|
1
|
Wo JY, Ashman JB, Bhadkamkar NA, Bradfield L, Chang DT, Hanna N, Hawkins M, Holtz M, Kim E, Kelly P, Ling DC, Olsen JR, Palta M, Raldow AC, Ruiz-Garcia E, Sheybani A, Stitzenberg KB, Das P. Radiation Therapy for Rectal Cancer: An ASTRO Clinical Practice Guideline Focused Update. Pract Radiat Oncol 2025; 15:124-143. [PMID: 39603501 DOI: 10.1016/j.prro.2024.11.003] [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: 10/08/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024]
Abstract
PURPOSE With the results of several recently published clinical trials, this guideline focused update provides evidence-based recommendations for the indications and dose-fractionation regimens for neoadjuvant radiation therapy (RT), optimal sequencing of RT and systemic therapy in the context of total neoadjuvant therapy (TNT), and considerations for selective omission of RT and surgery for rectal cancer. METHODS The American Society for Radiation Oncology convened a multidisciplinary task force to update 3 key questions that focused on the role of RT for patients with operable rectal cancer. The key questions addressed (1) indications for neoadjuvant RT, (2) selection of neoadjuvant regimens, and (3) indications for consideration of a nonoperative management (NOM) or local excision approach after definitive/preoperative chemoradiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS For patients with stage II-III rectal cancer, neoadjuvant RT was strongly recommended; however, among patients deemed at lower risk of locoregional recurrence, consideration of omission of neoadjuvant RT was conditionally recommended in favor of neoadjuvant chemotherapy with a favorable treatment response or upfront surgery. For patients with T3-T4 and node-positive rectal cancer undergoing neoadjuvant RT, a TNT approach was strongly recommended. Among patients with higher risk of locoregional recurrence, TNT with chemotherapy before or after long-course chemoradiation was strongly recommended, whereas TNT with short-course RT followed by chemotherapy was conditionally recommended. For patients with rectal cancer for whom NOM is a priority, concurrent chemoradiation followed by consolidation chemotherapy was strongly recommended. Selection of RT dose-fractionation regimen, sequencing of therapies, and consideration of NOM should be determined by multidisciplinary consensus and based on disease extent, disease location, patient preferences, and quality of life considerations. CONCLUSIONS The task force proposed recommendations to inform best clinical practices on the use of RT for rectal cancer with strong emphasis on multidisciplinary care. Future studies should focus on further addressing optimal treatment regimens to allow for more personalized recommendations based on individual risk stratification and patient priorities regarding quality of life.
Collapse
Affiliation(s)
- Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
| | | | - Nishin A Bhadkamkar
- Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Lisa Bradfield
- American Society for Radiation Oncology, Arlington, Virginia
| | - Daniel T Chang
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Nader Hanna
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
| | - Michael Holtz
- Patient Representative, Oak Ridge Associated Universities, Knoxville, Tennessee
| | - Edward Kim
- Department of Radiation Oncology, University of Washington, Seattle, Washington
| | - Patrick Kelly
- Department of Radiation Oncology, Orlando Health, Orlando, Florida
| | - Diane C Ling
- Department of Radiation Oncology, University of Southern California, Los Angeles, California
| | - Jeffrey R Olsen
- Department of Radiation Oncology, University of Colorado, Aurora, Colorado
| | - Manisha Palta
- Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina
| | - Ann C Raldow
- Department of Radiation Oncology, University of Southern California, Los Angeles, California
| | - Erika Ruiz-Garcia
- Department of Medical Oncology, Instituto Nacional de Cancerologia, Mexico City, Mexico
| | - Arshin Sheybani
- Department of Radiation Oncology, UnityPoint Health, Des Moines, Iowa
| | - Karyn B Stitzenberg
- Department of Surgery, University of North Carolina, Chapel Hill, North Carolina
| | - Prajnan Das
- Department of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
2
|
Rutenberg MS, Chuong MD, Frakes JM. Reirradiation in the Management of Locally Recurrent Rectal Adenocarcinoma. Pract Radiat Oncol 2025; 15:e166-e171. [PMID: 39672321 DOI: 10.1016/j.prro.2024.11.008] [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: 10/15/2024] [Accepted: 11/07/2024] [Indexed: 12/15/2024]
Abstract
Rectal cancer recurrence after prior radiation therapy presents a difficult treatment challenge. Salvage treatment can be curative; however, it often requires multimodality therapy which can come with significant treatment-related morbidity. Reirradiation is a common part of treatment considerations in this setting and presents challenges in balancing appropriately aggressive therapy to improve disease control and cure rates with the addition of excess toxicity. Surgery remains the mainstay of curative salvage therapy for locally recurrent rectal cancer (LRRC) after prior radiation. Preoperative reirradiation improves R0 resection rates and local control and is associated with improved disease control outcomes. Altered fractionation and intraoperative radiation therapy are often used to improve the therapeutic ratio in the setting of reirradiation for LRRC. Herein, we discuss the evidence supporting multimodality salvage therapy for LRRC, including the importance of surgical salvage, the benefits of reirradiation, various approaches for reirradiation, and treatment-associated toxicities. Finally, we provide our recommendations for how to approach reirradiation for locally recurrent rectal cancer.
Collapse
Affiliation(s)
- Michael S Rutenberg
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, Florida.
| | - Michael D Chuong
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Jessica M Frakes
- Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida
| |
Collapse
|
|
3
|
Yang Y, Pang K, Lin G, Liu X, Gao J, Zhou J, Xu L, Gao Z, Wu Y, Li A, Han J, Wu G, Wang X, Li F, Ye Y, Zhang J, Chen G, Wang H, Kong Y, Wu A, Xiao Y, Yao H, Zhang Z. Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial. Nat Med 2025; 31:449-456. [PMID: 39762418 DOI: 10.1038/s41591-024-03360-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 10/16/2024] [Indexed: 02/20/2025]
Abstract
Radiotherapy displays unique antitumor synergism with immune checkpoint inhibitors, which is indicated by high pathological complete response (pCR) rates from single-arm trials of locally advanced rectal cancer (LARC). Here we test the efficacy and safety of the radiation-immune checkpoint inhibitor combination in patients with LARC in a phase 2, randomized trial conducted in eight major colorectal cancer centers in Beijing. In total, 186 eligible all-comer (proficient mismatch repair and deficient mismatch repair) participants were enrolled. The patients were randomly assigned to receive neoadjuvant chemoradiation + concurrent/sequential PD-1 blockade (experiment groups A/B) or neoadjuvant chemoradiation alone (control group). Radical surgeries were scheduled after neoadjuvant treatments. The primary endpoint was the pCR rate. The pCR rates were 27.1%, 32.7% and 14.0% for experiment groups A and B and the control group, respectively. The difference in pCR rates between experiment group B and the control group reached statistical significance (risk ratio 2.332, 95% confidence interval 1.106-4.916; P = 0.019). No substantial differences between either one of the experiment groups and the control group were observed regarding adverse reaction, surgical complication and disease progression. Our results show that adding PD-1 blockade after neoadjuvant chemoradiation increases the pCR rate for patients with LARC and raises no substantial safety concerns. Phase 3 trials with larger sample sizes are warranted (ClinicalTrials.gov identifier NCT05245474 ).
