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Perez RO, Vailati BB, São Julião GP, Mazzucato F, Corbi LE. The Landmark Series: Organ Preservation in Rectal Cancer-The Watch and Wait Strategy. Ann Surg Oncol 2025:10.1245/s10434-025-17304-x. [PMID: 40287543 DOI: 10.1245/s10434-025-17304-x] [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: 02/10/2025] [Accepted: 03/24/2025] [Indexed: 04/29/2025]
Abstract
Radical treatment of rectal cancer has evolved quite significantly over the last few decades with the development of optimal local disease staging with magnetic resonance (MR), refined surgical techniques including total mesorectal excision (TME) with or without sphincter-preservation, and multimodality treatment with the use of chemotherapy and radiation. While oncological outcomes have shown some significant improvements in terms of local disease control and distant metastases rates, complication rates and functional sequelae remain quite significant for patients undergoing TME surgery. In this setting, organ-preserving alternatives, including transanal local excision (TAE) and Watch and Wait (WW), have become increasingly attractive to patients in an attempt to avoid major surgery (TME) as an alternative treatment strategy with no oncological compromise. In the present narrative review, the fundamentals of selection and outcomes of patients undergoing WW will be covered to provide updated information for colorectal surgeons and surgical oncologists interested in this treatment alternative in clinical practice.
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Affiliation(s)
- Rodrigo O Perez
- Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil.
- Hospital Beneficiência Portuguesa, São Paulo, Brazil.
| | - Bruna B Vailati
- Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil
- Hospital Beneficiência Portuguesa, São Paulo, Brazil
| | - Guilherme P São Julião
- Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil
- Hospital Beneficiência Portuguesa, São Paulo, Brazil
| | - Fernanda Mazzucato
- Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil
- Departamento de Radiologia e Oncologia da Faculdade de Medicina da USP, São Paulo, Brazil
- Instituto de Radiologia e Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil
| | - Leonardo E Corbi
- Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil
- Hospital Beneficiência Portuguesa, São Paulo, Brazil
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Liu YX, Yang XR, Peng LQ, Li ZH. A management of patients achieving clinical complete response after neoadjuvant therapy and perspectives: on locally advanced rectal cancer. Front Oncol 2025; 14:1450994. [PMID: 39845322 PMCID: PMC11750660 DOI: 10.3389/fonc.2024.1450994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 12/10/2024] [Indexed: 01/24/2025] Open
Abstract
Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) and selective use of adjuvant chemotherapy is currently considered the standard of care for locally advanced rectal cancer (LARC). Despite this, the concept of organ preservation is gradually challenging this approach. The management of complete clinical remission (cCR) lacks international consensus, leading scholars to develop their own perspectives based on well-designed studies and long-term data from large multicenter cohorts. To ensure appropriate treatment, this review focuses on the choice of neoadjuvant therapy, criteria for defining cCR, and treatment strategies for patients who achieve cCR after neoadjuvant therapy. By providing guidance on the accurate management of LARC patients after cCR, this review aims to prevent over- or under-treatment.
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Affiliation(s)
| | | | | | - Zhuo-Hong Li
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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Liu X, Duan B, Liu R, Zhu M, Zhao G, Guan N, Wang Y. Enhancing clinical complete response assessment in rectal cancer: integrating transanal multipoint full-layer puncture biopsy criteria: a systematic review. Front Oncol 2024; 14:1428583. [PMID: 39759129 PMCID: PMC11695227 DOI: 10.3389/fonc.2024.1428583] [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: 05/06/2024] [Accepted: 12/02/2024] [Indexed: 01/07/2025] Open
Abstract
There is currently a lack of standardized criteria for evaluating clinical complete response (cCR) in rectal cancer post-neoadjuvant chemoradiotherapy (nCRT), often resulting in discrepancies with true pathological complete response (pCR). Staging local lesions via MRI is challenged by tissue edema and fibrosis post-nCRT, while endoscopic biopsy accuracy is compromised by residual cancer foci in the muscular layer. Transanal local excision offers a relatively accurate assessment of lesion regression but poses challenges including impaired anal function and elevated complication rates. Building on current diagnostic frameworks, we propose enhancing cCR assessment by integrating histological criteria from transanal multipoint full-layer puncture biopsy (TMFP). This approach aims to improve accuracy while minimizing complications, offering promise for patients opting for observation-based treatments. Further research is needed for definitive conclusions.
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Affiliation(s)
- Xin Liu
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Boshi Duan
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Ruibin Liu
- Department of Clinical Integration of Traditional Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, China
- Department of Generall Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Mengying Zhu
- Department of Clinical Integration of Traditional Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, China
- Department of Generall Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Guohua Zhao
- Department of Generall Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Ning Guan
- Center of Medical Examination, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
| | - Yue Wang
- Department of Generall Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
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Chen SF, Yang SH, Jiang JK, Wang LW. Outcomes of Postchemoradiotherapy Watch-and-Wait Strategy in Patients With Rectal Cancer: A 20-Year, Single-Center Study. J Surg Oncol 2024. [PMID: 39635915 DOI: 10.1002/jso.28008] [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: 07/09/2024] [Revised: 11/03/2024] [Accepted: 11/09/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND AND OBJECTIVES The watch-and-wait (WW) strategy is a nonsurgical alternative for patients with rectal cancer exhibiting an excellent response to chemoradiotherapy. Studies on the WW strategy have primarily investigated 5-year oncological outcomes; few have focused on longer-term outcomes or the optimal patient selection approach for this therapeutic strategy. METHODS This retrospective study enrolled patients with locally advanced rectal adenocarcinoma who had achieved complete response after chemoradiotherapy. Patients who achieved pathological complete response were categorized into a control group (n = 95) and those who achieved clinical complete response and were managed using the WW strategy were categorized into a case group (n = 33). Kaplan-Meier estimates were calculated for the between-group comparison of survival. RESULTS The median follow-up duration was 89 months. Compared with the control group, the case group exhibited improved long-term sphincter preservation, particularly for low-lying tumors (p = 0.032), and inferior nonlocal-regrowth disease-free survival (p = 0.007). Within the case group, patients achieving a complete response by positron emission tomography exhibited 5-year survival rates similar to those achieving a complete endoscopic response. CONCLUSION The WW strategy is associated with improved sphincter preservation but worse nonlocal-regrowth disease-free survival. The potential of PET in patient selection for this strategy deserves further investigation.
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Affiliation(s)
- Shuo-Fu Chen
- Department of Heavy Particles & Radiation Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shung-Haur Yang
- Department of Surgery, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jeng-Kai Jiang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ling-Wei Wang
- Department of Heavy Particles & Radiation Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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Anijdan SHM, Moslemi D, Reiazi R, Tafti HF, Moghadamnia AA, Paydar R. Computed Tomography Scan and Clinical-based Complete Response Prediction in Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy: A Machine Learning Approach. JOURNAL OF MEDICAL SIGNALS & SENSORS 2024; 14:32. [PMID: 39741788 PMCID: PMC11687674 DOI: 10.4103/jmss.jmss_46_23] [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: 10/02/2023] [Revised: 08/12/2024] [Accepted: 08/20/2024] [Indexed: 01/03/2025]
Abstract
Background Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy (nCRT), followed by total mesorectal excision. Examining the response to treatment is one of the most important factors in the follow-up of patients; therefore, in this study, radiomics patterns derived from pretreatment computed tomography images in rectal cancer and its relationship with treatment response measurement criteria have been investigated. Methods Fifty patients with rectal adenocarcinoma who were candidates for nCRT and surgery were included. The information obtained from the tumor surgical pathology report, including pathological T and N, the degree of tumor differentiation, lymphovascular invasion, and perineural invasion along with radiomics characteristics to each patient, was assessed. Modeling with disturbed forest model was used for radiomics data. For other variables, Shapiro-Wilk, Chi-Square, and Pearson Chi-square tests were used. Results The participants of this study were 50 patients (23 males [46%] and 27 females [54%]). There was no significant difference in the rate of response to neoadjuvant treatment in between age and gender groups. According to the modeling based on combined clinical and radiomics data together, area under the curves for the nonresponders and complete respond group (responder group) was 0.97 and 0.99, respectively. Conclusion Random forests modeling based on combined radiomics and clinical characteristics of the pretreatment tumor images has the ability to predict the response or non-response to neoadjuvant treatment in LARC to an acceptable extent.
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Affiliation(s)
| | - Daryush Moslemi
- Department of Radiation Oncology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Reza Reiazi
- Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hamid Fallah Tafti
- Cancer Research Center, Babol University of Medical Sciences, Babol, Iran
| | - Ali Akbar Moghadamnia
- Department of Pharmacology and Toxicology, Babol University of Medical Sciences, Babol, Iran
| | - Reza Paydar
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
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Gheller A, Basílio DB, da Costa MCR, Tuma SA, Ferreira OMTA, Lyrio FG, Girardi DDM, de Sousa JB. Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer. Front Oncol 2024; 14:1386697. [PMID: 38974246 PMCID: PMC11224439 DOI: 10.3389/fonc.2024.1386697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 06/10/2024] [Indexed: 07/09/2024] Open
Abstract
Background Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.
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Affiliation(s)
- Alexandre Gheller
- Colorectal Surgery Department, Hospital de Base do Distrito Federal, Brasília, DF, Brazil
| | - Dunya Bachour Basílio
- Anatomopathology Department, Hospital de Base do Distrito Federal, Brasília, DF, Brazil
| | | | - Sussen Araújo Tuma
- Anatomopathology Department, Hospital de Base do Distrito Federal, Brasília, DF, Brazil
| | | | | | | | - João Batista de Sousa
- Division of Colorectal Surgery, Universidade de Brasília (UnB), Brasília, DF, Brazil
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Huang Y, Xie Y, Wang P, Chen Y, Qin S, Li F, Wu Y, Huang M, Hou Z, Cai Y, He X, Lin H, Hu B, Qin Q, Ma T, Tan S, Liao Y, Ke J, Zhang D, Lai S, Jiang Z, Wang H, Xiang J, Cai Z, Wang H, He X, Yang Z, Ren D, Wu X, Hong Y, Huang M, Luo Y, Liu G, Lin J. Evaluation of transrectal ultrasound-guided tru-cut biopsy as a complementary method for predicting pathological complete response in rectal cancer after neoadjuvant treatment: a phase II prospective and diagnostic trial. Int J Surg 2024; 110:3230-3236. [PMID: 38348893 PMCID: PMC11175734 DOI: 10.1097/js9.0000000000001152] [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: 10/08/2023] [Accepted: 01/26/2024] [Indexed: 06/15/2024]
Abstract
IMPORTANCE Patients with pathological complete response (pCR) of rectal cancer following neoadjuvant treatment had better oncological outcomes. However, reliable methods for accurately predicting pCR remain limited. OBJECTIVE To evaluate whether transrectal ultrasound-guided tru-cut biopsy (TRUS-TCB) adds diagnostic value to conventional modalities for predicting pathological complete response in patients with rectal cancer after neoadjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS This study evaluated data of patients with rectal cancer who were treated with neoadjuvant treatment and reassessed using TRUS-TCB and conventional modalities before surgery. This study is registered with ClinicalTrials.gov. MAIN OUTCOMES AND MEASURES The primary outcome was accuracy, along with secondary outcomes including sensitivity, specificity, negative predictive value, and positive predictive value in predicting tumour residues. Final surgical pathology was used as reference standard. RESULTS Between June 2021 and June 2022, a total of 74 patients were enroled, with 63 patients ultimately evaluated. Among them, 17 patients (28%) exhibited a complete pathological response. TRUS-TCB demonstrated an accuracy of 0.71 (95% CI, 0.58-0.82) in predicting tumour residues. The combined use of TRUS-TCB and conventional modalities significantly improved diagnostic accuracy compared to conventional modalities alone (0.75 vs. 0.59, P =0.02). Furthermore, TRUS-TCB correctly reclassified 52% of patients erroneously classified as having a complete clinical response by conventional methods. The occurrence of only one mild adverse event was observed. CONCLUSIONS AND RELEVANCE TRUS-TCB proves to be a safe and accessible tool for reevaluation with minimal complications. The incorporation of TRUS-TCB alongside conventional methods leads to enhanced diagnostic performance.
