.)
| | - Juan Madoz-Gúrpide
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.L.); (M.S.-A.); (S.Z.); (J.M.-G.); (F.R.)
| | - Federico Rojo
- Pathology Department, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain; (M.L.); (M.S.-A.); (S.Z.); (J.M.-G.); (F.R.)
| | - Jesús García-Foncillas
- Translational Oncology Division, Oncohealth Institute, IIS- Fundación Jiménez Díaz-UAM, E-28040 Madrid, Spain
- Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, E-28040 Madrid, Spain
- Correspondence: (I.C.); (J.G.-F.); Tel.: +34-915504800 (I.C. & J.G-F.)
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Wang Y, Chen L, Zhang B, Song W, Zhou G, Xie L, Yu D. Pretreatment Inflammatory-Nutritional Biomarkers Predict Responses to Neoadjuvant Chemoradiotherapy and Survival in Locally Advanced Rectal Cancer. Front Oncol 2021; 11:639909. [PMID: 33816284 PMCID: PMC8010250 DOI: 10.3389/fonc.2021.639909] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 02/03/2021] [Indexed: 12/18/2022] Open
Abstract
Background To evaluate the value of pretreatment inflammatory-nutritional biomarkers in predicting responses to neoadjuvant chemoradiotherapy (nCRT) and survival in patients with locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent nCRT and subsequent surgery between October 2012 and December 2019 were considered for inclusion. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prognostic nutritional index (PNI) were calculated from according to routine laboratory data within 1 week prior to nCRT. The correlations between baseline inflammatory-nutritional biomarkers and responses were analyzed using Chi-square test or Fisher’s exact test, and multivariate logistic regression analysis was performed to identify the independent predictors of pathological responses to nCRT. Univariate and multivariate Cox proportional hazard models were used to assess the correlations of predictors with disease-free survival (DFS) and overall survival (OS). Results A total of 273 patients with LARC were enrolled in this study. Higher LMR and PNI were observed in the good-response group, meanwhile higher NLR and PLR were observed in the poor-response group. Multivariate logistic regression analysis results revealed that PLR and PNI independently predicted responses to nCRT. Multivariable Cox regression analysis determined that PNI was an independent predictor of DFS and OS in patients with LARC. The value of pretreatment PNI in predicting responses and survival was continuously superior to those of NLR, PLR, and LMR. The optimal cutoff value of the PNI was approximate 45. Subgroup analyses indicated that the pathological responses and survival in the high PNI group (≥ 45) were significantly better than those in the low PNI group (< 45), especially in patients with clinical stage III rectal cancer. Conclusion The pretreatment PNI can serve as a promising predictor of response to nCRT and survival in patients with LACR, which is superior to NLR, PLR, and LMR, and the patients with clinical stage III rectal cancer who have a higher PNI are more likely to benefit from nCRT.
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Affiliation(s)
- Yijun Wang
- Department of Radiation Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lejun Chen
- Department of Radiation Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Biyun Zhang
- Department of Radiation Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Wei Song
- Department of Radiation Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Guowei Zhou
- Department of General Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Ling Xie
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Dahai Yu
- Department of Radiation Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Lu YJ, Chen CH, Lin EK, Wu SY. Neoadjuvant concurrent chemoradiotherapy followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery for low-lying rectal adenocarcinoma: a single center study. World J Surg Oncol 2020; 18:198. [PMID: 32782005 PMCID: PMC7422550 DOI: 10.1186/s12957-020-01980-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/31/2020] [Indexed: 11/10/2022] Open
Abstract
Purpose To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma. Methods and materials A total of 23 patients with clinical stage II-III low-lying (from anal verge 0-8 cm) rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student’s t testing were used to make parametric comparisons, and Fisher’s exact test or the Mann–Whitney U test were used to make nonparametric comparisons. Results Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 min and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested was 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS. Conclusion TaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT.
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Affiliation(s)
- Yen-Jung Lu
- Department of Colorectal Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chien-Hsin Chen
- Department of Colorectal Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - En-Kwang Lin
- Department of Colorectal Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Szu-Yuan Wu
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan. .,Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, No. 83, Nanchang St., Luodong Township, Yilan County, 265, Taiwan. .,Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. .,Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan. .,Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan. .,School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
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31
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Lino-Silva LS, Guzmán-López JC, Salazar-García JA, Chávez-Hernández JD, Gamboa-Domínguez A, Chiquete E, Mohar A, Morales-Soto J, Salcedo-Hernández RA. Interobserver Variability in Assessing Pathologic Response to Preoperative Treatment in Rectal Cancer: Standardization of an Evaluation Method and Comparisons Between Published Scales. J Gastrointest Cancer 2020; 51:709-713. [PMID: 31760577 DOI: 10.1007/s12029-019-00331-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Evaluating tumor response of rectal cancer to preoperative chemoradiotherapy (NCRT) has a prognostic value on overall survival; however, grading tumor response is a controversial issue due to lack of reproducibility and the lack of information about the standardization of the evaluation. METHODS We performed this study to examine the variability between observers' assessment of the pathological responses to NCRT using a systematic quantitative grading system based on a percentage of tumor response against the proportion of residual tumor burden. As a secondary aim, we classified the tumor response according to six published systems to determine the correlation between the observers into each grading system. RESULTS From 70 cases, the mean age was 60.6 ± 11.78 years, 36 (51.47%) patients were female, the pathological T stage was pT3 in 48.6% of cases, pT2 in 32.9%, pT1 in 11.4% and 7.1% in pT4, whereas 40% had lymph node metastasis. The median lymph node count was ten lymph nodes (range 6-43). Our method of tumor regression evaluation has a good intraclass correlation (ICC) value. From the scales compared regarding interobserver agreement, the Ryan's and Royal College of Pathologists showed fair agreement (but good ICC); the scales from Dworak, Becker, and Rizk showed substantial agreement (and good to excellent ICC values); and the scale from Rödel showed almost-perfect agreement. RESULTS All the evaluated systems showed good interobserver agreement, but the best interobserver agreement was reached with the Rödel's scale.
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Affiliation(s)
- Leonardo S Lino-Silva
- AFINES program, Medicine Faculty, Mexico's National Autonomus University (UNAM), Mexico City, Mexico.