Collapse
Affiliation(s)
- Yingchi Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Kai Pang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guole Lin
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Xinzhi Liu
- Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jiale Gao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jiaolin Zhou
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Lai Xu
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China
| | - Zhidong Gao
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China
| | - Yingchao Wu
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Ang Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jiagang Han
- Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Guoju Wu
- Department of General Surgery, Beijing Hospital, Beijing, China
| | - Xin Wang
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yingjiang Ye
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China
| | - Jie Zhang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guangyong Chen
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hao Wang
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Aiwen Wu
- Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute, Beijing, China.
| | - Yi Xiao
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China.
| | - Hongwei Yao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
| |
Collapse
|
|
4
|
Collard MK, Mineur L, Nekrouf C, Denost Q, Rouanet P, de Chaisemartin C, Merdrignac A, Jafari M, Cotte E, Desrame J, Manceau G, Benoist S, Buscail E, Karoui M, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Duchalais E, Lupinacci RM, Goasguen N, Simon T, Parc Y, Lefevre JH. Final Results of the GRECCAR-6 Trial on Waiting Period Following Neoadjuvant Radiochemotherapy for Locally Advanced Rectal Cancer: 5 Years of Follow-up. Dis Colon Rectum 2025; 68:199-208. [PMID: 39508462 DOI: 10.1097/dcr.0000000000003477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
BACKGROUND The potential oncological benefit of extending the waiting period between neoadjuvant radiochemotherapy and surgical resection for rectal cancer is debated. OBJECTIVE To evaluate the impact of prolonging this waiting period on the 5-year oncological prognosis and 2-year functional result of locally advanced rectal adenocarcinoma. DESIGN Phase III, multicenter, randomized, open-label, parallel-group, controlled trial. SETTINGS Patients were enrolled from 24 colorectal centers. PATIENTS Patients with nonmetastatic mid or lower cT3/T4Nx or cTxN+ rectal adenocarcinoma who had received radiochemotherapy (45-50 Gy radiation dose with fluorouracil or capecitabine). INTERVENTION Patients were randomly assigned to undergo total mesorectal excision either 7 weeks or 11 weeks after radiochemotherapy. MAIN OUTCOMES MEASURES Overall survival and disease-free survival at 5-year follow-up and low anterior resection syndrome score assessed after 2 years of follow-up. RESULTS Among 265 patients enrolled, 133 were randomized in the 7-week group and 132 in the 11-week group. Twelve patients were excluded because they did not undergo resection. Among 253 patients analyzed, 5-year overall survival was not different between the 2 groups (81.6% in the 7-week group vs 82.6% in the 11-week group, p = 0.827), and neither was the 5-year disease-free survival (70.4% in the 7-week group vs 69.5% in the 11-week group, p = 0.856). No difference was observed between the 2 groups for distant recurrence (27.4% in the 7-week group vs 25.7% in the 11-week group, p = 0.777) or local recurrence (8.4% in the 7-week group vs 10.2% in the 11-week group, p = 0.543). The low anterior resection syndrome score was similar between the 7-week (25.0; interquartile range, 15.0-34.0) and 11-week groups (23.0; interquartile range, 14.2-32.0; p = 0.743). LIMITATIONS The response rate to the low anterior resection syndrome questionnaire was only 52%. CONCLUSIONS Extending the waiting period between radiochemotherapy and resection from 7 to 11 weeks does not change the 5-year oncological prognosis in rectal cancer or the 2-year low anterior resection occurrence. See Video Abstract. RESULTADOS FINALES DEL ENSAYO GRECCAR SOBRE EL PERODO DE ESPERA TRAS LA RADIOQUIMIOTERAPIA NEOADYUVANTE PARA EL CNCER DE RECTO LOCALMENTE AVANZADO AOS DE SEGUIMIENTO ANTECEDENTES:Se debate el posible beneficio oncológico de prolongar el periodo de espera entre la radioquimioterapia neoadyuvante y la resección quirúrgica del cáncer de recto.OBJETIVO:Evaluar el impacto de la prolongación de este periodo de espera sobre el pronóstico oncológico a 5 años y el resultado funcional a 2 años del adenocarcinoma rectal localmente avanzado.DISEÑO:Ensayo controlado de fase III, multicéntrico, aleatorizado, abierto, de grupos paralelos.LUGAR:Se reclutaron pacientes de 24 centros colorrectales.PACIENTES:Pacientes con adenocarcinoma rectal de tercio medio o inferior, no metastásico cT3-4 o TxN+ que habían recibido radioquimioterapia (45 a 50 Gy con fluorouracilo o capecitabina).INTERVENCIÓN:Se asignaron aleatoriamente a los pacientes para ser sometidos a una escisión mesorrectal total 7 semanas (W7) u 11 semanas (W11) después de la radioquimioterapia.MEDIDAS DE RESULTADOS PRINCIPALES:Supervivencia global y supervivencia libre de enfermedad a los 5 años de seguimiento y puntuación del síndrome de resección anterior baja evaluada a los 2 años de seguimiento.RESULTADOS:De los 265 pacientes reclutados, 133 fueron asignados aleatoriamente al grupo de 7 semanas y 132 al grupo de 11 semanas. Doce pacientes fueron excluidos porque no fueron sometidos a resección. Entre los 253 pacientes analizados, la supervivencia global a 5 años no fue diferente entre los dos grupos (81,6% en el grupo de 7 semanas frente a 82,6% en el grupo de 11 semanas, p = 0,827), así como para la supervivencia libre de enfermedad a 5 años (70,4% en el grupo de 7 semanas frente a 69,5% en el grupo de 11 semanas, p = 0,856). No se observaron diferencias entre los dos grupos en cuanto a la recidiva a distancia (27,4% en el grupo de 7 semanas frente a 25,7% en el grupo de 11 semanas, p = 0,777) o la recidiva local (8,4% en el grupo de 7 semanas frente a 10,2% en el grupo de 11 semanas, p = 0,543). La puntuación del síndrome de resección anterior baja fue similar entre los grupos de 7 semanas (25,0 IQR [15,0-34,0]) y 11 semanas (23,0 IQR [14,2-32,0], p = 0,743).LIMITACIONES:La tasa de respuesta al cuestionario LARS fue sólo del 52%.CONCLUSIONES:Ampliar el periodo de espera entre radioquimioterapia y resección de 7 a 11 semanas no modifica el pronóstico oncológico a 5 años en cáncer de recto ni la baja incidencia de resección anterior a 2 años. (Traducción-Dr Osvaldo Gauto ).