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Affiliation(s)
- Yaoyi Huang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Yumo Xie
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Puning Wang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | | | | | | | - Yuanhui Wu
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Mingzhe Huang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Zehui Hou
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Yonghua Cai
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Xiaosheng He
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Hongcheng Lin
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Bang Hu
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Qiyuan Qin
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Tenghui Ma
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Shuyun Tan
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Yi Liao
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Jia Ke
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Di Zhang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Sicong Lai
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - ZhiPeng Jiang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Huaiming Wang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Jun Xiang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Zerong Cai
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Hui Wang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Xiaowen He
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Zuli Yang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Donglin Ren
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Xiaojian Wu
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Yisong Hong
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Meijin Huang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Yanxin Luo
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Guangjian Liu
- Medical Ultrasonics
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
| | - Jinxin Lin
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University
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Cui Y, Liu X, Li S, Wang H, Xiang Y, Zhang Y, Song M, Geng J, Liu Z, Teng H, Zhu X, Cai Y, Li Y, Wang W. The ypT may better predict the efficacy of neoadjuvant chemoradiotherapy than tumor regression grade in locally advanced rectal cancer patients diagnosed ypT1-4N0. Clin Transl Oncol 2024; 26:1012-1021. [PMID: 38051436 DOI: 10.1007/s12094-023-03343-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 10/30/2023] [Indexed: 12/07/2023]
Abstract
PURPOSE This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). METHODS We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan-Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. RESULTS The median follow-up was 35.8 months (range 2.8-71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. CONCLUSIONS For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.
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Affiliation(s)
- Yujun Cui
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Xinzhi Liu
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Shuai Li
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Hongzhi Wang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yirong Xiang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yangzi Zhang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Maxiaowei Song
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Jianhao Geng
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Zhiyan Liu
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Huajing Teng
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Xianggao Zhu
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yong Cai
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Yongheng Li
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
| | - Weihu Wang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
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9
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Klimkowski R, Krzyzkowiak J, Pilonis ND, Bujko K, Kaminski MF. Endoscopic resection of residual rectal neoplasia after definitive chemoradiotherapy for rectal cancer. Best Pract Res Clin Gastroenterol 2024; 68:101896. [PMID: 38522889 DOI: 10.1016/j.bpg.2024.101896] [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: 08/31/2023] [Revised: 02/21/2024] [Accepted: 02/25/2024] [Indexed: 03/26/2024]
Abstract
The conventional approach to treating locally advanced rectal cancer, commonly defined as cT3 or cT4 primary tumors or with nodal metastases, involves chemoradiation (CRT) followed by surgical resection. There is a growing recognition of the potential for nonsurgical management following CRT or total neoadjuvant therapy (TNT), which allows for organ preservation. "Watch and wait" strategy may be considered if complete clinical response is achieved. In cases when adenoma or superficial cancer is present, a novel approach known as "salvage endoscopic resection of the residual disease" is emerging as a viable nonsurgical option for carefully selected patients. This review discusses available evidence and future potential for endoscopic management of residual neoplasia after oncological treatment of rectal cancer.
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Affiliation(s)
- Robert Klimkowski
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Gastroenterology, Hepatology and Oncology, Medical Center for Postgraduate Education, Warsaw, Poland.
| | - Jakub Krzyzkowiak
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Nastazja Dagny Pilonis
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Gastroenterology, Hepatology and Oncology, Medical Center for Postgraduate Education, Warsaw, Poland; Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway; Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland
| | - Krzysztof Bujko
- Department of Radiotherapy I, National Research Institute of Oncology, Warsaw, Poland
| | - Michal F Kaminski
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Gastroenterology, Hepatology and Oncology, Medical Center for Postgraduate Education, Warsaw, Poland; Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway; Department of Surgical Oncology Medical University of Gdansk, Gdansk, Poland
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10
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Mahmoudi R, Afshar S, Amini R, Jalali A, Saidijam M, Najafi R. Evaluation of BMP-2 as a Differentiating and Radiosensitizing Agent for Colorectal Cancer Stem Cells. Curr Stem Cell Res Ther 2024; 19:83-93. [PMID: 36998132 DOI: 10.2174/1574888x18666230330085615] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 01/11/2023] [Accepted: 01/13/2023] [Indexed: 04/01/2023]
Abstract
BACKGROUND Despite effective clinical responses, a large proportion of patients undergo resistance to radiotherapy. The low response rate to current treatments in different stages of colorectal cancer depends on the prominent role of stem cells in cancer. OBJECTIVE In the present study, the role of BMP-2 as an ionizing radiation-sensitive factor in colorectal cancer cells was investigated. METHODS A sphere formation assay was used for the enrichment of HCT-116 cancer stem cells (CSCs). The effects of combination therapy (BMP-2+ radiation) on DNA damage response (DDR), proliferation, and apoptosis were evaluated in HCT-116 and CSCs. Gene expressions of CSCs and epithelialmesenchymal transition (EMT) markers were also evaluated. RESULTS We found that the sphere formation assay showed a significant increase in the percentage of CSCs. Moreover, expression of CSCs markers, EMT-related genes, and DNA repair proteins significantly decreased in HCT-116 cells compared to the CSCs group after radiation. In addition, BMP-2 promoted the radiosensitivity of HCT-116 cells by decreasing the survival rate of the treated cells at 2, 4, and 6 Gy compared to the control group in HCT-116 cells. CONCLUSION Our findings indicated that BMP-2 could affect numerous signaling pathways involved in radioresistance. Therefore, BMP-2 can be considered an appealing therapeutic target for the treatment of radioresistant human colorectal cancer.
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Affiliation(s)
- Roghayeh Mahmoudi
- Department of Molecular Medicine and Genetics, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Saeid Afshar
- Department of Molecular Medicine and Genetics, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Razieh Amini
- Department of Molecular Medicine and Genetics, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Akram Jalali
- Department of Molecular Medicine and Genetics, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Massoud Saidijam
- Department of Molecular Medicine and Genetics, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Rezvan Najafi
- Department of Molecular Medicine and Genetics, Hamadan University of Medical Sciences, Hamadan, Iran
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11
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Miranda J, Horvat N, Araujo-Filho JAB, Albuquerque KS, Charbel C, Trindade BMC, Cardoso DL, de Padua Gomes de Farias L, Chakraborty J, Nomura CH. The Role of Radiomics in Rectal Cancer. J Gastrointest Cancer 2023; 54:1158-1180. [PMID: 37155130 PMCID: PMC11301614 DOI: 10.1007/s12029-022-00909-w] [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] [Accepted: 12/26/2022] [Indexed: 05/10/2023]
Abstract
PURPOSE Radiomics is a promising method for advancing imaging assessment in rectal cancer. This review aims to describe the emerging role of radiomics in the imaging assessment of rectal cancer, including various applications of radiomics based on CT, MRI, or PET/CT. METHODS We conducted a literature review to highlight the progress of radiomic research to date and the challenges that need to be addressed before radiomics can be implemented clinically. RESULTS The results suggest that radiomics has the potential to provide valuable information for clinical decision-making in rectal cancer. However, there are still challenges in terms of standardization of imaging protocols, feature extraction, and validation of radiomic models. Despite these challenges, radiomics holds great promise for personalized medicine in rectal cancer, with the potential to improve diagnosis, prognosis, and treatment planning. Further research is needed to validate the clinical utility of radiomics and to establish its role in routine clinical practice. CONCLUSION Overall, radiomics has emerged as a powerful tool for improving the imaging assessment of rectal cancer, and its potential benefits should not be underestimated.
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Affiliation(s)
- Joao Miranda
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY, 10065, USA
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY, 10065, USA.
| | - Jose A B Araujo-Filho
- Department of Radiology, Hospital Sirio-Libanes, 91 Adma Jafet, Sao Paulo, SP, 01308-050, Brazil
| | - Kamila S Albuquerque
- Department of Radiology, Hospital Beneficência Portuguesa, 637 Maestro Cardim, Sao Paulo, SP, 01323-001, Brazil
| | - Charlotte Charbel
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY, 10065, USA
| | - Bruno M C Trindade
- Department of Radiology, University of Sao Paulo, 75 Dr. Ovídio Pires de Campos, Sao Paulo, SP, 05403-010, Brazil
| | - Daniel L Cardoso
- Department of Radiology, Hospital Sirio-Libanes, 91 Adma Jafet, Sao Paulo, SP, 01308-050, Brazil
| | | | - Jayasree Chakraborty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA
| | - Cesar Higa Nomura
- Department of Radiology, University of Sao Paulo, 75 Dr. Ovídio Pires de Campos, Sao Paulo, SP, 05403-010, Brazil
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12
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Kus Ozturk S, Graham Martinez C, Sheahan K, Winter DC, Aherne S, Ryan ÉJ, van de Velde CJ, Marijnen CA, Hospers GA, Roodvoets AG, Doukas M, Mens D, Verhoef C, van der Post RS, Nagtegaal ID. Relevance of shrinkage versus fragmented response patterns in rectal cancer. Histopathology 2023; 83:870-879. [PMID: 37609761 DOI: 10.1111/his.15027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/06/2023] [Accepted: 07/31/2023] [Indexed: 08/24/2023]
Abstract
AIMS Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. METHODS AND RESULTS The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. CONCLUSIONS The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.