- Gastrointestinal Pathology Division, Instituto Nacional de Cancerología de México (Mexico's National Cancer Institute), Av. San Fernando # 22, Sección XVI, Tlalpan, CP 14080, Mexico city, Mexico.
| | - Janet C Guzmán-López
- Gastrointestinal Pathology Division, Instituto Nacional de Cancerología de México (Mexico's National Cancer Institute), Av. San Fernando # 22, Sección XVI, Tlalpan, CP 14080, Mexico city, Mexico
| | - Jenny A Salazar-García
- AFINES program, Medicine Faculty, Mexico's National Autonomus University (UNAM), Mexico City, Mexico
| | - Jazmín D Chávez-Hernández
- Gastrointestinal Pathology Division, Instituto Nacional de Cancerología de México (Mexico's National Cancer Institute), Av. San Fernando # 22, Sección XVI, Tlalpan, CP 14080, Mexico city, Mexico
| | - Armando Gamboa-Domínguez
- Surgical pathology, Medical Sciences and Nutrition National Institute "Salvador Zubirán", Mexico City, Mexico
| | - Erwin Chiquete
- Neurology división, Medical Sciences and Nutrition National Institute "Salvador Zubirán", Mexico City, Mexico
| | - Alejandro Mohar
- Biomedics Research Institute, Mexico's National Autonomus University (UNAM), Mexico City, Mexico
| | - Jonathan Morales-Soto
- AFINES program, Medicine Faculty, Mexico's National Autonomus University (UNAM), Mexico City, Mexico
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32
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Peltrini R, Sacco M, Luglio G, Bucci L. Local excision following chemoradiotherapy in T2-T3 rectal cancer: current status and critical appraisal. Updates Surg 2020; 72:29-37. [PMID: 31621033 DOI: 10.1007/s13304-019-00689-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 10/10/2019] [Indexed: 12/18/2022]
Abstract
Local excision following chemoradiotherapy in rectal cancer is an organ-preserving procedure which aims at reducing morbidity and functional disorders associated with total mesorectal excision (TME) in selected patients. Although TME after chemoradiotherapy remains the gold standard for locally advanced mid and low rectal cancer, in the last years multicenter research trials have offered encouraging oncologic results which have allowed to preserve the rectum in patients with a pathologic complete response after chemoradiotherapy. A review of the available literature on this topic was conducted to define the state of the art of this conservative approach and to focus on the most controversial aspects concerning local excision performed after chemoradiotherapy, in particular tumor scatter and lymph node status, completion and salvage surgery, morbidity and quality of life. The analysis of these topics should be considered, in trial setting or in current practice, for their clinical implications. Oncologic outcomes of recent trials are encouraging for part of the patients presenting T2 rectal cancer; however, TME still remains the standard treatment in clinical practice. In such cases, local excision should include a surgical safety margin of at least 1 cm from the resection margin to achieve a true negative margin from residual tumor cells. The selection of the patients should be carefully performed and their consensus extremely detailed because TME is necessary in about 30% of cases. Failing that, morbidity and quality of life are negatively affected. However, about half of these patients refuse radical surgery (45%), thus undergoing only palliative care.
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Affiliation(s)
- Roberto Peltrini
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
| | - Michele Sacco
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Gaetano Luglio
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Luigi Bucci
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
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Manceau G, Margot N, Augustin J, Bardier A, Simon JM, Bachet JB, Spano JP, Maingon P, Vaillant JC, Karoui M. YpN0 rectal cancer patients with sterilized lymph nodes after neoadjuvant chemoradiotherapy are of greater risk of recurrence. Dig Liver Dis 2020; 52:214-220. [PMID: 31427089 DOI: 10.1016/j.dld.2019.07.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 07/13/2019] [Accepted: 07/17/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Indication for adjuvant chemotherapy in ypN0 rectal cancer patients after chemoradiotherapy (CRT) is debated. The clinical significance of the presence of sterilized lymph nodes (LNS) in ypN0 patients remains to be determined. AIMS To assess the prognostic value of LNS in ypN0 rectal cancers after neoadjuvant CRT. METHODS From 2006-2016, 235 patients underwent TME surgery for non-metastatic mid-low rectal cancer after CRT. A lymph node was considered sterilized if there were signs of treatment response (fibrosis, necrosis or mucus) without residual tumor cells. RESULTS 180 patients (77%) were classified ypN0 and 55 (23%) ypN+. LNS was present in 20 patients (9%). In ypN0 patients, 5-year OS was similar between patients with and without LNS. In contrast, 5-year DFS was significantly lower in ypN0/LNS + patients (58% vs. 78%, p = 0.043) and was similar to those staged ypN+. In multivariate analysis, two factors were independent predictors of DFS: mesorectal grading (OR = 3.14; 95%CI: 1.10-8.34; p = 0.033) and the presence of LNS (OR = 3.93, 95% CI: 1.06-11.81, p = 0.042) CONCLUSION: The presence of LNS in ypN0 rectal cancer after neoadjuvant CRT is associated with an increased risk of recurrence and may be taken into account for the discussion of adjuvant chemotherapy.
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Affiliation(s)
- Gilles Manceau
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Nicolas Margot
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Jeremy Augustin
- Department of Pathology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Armelle Bardier
- Department of Pathology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Jean-Marc Simon
- Department of Radiotherapy, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Jean-Baptiste Bachet
- Department of Hepato-Gastroenterology and Digestive Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Jean-Philippe Spano
- Department of Medical Oncology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Philippe Maingon
- Department of Radiotherapy, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Jean-Christophe Vaillant
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France
| | - Mehdi Karoui
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Paris, France.
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Kammar P, Chaturvedi A, Sivasanker M, de’Souza A, Engineer R, Ostwal V, Saklani A. Impact of delaying surgery after chemoradiation in rectal cancer: outcomes from a tertiary cancer centre in India. J Gastrointest Oncol 2020; 11:13-22. [PMID: 32175101 PMCID: PMC7052773 DOI: 10.21037/jgo.2019.12.04] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 11/06/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Delaying surgery after chemoradiation is one of the strategies for increasing tumor regression in rectal cancer. Tumour regression and PCR are known to have positive impact on survival. METHODS It's a retrospective study of 161 patients undergoing surgery after neoadjuvant chemoradiation (NCRT) for locally advanced rectal cancer (LARC). Patients were divided into three categories based on the gap between NCRT and surgery, i.e., <8, 8-12 and >12 weeks. Tumor regression grades (TRG), sphincter preservation, post-operative morbidity-mortality and survival were evaluated. RESULTS Sphincter preservation was significantly less in >12 weeks group compared to the other two groups (P=0.003). Intraoperative blood loss was significantly higher in >12 weeks group compared to 8-12 weeks group (P=0.001).There was no difference in major postoperative morbidity and hospital stay among the groups. There was no significant correlation between delay and TRG (P=0.644). At Median follow up of 49.5 months the projected 3-year overall survival (OS) and disease free survival (DFS) were not significantly different among the 3 groups (OS: 79.5% vs. 83.3% vs. 76.5%; P=0.849 and DFS 50.4% vs. 70.6% vs. 62%; P=0.270 respectively). CONCLUSIONS Delaying surgery by more than 12 weeks causes more blood loss but no change in morbidity or hospital stay. Increased time interval between radiation and surgery does not improve tumor regression and has no effect on survival.