Collapse
Affiliation(s)
- Maxime K Collard
- Department of Digestive Surgery, Sorbonne Université, AP-HP, Hôpital Saint Antoine, F-75012, Paris, France
| | - Laurent Mineur
- Oncology, Radiotherapy, Sainte-Camille Institut, Avignon, France
| | - Célia Nekrouf
- Department of Clinical Pharmacology and Clinical Research Platform of the East of Paris (URC-CRC-CRB), Assistance Publique Hôpitaux de Paris, Hôpital St Antoine, Paris, France
| | - Quentin Denost
- Bordeaux Colorectal Institute, Clinique Tivoli-Ducos, Bordeaux, France
| | - Philippe Rouanet
- Department of Oncological Surgery, Val d'Aurelle Institut, Montpellier, France
| | | | - Aude Merdrignac
- Department of Hepatobiliary and Digestive Surgery, CHU, Rennes, France
| | - Mehrdad Jafari
- Department of Oncological Surgery, Oscar Lambret Center, Lille, France
| | - Eddy Cotte
- Department of Digestive Surgery, CHU Lyon-Sud, Pierre-Bénite, France
| | - Jérôme Desrame
- Department of Gastrology and Hepatology, Jean Mermoz Institut, Lyon, France
| | - Gilles Manceau
- Department of Digestive and Hepatobiliary Surgery, CHU Pitié-Salpétrière, Paris, France
| | - Stéphane Benoist
- Department of Digestive and Oncological Surgery, CHU Bicètre, Le Kremlin-Bicêtre, France
| | | | - Mehdi Karoui
- Department of Digestive, Oncological and General Surgery, Paris, France
| | - Yves Panis
- Colorectal Center, Groupe Hospitalier privé Ambroise Paré-Hartmann, Neuilly-sur-Seine, France
| | | | - Alain Saudemont
- Department of Digestive Surgery and Transplant Surgery, CHRU, Lille, France
| | - Michel Prudhomme
- Department of Digestive and Oncological Surgery, CHU Carémeau, Nîmes, France
| | - Frédérique Peschaud
- Department of Digestive Surgery, CHU Ambroise-Paré, Boulogne-Billancourt, France
| | - Anne Dubois
- Department of Digestive Surgery, CHU Estaing, Clermont-Ferrand, France
| | - Jérôme Loriau
- Department of Digestive Surgery, St-Joseph Hospital, Paris, France
| | | | | | - Renato M Lupinacci
- Department of General and Endocrine Surgery, Pitié Salpêtrière Hospital, APHP, Sorbonne University, Paris, France
| | - Nicolas Goasguen
- Department of Digestive Surgery, Croix Saint-Simon Hospital, Paris, France
| | - Tabassome Simon
- Department of Clinical Pharmacology and Clinical Research Platform of the East of Paris (URC-CRC-CRB), Assistance Publique Hôpitaux de Paris, Hôpital St Antoine, Paris, France
| | - Yann Parc
- Department of Digestive Surgery, Sorbonne Université, AP-HP, Hôpital Saint Antoine, F-75012, Paris, France
| | - Jérémie H Lefevre
- Department of Digestive Surgery, Sorbonne Université, AP-HP, Hôpital Saint Antoine, F-75012, Paris, France
| |
Collapse
|
|
5
|
Harada T, Numata M, Atsumi Y, Fukuda T, Izukawa S, Suwa Y, Watanabe J, Sato T, Saito A. Risk factors for anastomotic leakage in rectal cancer surgery reflecting current practices. Surg Today 2025:10.1007/s00595-024-02988-7. [PMID: 39797981 DOI: 10.1007/s00595-024-02988-7] [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: 08/15/2024] [Accepted: 12/02/2024] [Indexed: 01/13/2025]
Abstract
PURPOSE In recent years, major advancements have been made in rectal cancer surgery with the introduction of new techniques such as robotic surgery and indocyanine green fluorescence imaging (ICG-FI). This study aimed to evaluate the comprehensive risk factors for anastomotic leakage (AL) following rectal cancer surgery, incorporating recently introduced techniques and other existing factors, to reflect current practices. METHODS A retrospective analysis was conducted of 304 patients who underwent either robotic or laparoscopic anterior resection between January 2019 and December 2023. The study analyzed patient, tumor, and surgical factors, with AL defined by clinical or radiological findings requiring intervention within 30 days after surgery. RESULTS A univariate analysis indicated that moderate or severe anemia and the non-use of ICG-FI were strongly associated with AL. A multivariate analysis identified moderate or more severe anemia (hemoglobin ≤10.9 g/dL for males and ≤9.9 g/dL for females) (odds ratio [OR]: 9.94, p = 0.002) and non-use of ICG-FI (OR: 10.40, p < 0.001) as independent risk factors for AL. CONCLUSION Moderate or severe anemia and absence of ICG-FI were found to significantly increase the risk of AL. Preoperative anemia correction and the routine use of ICG-FI may help mitigate this risk, thus suggesting the need for further research in these areas.
Collapse
Affiliation(s)
- Tatsunosuke Harada
- Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Masakatsu Numata
- Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan.
| | - Yosuke Atsumi
- Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Toshiyuki Fukuda
- Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Shota Izukawa
- Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Yusuke Suwa
- Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Jun Watanabe
- Department of Colorectal Surgery, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Tsutomu Sato
- Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Aya Saito
- Department of Surgery, Yokohama City University Hospital, 3-9, Fukuura, Kanazawa-Ku, Yokohama, Kanagawa, 236-0004, Japan
| |
Collapse
|
|
6
|
Chen J, Zhang Y, Chen X, Luo D, Liu D, Yu Z, Lin Y, He X, Huang J, Lian L. Raddeanin A Inhibits Colorectal Cancer Growth and Ameliorates Oxaliplatin Resistance Through the WNT/β-Catenin Signaling Pathway. Cancer Biother Radiopharm 2025; 40:41-53. [PMID: 39585204 DOI: 10.1089/cbr.2024.0061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2024] Open
Abstract
Background: Chemotherapy based on oxaliplatin (OXA) is the first-line treatment for advanced colorectal cancer (CRC), and acquired resistance to OXA is the main reason for clinical treatment failure in CRC. Methods: To search for compounds that can reverse OXA resistance, we screened a small molecule inhibitor drug library and identified a drug, Raddeanin A (RA), that enhanced the anticancer effect of OXA. Using human CRC cell lines, CRC organoid models, and in vivo subcutaneous tumorigenic studies, we determined that RA inhibits the proliferation of CRC cells by promoting apoptosis and inducing cell cycle arrest. Results: We constructed OXA-resistant CRC cell lines and demonstrated that RA enhances the sensitivity of these cells to OXA. Further experiments showed that the mechanism by which RA enhanced the anticancer effects of OXA in CRC was by inhibiting the activation of the WNT/β-catenin signaling pathway. Conclusions: Because RA has been shown to be biocompatible in animal models, there is a possibility that RA could be developed as a sensitizer for resistant cancer cells or as a novel lead compound to enhance the therapeutic efficacy of OXA in resistant CRCs.
Collapse
Affiliation(s)
- Junguo Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanhong Zhang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xijie Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of General Surgery (Gastrointestinal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dandong Luo
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of General Surgery (Gastrointestinal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Danlin Liu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhaoliang Yu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanyun Lin
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaosheng He
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Juanni Huang
- Department of Geriatrics, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Lei Lian
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of General Surgery (Gastrointestinal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
7
|
Williams H, Lee C, Garcia-Aguilar J. Nonoperative management of rectal cancer. Front Oncol 2024; 14:1477510. [PMID: 39711959 PMCID: PMC11659252 DOI: 10.3389/fonc.2024.1477510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 11/21/2024] [Indexed: 12/24/2024] Open
Abstract
The management of locally advanced rectal cancer has changed drastically in the last few decades due to improved surgical techniques, development of multimodal treatment approaches and the introduction of a watch and wait (WW) strategy. For patients with a complete response to neoadjuvant treatment, WW offers an opportunity to avoid the morbidity associated with total mesorectal excision in favor of organ preservation. Despite growing interest in WW, prospective data on the safety and efficacy of nonoperative management are limited. Challenges remain in optimizing multimodal treatment regimens to maximize tumor regression and in improving the accuracy of patient selection for WW. This review summarizes the history of treatment for rectal cancer and the development of a WW strategy. It also provides an overview of clinical considerations for patients interested in nonoperative management, including restaging strategies, WW selection criteria, surveillance protocols and long-term oncologic outcomes.
Collapse
Affiliation(s)
| | | | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer
Center, New York, NY, United States
| |
Collapse
|
|
8
|
Luengo Gómez D, Salmerón Ruiz Á, Medina Benítez A, Láinez Ramos-Bossini A. Papel de la resonancia magnética en la evaluación del cáncer de recto tras terapia neoadyuvante. RADIOLOGIA 2024. [DOI: 10.1016/j.rx.2024.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2024]
|
|
9
|
Bandidwattanawong C. Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: How to Select the Most Suitable? J Clin Med 2024; 13:5061. [PMID: 39274273 PMCID: PMC11396572 DOI: 10.3390/jcm13175061] [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: 07/16/2024] [Revised: 08/12/2024] [Accepted: 08/20/2024] [Indexed: 09/16/2024] Open
Abstract
Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6-7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC.