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Affiliation(s)
- Sonay Kus Ozturk
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | | | - Kieran Sheahan
- Department of Pathology, St. Vincent's University Hospital, Dublin, Ireland
| | - Desmond C Winter
- Department of Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Susan Aherne
- Department of Pathology, St. Vincent's University Hospital, Dublin, Ireland
| | - Éanna J Ryan
- Department of Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | | | - Corrie Am Marijnen
- Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands
| | - Geke Ap Hospers
- Department of Oncology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Annet Gh Roodvoets
- Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - David Mens
- Department of Surgical Oncology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Rachel S van der Post
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
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13
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Stefanou AJ, Dessureault S, Sanchez J, Felder S. Clinical Tools for Rectal Cancer Response Assessment following Neoadjuvant Treatment in the Era of Organ Preservation. Cancers (Basel) 2023; 15:5535. [PMID: 38067239 PMCID: PMC10705332 DOI: 10.3390/cancers15235535] [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: 09/22/2023] [Revised: 11/04/2023] [Accepted: 11/10/2023] [Indexed: 09/16/2024] Open
Abstract
Local tumor response evaluation following neoadjuvant treatment(s) in rectal adenocarcinoma requires a multi-modality approach including physical and endoscopic evaluations, rectal protocoled MRI, and cross-sectional imaging. Clinical tumor response exists on a spectrum from complete clinical response (cCR), defined as the absence of clinical evidence of residual tumor, to near-complete response (nCR), which assumes a significant reduction in tumor burden but with increased uncertainty of residual microscopic disease, to incomplete clinical response (iCR), which incorporates all responses less than nCR that is not progressive disease. This article aims to review the clinical tools currently routinely available to evaluate treatment response and offers a potential management approach based on the extent of local tumor response.
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Affiliation(s)
| | | | | | - Seth Felder
- Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL 33612, USA; (A.J.S.); (S.D.); (J.S.)
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14
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Ou X, van der Reijd DJ, Lambregts DMJ, Grotenhuis BA, van Triest B, Beets GL, Beets-Tan RGH, Maas M. Sense and non-sense of imaging in the era of organ preservation for rectal cancer. Br J Radiol 2023; 96:20230318. [PMID: 37750870 PMCID: PMC10607404 DOI: 10.1259/bjr.20230318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/17/2023] [Accepted: 08/01/2023] [Indexed: 09/27/2023] Open
Abstract
This review summarizes the current applications and benefits of imaging modalities for organ preservation in the treatment of rectal cancer. The concept of organ preservation in the treatment of rectal cancer has revolutionized the way rectal cancer is managed. Initially, organ preservation was limited to patients with locally advanced rectal cancer who needed neoadjuvant therapy to reduce tumor size before surgery and achieved complete response. However, neoadjuvant therapy is now increasingly utilized for smaller and less aggressive tumors to achieve primary organ preservation. Additionally, more intensive neoadjuvant strategies are employed to improve complete response rates and increase the chances of successful organ preservation. The selection of patients for organ preservation is a critical component of treatment, and imaging techniques such as digital rectal exam, endoscopy, and MRI are commonly used for this purpose. In this review, we provide an overview of what imaging modalities should be chosen and how they can aid in the selection and follow-up of patients undergoing organ-preserving strategies.
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Affiliation(s)
| | | | | | | | - Baukelien van Triest
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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15
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Elazzamy H, Bhatt M, Mazzara P, Barawi M, Zeni A, Aref A. Pattern of Residual Submucosal Involvement after Neoadjuvant Therapy for Rectal Cancer: A Rationale for the Utility of Endoscopic Submucosal Resection. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1807. [PMID: 37893525 PMCID: PMC10608064 DOI: 10.3390/medicina59101807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 10/05/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023]
Abstract
Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We describe the incidence and pattern of submucosal involvement in surgical specimens following neoadjuvant therapy for LARC and whether limiting local excision of the residual tumor bed to only mucosal/submucosal layers of the rectal wall is sufficient for accurately predicting the ypT status of residual cancer, providing a pathological rationale to replace full-thickness local excision by endoscopic submucosal resection. Materials and Methods: This was a single-institution retrospective study conducted at a teaching community hospital. We reviewed clinical and pathological findings with slides of 82 patients diagnosed with LARC treated at our center between 2006 and 2020. Eligibility criteria mirrored our current organ preservation trials. Results: No tumor was found in surgical specimens in 28 cases (34%). Additionally, 4, 22, 27, and 1 cases were staged as ypT1, ypT2, ypT3, and ypT4, respectively. Residual malignant cells were found in the submucosal layer in 98% of cases with ypT+ stage, with 'skip lesions' in only 2% of cases. Conclusions: A very high incidence of submucosal involvement is noticed in residual tumors after neoadjuvant therapy, providing pathological rationale to study the role of endoscopic submucosal resection as a restaging tool for tumors with favorable response after neoadjuvant therapy when organ preservation strategy is pursued. This study was limited by its retrospective design and relatively small number of patients.
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Affiliation(s)
- Haidy Elazzamy
- Pathology Department, Ascension St. John Hospital, Detroit, MI 48236, USA (P.M.)
| | - Monika Bhatt
- Pathology Department, Ascension St. John Hospital, Detroit, MI 48236, USA (P.M.)
| | - Paul Mazzara
- Pathology Department, Ascension St. John Hospital, Detroit, MI 48236, USA (P.M.)
| | - Mohammed Barawi
- Gastroenterology, Ascension St. John Hospital, Detroit, MI 48236, USA
| | - Amer Zeni
- Rectal Surgery, Ascension St. John Hospital, Detroit, MI 48236, USA;
| | - Amr Aref
- Radiation Oncology, Ascension St. John Hospital, Detroit, MI 48236, USA
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16
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Kimura C, Crowder SE, Kin C. Is It Really Gone? Assessing Response to Neoadjuvant Therapy in Rectal Cancer. J Gastrointest Cancer 2023; 54:703-711. [PMID: 36417142 DOI: 10.1007/s12029-022-00889-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE Non-operative management of rectal cancer is a feasible and appealing treatment option for patients who develop a complete response after neoadjuvant therapy. However, identifying patients who are complete responders is often a challenge. This review aims to present and discuss current evidence and recommendations regarding the assessment of treatment response in rectal cancer. METHODS A review of the current literature on rectal cancer restaging was performed. Studies included in this review explored the optimal interval between the end of neoadjuvant therapy and restaging, as well as modalities of assessment and their diagnostic performance. RESULTS The current standard for restaging rectal cancer is a multimodal assessment with the digital rectal examination, endoscopy, and T2-weighted MRI with diffusion-weighted imaging. Other diagnostic procedures under investigation are PET/MRI, radiomics, confocal laser endomicroscopy, artificial intelligence-assisted endoscopy, cell-free DNA, and prediction models incorporating one or more of the above-mentioned exams. CONCLUSION Non-operative management of rectal cancer requires a multidisciplinary approach. Understanding of the robustness and limitations of each exam is critical to inform patient selection for that treatment strategy.
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Affiliation(s)
- Cintia Kimura
- Department of Surgery, Division of General Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, H3680K94305, USA
| | - Sarah Elizabeth Crowder
- Department of Surgery, Division of General Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, H3680K94305, USA
- Brigham Young University, Provo, UT, USA
| | - Cindy Kin
- Department of Surgery, Division of General Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, H3680K94305, USA.
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17
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Daprà V, Airoldi M, Bartolini M, Fazio R, Mondello G, Tronconi MC, Prete MG, D’Agostino G, Foppa C, Spinelli A, Puccini A, Santoro A. Total Neoadjuvant Treatment for Locally Advanced Rectal Cancer Patients: Where Do We Stand? Int J Mol Sci 2023; 24:12159. [PMID: 37569532 PMCID: PMC10418822 DOI: 10.3390/ijms241512159] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 07/20/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
The therapeutic landscape in locally advanced rectal cancer (LARC) has undergone a significant paradigm shift in recent years with the rising adoption of total neoadjuvant treatment (TNT). This comprehensive approach entails administering chemotherapy and radiation therapy before surgery, followed by optional adjuvant chemotherapy. To establish and deliver the optimal tailored treatment regimen to the patient, it is crucial to foster collaboration among a multidisciplinary team comprising healthcare professionals from various specialties, including medical oncology, radiation oncology, surgical oncology, radiology, and pathology. This review aims to provide insights into the current state of TNT for LARC and new emerging strategies to identify potential directions for future research and clinical practice, such as circulating tumor-DNA, immunotherapy in mismatch-repair-deficient tumors, and nonoperative management.
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Affiliation(s)
- Valentina Daprà
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Marco Airoldi
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Michela Bartolini
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Roberta Fazio
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Giuseppe Mondello
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Maria Chiara Tronconi
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Maria Giuseppina Prete
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Giuseppe D’Agostino
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Caterina Foppa
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Alberto Puccini
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
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18
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Cuicchi D, Castagna G, Cardelli S, Larotonda C, Petrello B, Poggioli G. Restaging rectal cancer following neoadjuvant chemoradiotherapy. World J Gastrointest Oncol 2023; 15:700-712. [PMID: 37275455 PMCID: PMC10237020 DOI: 10.4251/wjgo.v15.i5.700] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 03/01/2023] [Accepted: 03/29/2023] [Indexed: 05/12/2023] Open
Abstract
Correct tumour restaging is pivotal for identifying the most personalised surgical treatment for patients with locally advanced rectal cancer undergoing neoadjuvant therapy, and works to avoid both poor oncological outcome and overtreatment. Digital rectal examination, endoscopy, and pelvic magnetic resonance imaging are the recommended modalities for local tumour restaging, while chest and abdominal computed tomography are utilised for the assessment of distant disease. The optimal length of time between neoadjuvant treatment and restaging, in terms of both oncological safety and clinical effectiveness of treatment, remains unclear, especially for patients receiving prolonged total neoadjuvant therapy. The timely identification of patients who are radioresistant and at risk of disease progression remains challenging.