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Affiliation(s)
- Praveen Kammar
- Colorectal Division, GI Services, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Aditi Chaturvedi
- Colorectal Division, GI Services, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Masillamany Sivasanker
- Colorectal Division, GI Services, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Ashwin de’Souza
- Colorectal Division, GI Services, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - Avanish Saklani
- Colorectal Division, GI Services, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
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Li Y, Liu W, Pei Q, Zhao L, Güngör C, Zhu H, Song X, Li C, Zhou Z, Xu Y, Wang D, Tan F, Yang P, Pei H. Predicting pathological complete response by comparing MRI-based radiomics pre- and postneoadjuvant radiotherapy for locally advanced rectal cancer. Cancer Med 2019; 8:7244-7252. [PMID: 31642204 PMCID: PMC6885895 DOI: 10.1002/cam4.2636] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/01/2019] [Accepted: 10/07/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Total mesorectal excision following neoadjuvant chemoradiotherapy (nCRT) is recommended in the latest treatment of locally advanced rectal cancer (LARC). OBJECTIVE To predict whether patients with LARC can achieve pathologic complete response (pCR), comparing MRI-based radiomics between before and after neoadjuvant radiotherapy (nRT) was performed. METHODS One hundred and sixty-five MRI-based radiomics features in axial T2-weighted images were obtained quantitatively from Imaging Biomarker Explorer Software. The specific features of conventional and developing radiomics were selected with the analysis of least absolute shrinkage and selection operator logistic regression, of which the predictive performance was analyzed with receiver operating curve and calibration curve, and applied to an independent cohort. RESULTS One hundred and thirty-one target patients were enrolled in the present study. A radiomics signature founded on seven radiomics features was generated in the primary cohort. A remarkable difference about Rad-score between pCR and non-pCR group occurred in both of primary (P < .001) or validation cohorts (P < .001). The value of area under the curves was 0.92 (95% CI, 0.86-0.99) and 0.87 (95% CI, 0.74-1.00) in the primary and validation cohorts, respectively. The Rad-score (OR = 23.581; P < .001) from multivariate logistic regression analysis was significant as an independent factor of pCR. CONCLUSION Our predictive model based on radiomics features was an independent predictor for pCR in LARC and could be a candidate in clinical practice.
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Affiliation(s)
- Yuqiang Li
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China.,Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Wenxue Liu
- Department of Rheumatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.,Department of Cardiology, Xiangya Hospital, Central South University, Changsha, China
| | - Qian Pei
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Lilan Zhao
- Department of Thoracic surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Cenap Güngör
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Hong Zhu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiangping Song
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Chenglong Li
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Zhongyi Zhou
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Yang Xu
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dan Wang
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Fengbo Tan
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Pei Yang
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China.,Department of Oncology, Hunan Cancer Hospital, Changsha, China
| | - Haiping Pei
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
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Kang J, Park MC, Kim J, Hur H, Min BS, Baik SH, Lee KY, Kim NK. Prediction of tumor response of rectal cancer cells via 3D cell culture and in vitro cytotoxicity assay before initiating preoperative chemoradiotherapy. Oncol Lett 2019; 18:3863-3872. [PMID: 31516597 DOI: 10.3892/ol.2019.10702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 07/23/2019] [Indexed: 11/05/2022] Open
Abstract
The aim of the present study was to investigate the utility of 3D cell culture and in vitro cytotoxicity assays, performed using cells derived from biopsies obtained prior to the initiation of preoperative chemoradiotherapy (preop-CRT), in predicting tumor response to chemoradiotherapy following preop-CRT in rectal cancer. Biopsies were obtained from 49 patients with locally advanced rectal cancer that underwent preop-CRT between August 2015 and March 2017. Tumor tissue was obtained before initiating preop-CRT. The response to chemoradiation was assessed by in vitro cytotoxicity assay following 3D cell culture and radiation treatment. The associations between the results from the cytotoxicity assay, and tumor regression grade (TRG) and yp node (ypN) positivity were investigated. Among 49 patients, 26 patients were available for analysis. Cytotoxicity ranged from 25.5-72.6% (median, 47.6%). There was no difference in cytotoxicity according to the TRGs 1-5 (P=0.940), or good tumor response (TRGs 1-2 vs. TRGs 3-5; P=0.729). However, there was a significant difference in cytotoxicity between the ypN-negative and -positive groups (53.2±14.1 and 38.7±10.1, respectively; P=0.021). Following dichotomization of patients with 45% cut-off value, the cytotoxicity assay was the only factor that predicted ypN positivity in multivariate analysis (odds ratio, 13; 95% confidence interval, 1.2-133.2; P=0.031). In conclusion, the cytotoxicity assay using the 3D cell culture method can be used to predict tumor response, particularly ypN positivity, in patients with rectal cancer who are scheduled for preop-CRT.
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Affiliation(s)
- Jeonghyun Kang
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Min Chul Park
- CureBio Co., Ltd., Suwon, Gyeonggi 16229, Republic of Korea
| | - Jina Kim
- CureBio Co., Ltd., Suwon, Gyeonggi 16229, Republic of Korea
| | - Hyuk Hur
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Byung Soh Min
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Seung Hyuk Baik
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Kang Young Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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37
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Meillan N, Vernerey D, Lefèvre JH, Manceau G, Svrcek M, Augustin J, Fléjou JF, Lascols O, Simon JM, Cohen R, Maingon P, Bachet JB, Huguet F. Mismatch Repair System Deficiency Is Associated With Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer. Int J Radiat Oncol Biol Phys 2019; 105:824-833. [PMID: 31404579 DOI: 10.1016/j.ijrobp.2019.07.057] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 06/24/2019] [Accepted: 07/04/2019] [Indexed: 12/22/2022]
Abstract
PURPOSE Defective mismatch repair system (dMMR) has been shown to have a favorable impact on outcome in patients with colorectal cancer treated with surgery or immunotherapy, with adjuvant chemotherapy being discouraged unless there is nodal involvement. Its impact on radiosensitivity is unknown in patients with colorectal cancer. METHODS AND MATERIALS Patients treated for locally advanced rectal cancer between 2000 and 2016 were studied. Reported points included age, sex, clinical and radiologic tumor stages at diagnosis, modalities of neoadjuvant treatment, posttreatment pathologic staging, tumor regression score, and local, distant relapse-free, and overall survival. An inverse probability of treatment weighting propensity score analysis was performed to evaluate the association of mismatch repair proficiency with surgical and clinical outcomes. RESULTS Among the 296 patients included, 23 (7.8%) had dMMR. Median follow-up was 43.0 months (interquartile range, 27.9-66.7). Patients with dMMR were significantly younger than the others. After inverse probability of treatment weighting propensity score matching, dMMR patients had higher pathologic downstaging rate (P < .0001), higher tumor regression grade (P = .024), and a longer recurrence-free survival (P < .0001). CONCLUSIONS dMRR was associated with significant tumor downstaging after neoadjuvant chemoradiation and with increased recurrence-free survival. dMMR patients may have more radiosensitive tumors.