Collapse
Affiliation(s)
- Chanyoot Bandidwattanawong
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Navamindradhiraj University, Bangkok 10300, Thailand
| |
Collapse
|
|
10
|
Gaetani RS, Ladin K, Abelson JS. Journey through the Decades: The Evolution in Treatment and Shared Decision Making for Locally Advanced Rectal Cancer. Cancers (Basel) 2024; 16:2807. [PMID: 39199579 PMCID: PMC11353159 DOI: 10.3390/cancers16162807] [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: 07/12/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 09/01/2024] Open
Abstract
The management of locally advanced rectal cancer has undergone significant transformations over the decades and optimal treatment approaches continue to evolve. There have been numerous advances in surgery, chemotherapy, and radiation therapy from the first description of the abdominoperineal resection in 1908, timing of chemotherapy and radiation therapy in the late 20th and early 21st century, and most recently, the introduction of organ preservation or nonoperative management in 2004. Alongside these advancements, the concept of shared decision making in medicine has evolved, prompting a focus on patient-centered care. This evolution in practice has been fueled by a growing recognition of the importance of patient autonomy and the alignment of treatment options with patients' values and preferences. With the growing number of possible treatment options, variability in patient counseling exists, highlighting the need for a standardized approach to shared decision making in locally advanced rectal cancer. This narrative review will describe the evolution of treatment options of locally advanced rectal cancer as well as the concept of shared decision making and decision aids, and will introduce a decision aid for patients with locally advanced rectal cancer who have achieved a complete clinical response and are eligible for watch and wait.
Collapse
Affiliation(s)
- Racquel S. Gaetani
- Department of Colon and Rectal Surgery, Lahey Hospital and Medical Center, Burlington, MA 01805, USA;
| | - Keren Ladin
- Department of Community Health, Tufts University, Medford, MA 02155, USA
| | - Jonathan S. Abelson
- Department of Colon and Rectal Surgery, Lahey Hospital and Medical Center, Burlington, MA 01805, USA;
| |
Collapse
|
|
11
|
Chen W, Wang W, Huang S, Zhou L, Wang G, Chen W. Clinical Analysis of the Efficacy and Safety of Different Neoadjuvant Strategies in the Treatment of Locally Advanced Rectal Cancer. Cancer Invest 2024; 42:661-670. [PMID: 39037150 DOI: 10.1080/07357907.2024.2381197] [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: 10/25/2023] [Accepted: 07/14/2024] [Indexed: 07/23/2024]
Abstract
OBJECTIVE In this study, we retrospectively analysed the efficacy and safety of three treatment models, namely, short-course radiotherapy sequential XELOX chemotherapy, neoadjuvant mFOLFOX6 concurrent radiotherapy and long-course concurrent radiotherapy with total mesorectal excision (TME) after treatment of locally advanced rectal cancer with high-risk factors. METHODS We collected clinical data on 177 patients with locally advanced rectal cancer (cT3-4 and/or cN+) who were treated at the Department of Abdominal Oncology of the Affiliated Cancer Hospital of Guizhou Medical University from December 2017 to December 2022. All patients were associated with 2-3 risk factors [T4b, N2, Extramural Vascular Invasion (EMVI), Mesorectal Fascia (MRF) positivity], positive lateral lymph nodes. Among them, there were 45 cases in the short course radiotherapy sequential XELOX chemotherapy group (RT + XELOX group); 64 cases in the neoadjuvant mFOLFOX6 concurrent radiotherapy group (mFOLFOX6 + CRT group); and 68 cases in the long course concurrent radiotherapy group (CRT group). The RT + XELOX group and mFOLFOX6 + CRT group completed radiotherapy and 4 cycles of neoadjuvant chemotherapy, respectively, and then rested for 1-2 weeks before TME surgery; the CRT group completed concurrent radiotherapy and then rested for 6-8 weeks before TME surgery.Adjuvant chemotherapy was conducted after surgery in each of the three groups: 2 cycles of adjuvant chemotherapy with XELOX regimen in the RT + XELOX group, 4-6 cycles of adjuvant chemotherapy with mFOLFOX6 in the mFOLFOX6 + CRT group, and 8-12 cycles of adjuvant chemotherapy with mFOLFOX6 in the CRT group.The pathological complete response rate (pCR rate), tumour downstage rate, tumour complete resection rate (R0 resection rate), local recurrence rate, distant metastasis rate, overall survival rate, incidence of adverse reactions, surgical complications and completion rate of perioperative systemic chemotherapy were compared among patients in the three groups of cases after TME. RESULTS The pCR rate (21.95% vs 17.24% vs 5.00%, p = 0.034) and and tumour downstage rate (78.05% vs 68.97% vs 53.33%, p = 0.029) were higher in the RT + XELOX group and mFOLFOX6 + CRT group compared to the CRT group. The RT + XELOX group had a lower 3-year distant metastasis rate (14.63% vs 36.67%, p = 0.048) and improved 3-year overall survival (76.57% vs 48.56%, p < 0.001) compared to the CRT group. There was no significant reduction in the 3-year distant metastasis rate in the mFOLFOX6 + CRT group versus the CRT group (27.59% vs 36.67%, p = 0.719), and the 3-year overall survival was similar (51.23% vs 48.56%, p = 0.35). Multi-logistic regression analysis and stratified analysis showed that patients in the RT + XELOX group and mFOLFOX6 + CRT group were more likely to achieve pCR than the CRT group (RT + XELOX group: OR 7.3, 95% CI [2.6-20.8], p < 0.001; mFOLFOX6 + CRT group OR 2.9, 95% CI [1.1-7.9], p = 0.036). The completion rates of perioperative systemic chemotherapy in the RT + XELOX, mFOLFOX6 + CRT, and CRT groups were 82.93% vs. 84.48% vs. 61.67% (χ2=9.95, p = 0.007), respectively. And there were significant differences in grade 3-4 leukopenia and thrombocytopenia (incidence of leukopenia: 15.50% vs. 7.81% vs. 1.47%, p = 0.045; incidence of thrombocytopenia: 13.33% vs 7.81% vs 1.47%, p = 0.027). There was no significant difference in the incidence of intraoperative and postoperative complications among the three groups (p > 0.05). CONCLUSIONS RT + XELOX group and mFOLFOX6 + CRT group significantly improved the near-term outcome (e.g., pCR rate) in patients with locally advanced rectal cancer with high-risk factors compared with CRT group. The RT + XELOX group also reduced the 3-year distant metastasis rate, increased the 3-year overall survival rate, and did not increase the incidence of perioperative surgical complications. It provides an effective means for the comprehensive treatment of locally advanced rectal cancer and has important clinical guidance and application value.
Collapse
Affiliation(s)
- Wanghua Chen
- Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Wenling Wang
- Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Sicheng Huang
- Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University Guizhou Hospital, Guian new area, China
| | - Lili Zhou
- Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
| | - Gang Wang
- Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Weiwei Chen
- Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
- Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| |
Collapse
|
|
12
|
Rajeev-Kumar G, Katipally RR, Li S, Shogan BD, Olortegui KS, Chin J, Polite BN, Liauw SL. Point/Counterpoint #2: Current Clinical Considerations With Nonoperative Management of Rectal Cancer. Cancer J 2024; 30:256-263. [PMID: 39042777 DOI: 10.1097/ppo.0000000000000732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2024]
Abstract
ABSTRACT Locally advanced rectal cancer has historically been treated with multimodal therapy consisting of radiation therapy, chemotherapy, and total mesorectal excision. However, recent prospective trials and registry studies have demonstrated similar disease outcomes with nonoperative management for patients who experience an excellent clinical response to radiation and chemotherapy. This article reviews data regarding nonoperative management for rectal cancer, and highlights current challenges and limitations in a point-counterpoint format, in the context of two clinical cases.
Collapse
Affiliation(s)
| | | | - Shen Li
- Sections of Surgical Oncology
| | | | | | - Janet Chin
- Department of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL
| | - Blase N Polite
- Department of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL
| | | |
Collapse
|
|
13
|
Owens PW, Saeed M, McCawley N, Loughlin P, Kearney DE, Burke JP, McNamara DA, Sahebally SM. Prolonged interval to surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A meta-analysis of randomized controlled trials. Surgeon 2024; 22:166-173. [PMID: 38521683 DOI: 10.1016/j.surge.2024.03.001] [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: 03/08/2023] [Revised: 02/05/2024] [Accepted: 03/12/2024] [Indexed: 03/25/2024]
Abstract
BACKGROUND Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI = 0.39-0.95, p = 0.03), and more TD (OR 0.60, 95%CI = 0.37-0.97, p = 0.04) compared to SI. However, there was no difference in rates of R0 resection (p = 0.87), +CRM (p = 0.66), sphincter preservation (p = 0.26), incomplete TME (p = 0.49), LNY (p = 0.55), SSI (p = 0.33), AL (p = 0.20), operative duration (p = 0.07), mortality (p = 0.89) or any surgical complication (p = 0.91). CONCLUSIONS A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.