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Affiliation(s)
- Dajana Cuicchi
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Giovanni Castagna
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Stefano Cardelli
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Cristina Larotonda
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Benedetta Petrello
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Gilberto Poggioli
- Department of Medical and Surgical Sciences, Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
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Quantitative synthetic MRI for predicting locally advanced rectal cancer response to neoadjuvant chemoradiotherapy. Eur Radiol 2023; 33:1737-1745. [PMID: 36380196 DOI: 10.1007/s00330-022-09191-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/08/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022]
Abstract
OBJECTIVES To investigate the value of pre-treatment quantitative synthetic MRI (SyMRI) for predicting a good response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. METHODS This prospective study enrolled 63 patients with locally advanced rectal cancer scheduled to undergo preoperative chemoradiotherapy from January 2019 to June 2021. T1 relaxation time (T1), T2 relaxation time (T2), proton density (PD) from synthetic MRI, and apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) were measured. Independent-sample t-test, the Mann-Whitney U test, the Delong test, and receiver operating characteristic curve (ROC) analyses were used to predict the pathologic complete response (pCR) and T-downstaging. RESULTS Among the 63 patients, 19 (30%) achieved pCR and 44 (70%) did not, and 24 (38%) achieved T-downstaging, while 44 (62%) did not. The mean T1 and T2 values were significantly lower in the pCR group compared with those in the non-pCR group and in the T-downstage group compared with those in the non-T-downstage group (all p < 0.05). There were no significant differences in the PD and ADC values between the two groups. There were no significant differences between the mean values of T1 and T2 for predicting pCR after CRT (AUC, 0.767 vs. 0.831, p = 0.37). There were no significant differences between the AUC values of T1 and T2 values for the assessment of post-CRT T-downstaging (AUC, 0.746 vs. 0.820, p = 0.506). CONCLUSIONS In patients with locally advanced rectal cancer, the synthetic MRI-derived T1 relaxation time and T2 relaxation time values are promising imaging markers for predicting a good response to neoadjuvant chemoradiotherapy. KEY POINTS • Mean T1 and T2 values were significantly lower in the pathologic complete response group and the T-downstage group. • There were no significant differences in the proton density and apparent diffusion coefficient values between the two groups.
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20
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Horvat N, El Homsi M, Miranda J, Mazaheri Y, Gollub MJ, Paroder V. Rectal MRI Interpretation After Neoadjuvant Therapy. J Magn Reson Imaging 2023; 57:353-369. [PMID: 36073323 PMCID: PMC9851947 DOI: 10.1002/jmri.28426] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/23/2022] [Accepted: 08/25/2022] [Indexed: 02/01/2023] Open
Abstract
In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.
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Affiliation(s)
- Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maria El Homsi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joao Miranda
- Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil
| | - Yousef Mazaheri
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Marc J. Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Viktoriya Paroder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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21
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Dai D, Liu G, Liu H, Liu Y, Liu X, Li S, Lei Y, Gao Y, Wang Y, Zhang S, Zhang R. Clinical feasibility of the therapeutic strategies total neoadjuvant therapy and "watch and wait" in the treatment of rectal cancer patients with recurrence after clinical complete response. Front Surg 2023; 9:1006624. [PMID: 36726944 PMCID: PMC9885041 DOI: 10.3389/fsurg.2022.1006624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 12/28/2022] [Indexed: 01/17/2023] Open
Abstract
Purpose In recent years, total neoadjuvant therapy (TNT) has emerged as a new therapeutic strategy against advanced rectal cancer (RC). After administration of TNT, some patients show complete clinical response (cCR) to treatment however, disputes about the effects of TNT and the alternative treatment plans in case of recurrence after cCR still exist. Methods A total of 100 patients were included in this paper. CR and non-CR was observed when these patients were administered with TNT at the First Affiliated Hospital of Dalian Medical University, China from May 2015 to June 2021. These patients received different chemotherapeutic regimens, with close monitoring and watch and wait (W&W) strategy being applied by a multidisciplinary team (MDT). According to treatment results, patients were divided into a cCR group and a non-cCR group; according to the recurrence during W&W, they were divided into a recurrence group and a no-local-recurrence group. This study analyzed the factors that may affect the prognosis, and summarized the surgery and treatment after recurrence. Results The TNT strategy was effective, and 85% of patients achieved local remission. However, W&W did not affect the survival time of CR patients, nor did it cause new distant metastasis due to local recurrence during the observation period (P > 0.05). However, for patients with positive CRM, we do not recommend W&W as the first choice of treatment (P < 0.05). Conclusion (1) Whole-course neoadjuvant therapy was an effective treatment scheme for advanced mid-term rectal cancer. The total local reduction rate of this group of cases was 85.00%, meaning that 25 patients achieved CR. (2) W&W was safe and reliable, and CR patients could receive it as the preferred treatment. (3) CRM was an independent risk factor for local recurrence in CR patients. We do not recommend W&W as the preferred treatment for CR patients with positive CRM.
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Affiliation(s)
- Dianyin Dai
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ge Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China,Correspondence: Ge Liu
| | - Huanran Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yanfeng Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xinlu Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shuang Li
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yanan Lei
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yun Gao
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yuezhu Wang
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shoujia Zhang
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ran Zhang
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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22
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van der Bogt RD, van der Wilk BJ, Oudijk L, Schoon EJ, van Lijnschoten G, Corporaal S, Nieken J, Siersema PD, Bisseling TM, van der Post RS, Quispel R, van Tilburg A, Oostenbrug LE, Riedl RG, Hol L, Kliffen M, Nikkessen S, Eyck BM, van Lanschot JJB, Doukas M, Spaander MCW. Bite-on-bite biopsies for the detection of residual esophageal cancer after neoadjuvant chemoradiotherapy. Endoscopy 2022; 54:1131-1138. [PMID: 35668664 DOI: 10.1055/a-1846-1025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Active surveillance after neoadjuvant treatment is increasingly implemented. The success of this strategy relies on the accurate detection of residual cancer. This study aimed to assess the diagnostic value of a second (bite-on-bite) biopsy for the detection of residual esophageal cancer and to correlate outcomes to the distribution of residual cancer found in the resection specimen. METHODS A multicenter prospective study of esophageal cancer patients undergoing active surveillance after neoadjuvant chemoradiotherapy was performed. At clinical response evaluations, an upper gastrointestinal (GI) endoscopy was performed with at least four bite-on-bite biopsies of the primary tumor site. First and second biopsies were analyzed separately. Patients with histopathological evidence of residual cancer were included in the primary analysis. Two pathologists blinded for biopsy outcome examined all resection specimens. RESULTS Between October 2017 and July 2020, 626 upper GI endoscopies were performed in 367 patients. Of 138 patients with residual cancer, 112 patients (81 %) had at least one positive biopsy. In 14 patients (10 %) only the first biopsy was positive and in 25 patients (18 %) only the second biopsy (P = 0.11). Remarkably, the rates of patients with tumor-free mucosa and deeper located tumors were higher in patients detected by the first biopsy. The second biopsy increased the false-positive rate by 3 percentage points. No adverse events occurred. CONCLUSIONS A second (bite-on-bite) biopsy improves the detection of residual esophageal cancer by almost 20 percentage points, at the expense of increasing the false-positive rate by 3 percentage points. The higher detection rate is explained by the higher number of biopsies obtained rather than by the penetration depth.
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Affiliation(s)
- Ruben D van der Bogt
- Department of Gastroenterology and Hepatology, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Berend J van der Wilk
- Department of Surgery, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Lindsey Oudijk
- Department of Pathology, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Erik J Schoon
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands.,GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | | | - Sietske Corporaal
- Department of Gastroenterology and Hepatology, Leeuwarden Medical Center, Leeuwarden, The Netherlands
| | - Judith Nieken
- Department of Pathology, Pathology Friesland, Leeuwarden, The Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Tanya M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Rachel S van der Post
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Rutger Quispel
- Department of Gastroenterology and Hepatology, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Arjan van Tilburg
- Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Liekele E Oostenbrug
- Department of Gastroenterology and Hepatology, Zuyderland Medical Center, Heerlen, The Netherlands
| | - Robert G Riedl
- Department of Pathology, Zuyderland Medical Center, Heerlen, The Netherlands
| | - Lieke Hol
- Department of Gastroenterology and Hepatology, Maasstad Hospital, Rotterdam, The Netherlands
| | - Mike Kliffen
- Department of Pathology, Maasstad Hospital, Rotterdam, The Netherlands
| | - Suzan Nikkessen
- Department of Gastroenterology and Hepatology, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Ben M Eyck
- Department of Surgery, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - J Jan B van Lanschot
- Department of Surgery, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Michael Doukas
- Department of Pathology, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus Cancer Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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23
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Tumour-stroma ratio to predict pathological response to neo-adjuvant treatment in rectal cancer. Surg Oncol 2022; 45:101862. [DOI: 10.1016/j.suronc.2022.101862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 09/05/2022] [Accepted: 10/02/2022] [Indexed: 11/21/2022]
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24
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Mills MN, Naz A, Sanchez J, Dessureault S, Imanirad I, Lauwers G, Moore M, Hoffe S, Frakes J, Felder S. Rectal tumor fragmentation as a response pattern following chemoradiation. J Gastrointest Oncol 2022; 13:2951-2962. [PMID: 36636056 PMCID: PMC9830359 DOI: 10.21037/jgo-22-477] [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: 05/14/2022] [Accepted: 09/05/2022] [Indexed: 11/23/2022] Open
Abstract
Background Tumor response to neoadjuvant therapy is heterogenous and prognostically important for locally advanced rectal adenocarcinoma (LARC) patients. Commonly applied response classification approaches including tumor regression grading (TRG) and TN downstaging can be discordant. The aim of this study is to compare the prognostic value of discordant tumor response measurement categorized according to the AJCC/CAP TRG schema and ypTN stage. Methods This is a single-center retrospective review of 90 consecutive patients with stage II-III rectal cancer receiving neoadjuvant chemoradiation (nCRT), total mesorectal excision (TME) and adjuvant chemotherapy (ACT) between 2007 and 2018. Two pathologists re-examined each case to assign a consensus AJCC TRG. A Cox proportional hazards ratio model assessed the effect of patient, tumor, and treatment factors on disease-free survival (DFS). Results Median follow-up after surgery was 46 months (95% CI: 41-50 months). Median age at diagnosis was 55 years (range: 27-80). Most patients were male (58%) and Caucasian (92%) with clinical stage III disease (68%). Seventy-three patients (81%) underwent low anterior resection (LAR), 17 (19%) underwent abdominoperineal resection (APR). The median interval from completion of nCRT to surgery was 62 days (IQR: 56-70 days). The 4-year OS, DFS, and LC was 92.4%, 74.4%, and 90.2%, respectively. In the multivariate analysis, ypTN downstaging was not prognostically significant; however, AJCC TRG score 3 (minimal tumor response to treatment) was strongly predictive for inferior DFS (3-year DFS 79% vs. 25%, P<0.001). Patients with TRG 3 had a significantly higher risk of both local (75% vs. 5%) and distant failure (75% vs. 19%). Conclusions Minimal tumor response to neoadjuvant therapy, AJCC TRG 3, irrespective of ypTN downstaging, is a pattern of residual disease that is at highest risk for recurrence. Response categorization discrepancies may be partly explained by alternative patterns of residual disease, including tumor fragmentation, and may be best reflected by TRG. The optimal tumor response categorization method requires further study to best stratify patient risk and management.