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Affiliation(s)
- Nicolas Meillan
- Department of Radiation Oncology, Tenon Hospital, Hôpitaux Universitaires Paris Est, APHP, Paris, France
| | - Dewi Vernerey
- Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, Besançon, France
| | - Jérémie H Lefèvre
- Department of Digestive Surgery, Saint-Antoine Hospital, APHP, Paris, France; Sorbonne Université, Paris, France
| | - Gilles Manceau
- Sorbonne Université, Paris, France; Department of Digestive and Hepato-Pancreato-Biliary Surgery, Pitié Salpêtrière Hospital, APHP, Paris, France
| | - Magali Svrcek
- Sorbonne Université, Paris, France; Department of Pathology, Saint-Antoine Hospital, APHP, Paris, France
| | - Jeremy Augustin
- Department of Pathology, Pitié Salpêtrière Hospital, APHP, Paris, France
| | - Jean-François Fléjou
- Sorbonne Université, Paris, France; Department of Pathology, Saint-Antoine Hospital, APHP, Paris, France
| | - Olivier Lascols
- Department of Biology and Molecular Genetics, Saint-Antoine Hospital, APHP, Paris, France
| | - Jean-Marc Simon
- Department of Radiation Oncology, Pitié Salpêtrière Hospital, APHP, Paris, France
| | - Romain Cohen
- Sorbonne Université, Paris, France; Department of Medical Oncology, Saint-Antoine Hospital, APHP, Paris, France
| | - Philippe Maingon
- Sorbonne Université, Paris, France; Department of Radiation Oncology, Pitié Salpêtrière Hospital, APHP, Paris, France
| | - Jean-Baptiste Bachet
- Sorbonne Université, Paris, France; Department of Hepato-Gastroenterology, Pitié Salpêtrière Hospital, APHP, Paris, France
| | - Florence Huguet
- Department of Radiation Oncology, Tenon Hospital, Hôpitaux Universitaires Paris Est, APHP, Paris, France; Sorbonne Université, Paris, France.
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Tan Y, Fu D, Li D, Kong X, Jiang K, Chen L, Yuan Y, Ding K. Predictors and Risk Factors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Population-Based Analysis. Front Oncol 2019; 9:497. [PMID: 31263674 PMCID: PMC6585388 DOI: 10.3389/fonc.2019.00497] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Accepted: 05/24/2019] [Indexed: 12/25/2022] Open
Abstract
Background: Patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) may have a better prognosis and may be eligible for non-operative management. The aim of this research was to identify variables for predicting pCR in rectal cancer patients after nCRT and to define clinical risk factors for poor outcome after pCR to nCRT and radical resection in rectal cancer patients. Methods: A retrospective review was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013. Non-metastatic rectal cancer patients who received radical resection after neoadjuvant chemoradiotherapy were included in this study. Multivariate analysis of the association between clinicopathological characteristics and pCR was performed, and a logistic regression model was used to identify independent predictors for pCR. A nomogram based on the multivariate logistics regression was built with decision curve analyses to evaluate the clinical usefulness. Results: A total of 6,555 patients were included in this study. The proportion of patients with pCR was 20.5% (n = 1,342). The nomogram based on multivariate logistic regression analysis showed that clinical T4 and N2 stages were the most significant independent clinical predictors for not achieving pCR, followed by mucinous adenocarcinoma and positive pre-treatment serum CEA results. The 3-year overall survival rate was 92.4% for those with pCR and 88.2% for those without pCR. Among all the pCR patients, mucinous adenocarcinoma patients had the worst survival, with a 3-year overall survival rate of 67.5%, whereas patients with common adenocarcinoma had an overall survival rate of 93.8% (P < 0.001). Univariate and multivariate analyses showed that histology and clinical N2 stage were independent risk factors. Conclusion: Mucinous adenocarcinoma, positive pre-treatment serum CEA results, and clinical T4 and N2 stages may impart difficulty for patients to achieve pCR. Mucinous adenocarcinoma and clinical N2 stage might be indicative of a prognostically unfavorable biological tumor profile with a greater propensity for local or distant recurrence and decreased survival.
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Affiliation(s)
- Yinuo Tan
- Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Dongliang Fu
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Dan Li
- Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xiangxing Kong
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Kai Jiang
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Liubo Chen
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Yuan
- Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Kefeng Ding
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
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Abstract
Despite advances in technique, surgical resection of rectal cancer remains a morbid procedure that can lead a profound decrease in a patient's quality of life. A novel method of management, termed "Non-operative management" (NOM), mirrors the management of anal carcinoma. Patients undergo definitive treatment with only chemotherapy and radiation, with resection reserved only for salvage. Current data is encouraging- both in reduction in morbidity and similar, if not superior oncologic results. However, there are a number of barriers to the wide adoption of this practice. This manuscript seeks to describe the rationale and execution of NOM as well as present the current data and pitfalls of the approach.
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Affiliation(s)
- Jonathan B Greer
- Johns Hopkins University School of Medicine, Department of Surgery, Division of Surgical Oncology, Baltimore, MD
| | - Alexander T Hawkins
- Vanderbilt University Medical Center, Division of General Surgery, Section of Colon & Rectal Surgery, Nashville, TN
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Cho E, Park IJ, Hong SM, Lee JL, Kim CW, Yoon YS, Lim SB, Yu CS, Kim JC. Poorer Oncologic Outcome of Good Responders to PCRT With Remnant Lymph Nodes Defies the Oncologic Paradox in Patients With Rectal Cancer. Clin Colorectal Cancer 2019; 18:e171-e178. [PMID: 31027968 DOI: 10.1016/j.clcc.2019.03.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Revised: 03/09/2019] [Accepted: 03/27/2019] [Indexed: 11/20/2022]
Abstract
INTRODUCTION We evaluated the oncologic outcome of (y)pT0-2N+ rectal cancer and investigated the impact of metastatic lymph nodes (LNs) on oncologic outcome in the setting of preoperative chemoradiotherapy (PCRT). MATERIALS AND METHODS The records of 1403 patients who underwent surgery for rectal cancer between January 2005 and December 2012 were analyzed. The patients were categorized according to the pathologic stage, including 728 patients with ypT0-2 and 675 with ypT3-4 disease. The oncologic outcomes in terms of the 5-year recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS Metastatic LNs were observed in 11.5% (n = 84) of patients with ypT0-2 and 42.9% (n = 290) of patients with ypT3-4 disease. The RFS and OS were stratified according to ypT and ypN stage as ypT0-2N0, T0-2N+, T3-4N0, and T3-4N+. The ypT0-2N+ group had slightly lower RFS and OS than those in the ypT3-4N0 group. LN metastasis was significantly associated with RFS in both ypT0-2 and ypT3-4 disease, with a stronger association for ypT0-2 disease (hazard ratio, 3.473, 95% confidence interval, 2.058-5.261; P < .001 for ypT0-2 and hazard ratio, 2.038; 95% confidence interval, 1.601-2.684; P < .001 for ypT3-4, respectively). CONCLUSION The oncologic outcomes of ypT0-2N+ disease were not favorable compared with those of ypT3-4N0 disease. These outcomes dispute the survival paradox traditionally believed for non-PCRT-treated patients with rectal cancer, and highlight the underestimated significance of post-PCRT nodal involvement. The prognostic importance of metastatic LNs should be considered when deciding the surgical strategy after PCRT. Further studies including larger numbers of patients with sufficient follow-up are needed to verify the oncologic impact of metastatic LNs within tumors contained within the bowel wall after PCRT.