Collapse
Affiliation(s)
- P W Owens
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| | - M Saeed
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| | - N McCawley
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| | - P Loughlin
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| | - D E Kearney
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| | - J P Burke
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| | - D A McNamara
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| | - S M Sahebally
- Dept of Surgery, Beaumont Hospital, Dublin, Ireland.
| |
Collapse
|
|
14
|
Janczak J, Ukegjini K, Bischofberger S, Turina M, Müller PC, Steffen T. Quality of Surgical Outcome Reporting in Randomised Clinical Trials of Multimodal Rectal Cancer Treatment: A Systematic Review. Cancers (Basel) 2023; 16:26. [PMID: 38201454 PMCID: PMC10778098 DOI: 10.3390/cancers16010026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/07/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open
Abstract
INTRODUCTION Randomised controlled trials (RCTs) continue to provide the best evidence for treatment options, but the quality of reporting in RCTs and the completeness rate of reporting of surgical outcomes and complication data vary widely. The aim of this study was to measure the quality of reporting of the surgical outcome and complication data in RCTs of rectal cancer treatment and whether this quality has changed over time. METHODS Eligible articles with the keywords ("rectal cancer" OR "rectal carcinoma") AND ("radiation" OR "radiotherapy") that were RCTs and published in the English, German, Polish, or Italian language were identified by reviewing all abstracts published from 1982 through 2022. Two authors independently screened and analysed all studies. The quality of the surgical outcome and complication data was assessed based on fourteen criteria, and the quality of RCTs was evaluated based on a modified Jadad scale. The primary outcome was the quality of reporting in RCTs and the completeness rate of reporting of surgical results and complication data. RESULTS A total of 340 articles reporting multimodal therapy outcomes for 143,576 rectal cancer patients were analysed. A total of 7 articles (2%) met all 14 reporting criteria, 13 met 13 criteria, 27 met from 11 to 12 criteria, 36 met from 9 to 10 criteria, 76 met from 7 to 8 criteria, and most articles met fewer than 7 criteria (mean 5.5 criteria). Commonly underreported criteria included complication severity (15% of articles), macroscopic integrity of mesorectal excision (17% of articles), length of stay (18% of articles), number of lymph nodes (21% of articles), distance between the tumour and circumferential resection margin (CRM) (26% of articles), surgical radicality according to the site of the primary tumour (R0 vs. R1 + R2) (29% of articles), and CRM status (38% of articles). CONCLUSION Inconsistent surgical outcome and complication data reporting in multimodal rectal cancer treatment RCTs is standard. Standardised reporting of clinical and oncological outcomes should be established to facilitate comparing studies and results of related research topics.
Collapse
Affiliation(s)
- Joanna Janczak
- Clinic for General and Visceral Surgery, Hospital for the Region Fürstenland Toggenburg, CH-9500 Wil, Switzerland;
| | - Kristjan Ukegjini
- Department of Surgery, Hospital of the Canton of St. Gallen, CH-9007 St. Gallen, Switzerland; (K.U.); (S.B.)
| | - Stephan Bischofberger
- Department of Surgery, Hospital of the Canton of St. Gallen, CH-9007 St. Gallen, Switzerland; (K.U.); (S.B.)
| | - Matthias Turina
- Department of Surgery and Transplantation, University Hospital Zurich, CH-8091 Zurich, Switzerland;
| | - Philip C. Müller
- Department of Surgery, Clarunis—University Centre for Gastrointestinal and Hepatopancreatobiliary Diseases, CH-4002 Basel, Switzerland;
| | - Thomas Steffen
- Department of Surgery, Hospital of the Canton of St. Gallen, CH-9007 St. Gallen, Switzerland; (K.U.); (S.B.)
| |
Collapse
|
|
15
|
Ling Q, Huang ST, Yu TH, Liu HL, Zhao LY, Chen XL, Liu K, Chen XZ, Yang K, Hu JK, Zhang WH. Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis. World J Surg Oncol 2023; 21:377. [PMID: 38037067 PMCID: PMC10690980 DOI: 10.1186/s12957-023-03251-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 11/13/2023] [Indexed: 12/02/2023] Open
Abstract
BACKGROUND Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.
Collapse
Grants
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 21PJ043 1. Medical Science and Technique Project of Health Commission of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 23NSFSC1611 2. Natural Science Foundation of Sichuan Province
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
- No. 2020HXBH162 3. Post-Doctor Research Project, West China Hospital, Sichuan University
Collapse
Affiliation(s)
- Qi Ling
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Shi-Ting Huang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tian-Hang Yu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Han-Lin Liu
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Lin-Yong Zhao
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Long Chen
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Kai Liu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Kun Yang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jian-Kun Hu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
| | - Wei-Han Zhang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
| |
Collapse
|
|
16
|
Donnelly M, Ryan OK, Ryan ÉJ, Creavin B, O'Reilly M, McDermott R, Kennelly R, Hanly A, Martin ST, Winter DC. Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials. Br J Surg 2023; 110:1316-1330. [PMID: 37330950 DOI: 10.1093/bjs/znad177] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 05/10/2023] [Accepted: 05/20/2023] [Indexed: 06/20/2023]
Abstract
BACKGROUND This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.
Collapse
Affiliation(s)
- Mark Donnelly
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College, Dublin, Ireland
| | - Odhrán K Ryan
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College, Dublin, Ireland
| | - Éanna J Ryan
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
| | - Ben Creavin
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
| | - Mary O'Reilly
- Department of Oncology, St Vincent's University Hospital, Dublin, Ireland
| | - Ray McDermott
- School of Medicine, University College, Dublin, Ireland
- Department of Oncology, St Vincent's University Hospital, Dublin, Ireland
| | - Rory Kennelly
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Ann Hanly
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Seán T Martin
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Des C Winter
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| |
Collapse
|
|
17
|
SENYUREK SUKRAN, SAGLAM SEZER, SAGLAM ESRAKAYTAN, YANAR HAKAN, GOK KAAN, TASTEKIN DIDEM, AKBAS CANANKOKSAL, SAKIN NERGIZDAGOGLU, KARTAL GULBIZDAGOGLU, BALIK EMRE, KESKIN METIN, SANLI YASEMIN, GULLUOGLU MINE, AKGUN ZULEYHA. Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+ rectal cancer: Istanbul R-02 phase II randomized study. Oncol Res 2023; 31:689-696. [PMID: 37547762 PMCID: PMC10398395 DOI: 10.32604/or.2023.030351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 06/09/2023] [Indexed: 08/08/2023] Open
Abstract
Radiation therapy (RT) is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer (LARC): short-course RT (SC-RT) alone or long-course RT (LC-RT) with concurrent fluorouracil (5-FU) chemotherapy. The Phase II single-arm KROG 11-02 study using intermediate-course (IC) (33 Gy (Gray)/10 fr (fraction) with concurrent capecitabine) preoperative chemoradiotherapy (CRT) demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT. The current trial aim to compare the pathological/oncological outcomes, toxicity, and quality of life results of LC-CRT and IC-CRT in cases of LARC. The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group. Concurrent chronomodulated capecitabine (Brunch regimen) 1650 mg/m2/daily chemotherapy treatment was applied in both groups. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module (EORTC QLQ-CR29) was administered at baseline and at three and six months after CRT. A total of 60 patients with LARC randomized to receive IC-CRT (n = 30) or LC-CRT (n = 30) were included in this phase II randomized trial. No significant difference was noted between groups in terms of pathological outcomes, including pathological response rates (ypT0N0-complete response: 23.3% vs. 16.7%, respectively, and ypT0-2N0-downstaging: 50% for each; p = 0.809) and Dworak score-based pathological tumor regression grade (Grade 4-complete response: 23.3 vs. 16.7%, p = 0.839). The 5-year overall survival (73.3 vs. 86.7%, p = 0.173) rate was also similar. The acute radiation dermatitis (p < 0.001) and any hematological toxicity (p = 0.004) rates were significantly higher in the LC-CRT group, while no significant difference was noted between treatment groups in terms of baseline, third month, and sixth month EORTC QLQ-CR29 scores.