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Affiliation(s)
- Matthew N. Mills
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Afrin Naz
- University of South Florida, Morsani College of Medicine, Tampa, FL, USA
| | - Julian Sanchez
- Department of Surgery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Sophie Dessureault
- Department of Surgery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Iman Imanirad
- Department of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Gregory Lauwers
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Michelle Moore
- Department of Cellular Pathology, Belfast Health and Social Care Trust, Belfast, UK
| | - Sarah Hoffe
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Jessica Frakes
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Seth Felder
- Department of Surgery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
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25
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Ryu HS, Lee JL, Kim CW, Yoon YS, Park IJ, Lim SB, Yu CS, Kim JH, Kim JC. Correlative Significance of Tumor Regression Grade and ypT Category in Patients Undergoing Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer. Clin Colorectal Cancer 2022; 21:212-219. [PMID: 35300935 DOI: 10.1016/j.clcc.2022.02.001] [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: 12/09/2021] [Revised: 01/28/2022] [Accepted: 02/07/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND In patients with locally advanced rectal cancer, the treatment response to preoperative chemoradiotherapy (PRCRT) varies, and the ypT stage may change as a result of tumor shrinkage. The purpose of this study was to evaluate the correlative significance and determine the prognostic value of tumor regression grade and ypT category staging systems. MATERIALS AND METHODS This retrospective observational study was conducted in a tertiary center. A total of 1240 patients with rectal cancer who underwent curative resection after PRCRT between January 2007 and December 2016 were consecutively included. RESULTS A significant association was found between the American Joint Committee on Cancer/College of American Pathology tumor regression grading system and ypT category, indicating a potential correlation between worse tumor regression grade and more advanced T stage (Cramer's V = 0.255, P < .001). The ypT stage and tumor regression grade were independent predictors of each other (P < .001). The good response group (tumor regression grades 0-1) had significantly higher 5-year disease-free survival (85.5% vs. 68.2%, P < .001) and overall survival (92.1% vs. 81.0%, P < .001) rates than the poor response group (tumor regression grades 2-3). However, the ypT and ypN categories were the most important independent prognostic factors for disease-free and overall survival. CONCLUSIONS Tumor regression grade and ypT category were significantly correlated. Although tumor regression grade alone is not definitive, it is closely related to the ypT stage and impacts oncologic outcomes. These findings should be taken into consideration when stratifying the prognosis of patients undergoing PRCRT.
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Affiliation(s)
- Hyo Seon Ryu
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Lyul Lee
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chan Wook Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seok-Byung Lim
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Sik Yu
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Hun Kim
- Department of Pathology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea
| | - Jin Cheon Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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26
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Shahzadi I, Zwanenburg A, Lattermann A, Linge A, Baldus C, Peeken JC, Combs SE, Diefenhardt M, Rödel C, Kirste S, Grosu AL, Baumann M, Krause M, Troost EGC, Löck S. Analysis of MRI and CT-based radiomics features for personalized treatment in locally advanced rectal cancer and external validation of published radiomics models. Sci Rep 2022; 12:10192. [PMID: 35715462 PMCID: PMC9205935 DOI: 10.1038/s41598-022-13967-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/17/2022] [Indexed: 11/21/2022] Open
Abstract
Radiomics analyses commonly apply imaging features of different complexity for the prediction of the endpoint of interest. However, the prognostic value of each feature class is generally unclear. Furthermore, many radiomics models lack independent external validation that is decisive for their clinical application. Therefore, in this manuscript we present two complementary studies. In our modelling study, we developed and validated different radiomics signatures for outcome prediction after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) based on computed tomography (CT) and T2-weighted (T2w) magnetic resonance (MR) imaging datasets of 4 independent institutions (training: 122, validation 68 patients). We compared different feature classes extracted from the gross tumour volume for the prognosis of tumour response and freedom from distant metastases (FFDM): morphological and first order (MFO) features, second order texture (SOT) features, and Laplacian of Gaussian (LoG) transformed intensity features. Analyses were performed for CT and MRI separately and combined. Model performance was assessed by the area under the curve (AUC) and the concordance index (CI) for tumour response and FFDM, respectively. Overall, intensity features of LoG transformed CT and MR imaging combined with clinical T stage (cT) showed the best performance for tumour response prediction, while SOT features showed good performance for FFDM in independent validation (AUC = 0.70, CI = 0.69). In our external validation study, we aimed to validate previously published radiomics signatures on our multicentre cohort. We identified relevant publications on comparable patient datasets through a literature search and applied the reported radiomics models to our dataset. Only one of the identified studies could be validated, indicating an overall lack of reproducibility and the need of further standardization of radiomics before clinical application.
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Affiliation(s)
- Iram Shahzadi
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Alex Zwanenburg
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany
| | - Annika Lattermann
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Annett Linge
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Christian Baldus
- Department of Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Jan C Peeken
- German Cancer Consortium (DKTK) partner site Munich, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, München, Germany.,Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Neuherberg, Germany
| | - Stephanie E Combs
- German Cancer Consortium (DKTK) partner site Munich, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, München, Germany.,Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Neuherberg, Germany
| | - Markus Diefenhardt
- Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt am Main, Germany.,German Cancer Consortium (DKTK) partner site Frankfurt, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Frankfurt Cancer Institute, Frankfurt, Germany
| | - Claus Rödel
- Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt am Main, Germany.,German Cancer Consortium (DKTK) partner site Frankfurt, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Frankfurt Cancer Institute, Frankfurt, Germany
| | - Simon Kirste
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK) partner site Freiburg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK) partner site Freiburg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Baumann
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Mechthild Krause
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany
| | - Esther G C Troost
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.,National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.,Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany
| | - Steffen Löck
- OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. .,German Cancer Consortium (DKTK) partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany. .,Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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27
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Bates DD, Homsi ME, Chang K, Lalwani N, Horvat N, Sheedy S. MRI for Rectal Cancer: Staging, mrCRM, EMVI, Lymph Node Staging and Post-Treatment Response. Clin Colorectal Cancer 2022; 21:10-18. [PMID: 34895835 PMCID: PMC8966586 DOI: 10.1016/j.clcc.2021.10.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 10/26/2021] [Accepted: 10/31/2021] [Indexed: 12/16/2022]
Abstract
Rectal cancer is a relatively common malignancy in the United States. Magnetic resonance imaging (MRI) of rectal cancer has evolved tremendously in recent years, and has become a key component of baseline staging and treatment planning. In addition to assessing the primary tumor and locoregional lymph nodes, rectal MRI can be used to help with risk stratification by identifying high-risk features such as extramural vascular invasion and can assess treatment response for patients receiving neoadjuvant therapy. As the practice of rectal MRI continues to expand further into academic centers and private practices, standard MRI protocols, and reporting are critical. In addition, it is imperative that the radiologists reading these cases work closely with surgeons, medical oncologists, radiation oncologists, and pathologists to ensure we are providing the best possible care to patients. This review aims to provide a broad overview of the role of MRI for rectal cancer.
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Affiliation(s)
- David D.B. Bates
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maria El Homsi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kevin Chang
- Department of Radiology, Boston University Medical Center, Boston, MA, USA
| | - Neeraj Lalwani
- Department of Radiology, Virginia Commonwealth University, Richmond, VA, USA
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Shannon Sheedy
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
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Fernandes MC, Gollub MJ, Brown G. The importance of MRI for rectal cancer evaluation. Surg Oncol 2022; 43:101739. [PMID: 35339339 PMCID: PMC9464708 DOI: 10.1016/j.suronc.2022.101739] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 02/20/2022] [Indexed: 12/19/2022]
Abstract
Magnetic resonance imaging (MRI) has gained increasing importance in the management of rectal cancer over the last two decades. The role of MRI in patients with rectal cancer has expanded beyond the tumor-node-metastasis (TNM) system in both staging and restaging scenarios and has contributed to identifying "high" and "low" risk features that can be used to tailor and personalize patient treatment; for instance, selecting the patients for neoadjuvant chemoradiation (NCRT) before the total mesorectal excision (TME) surgery based on risk of recurrence. Among those features, the status of the circumferential resection margin (CRM), extramural vascular invasion (EMVI), and tumor deposits (TD) have stood out. Moreover, MRI also has played a role in surgical planning, especially when the tumor is located in the low rectum, when the relationship between tumor and the anal canal is important to choose the best surgical approach, and in cases of locally advanced or recurrent tumors invading adjacent pelvic organs that may require more complex surgeries such as pelvic exenteration. As approaches using organ preservation emerge, including transanal local excision and "watch-and-wait", MRI may help in the patient selection for those treatments, follow up, and detection of tumor regrowth. Additionally, potential MRI-based prognostic and predictive biomarkers, such as quantitative and semi-quantitative metrics derived from functional sequences like diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE), and radiomics, are under investigation. This review provides an overview of the current role of MRI in rectal cancer in staging and restaging and highlights the main areas under investigation and future perspectives.
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29
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Perez RO, Julião GPS, Vailati BB. Transanal Local Excision of Rectal Cancer after Neoadjuvant Chemoradiation: Is There a Place for It or Should Be Avoided at All Costs? Clin Colon Rectal Surg 2022; 35:122-128. [PMID: 35237107 PMCID: PMC8885162 DOI: 10.1055/s-0041-1742112] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Tumor response to neoadjuvant chemoradiation (nCRT) with tumor downsizing and downstaging has significantly impacted the number of patients considered to be appropriate candidates for transanal local excision (TLE). Some patients may harbor small residual lesions, restricted to the bowel wall. These patients, who exhibit major response ("near-complete") by digital rectal examination, endoscopic assessment, and radiological assessment may be considered for this approach. Although TLE is associated with minimal postoperative morbidity, a few clinical consequences and oncological outcomes must be evaluated in advance and with caution. In the setting of nCRT, a higher risk for clinically relevant wound dehiscences leading to a considerable risk for readmission for pain management has been observed. Worse anorectal function (still better than after total mesorectal excision [TME]), worsening in the quality of TME specimen, and higher rates of abdominal resections (in cases requiring completion TME) have been reported. The exuberant scar observed in the area of TLE also represents a challenging finding during follow-up of these patients. Local excision should be probably restricted for patients with primary tumors located at or below the level of the anorectal ring (magnetic resonance defined). These patients are otherwise candidates for abdominal perineal resections or ultra-low anterior resections with coloanal anastomosis frequently requiring definitive stomas or considerably poor anorectal function.