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Affiliation(s)
- Eunhae Cho
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - In Ja Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Seung Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jong Lyul Lee
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chan Wook Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Sik Yoon
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seok-Byung Lim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Cheon Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Manur JG, Patel RB, Chandramouli S. Efficacy of preoperative chemoradiotherapy in downstaging rectal cancer and its impact on the long-term outcome. South Asian J Cancer 2019; 8:98-101. [PMID: 31069187 PMCID: PMC6498706 DOI: 10.4103/sajc.sajc_203_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Introduction: Response to preoperative chemoradiation (PRTCT) for rectal cancer predicts the long-term outcome. Context: Tertiary care hospital. Aims: The aim is to study the factors affecting the response to chemoradiation. Settings and Design: Retrospective. Materials and Methods: Twenty-three patients of rectal cancer undergoing PRTCT followed by surgery and adjuvant chemotherapy were followed up for 20–56 months. Postoperative response, tumor downstaging and nodal downstaging were correlated with the disease status. Results: Tumor downstaging was seen in 11 (50%) and nodal downstaging in 12 (63.15%) patients. Nodal downstaging was statistically significant with P = 0.004. Pathological complete response (PCR) was seen in one patient and partial response (PR) in 17 patients. Thirteen (72.2% of patients) were alive and disease free and the negative nodal status correlated with long-term control with P = 0.04. Conclusion: Most patients of rectal cancer show PR to PRTCT, and the benefit is more for node-positive patients. Nodal PCR is associated with a higher chance of long-term disease control.
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Affiliation(s)
| | | | - Sathish Chandramouli
- Department of Surgical Oncology, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India
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Azin A, Khorasani M, Quereshy FA. Neoadjuvant chemoradiation in locally advanced rectal cancer: the surgeon's perspective. J Clin Pathol 2019; 72:133-134. [PMID: 30670565 DOI: 10.1136/jclinpath-2018-205595] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 11/23/2018] [Indexed: 01/12/2023]
Affiliation(s)
- Arash Azin
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | | | - Fayez A Quereshy
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada .,Division of General Surgery, University Health Network, Toronto, Ontario, Canada
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Lee HG, Kim SJ, Park IJ, Hong SM, Lim SB, Lee JB, Yu CS, Kim JC. Effect of Responsiveness of Lymph Nodes to Preoperative Chemoradiotherapy in Patients With Rectal Cancer on Prognosis After Radical Resection. Clin Colorectal Cancer 2019; 18:e191-e199. [PMID: 31014994 DOI: 10.1016/j.clcc.2019.03.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 03/05/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The influence of lymph node (LN) response to preoperative chemoradiotherapy (PCRT) has not been well evaluated for prognosis and additional use of adjuvant treatment after PCRT in rectal cancer patients. The aim of this study was to evaluate the prognostic effect of LN regression grade (LRG) in rectal cancer after PCRT and radical resection. PATIENTS AND METHODS From 2008 to 2011, 389 patients with rectal cancer treated with PCRT followed by radical resection were identified. The pathologic LRG (pLRG) score was determined on the basis of the proportion of tumor cells and fibrosis. The sum of the pLRG of each evaluated LN was used as the final LRG score, LRG-sum. Cox regression analysis was used to evaluate the association of LRG-sum and recurrence-free survival (RFS). RESULTS The distribution of LRG-sum was significantly associated with tumor regression grade of the primary tumor (P < .001). LRG-sum showed different values even in patients with the same number of metastatic LNs. LRG-sum was confirmed as the most relevant associated factor among LN-related variables with RFS along with ypT stage in multivariate analysis. Patients were categorized according to the cutoff points of LRG-sum distribution: LRG1 (LRG-sum 0 to ≤3), LRG2 (LRG-sum 3 to ≤21), and LRG3 (LRG-sum >21). RFS showed a significant difference according to LRG group (P < .001) and showed more effective difference in RFS in the same ypN stage subgroup on the basis of the number of metastatic LNs. CONCLUSION LRG was a prognostic factor of oncologic outcomes of rectal cancer. LN response to PCRT might help in prognostication and determination of treatments after PCRT.