Collapse
Affiliation(s)
- SUKRAN SENYUREK
- Department of Radiation Oncology, Koc University School of Medicine, Istanbul, 34450, Türkiye
| | - SEZER SAGLAM
- Department of Medical Oncology, Demiroglu Bilim University Faculty of Medicine, Istanbul, 34394, Türkiye
| | - ESRA KAYTAN SAGLAM
- Department of Radiation Oncology, Istanbul University Oncology Institute, Istanbul, 34093, Türkiye
| | - HAKAN YANAR
- Department of General Surgery, Istanbul University Istanbul Faculty of Medicine, Istanbul, 34093, Türkiye
| | - KAAN GOK
- Department of General Surgery, Istanbul University Istanbul Faculty of Medicine, Istanbul, 34093, Türkiye
| | - DIDEM TASTEKIN
- Department of Medical Oncology, Istanbul University Oncology Institute, Istanbul, 34093, Türkiye
| | - CANAN KOKSAL AKBAS
- Department of Medical Physics, Istanbul University Oncology Institute, Istanbul, 34093, Türkiye
| | - NERGIZ DAGOGLU SAKIN
- Department of Radiation Oncology, Istanbul University Oncology Institute, Istanbul, 34093, Türkiye
| | - GULBIZ DAGOGLU KARTAL
- Department of Radiology, Istanbul University Istanbul Faculty of Medicine, Istanbul, 34093, Türkiye
| | - EMRE BALIK
- Department of General Surgery, Koc University School of Medicine, Istanbul, 34450, Türkiye
| | - METIN KESKIN
- Department of General Surgery, Istanbul University Istanbul Faculty of Medicine, Istanbul, 34093, Türkiye
| | - YASEMIN SANLI
- Department of Nuclear Medicine, Istanbul University Istanbul Faculty of Medicine, Istanbul, 34093, Türkiye
| | - MINE GULLUOGLU
- Department of Pathology, Istanbul University Istanbul Faculty of Medicine, Istanbul, 34093, Türkiye
| | - ZULEYHA AKGUN
- Department of Radiation Oncology, Memorial Sisli Hospital, Istanbul, 34384, Türkiye
| |
Collapse
|
|
18
|
Chen M, Wang C, Liu H, Liang Z, Ye F, Luo S, Liu Z, Hu H, Lai S, Hou Y, Kang L, Huang L. The Deepest Extent of Acellular Mucin Pools in Resected Locally Advanced Rectal Cancer With Pathological Complete Response After Preoperative Chemoradiotherapy: A Hidden Killer? Am J Surg Pathol 2023; 47:812-818. [PMID: 37194966 DOI: 10.1097/pas.0000000000002055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
For patients with locally advanced rectal cancer (LARC) with pathological complete response (pCR), the clinical significance of the distribution extent of acellular mucin pools (AMP) distribution remains unclear, so this study was conducted to address key unanswered questions. We performed a retrospective analysis of 317 patients with LARC with pCR after preoperative chemoradiotherapy and total mesorectal resection from January 2011 to June 2020. Based on AMP existence and the deepest tissue layer of distribution, patients were assigned new stages. The patient information was recorded, and the main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival (OS). A total of 83/317 (26.2%) patients exhibited AMP, and disease recurrence occurred in 46/317 (14.5%) patients. Over the 5-year median follow-up period, the patients with AMP showed 5-year DFS rates (75.9% vs. 88.9%, P =0.004) and 5-year OS rates (85.5% vs. 95.7%, P =0.002) statistically lower than those of patients without AMP. Disease recurrence was seen in 15/54 (27.8%) patients with AMP within the subserosa and/or the serosa, or adipose tissue. Univariate and multivariate analysis showed that the existence of AMP within the subserosa and/or the serosa, or adipose tissue was an independent risk factor for DFS [hazard ratio (HR): 2.344; 95% confidence interval (CI): 1.256-4.376; P =0.007] and OS [HR: 3.374; 95% CI: 1.438-7.917; P =0.005]. The new stages based on the deepest extent of AMP were related to worse DFS ( P =0.004) and OS ( P =0.003) rates among patients with pCR. In conclusion, the presence of AMP might reduce the prognosis of LARC patients with pCR after chemoradiotherapy, especially in patients with AMP in deeper tissue layers. Therefore, the influence of the deepest AMP extent might be worth considering in staging. Moreover, the revised staging of patients with pCR according to the deepest extent of AMP, which is unrelated to the clinical T stage, might facilitate postoperative management.
Collapse
Affiliation(s)
- Mian Chen
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chao Wang
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huashan Liu
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhenxing Liang
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Fujin Ye
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shuangling Luo
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhanzhen Liu
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huanxin Hu
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Sicong Lai
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yujie Hou
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Kang
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Huang
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| |
Collapse
|
|
19
|
Yu M, Wang DC, Li S, Huang LY, Wei J. Efficacy and Safety of Preoperative Radiotherapy Versus Chemoradiotherapy in Advanced Rectal Cancer: A Meta-analysis of Randomized Controlled Trials. Am Surg 2023; 89:2262-2271. [PMID: 35435026 DOI: 10.1177/00031348221086790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE This meta-analysis was conducted to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with surgery and preoperative chemoradiotherapy (CRT) combined with surgery for locally advanced rectal cancer. METHODS PubMed, EMBASE and Cochrane Library were searched to collect published randomized controlled trials of preoperative radiotherapy or preoperative CRT combined with surgery for the treatment of locally advanced rectal cancer. Studies were screened according to inclusion and exclusion criteria, and quality was evaluated; RevMan 5.3 software was used for meta-analysis. RESULTS In total, 7 related studies involving 3100 patients with locally advanced rectal cancer were evaluated. The pathological complete response rate, negative lymph node rate, R0 resection rate, and incidence of grade III/IV adverse reactions were lower in the RT group than in the CRT group. In the absence of postoperative chemotherapy, the 5-year local recurrence rate of RT was higher than that of CRT, but there was no significant difference between the groups among those who underwent postoperative chemotherapy. Moreover, there was no significant difference between the groups with regard to the 5-year survival rate, anal-preserving rate, or incidence of anastomotic leakage. CONCLUSION Preoperative CRT is better than preoperative RT for the treatment of advanced rectal cancer, though the adverse reaction rate is higher.