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Affiliation(s)
- Rodrigo Oliva Perez
- Department of Surgical Oncology, Hospital Beneficencia Portuguesa, São Paulo, Brazil,Division of Colorectal Surgery, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil,Address for correspondence Rodrigo Oliva Perez, MD, PhD Department of Surgical Oncology, Hospital Beneficencia PortuguesaSão Paulo 01323-001Brazil
| | - Guilherme Pagin São Julião
- Department of Surgical Oncology, Hospital Beneficencia Portuguesa, São Paulo, Brazil,Division of Colorectal Surgery, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | - Bruna Borba Vailati
- Department of Surgical Oncology, Hospital Beneficencia Portuguesa, São Paulo, Brazil,Division of Colorectal Surgery, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
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30
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Miranda J, Tan GXV, Fernandes MC, Yildirim O, Sims JA, de Arimateia Batista Araujo-Filho J, Machado FADM, Assuncao AN, Nomura CH, Horvat N. Rectal MRI radiomics for predicting pathological complete response: Where we are. Clin Imaging 2022; 82:141-149. [PMID: 34826772 PMCID: PMC9119743 DOI: 10.1016/j.clinimag.2021.10.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/21/2021] [Accepted: 10/11/2021] [Indexed: 02/03/2023]
Abstract
Radiomics using rectal MRI radiomics has emerged as a promising approach in predicting pathological complete response. In this study, we present a typical pipeline of a radiomics analysis and review recent studies, exploring applications, development of radiomics methodologies and model construction in pCR prediction. Finally, we will offer our opinion about the future and discuss the next steps of rectal MRI radiomics for predicting pCR.
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Affiliation(s)
- Joao Miranda
- Department of Radiology, University of Sao Paulo, Sao Paulo, SP, Brazil,Department of Radiology, Diagnosticos da America SA (DASA), Sao Paulo, SP, Brazil
| | - Gary Xia Vern Tan
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Onur Yildirim
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - John A. Sims
- Department of Biomedical Engineering, Universidade Federal do ABC, Santo Andre, SP, Brazil
| | | | | | | | - Cesar Higa Nomura
- Department of Radiology, University of Sao Paulo, Sao Paulo, SP, Brazil,Department of Radiology, Hospital Sirio-Libanes, Sao Paulo, Brazil
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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31
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Wada Y, Shimada M, Morine Y, Ikemoto T, Saito Y, Zhu Z, Wang X, Etxart A, Park Y, Bujanda L, Park IJ, Goel A. Circulating miRNA Signature Predicts Response to Preoperative Chemoradiotherapy in Locally Advanced Rectal Cancer. JCO Precis Oncol 2021; 5:PO.21.00015. [PMID: 34913022 PMCID: PMC8668014 DOI: 10.1200/po.21.00015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 08/22/2021] [Accepted: 10/15/2021] [Indexed: 11/20/2022] Open
Abstract
UNLABELLED Patients with locally advanced rectal cancer (LARC) are recommended to receive preoperative chemoradiotherapy (PCRT) followed by surgery. Response to PCRT varies widely: 60%-70% of patients with LARC do not derive therapeutic benefit from PCRT, whereas 15%-20% of patients achieve pathologic complete response (pCR). We sought to develop a liquid biopsy assay for identifying response to PCRT in patients with LARC. MATERIALS AND METHODS We analyzed two genome-wide microRNA (miRNA) expression profiling data sets from tumor tissue samples for in silico discovery (GSE68204) and validation (GSE29298). We prioritized biomarkers in pretreatment plasma specimens from clinical training (n = 41; 15 responders and 26 nonresponders) and validation (n = 65; 29 responders and 36 nonresponders) cohorts of patients with LARC. We developed an integrated miRNA panel and established a risk assessment model, which was combined with the miRNA panel and carcinoembryonic antigen levels. RESULTS Our comprehensive discovery effort identified an 8-miRNA panel that robustly predicted response to PCRT, with an excellent accuracy in the discovery (area under the curve [AUC] = 0.95) and validation (AUC = 0.92) cohorts. We successfully established a circulating miRNA panel with remarkable diagnostic accuracy in the clinical training (AUC = 0.82) and validation (AUC = 0.81) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to conventional clinical factors in both cohorts (P < .01) and the risk assessment model was superior (AUC = 0.83). Finally, we applied our model to detect patients with pathologic complete response and showed that it was dramatically superior to currently used pathologic features (AUC = 0.92). CONCLUSION Our novel risk assessment signature for predicting response to PCRT has a potential for clinical translation as a liquid biopsy assay in patients with LARC.
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Affiliation(s)
- Yuma Wada
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA
- Department of Surgery, Tokushima University, Tokushima, Japan
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yu Saito
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Zhongxu Zhu
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
| | - Xin Wang
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
| | - Ane Etxart
- Department of Surgery, Donostia Hospital University, Instituto Biodonostia, San Sebastián, Spain
| | - Yangsoon Park
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Luis Bujanda
- Gastroenterology Department, Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX
- City of Hope Comprehensive Cancer Center, Duarte, CA
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32
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Fokas E, Appelt A, Glynne-Jones R, Beets G, Perez R, Garcia-Aguilar J, Rullier E, Smith JJ, Marijnen C, Peters FP, van der Valk M, Beets-Tan R, Myint AS, Gerard JP, Bach SP, Ghadimi M, Hofheinz RD, Bujko K, Gani C, Haustermans K, Minsky BD, Ludmir E, West NP, Gambacorta MA, Valentini V, Buyse M, Renehan AG, Gilbert A, Sebag-Montefiore D, Rödel C. International consensus recommendations on key outcome measures for organ preservation after (chemo)radiotherapy in patients with rectal cancer. Nat Rev Clin Oncol 2021; 18:805-816. [PMID: 34349247 DOI: 10.1038/s41571-021-00538-5] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/16/2021] [Indexed: 02/07/2023]
Abstract
Multimodal treatment strategies for patients with rectal cancer are increasingly including the possibility of organ preservation, through nonoperative management or local excision. Organ preservation strategies can enable patients with a complete response or near-complete clinical responses after radiotherapy with or without concomitant chemotherapy to safely avoid the morbidities associated with radical surgery, and thus to maintain anorectal function and quality of life. However, standardization of the key outcome measures of organ preservation strategies is currently lacking; this includes a lack of consensus of the optimal definitions and selection of primary end points according to the trial phase and design; the optimal time points for response assessment; response-based decision-making; follow-up schedules; use of specific anorectal function tests; and quality of life and patient-reported outcomes. Thus, a consensus statement on outcome measures is necessary to ensure consistency and facilitate more accurate comparisons of data from ongoing and future trials. Here, we have convened an international group of experts with extensive experience in the management of patients with rectal cancer, including organ preservation approaches, and used a Delphi process to establish the first international consensus recommendations for key outcome measures of organ preservation, in an attempt to standardize the reporting of data from both trials and routine practice in this emerging area.
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Affiliation(s)
- Emmanouil Fokas
- Department of Radiotherapy of Oncology, University of Frankfurt, Frankfurt, Germany.
- German Cancer Research Center (DKFZ), Heidelberg, Germany.
- German Cancer Consortium (DKTK), Frankfurt, Germany.
- Frankfurt Cancer Institute (FCI), Frankfurt, Germany.
| | - Ane Appelt
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Robert Glynne-Jones
- Department of Radiotherapy, Mount Vernon Centre for Cancer Treatment, Northwood, UK
| | - Geerard Beets
- GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands
- Department of Surgery, Netherlands Cancer Institute Amsterdam, Amsterdam, Netherlands
| | - Rodrigo Perez
- Department of Surgery, Angelita & Joaquim Institute, São Paulo, Brazil
| | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Eric Rullier
- Department of Colorectal Surgery, Haut-Lévèque Hospital, Centre Hospitalier Universitaire (CHU) Bordeaux, Bordeaux, France
| | - J Joshua Smith
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Corrie Marijnen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Femke P Peters
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Maxine van der Valk
- Department of Surgery, Netherlands Cancer Institute Amsterdam, Amsterdam, Netherlands
| | - Regina Beets-Tan
- GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Arthur S Myint
- The Clatterbridge Cancer Centre, Royal Liverpool University Hospital, Liverpool, UK
| | | | - Simon P Bach
- Academic Department of Surgery, University of Birmingham, Birmingham, UK
| | - Michael Ghadimi
- Department of General, Visceral, and Paediatric Surgery, University Medical Center, Göttingen, Germany
| | - Ralf D Hofheinz
- Department of Medical Oncology, University Hospital Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Krzysztof Bujko
- Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Cihan Gani
- Department of Radiation Oncology, University Hospital and Medical Faculty Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
- German Cancer Research Center (DKFZ) Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Site Tübingen, Tübingen, Germany
| | - Karin Haustermans
- Department of Radiation Oncology, University Hospital Leuven, Leuven, Belgium
| | - Bruce D Minsky
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ethan Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nicholas P West
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James's, School of Medicine, University of Leeds, Leeds, UK
| | - Maria A Gambacorta
- Department of Radiation Oncology and Medical Oncology, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Valentini
- Department of Radiation Oncology and Medical Oncology, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marc Buyse
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium
- International Drug Development Institute, San Francisco, CA, USA
| | - Andrew G Renehan
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
- Colorectal and Peritoneal Oncology Centre, Christie NHS Foundation Trust, Manchester, UK
| | - Alexandra Gilbert
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | | | - Claus Rödel
- Department of Radiotherapy of Oncology, University of Frankfurt, Frankfurt, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), Frankfurt, Germany
- Frankfurt Cancer Institute (FCI), Frankfurt, Germany
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Wan L, Peng W, Zou S, Ye F, Geng Y, Ouyang H, Zhao X, Zhang H. MRI-based delta-radiomics are predictive of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Acad Radiol 2021; 28 Suppl 1:S95-S104. [PMID: 33189550 DOI: 10.1016/j.acra.2020.10.026] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/20/2020] [Accepted: 10/20/2020] [Indexed: 02/07/2023]
Abstract
RATIONALE AND OBJECTIVES To investigate the capability of delta-radiomics to predict pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS This retrospective study enrolled 165 consecutive patients with LARC (training set, n = 116; test set, n = 49) who received nCRT before surgery. All patients underwent pre- and post-nCRT MRI examination from which radiomics features were extracted. A delta-radiomics feature was defined as the percentage change in a radiomics feature from pre- to post-nCRT MRI. A data reduction and feature selection process including the least absolute shrinkage and selection operator algorithm was performed for building T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) delta-radiomics signature. Logistic regression was used to build a T2WI and DWI combined radiomics model. Receiver operating characteristic analysis was performed to assess diagnostic performance. Delong method was used to compare the performance of delta-radiomics model with that of magnetic resonance tumor regression grade (mrTRG). RESULTS Twenty-seven of 165 patients (16.4%) achieved pCR. T2WI and DWI delta-radiomics signature, and the combined model showed good predictive performance for pCR. The combined model achieved the highest areas under the receiver operating characteristic curves of 0.91 (95% confidence interval: 0.85-0.98) and 0.91 (95% confidence interval: 0.83-0.99) in the training and test sets, respectively (significantly greater than those for mrTRG; training set, p < 0.001; test set, p = 0.04). CONCLUSION MRI-based delta-radiomics can help predict pCR after nCRT in patients with LARC with better performance than mrTRG.