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Affiliation(s)
- Hyun Gu Lee
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sung Joo Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - In Ja Park
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
| | - Seung Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Seok-Byung Lim
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jung Bok Lee
- Departments of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jin Cheon Kim
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Is the Pathologic Response of T3 Rectal Cancer to High-Dose-Rate Endorectal Brachytherapy Comparable to External Beam Radiotherapy? Dis Colon Rectum 2019; 62:294-301. [PMID: 30741768 DOI: 10.1097/dcr.0000000000001220] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Endorectal brachytherapy is an attractive option in the neoadjuvant setting for locally advanced rectal cancer, but it is not considered standard of care. OBJECTIVE This study aimed to compare pathologic outcomes of patients with clinical T3 rectal cancer who underwent high-dose-rate endorectal brachytherapy with those who underwent conventional external beam radiotherapy. DESIGN This study is a retrospective chart review. SETTINGS This study was conducted in a single large tertiary academic colorectal surgery practice in Canada. PATIENTS Adult patients with MRI-staged T3 rectal adenocarcinoma treated with neoadjuvant radiotherapy followed by total mesorectal excision from 2007 to 2016 were included. INTERVENTIONS Neoadjuvant radiotherapy was delivered by high-dose-rate endorectal brachytherapy or conventional external beam radiotherapy. MAIN OUTCOME MEASURES Primary outcome was pathologic complete response, defined as ypT0N0. Secondary outcomes included tumor (T stage) and lymph node (N stage) downstaging and tumor regression grade. RESULTS Ninety-nine patients were identified as having clinical T3 rectal cancer based on blinded pretreatment MRI review. Mean age was 66.2 years (± 6.2) and 59 patients (59.6%) were male. Thirty-three patients were clinically node negative (33.3%), 45 had c-N1 disease (45.5%), and 21 had c-N2 disease (21.2%). Sixty-four patients (64.6%) underwent high-dose-rate endorectal brachytherapy and 35 (35.4%) underwent external beam radiotherapy. The high-dose-rate endorectal brachytherapy group had a lower median mesorectal depth of invasion (4 mm vs 5 mm, p = 0.010); all other preoperative tumor characteristics were similar in both groups. Eighteen patients (18.2%) achieved pathologic complete response: 12 in the high-dose-rate endorectal brachytherapy group and 6 in the conventional external beam radiotherapy group (18.8% vs 17.1%, p = 0.84). High-dose-rate endorectal brachytherapy was superior to conventional radiotherapy for tumor (T stage) downstaging (59.4% vs 28.6%, p = 0.0030) but not for lymph node (N stage) downstaging (35.9% vs 51.4%, p = 0.14). LIMITATIONS This study was limited by its retrospective nature and modest sample size. CONCLUSIONS Neoadjuvant treatment of T3 rectal cancer with high-dose-rate endorectal brachytherapy appears to achieve equivalent rates of pathologic complete response and superior T-stage downstaging compared with conventional external beam radiotherapy. See Video Abstract at http://links.lww.com/DCR/A905.
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Lino-Silva LS, Gamboa-Domínguez A, Zúñiga-Tamayo D, Salcedo-Hernández RA, Cetina L, Cantú-de-León D. Mismatch repair protein expression and intratumoral budding in rectal cancer are associated with an increased pathological complete response to preoperative chemoradiotherapy: A case-control study. World J Clin Oncol 2018; 9:133-139. [PMID: 30425938 PMCID: PMC6230920 DOI: 10.5306/wjco.v9.i7.133] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 08/18/2018] [Accepted: 10/24/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether the association of rectal adenocarcinoma with a defective-mismatch repair system (dMMR) was associated with a pathological complete response (pCR) to preoperative chemoradiotherapy. METHODS A case-control study was designed with the aim of determining if patients with rectal adenocarcinoma with dMMR had an associated high pCR rate in response to neoadjuvant chemoradiotherapy (nCRT). RESULTS Seventy-two cases with pCR were compared against 144 controls without pCR. Across 216 cases, the mean age was 56.8 years, 140 (64.8%) were men, and 63 (29.2%) demonstrated the dMMR system. The pCR was associated with G1 tumors, dMMR, the absence of vascular invasion, and low tumor budding in the pretreatment biopsy. In a multivariant analysis, the factors associated with pCR were dMMR (OR: 2.61; 95%CI: 1.355-5.040, P = 0.004) and a low degree of tumor budding (OR: 2.52; 95%CI: 1.366-4.894, P = 0.025). CONCLUSION We found an independent association between dMMR and a low rate of tumor budding, with a higher rate of pCR, in the basal biopsies of patients with rectal carcinoma subjected to nCRT.
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Affiliation(s)
| | - Armando Gamboa-Domínguez
- Surgical Pathology, Instituto Nacional de ciencias Médicas y Nutrición salvador Zubirán, Mexico City 14080, Mexico
| | - Diego Zúñiga-Tamayo
- Surgical Pathology, Instituto Nacional de ciencias Médicas y Nutrición salvador Zubirán, Mexico City 14080, Mexico
| | | | - Lucely Cetina
- Medical Oncology, Instituto Nacional de Cancerología, Mexico City 14080, Mexico
| | - David Cantú-de-León
- Surgical Oncology, Instituto Nacional de Cancerología, Mexico City 14080, Mexico
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Kim CA, Ahmed S, Ahmed S, Brunet B, Chalchal H, Deobald R, Doll C, Dupre MP, Gordon V, Lee-Ying RM, Lim H, Liu D, Loree JM, McGhie JP, Mulder K, Park J, Yip B, Wong RP, Zaidi A. Report from the 19th annual Western Canadian Gastrointestinal Cancer Consensus Conference; Winnipeg, Manitoba; 29-30 September 2017. ACTA ACUST UNITED AC 2018; 25:275-284. [PMID: 30111968 DOI: 10.3747/co.25.4109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The 19th annual Western Canadian Gastrointestinal Cancer Consensus Conference (wcgccc) was held in Winnipeg, Manitoba, 29-30 September 2017. The wcgccc is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.
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Affiliation(s)
- C A Kim
- Manitoba-Medical Oncology (Kim, Gordon, Wong) and Radiation Oncology (Shahida Ahmed), CancerCare Manitoba, University of Manitoba, Winnipeg; Surgery (Park, Yip) and Pathology (Dupre), University of Manitoba, Winnipeg
| | - S Ahmed
- Saskatchewan- Medical Oncology (Shahid Ahmed, Zaidi), Radiation Oncology (Brunet), and Surgery (Deobald), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Medical Oncology (Chalchal), Allan Blair Cancer Centre, Regina
| | - S Ahmed
- Manitoba-Medical Oncology (Kim, Gordon, Wong) and Radiation Oncology (Shahida Ahmed), CancerCare Manitoba, University of Manitoba, Winnipeg; Surgery (Park, Yip) and Pathology (Dupre), University of Manitoba, Winnipeg
| | - B Brunet
- Saskatchewan- Medical Oncology (Shahid Ahmed, Zaidi), Radiation Oncology (Brunet), and Surgery (Deobald), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Medical Oncology (Chalchal), Allan Blair Cancer Centre, Regina
| | - H Chalchal
- Saskatchewan- Medical Oncology (Shahid Ahmed, Zaidi), Radiation Oncology (Brunet), and Surgery (Deobald), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Medical Oncology (Chalchal), Allan Blair Cancer Centre, Regina
| | - R Deobald
- Saskatchewan- Medical Oncology (Shahid Ahmed, Zaidi), Radiation Oncology (Brunet), and Surgery (Deobald), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Medical Oncology (Chalchal), Allan Blair Cancer Centre, Regina
| | - C Doll