Collapse
Affiliation(s)
- Miao Yu
- Department of Basic Medicine, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan, China
| | - Deng-Chao Wang
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China
| | - Sheng Li
- Department of Basic Medicine, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan, China
| | - Li-Yan Huang
- Department of Pathology, West China Second Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jian Wei
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China
| |
Collapse
|
|
20
|
Cambray M, González-Viguera J, Losa F, Martínez-Villacampa M, Frago R, Mata F, Castellví J, Guinó E. Determining the optimal interval between neoadjuvant radiochemotherapy and surgery in rectal cancer: a retrospective cohort study. Int J Colorectal Dis 2023; 38:154. [PMID: 37261511 DOI: 10.1007/s00384-023-04457-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/25/2023] [Indexed: 06/02/2023]
Abstract
INTRODUCTION In locally advanced rectal cancer, the optimal interval between completion of neoadjuvant radiochemotherapy (RT-ChT) and surgical resection remains unclear due to contradictory data on the benefits of extending this interval. Therefore, the aim of this retrospective study was to determine the impact of this interval on outcomes in patients treated for rectal cancer at our center. METHODS We retrospectively reviewed 382 consecutive patients treated for stage II/III rectal cancer between October 1, 2012, and December 31, 2017. We evaluated four different cut-off points (56, 63, 70, and 77 days) to determine which had the greatest impact on treatment outcomes. RESULTS The median time between completion of RT-ChT and surgery was 67.2 days (range, 28-294). Intervals > 8 weeks (56 days) were associated with worse therapeutic outcomes. Specifically, an interval ≥ 77 days was associated with a significant decrease in overall survival (OS; 84% vs. 70%; p = 0.004), which is why we selected this interval for the comparative analysis. Several outcome variables were significantly better in the short interval (< 77 days) group, including margin involvement (5.2% vs. 13.9%; p = 0.01), sphincter preservation (78% vs. 59.3%; p = 0.003), and distant dissemination (22.6% vs. 32.5%; p = 0.04). No significant between-group differences were found in complete/nearly complete response rates (19.2% vs. 24.4%; p = 0.3). Time to surgery was statistically significant on both the univariate and multivariate analyses. CONCLUSIONS Our findings suggest that surgery should not be delayed more than 8 weeks (56 days) after neoadjuvant treatment. An interval > 8 weeks should only be considered in patients who demonstrate a good response to neoadjuvant RT-ChT.
Collapse
Affiliation(s)
- Maria Cambray
- Radiation Oncology Department, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Javier González-Viguera
- Radiation Oncology Department, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
| | - Ferran Losa
- Medical Oncology Department, Moisès Broggi Hospital, Sant Joan Despí, Barcelona, Spain
- Medical Oncology Department, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | - Ricard Frago
- General and Digestive Surgery Department, Bellvitge University Hospital, L'Hospitalet del Llobregat, Barcelona, Spain
| | - Fernando Mata
- General and Digestive Surgery Department, Moisès Broggi Hospital, Sant Joan Despí, Barcelona, Spain
| | - Jordi Castellví
- General and Digestive Surgery Department, Moisès Broggi Hospital, Sant Joan Despí, Barcelona, Spain
| | - Elisabet Guinó
- Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
| |
Collapse
|
|
21
|
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.
Collapse
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
| |
Collapse
|
|
22
|
Abstract
The current preferred standard of care management for patients with locally advanced rectal cancer is total neoadjuvant therapy, in which all chemotherapy and radiotherapy is delivered before surgery. Within this approach, developed in response to persistently high distant failure rates despite excellent local control with preoperative chemoradiotherapy, there remains questions regarding the optimal radiotherapy regimen (short course vs long course) and sequencing of chemotherapy (induction vs consolidation).
Collapse
Affiliation(s)
- Timothy Lin
- Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD 21287, USA
| | - Amol Narang
- Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD 21287, USA.
| |
Collapse
|
|
23
|
Simillis C, Khatri A, Dai N, Afxentiou T, Jephcott C, Smith S, Jadon R, Papamichael D, Khan J, Powar MP, Fearnhead NS, Wheeler J, Davies J. A systematic review and network meta-analysis of randomised controlled trials comparing neoadjuvant treatment strategies for stage II and III rectal cancer. Crit Rev Oncol Hematol 2023; 183:103927. [PMID: 36706968 DOI: 10.1016/j.critrevonc.2023.103927] [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: 12/15/2022] [Revised: 01/08/2023] [Accepted: 01/23/2023] [Indexed: 01/27/2023] Open
Abstract
AIM Multiple neoadjuvant therapy strategies have been used and compared for rectal cancer and there has been no true consensus as to the optimal neoadjuvant therapy regimen. The aim is to identify and compare the neoadjuvant therapies available for stage II and III rectal cancer. DESIGN A systematic literature review was performed, from inception to August 2022, of the following databases: MEDLINE, EMBASE, Science Citation Index Expanded, Cochrane Library. Only randomized controlled trials comparing neoadjuvant therapies for stage II and III rectal cancer were considered. Stata was used to draw network plots, and a Bayesian network meta-analysis was conducted through models utilizing the Markov Chain Monte Carlo method in WinBUGS. RESULTS A total of 58 articles were included based on 41 randomised controlled trials, reporting on 12,404 participants that underwent 15 neoadjuvant treatment regimens. No significant difference was identified between treatments for major or total postoperative complications, anastomotic leak rates, or sphincter-saving surgery. Straight to surgery (STS) ranked as best treatment for preoperative toxicity but ranked worst treatment for positive resection margins and complete response. STS had significantly increased positive resection margins compared to long-course chemoradiotherapy with short-wait (LCCRT-SW) or long-wait (LCCRT-LW) to surgery, or short-course radiotherapy with short-wait (SCRT-SW) or immediate surgery (SCRT-IS). LCCRT-SW or LCCRT-LW resulted in significantly increased complete response rates compared to STS. LCCRT-LW significantly improved 2-year overall survival compared to STS, SCRT-IS, SCRT-SW. Total neoadjuvant therapy regimes with short-course radiotherapy followed by consolidation chemotherapy (SCRT-CT-SW), induction chemotherapy followed by long-course chemoradiotherapy (CT-LCCRT-S), long-course chemoradiotherapy followed by consolidation chemotherapy (LCCRT-CT-S), significantly improved positive resection margins, complete response, and disease-free survival compared to STS. Chemotherapy with monoclonal antibodies followed by long-course chemoradiotherapy (CT+MAB-LCCRT+MAB-S) significantly improved complete response and positive resection margins compared to STS, and 2-year disease-free survival compared to STS, SCRT-IS, SCRT-SW, SCRT-CT-SW, LCCRT-SW, LCCRT-LW. CT+MAB-LCCRT+MAB-S ranked as best treatment for disease-free survival and overall survival. CONCLUSIONS Conventional neoadjuvant therapies with short-course radiation or long-course chemoradiotherapy have oncological benefits compared to no neoadjuvant therapy without increasing perioperative complication rates. Prolonged wait to surgery may improve oncological outcomes. Total neoadjuvant therapies provide additional benefits in terms of complete response, positive resection margins, and disease-free survival. Monoclonal antibody therapy may further improve oncological outcomes but currently is only applicable to a small subgroup of patients and requires further validation.