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Kokaine L, Gardovskis A, Gardovskis J. Evaluation and Predictive Factors of Complete Response in Rectal Cancer after Neoadjuvant Chemoradiation Therapy. ACTA ACUST UNITED AC 2021; 57:medicina57101044. [PMID: 34684080 PMCID: PMC8537499 DOI: 10.3390/medicina57101044] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/16/2021] [Accepted: 09/23/2021] [Indexed: 12/18/2022]
Abstract
The response to neoadjuvant chemoradiation therapy is an important prognostic factor for locally advanced rectal cancer. Although the majority of the patients after neoadjuvant therapy are referred to following surgery, the clinical data show that complete clinical or pathological response is found in a significant proportion of the patients. Diagnostic accuracy of confirming the complete response has a crucial role in further management of a rectal cancer patient. As the rate of clinical complete response, unfortunately, is not always consistent with pathological complete response, accurate diagnostic parameters and predictive markers of tumor response may help to guide more personalized treatment strategies and identify potential candidates for nonoperative management more safely. The management of complete response demands interdisciplinary collaboration including oncologists, radiotherapists, radiologists, pathologists, endoscopists and surgeons, because the absence of a multidisciplinary approach may compromise the oncological outcome. Prediction and improvement of rectal cancer response to neoadjuvant therapy is still an active and challenging field of further research. This literature review is summarizing the main, currently known clinical information about the complete response that could be useful in case if encountering such condition in rectal cancer patients after neoadjuvant chemoradiation therapy, using as a source PubMed publications from 2010–2021 matching the search terms “rectal cancer”, “neoadjuvant therapy” and “response”.
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Affiliation(s)
- Linda Kokaine
- Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia; or
- Pauls Stradins Clinical University Hospital, Pilsoņu Street 13, LV-1002 Riga, Latvia
- Correspondence: (L.K.); (J.G.); Tel.: +371-2635-9472 (L.K.)
| | - Andris Gardovskis
- Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia; or
- Pauls Stradins Clinical University Hospital, Pilsoņu Street 13, LV-1002 Riga, Latvia
| | - Jānis Gardovskis
- Department of Surgery, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia; or
- Pauls Stradins Clinical University Hospital, Pilsoņu Street 13, LV-1002 Riga, Latvia
- Correspondence: (L.K.); (J.G.); Tel.: +371-2635-9472 (L.K.)
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35
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Oi H, Okuyama T, Miyazaki S, Ono Y, Oya M. CD133 Expression Predicts Relapse in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemotherapy. In Vivo 2021; 35:437-445. [PMID: 33402494 DOI: 10.21873/invivo.12276] [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: 09/27/2020] [Revised: 10/13/2020] [Accepted: 10/14/2020] [Indexed: 11/10/2022]
Abstract
AIM The aim of the present study was to explore the association between CD133 expression and postoperative relapses in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS We retrospectively examined 52 patients with LARC (cT3-4, Nany, M0) who received oxaliplatin-based NAC before surgery. CD133 expression was evaluated using immunohistochemistry and divided into low and high expression groups. RESULTS High CD133 expression was observed in 22 patients (42.3%). Patients with high CD133 expression had more frequent vessel invasion and relapse than those with low CD133 expression (p=0.013 and p=0.036, respectively). Comparing the low with high CD133 expression groups, the 4-year relapse-free survival rates were 82.2% vs. 46.3% (p=0.009). Multivariate analysis indicated that CD133 expression was an independent risk factor for relapse (HR=3.138; 95%CI=1.046-9.412; p=0.041). CONCLUSION CD133 expression may be a predictive biomarker for postoperative relapse in patients with LARC who received NAC before surgery.
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Affiliation(s)
- Haruka Oi
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, Saitama, Japan
| | - Takashi Okuyama
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, Saitama, Japan
| | - Shunya Miyazaki
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, Saitama, Japan
| | - Yuko Ono
- Department of Pathology, Saitama Medical Center, Dokkyo Medical University, Saitama, Japan
| | - Masatoshi Oya
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, Saitama, Japan
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36
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Felder SI, Feuerlein S, Parsee A, Imanirad I, Sanchez J, Dessureault S, Kim R, Hoffe S, Frakes J, Costello J. Endoscopic and MRI response evaluation following neoadjuvant treatment for rectal cancer: a pictorial review with matched MRI, endoscopic, and pathologic examples. Abdom Radiol (NY) 2021; 46:1783-1804. [PMID: 33111189 DOI: 10.1007/s00261-020-02827-6] [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: 07/16/2020] [Revised: 10/05/2020] [Accepted: 10/10/2020] [Indexed: 10/23/2022]
Abstract
A nonoperative management strategy, or Watch-and-Wait, following neoadjuvant therapies of locally advanced rectal adenocarcinoma is increasingly considered for select patients. Yet, standardized tumor response assessment to best select and surveil suitable patients remains an unmet clinical challenge. Endoscopic and MRI currently provide the most reliable tumor response estimations. However, resources illustrating variable tumor responses to neoadjuvant therapies remain limited. This pictorial review aims to provide detailed and annotated examples of common endoscopic and MRI findings of rectal cancer treatment response, while also emphasizing their respective diagnostic shortcomings and consequently, the necessity for a multidisciplinary approach to optimally manage these patients.
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37
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Al-Najami I, Jones HJ, Dickson EA, Muirhead R, Deding U, James DR, Cunningham C. Rectal cancer: Watch-and-wait and continuing the rectal-preserving strategy with local excision for incomplete response or limited regrowth. Surg Oncol 2021; 37:101574. [PMID: 33853031 DOI: 10.1016/j.suronc.2021.101574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/07/2021] [Accepted: 03/29/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND Deferral of conventional surgery for rectal cancer after neo-adjuvant chemo-radiotherapy is gaining increasing interest, particularly for patients who are too frail to undergo major surgery but also those who wish to avoid the adverse effects of major surgery. We elected to undertake a pragmatic approach to include all comers in a cohort with the aim of reflecting the clinical outcomes for patients on a deferral from conventional rectal surgery pathway, treated with neo-adjuvant chemo-radiation (CRT) with or without selective local excision (LE) offered to those who failed to demonstrate a complete clinical response (cCR). METHODS Rectal cancer patients treated with neo-adjuvant CRT were stratified to a group of complete responders to CRT on a "watch and wait" (WW) pathway and a group who were treated with an additional local excision for persistent tumour. RESULTS Regrowth was noted in 26% (11/42) in the WW group after 2 years surveillance, disease free survival was 94.5% (80-99%) at 1 year and 74.9% (44-76.4%) at 3 years. Recurrence was noted in 45% (10/22) in the CRT + LE group, disease free survival at 1 and 3 years was 74% (53.4-88.1) and 66.2% (45.6-82.4) respectively. CONCLUSION A WW strategy for cCR is a viable pathway in the non-operative management of rectal cancer. We found the use of CRT + LE is a useful option for those who hope to avoid surgery but caution should be exercised due to substantially higher risk of recurrence.
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Affiliation(s)
- Issam Al-Najami
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, UK; Department of Clinical Research, University of Southern Denmark, Denmark.
| | - Helen Js Jones
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, UK
| | - Edward A Dickson
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, UK
| | - Rebecca Muirhead
- Department of Oncology, Oxford University Hospitals NHS Foundation Trust, UK
| | - Ulrik Deding
- Department of Clinical Research, University of Southern Denmark, Denmark
| | - David Rc James
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, UK
| | - Chris Cunningham
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, UK
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Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results. BMC Cancer 2020; 20:1164. [PMID: 33246428 PMCID: PMC7694337 DOI: 10.1186/s12885-020-07661-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 11/18/2020] [Indexed: 12/19/2022] Open
Abstract
Background Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The “Tratamiento de Tumores Digestivos” group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. Methods Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). Results In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). Conclusions the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. Trial registration EudraCT number: 2009–010192-24. Clinicaltrials.gov number: NCT01043484. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07661-z.
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Seo N, Kim H, Cho MS, Lim JS. Response Assessment with MRI after Chemoradiotherapy in Rectal Cancer: Current Evidences. Korean J Radiol 2020; 20:1003-1018. [PMID: 31270972 PMCID: PMC6609432 DOI: 10.3348/kjr.2018.0611] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 04/07/2019] [Indexed: 12/20/2022] Open
Abstract
Baseline magnetic resonance imaging (MRI) has become the primary staging modality for surgical plans and stratification of patient populations for more efficient neoadjuvant treatment. Patients who exhibit a complete response to chemoradiotherapy (CRT) may achieve excellent local tumor control and better quality of life with organ-preserving treatments such as local excision or even watch-and-wait management. Therefore, the evaluation of tumor response is a key factor for determining the appropriate treatment following CRT. Although post-CRT MRI is generally accepted as the first-choice method for evaluating treatment response after CRT, its application in the clinical decision process is not fully validated. In this review, we will discuss various oncologic treatment options from radical surgical technique to organ-preservation strategies for achieving better cancer control and improved quality of life following CRT. In addition, the current status of post-CRT MRI in restaging rectal cancer as well as the main imaging features that should be evaluated for treatment planning will also be described for the tailored treatment.
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Affiliation(s)
- Nieun Seo
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Honsoul Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min Soo Cho
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Seok Lim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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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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How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement. Cancer Treat Rev 2020; 84:101964. [PMID: 32000055 DOI: 10.1016/j.ctrv.2020.101964] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 01/06/2020] [Accepted: 01/07/2020] [Indexed: 02/06/2023]
Abstract
Various methods categorize tumour response after neoadjuvant therapy, including down-staging and tumour regression grading. Response categories allow comparison of different treatments within clinical trials and predict outcome. A reproducible response categorization could identify subgroups with high or low risk for the most appropriate subsequent treatments, like watch and wait. Lack of standardization and interpretation difficulties currently limit the usability of these approaches. In this review we describe these difficulties for the evaluation of chemoradiation in rectal cancer. An alternative approach of tumour response is based on patterns of residual disease, including fragmentation. We summarise the evidence behind this alternative method of response categorisation, which explains a number of very relevant clinical discrepancies. These issues include differences between downstaging and tumour regression, high local regrowth in advanced tumours during watchful waiting procedures, the importance of resection margins, the limited value of post-treatment biopsies and the relatively poor outcome of patients with a near complete pathological response. Recognition of these patterns of response can allow meaningful development of novel biomarkers in the future.
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Fanelli GN, Loupakis F, Smyth E, Scarpa M, Lonardi S, Pucciarelli S, Munari G, Rugge M, Valeri N, Fassan M. Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients' Prognosis. Int J Surg Pathol 2019; 27:816-835. [PMID: 31416371 DOI: 10.1177/1066896919869477] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.