- Alberta-Medical Oncology (Mulder), Cross Cancer Institute, University of Alberta, Edmonton; Medical Oncology (Lee-Ying) and Radiation Oncology (Doll), Tom Baker Cancer Centre, University of Calgary, Calgary
| | - M P Dupre
- Manitoba-Medical Oncology (Kim, Gordon, Wong) and Radiation Oncology (Shahida Ahmed), CancerCare Manitoba, University of Manitoba, Winnipeg; Surgery (Park, Yip) and Pathology (Dupre), University of Manitoba, Winnipeg
| | - V Gordon
- Manitoba-Medical Oncology (Kim, Gordon, Wong) and Radiation Oncology (Shahida Ahmed), CancerCare Manitoba, University of Manitoba, Winnipeg; Surgery (Park, Yip) and Pathology (Dupre), University of Manitoba, Winnipeg
| | - R M Lee-Ying
- Alberta-Medical Oncology (Mulder), Cross Cancer Institute, University of Alberta, Edmonton; Medical Oncology (Lee-Ying) and Radiation Oncology (Doll), Tom Baker Cancer Centre, University of Calgary, Calgary
| | - H Lim
- British Columbia-Medical Oncology (Lim, Loree), BC Cancer, University of British Columbia, Vancouver; Medical Oncology (McGhie), BC Cancer, University of British Columbia, Victoria; Radiology (Liu), University of British Columbia, Vancouver
| | - D Liu
- British Columbia-Medical Oncology (Lim, Loree), BC Cancer, University of British Columbia, Vancouver; Medical Oncology (McGhie), BC Cancer, University of British Columbia, Victoria; Radiology (Liu), University of British Columbia, Vancouver
| | - J M Loree
- British Columbia-Medical Oncology (Lim, Loree), BC Cancer, University of British Columbia, Vancouver; Medical Oncology (McGhie), BC Cancer, University of British Columbia, Victoria; Radiology (Liu), University of British Columbia, Vancouver
| | - J P McGhie
- British Columbia-Medical Oncology (Lim, Loree), BC Cancer, University of British Columbia, Vancouver; Medical Oncology (McGhie), BC Cancer, University of British Columbia, Victoria; Radiology (Liu), University of British Columbia, Vancouver
| | - K Mulder
- Alberta-Medical Oncology (Mulder), Cross Cancer Institute, University of Alberta, Edmonton; Medical Oncology (Lee-Ying) and Radiation Oncology (Doll), Tom Baker Cancer Centre, University of Calgary, Calgary
| | - J Park
- Manitoba-Medical Oncology (Kim, Gordon, Wong) and Radiation Oncology (Shahida Ahmed), CancerCare Manitoba, University of Manitoba, Winnipeg; Surgery (Park, Yip) and Pathology (Dupre), University of Manitoba, Winnipeg
| | - B Yip
- Manitoba-Medical Oncology (Kim, Gordon, Wong) and Radiation Oncology (Shahida Ahmed), CancerCare Manitoba, University of Manitoba, Winnipeg; Surgery (Park, Yip) and Pathology (Dupre), University of Manitoba, Winnipeg
| | - R P Wong
- Manitoba-Medical Oncology (Kim, Gordon, Wong) and Radiation Oncology (Shahida Ahmed), CancerCare Manitoba, University of Manitoba, Winnipeg; Surgery (Park, Yip) and Pathology (Dupre), University of Manitoba, Winnipeg
| | - A Zaidi
- Saskatchewan- Medical Oncology (Shahid Ahmed, Zaidi), Radiation Oncology (Brunet), and Surgery (Deobald), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Medical Oncology (Chalchal), Allan Blair Cancer Centre, Regina
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Shoji H, Motegi M, Osawa K, Asao T, Kuwano H, Takahashi T, Ogoshi K. The first thermic treatment predicts following chemoradiation response with concurrent thermal therapy for the treatment of rectal cancer. Oncol Lett 2018; 16:497-504. [PMID: 29928438 DOI: 10.3892/ol.2018.8630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 04/26/2018] [Indexed: 11/05/2022] Open
Abstract
The present study aimed to evaluate whether the neoadjuvant chemoradiation response with concurrent thermal therapy for the treatment of rectal cancer can be predicted following the first thermic treatment. Eighty patients with primary rectal adenocarcinoma (≤12 cm from the anal verge) were included in this study. Fifty-four received surgery and pathological response was evaluated. Intensity-modulated radiotherapy was administered conventionally once daily 5 times/week. Neoadjuvant radiotherapy consisted of 50 Gy delivered to the planning target volume in 25 fractions. Concurrent neoadjuvant chemotherapy was delivered in 5-day courses. Capecitabine was administered orally at 1,700 mg/m2/day for 5 days/week. Thermic treatment was performed using the Thermotron-RF 8 and administered once/week for 5 weeks with 50 min irradiation. Patients with a gross tumor volume (GTV) ≤32 cm3 and a radiofrequency (RF) output difference (RO difference) ≥77 Watt/min exhibited pathological complete response (pCR) and CR rates of 50 and 75%, respectively. Those with a GTV ≥80 cm3 and a RO difference ≥77 Watt/min exhibited pCR and CR rates of 42.9 and 42.9%, respectively. The changes in the skin temperature during RF treatment in patients with pCR with a RO difference ≥77 Watt/min increased significantly compared with those of other outcomes, and progressive disease. These data suggest a strategy for predicting which patients will respond best following the first thermic treatment. The results identified that the group of patients with a GTV ≤32 cm3 and a RO difference ≥77 Watt/min (outputable/heatable patients) may respond best.
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Affiliation(s)
- Hisanori Shoji
- Division of Surgery, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
| | - Masahiko Motegi
- Division of Surgery, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
| | - Kiyotaka Osawa
- Division of Surgery, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
| | - Takayuki Asao
- Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan
| | - Takeo Takahashi
- Department of Radiation Oncology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama 350-8550, Japan
| | - Kyoji Ogoshi
- Division of Cancer Diagnosis and Cancer Treatment, Hidaka Hospital, Takasaki, Gunma 370-0001, Japan
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Loftås P, Sturludóttir M, Hallböök O, Almlöv K, Arbman G, Blomqvist L. Assessment of remaining tumour involved lymph nodes with MRI in patients with complete luminal response after neoadjuvant treatment of rectal cancer. Br J Radiol 2018; 91:20170938. [PMID: 29668301 DOI: 10.1259/bjr.20170938] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVE To assess the accuracy of MRI to predict remaining lymph node metastases in patients with complete pathological luminal response (ypT0) after neoadjuvant therapy. METHODS Data from a national registry were used. 19 patients with histopathologically remaining lymph node metastases (ypT0N+) were identified. Another 19 patients without lymph node metastases (ypT0N0) were used as matched controls. Two radiologists blinded to all patient information evaluated staging and restaging MRI that was compared to histopathological findings of the resected specimen. RESULTS The average size of the largest lymph node on restaging MRI was significantly larger (4.5 mm) in the ypT0N+ group than in the ypT0N0 group (2.6 mm) (p = 0.04). Presence of ypN+ was correctly predicted by MRI in 7 of 19 patients. In patients without lymph node metastases (ypT0N0), these were correctly classified by MRI in 16 of 19 patients. All patients who had MR-identified lymph nodes larger than 8 mm at restaging were ypTN+. The sensitivity, specificity, positive predictive value and negative for prediction of remaining lymph node metastasis with MRI were 37, 84, 70 and 57%. CONCLUSION In patients with ypT0 in rectal cancer after neoadjuvant treatment, remaining regional lymph node metastases cannot safely be predicted by restaging MRI alone using presently known criteria. Presence of a lymph node over 8 mm on restaging MRI strongly indicates yPN+. Advances in knowledge: This is one of the first studies on MRI lymph node assessment after chemo-radiotherapy (CRT) in luminal complete response.
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Affiliation(s)
- Per Loftås
- 1 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Linköping , Sweden
| | - Margrét Sturludóttir
- 2 Department of Diagnostic Radiology, Karolinska University hospital , Stockholm , Sweden.,3 Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm , Sweden
| | - Olof Hallböök
- 1 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Linköping , Sweden
| | - Karin Almlöv
- 4 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Norrköping , Sweden
| | - Gunnar Arbman
- 4 Department of Surgery, Institution for clinical and experimental medicine, Linköping University , Norrköping , Sweden
| | - Lennart Blomqvist
- 2 Department of Diagnostic Radiology, Karolinska University hospital , Stockholm , Sweden.,3 Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm , Sweden
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Yang KM, Lim SB, Lee JL, Kim CW, Yoon YS, Park IJ, Yu CS, Kim JC. Local excision for ypT2 rectal cancer following preoperative chemoradiation therapy: it should not be justified. Int J Colorectal Dis 2018; 33:487-491. [PMID: 29468352 DOI: 10.1007/s00384-018-2973-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/03/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE Among individuals who respond well to preoperative chemoradiation therapy (CRT) for ypT0-1, local excision (LE) could provide acceptable oncological outcomes. However, in ypT2 cases, the oncological safety of LE has not been determined. This study aimed to compare oncological outcomes between LE and total mesorectal excision of ypT2-stage rectal cancer after chemoradiation therapy and investigate the oncological safety of LE in these patients. METHODS We included 351 patients who exhibited ypT2-stage rectal cancer after CRT followed by LE (n = 16 [5%]) or total mesorectal excision (TME) (n = 335 [95%]) after preoperative CRT between January 2007 and December 2013. After propensity matching, oncological outcomes between LE group and TME group were compared. RESULTS The median follow-up period was 57 months (range, 12-113 months). In the LE group, local recurrence occurred more frequently (18 vs. 4%; p = 0.034) but not distant metastases (12 vs. 11%; p = 0.690). The 5-year local recurrence-free (76 vs. 96%; p = 0.006), disease-free (64 vs. 84%; p = 0.075), and overall survival (79 vs. 93%; p = 0.045) rates of the LE group were significantly lower than those of the TME group. After propensity matching, 5-year local recurrence-free survival of the LE group was significantly lower than that of the TME group (76 vs. 97%, p = 0.029). CONCLUSION The high local failure rate and poor oncological outcomes for ypT2-stage rectal cancer patients who undergo CRT followed by LE cannot be justified as an indication for LE. Salvage surgery should be recommended in these patients.
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Affiliation(s)
- Kwan Mo Yang
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea
| | - Seok-Byung Lim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea.
| | - Jong Lyul Lee
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea
| | - Chan Wook Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea
| | - Chang Sik Yu
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea
| | - Jin Cheon Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-Ro 43-Gil Songpa-Gu, Seoul, 05505, South Korea
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50
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Meng Y, Zhang Y, Dong D, Li C, Liang X, Zhang C, Wan L, Zhao X, Xu K, Zhou C, Tian J, Zhang H. Novel radiomic signature as a prognostic biomarker for locally advanced rectal cancer. J Magn Reson Imaging 2018; 48:605-614. [PMID: 29437271 DOI: 10.1002/jmri.25968] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 01/22/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Locally advanced rectal cancer (LARC) patient stratification by clinicoradiologic factors may yield variable results. Therefore, more efficient prognostic biomarkers are needed for improved risk stratification of LARC patients, personalized treatment, and prognostication. PURPOSE/HYPOTHESIS To compare the ability of a radiomic signature to predict disease-free survival (DFS) with that of a clinicoradiologic risk model in individual patients with LARC. STUDY TYPE Retrospective study. POPULATION In all, 108 consecutive patients (allocated to a training and validation set with a 1:1 ratio) with LARC treated with neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). FIELD STRENGTH/SEQUENCE Axial 3D LAVA multienhanced MR sequence at 3T. ASSESSMENT ITK-SNAP software was used for manual segmentation of 3D pre-nCRT MR images. All manual tumor segmentations were performed by a gastrointestinal tract radiologist, and validated by a senior radiologist. The clinicoradiologic risk factors with potential prognostic outcomes were identified in univariate analysis based on the Cox regression model for the whole set. The results showed that ypT, ypN, EMVI, and MRF were potential clinicoradiologic risk factors. Interestingly, only ypN and MRF were identified as independent predictors in multivariate analysis based on the Cox regression model. STATISTICAL TESTS A radiomic signature based on 485 3D features was generated using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The association of the radiomic signature with DFS was investigated by Kaplan-Meier survival curves. Survival curves were compared by the log-rank test. Three models were built and assessed for their predictive values, using the Harrell concordance index and integrated time-dependent area under the curve. RESULTS The novel radiomic signature stratified patients into low- and high-risk groups for DFS in the training set (hazard ratio [HR] = 6.83; P < 0.001), and was successfully validated in the validation set (HR = 2.92; P < 0.001). The model combining the radiomic signature and clinicoradiologic findings had the best performance (C index = 0.788, 95% confidence interval [CI] 0.72-0.86; integrated time-dependent area under the curve of 0.837 at 3 years). DATA CONCLUSION The novel radiomic signature could be used to predict DFS in patients with LARC. Furthermore, combining this radiomic signature with clinicoradiologic features significantly improved the ability to estimate DFS (P = 0.001, 0.005 in training set and in validation set, respectively), and may help guide individualized treatment in such patients. LEVEL OF EVIDENCE 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.
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Affiliation(s)
- Yankai Meng
- Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Yuchen Zhang
- University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, P.R. China
| | - Di Dong
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, P.R. China
- University of Chinese Academy of Sciences, Beijing, China
| | - Chunming Li
- University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China
| | - Xiao Liang
- Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Chongda Zhang
- Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Lijuan Wan
- Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Xinming Zhao
- Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Kai Xu
- Department of Radiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, P.R. China
| | - Chunwu Zhou
- Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Jie Tian
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, P.R. China
| | - Hongmei Zhang
- Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
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