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Affiliation(s)
| | | | | | - Marco Scarpa
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Sara Lonardi
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | | | | | | | - Nicola Valeri
- Royal Marsden Hospital, London and Sutton, UK
- The Institute of Cancer Research, London and Sutton, UK
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Glynne-Jones R. TNT in rectal cancer may not be the new testament? EClinicalMedicine 2019; 16:4-5. [PMID: 31832607 PMCID: PMC6890983 DOI: 10.1016/j.eclinm.2019.10.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 10/09/2019] [Indexed: 11/28/2022] Open
Affiliation(s)
- Rob Glynne-Jones
- Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK
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Erkan A, Mendez A, Trepanier M, Kelly J, Nassif G, Albert MR, Lee L, Monson JR. Impact of residual nodal involvement after complete tumor response in patients undergoing neoadjuvant (chemo)radiotherapy for rectal cancer. Surgery 2019; 166:648-654. [DOI: 10.1016/j.surg.2019.03.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 03/18/2019] [Accepted: 03/29/2019] [Indexed: 02/08/2023]
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Cho MS, Kim H, Han YD, Hur H, Min BS, Baik SH, Cheon JH, Lim JS, Lee KY, Kim NK. Endoscopy and magnetic resonance imaging-based prediction of ypT stage in patients with rectal cancer who received chemoradiotherapy: Results from a prospective study of 110 patients. Medicine (Baltimore) 2019; 98:e16614. [PMID: 31464897 PMCID: PMC6736480 DOI: 10.1097/md.0000000000016614] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Accurate tumor response determination remains inconclusive after preoperative chemoradiation therapy (CRT) for rectal cancer. This study aimed to investigate whether clinical assessment, such as endoscopy and magnetic resonance imaging (MRI), can accurately predict ypT stage and select candidates for pelvic organ-preserving surgery in rectal cancer after preoperative CRT. A total of 110 patients who underwent preoperative CRT followed by curative resection for rectal cancer were prospectively enrolled. Magnetic resonance tumor regression grade (mrTRG) using T2-MRI, endoscopic evaluation, and combination modality (combination of endoscopy and mrTRG) were used to analyze tumor response after preoperative CRT. Endoscopic findings were categorized as 3 grades and the mrTRG was assessed into 5 grades. Twenty-nine patients (26.4%) had achieved pathologic complete response. When predicting ypT0, endoscopy showed significantly higher area under the curve (AUC 0.818) than did mrTRG (AUC 0.568) and combination modality (AUC 0.768) in differentiating good response from poor response (P < .001). Both endoscopy and combination modality showed significantly higher diagnostic performance in sensitivity (79.31%), positive predictive value (PPV 67.65%), negative predictive value (NPV 92.11%), and accuracy (84.55%) than those of MR tumor response (sensitivity 37.93%, PPV 36.67%, NPV 77.50%, and accuracy 66.36%) for the prediction of ypT0 (P < .001). Combination modality showed significantly higher diagnostic performance in sensitivity (56.92%), NPV (56.92%), and accuracy (67.27%) compared with those of mrTRG. Neither endoscopy, nor mrTRG, nor the combination modality had adequate diagnostic performances to be clinically acceptable in selecting candidates for nonoperative treatment strategies. However, endoscopy may be incorporated in clinical restaging strategy in planning the extent of surgical resection in patients with rectal cancer.
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Affiliation(s)
- Min Soo Cho
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - HonSoul Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Yoon Dae Han
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Hyuk Hur
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Byung Soh Min
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology
| | - Joon Seok Lim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
| | - Kang Young Lee
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Nam Kyu Kim
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
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Kim SM, Yoon G, Seo AN. What are the most important prognostic factors in patients with residual rectal cancer after preoperative chemoradiotherapy? Yeungnam Univ J Med 2019; 36:124-135. [PMID: 31620624 PMCID: PMC6784638 DOI: 10.12701/yujm.2019.00157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/15/2019] [Accepted: 03/18/2019] [Indexed: 01/01/2023] Open
Abstract
Background We aimed to establish robust histoprognostic predictors on residual rectal cancer after preoperative chemoradiotherapy (CRT). Methods Analyzing known histoprognostic factors in 146 patients with residual disease allows associations with patient outcome to be evaluated. Results The median follow-up time was 77.8 months, during which 59 patients (40.4%) experienced recurrence and 41 (28.1%) died of rectal cancer. On univariate analysis, residual tumor size, ypT category, ypN category, ypTNM stage, downstage, tumor regression grade, lymphatic invasion, perineural invasion, venous invasion, and circumferential resection margin (CRM) were significantly associated with recurrence free survival (RFS) or/and cancer-specific survival (CSS) (all p<0.005). On multivariate analysis, higher ypTNM stage and CRM positivity were identified as independent prognostic factors for RFS (ypTNM stage, p=0.024; CRM positivity, p<0.001) and CSS (p=0.022, p=0.017, respectively). Furthermore, CRM positivity was an independent predictor of reduced RFS and CSS, irrespective of subgrouping according to downstage (non-downstage, p<0.001 and p<0.001; downstage, p=0.002 and p=0.002) or lymph node metastasis (non-metastasis, p<0.001 and p=0.001; metastasis, p<0.001 and p<0.001). Conclusion CRM status may be as powerful as ypTNM stage as a prognostic indicator for patient outcome in patients with residual rectal cancer after preoperative CRT.
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Affiliation(s)
- Sol-Min Kim
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Ghilsuk Yoon
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea.,Department of Pathology, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - An Na Seo
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea.,Department of Pathology, Kyungpook National University Chilgok Hospital, Daegu, Korea
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Horvat N, Carlos Tavares Rocha C, Clemente Oliveira B, Petkovska I, Gollub MJ. MRI of Rectal Cancer: Tumor Staging, Imaging Techniques, and Management. Radiographics 2019; 39:367-387. [PMID: 30768361 DOI: 10.1148/rg.2019180114] [Citation(s) in RCA: 300] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Rectal cancer is prone to local recurrence and systemic metastasis. However, owing to improvements in TNM staging and treatment, including a more widespread use of rectal MRI and increased radiologist awareness of the key rectal cancer TNM staging features, the mortality rate of rectal cancer has been declining over the past few decades in adults over 50 years of age. Currently, rectal MRI plays a key role in the pre- and posttreatment evaluation of rectal cancer, assisting the multidisciplinary team in tailoring the most appropriate treatment option. The benefits achieved with rectal MRI are strictly dependent on obtaining good-quality images, which is important for the characterization of the main anatomic structures and their relationship with the tumor. In primary staging, rectal MRI helps the radiologist (a) describe the tumor location and morphology, (b) provide its T and N categories, (c) detect the presence of extramural vascular invasion, and (d) identify its relationship with surrounding structures, including the sphincter complex and involvement of the mesorectal fascia. These features help diagnose locally advanced rectal tumors (categories T3c-d, T4, N1, and N2), for which neoadjuvant chemoradiotherapy (CRT) is indicated. In restaging after neoadjuvant CRT, in addition to reassessing the features noted during primary staging, rectal MRI can help in the assessment of treatment response, especially with the emergence of nonsurgical approaches such as "watch and wait." ©RSNA, 2019.
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Affiliation(s)
- Natally Horvat
- From the Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (N.H., I.P., M.J.G.); Department of Radiology, Hospital Sírio-Libanês, Adma Jafet 91, 01308-050 Bela Vista, São Paulo, Brazil (N.H., B.C.O.); and Department of Radiology, University of São Paulo, São Paulo, Brazil (N.H., C.C.T.R., B.C.O.)
| | - Camila Carlos Tavares Rocha
- From the Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (N.H., I.P., M.J.G.); Department of Radiology, Hospital Sírio-Libanês, Adma Jafet 91, 01308-050 Bela Vista, São Paulo, Brazil (N.H., B.C.O.); and Department of Radiology, University of São Paulo, São Paulo, Brazil (N.H., C.C.T.R., B.C.O.)
| | - Brunna Clemente Oliveira
- From the Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (N.H., I.P., M.J.G.); Department of Radiology, Hospital Sírio-Libanês, Adma Jafet 91, 01308-050 Bela Vista, São Paulo, Brazil (N.H., B.C.O.); and Department of Radiology, University of São Paulo, São Paulo, Brazil (N.H., C.C.T.R., B.C.O.)
| | - Iva Petkovska
- From the Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (N.H., I.P., M.J.G.); Department of Radiology, Hospital Sírio-Libanês, Adma Jafet 91, 01308-050 Bela Vista, São Paulo, Brazil (N.H., B.C.O.); and Department of Radiology, University of São Paulo, São Paulo, Brazil (N.H., C.C.T.R., B.C.O.)
| | - Marc J Gollub
- From the Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (N.H., I.P., M.J.G.); Department of Radiology, Hospital Sírio-Libanês, Adma Jafet 91, 01308-050 Bela Vista, São Paulo, Brazil (N.H., B.C.O.); and Department of Radiology, University of São Paulo, São Paulo, Brazil (N.H., C.C.T.R., B.C.O.)
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Ren DL, Li J, Yu HC, Peng SY, Lin WD, Wang XL, Ghoorun RA, Luo YX. Nomograms for predicting pathological response to neoadjuvant treatments in patients with rectal cancer. World J Gastroenterol 2019; 25:118-137. [PMID: 30643363 PMCID: PMC6328965 DOI: 10.3748/wjg.v25.i1.118] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/16/2018] [Accepted: 12/20/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent decades, neoadjuvant therapy (NT) has been the standardized treatment for locally advanced rectal cancer (LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response (pCR). If the pathological response (PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore, developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients.
AIM To establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC.
METHODS Rectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0 (ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens (capecitabine/deGramont-RT, mFOLFOX6, and mFOLFOX6-RT) to predict pCR probability.
RESULTS Four hundred and three patients were included in this study; 72 (17.9%) had pCR at the final pathology report, and 177 (43.9%) achieved good downstaging to ypT0-2N0M0 (ypTNM 0-I). The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia (MRF) status, and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio (NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the mFOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation.
CONCLUSION We established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.
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Affiliation(s)
- Dong-Lin Ren
- Department of Colorectal and Anal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Juan Li
- Department of Colorectal and Anal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Hui-Chuan Yu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Shao-Yong Peng
- Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Wei-Da Lin
- Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Xiao-Lin Wang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Roshan Ara Ghoorun
- Department of Colorectal and Anal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Yan-Xin Luo
- Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
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Abstract
The management of locally-advanced rectal cancer involves a combination of chemotherapy, chemoradiation, and surgical resection to provide excellent local tumor control and overall survival. However, aspects of this multimodality approach are associated with significant morbidity and long-term sequelae. In addition, there is growing evidence that patients with a clinical complete response to chemotherapy and chemoradiation treatments may be safely offered initial non-operative management in a rigorous surveillance program. Weighed against the morbidity and significant sequelae of rectal resection, recognizing how to best optimize non-operative strategies without compromising oncologic outcomes is critical to our understanding and treatment of this disease.
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Affiliation(s)
- Iris H Wei
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering, New York, NY, USA -
| | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering, New York, NY, USA
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