Collapse
Affiliation(s)
- Constantinos Simillis
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
| | - Amulya Khatri
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nick Dai
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Thalia Afxentiou
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Catherine Jephcott
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sarah Smith
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Rashmi Jadon
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - Jim Khan
- Department of Colorectal Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Michael P Powar
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nicola S Fearnhead
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - James Wheeler
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Justin Davies
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK
| |
Collapse
|
|
24
|
Abstract
BACKGROUND Increased experience with total neoadjuvant therapy for rectal cancer suggests significantly more tumor regression and increased rates of complete clinical response as measured by pathological complete response and clinical complete response. OBJECTIVE This study aimed to assess outcomes after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer. DESIGN This is a retrospective cohort study. SETTINGS A database of patients with rectal cancer from 2015 to 2019 at a large integrated health care system was reviewed. PATIENTS Demographics of the 2 groups revealed no significant difference in clinical stage or patient characteristics. Of 465 patients, 66 patients underwent total neoadjuvant therapy and 399 underwent standard neoadjuvant chemoradiotherapy. Fifty-six patients underwent consolidation chemotherapy, and 10 underwent induction chemotherapy. MAIN OUTCOME MEASURES Complete clinical response, disease-free survival, proctectomy-free survival, and organ preservation rates were the main outcome measures. RESULTS Complete clinical response was achieved in 36 patients (58.1%) versus 59 patients (14.8%; p < 0.001), favoring the total neoadjuvant therapy group. Three-year overall survival was similar between groups (85.6% standard neoadjuvant chemoradiotherapy versus 86.0% total neoadjuvant therapy). Three-year distant metastasis-free survival was 67.4% in the total neoadjuvant therapy group compared to 77.7% in the standard neoadjuvant chemoradiotherapy group. Three-year proctectomy-free survival was 44% in the total neoadjuvant therapy group compared to 6% in the standard neoadjuvant chemoradiotherapy group. Twenty-two patients (37.3% of complete clinical responders) in the standard neoadjuvant chemoradiotherapy group elected to pursue organ preservation, whereas 31 patients (86.1% of complete clinical responders) from the total neoadjuvant therapy group chose organ preservation. LIMITATIONS This study is limited by its retrospective nature with a shorter follow-up of 3 years. CONCLUSIONS Total neoadjuvant therapy for rectal cancer significantly increased complete clinical response. This allowed patients to have greater organ preservation with no significant difference in overall survival or disease control. See Video Abstract at http://links.lww.com/DCR/B934 . LA TERAPIA NEOADYUVANTE TOTAL AUMENTA SIGNIFICATIVAMENTE LA RESPUESTA CLNICA COMPLETA ANTECEDENTES:La mayor experiencia con la terapia neoadyuvante total para el cáncer de recto sugiere una regresión tumoral significativamente mayor y mayores tasas de respuesta clínica completa, medidas por respuesta patológica completa y respuesta clínica completa.OBJETIVO:Este estudio evaluó los resultados después de la terapia neoadyuvante total versus la quimiorradioterapia neoadyuvante estándar para pacientes con cáncer de recto localmente avanzado.DISEÑO:Este es un estudio de cohorte retrospectivo.ESCENARIO:Se revisó una base de datos de pacientes con cáncer de recto de 2015 a 2019 en un sistema de salud integrado grande.PACIENTES:La demografía de los dos grupos no revela diferencias significativas en el estadio clínico o las características de los pacientes. De 465 pacientes, 66 pacientes recibieron terapia neoadyuvante total y 399 quimiorradioterapia neoadyuvante estándar. Cincuenta y seis se sometieron a quimioterapia de consolidación mientras que 10 pacientes a quimioterapia de inducción.PRINCIPALES MEDIDAS DE RESULTADO:Se midieron la respuesta clínica completa, la sobrevida libre de enfermedad, la sobrevida libre de proctectomía y las tasas de preservación de órgano.RESULTADOS:Se logró una respuesta clínica completa en 36 pacientes (58.1 %) frente a 59 pacientes (14.8 %) (p < 0,001) a favor del grupo de terapia neoadyuvante total. La sobrevida general a tres años fue similar entre los grupos (85.6 % quimiorradioterapia neoadyuvante estándar frente a 86.0 % terapia neoadyuvante total). La sobrevida libre de metástasis a distancia a los tres años fue del 67.4 % en el grupo de terapia neoadyuvante total y del 77.7 % en el grupo de quimiorradioterapia neoadyuvante estándar. La sobrevida sin proctectomía a los tres años fue del 44 % en el grupo de terapia neoadyuvante total frente al 6 % en el grupo de quimiorradioterapia neoadyuvante estándar. Veintidós pacientes (37.3 % con respuesta clínica completa) en el grupo de quimiorradioterapia neoadyuvante estándar optaron por la preservación de órgano, mientras que 31 pacientes (86.1 % respuesta clínica completa) del grupo de terapia neoadyuvante total eligieron la preservación de órgano.LIMITACIONES:Este estudio es un estudio retrospectivo con un seguimiento más corto de 3 años.CONCLUSIONES:La terapia neoadyuvante total para el cáncer de recto aumentó significativamente la respuesta clínica completa. Esto permitió a los pacientes tener una mayor preservación de órgano sin diferencias significativas en la sobrevida general o el control de la enfermedad. Consulte Video Resumen en http://links.lww.com/DCR/B934 . (Traducción-Dr. Jorge Silva Velazco ).
Collapse
|
|
25
|
Chen M, Chen J, Huang J, Liu H, Cao W, Luo S, Liu Z, Hu H, Lai S, Hou Y, Kang L, Huang L. Clinical significance of neoadjuvant chemotherapy for locally advanced colorectal cancer patients with deficient mismatch repair: possibly residual value in the era of immunotherapy. Therap Adv Gastroenterol 2023; 16:17562848221150306. [PMID: 36742014 PMCID: PMC9893354 DOI: 10.1177/17562848221150306] [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: 07/19/2022] [Accepted: 12/22/2022] [Indexed: 01/22/2023] Open
Abstract
Background Deficient mismatch repair (dMMR) or microsatellite instability is one of the well-established molecular biomarkers in colorectal cancer (CRC). The efficiency of neoadjuvant chemotherapy (NAC) in locally advanced colorectal cancer (LACC) patients with dMMR is unclear. Objectives We assessed the tumor response and clinical outcome in LACC patients with dMMR received NAC. Design Retrospective, single-center analysis. Methods From 2013 to 2018, a total of 577 LACC patients with dMMR who underwent radical surgery were identified. Among them, 109 patients who received adjuvant chemotherapy were further screened out for analysis. According to whether receiving NAC or not, 109 patients were divided into two groups with the purpose of retrospectively analyzing their characteristics, treatment, and survival results, especially the 5-year disease-free survival (DFS) and 5-year overall survival. Results Baseline characteristics were matched between the two groups. One of 40 patients in NAC group recurred, while 13 of 69 patients in non-NAC group recurred. Univariate and multivariate analyses showed that NAC (hazard ratio: 0.115; 95% confidence interval: 0.015-0.897; p = 0.039) was independent influence factor for DFS. In NAC group, there were 13/40 (32.5%) patients for tumor regression grade 1 and 27/40 (67.5%) patients converted clinical positive N-stage into negative N-stage. Conclusion In this study, NAC was associated with better tumor downstaging and longer 5-year DFS in LACC patients with dMMR. Consequently, NAC might be an additional treatment choice when it comes to such patients in the future.
Collapse
Affiliation(s)
| | | | | | - Huashan Liu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wuteng Cao
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shuangling Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhanzhen Liu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huanxin Hu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Sicong Lai
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yujie Hou
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | | | | |
Collapse
|
|
26
|
Akgun E, Caliskan C, Bozbiyik O, Yoldas T, Doganavsargil B, Ozkok S, Kose T, Karabulut B, Elmas N, Ozutemiz O. Effect of interval between neoadjuvant chemoradiotherapy and surgery on disease recurrence and survival in rectal cancer: long-term results of a randomized clinical trial. BJS Open 2022; 6:6762515. [PMID: 36254732 PMCID: PMC9577542 DOI: 10.1093/bjsopen/zrac107] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 07/18/2022] [Accepted: 08/01/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND The optimal timing of surgery following chemoradiotherapy (CRT) is controversial. This trial aimed to assess disease recurrence and survival rates between patients with locally advanced rectal adenocarcinoma (LARC) who underwent total mesorectal excision (TME) after a waiting interval of 8 weeks or less (classic interval; CI) versus more than 8 weeks (long interval; LI) following preoperative CRT. METHODS This was a phase III, single-centre, randomized clinical trial. Patients with LARC situated within 12 cm of the anal verge (T3-T4 or N+ disease) were randomized to undergo TME within or after 8 weeks after CRT. RESULTS Between January 2006 and January 2017, 350 patients were randomized, 175 to each group. As of February 2022, the median follow-up time was 80 (6-174) months. Among the 322 included patients (CI, 159; LI, 163) the cumulative incidence of locoregional recurrence at 5 years was 10.1 per cent in the CI group and 6.9 per cent in the LI group (P = 0.143). The cumulative incidence of distant metastasis at 5 years was 30.8 per cent in the CI group and 18.6 per cent in the LI group (sub-HR = 1.78; 95 per cent c.i. 1.14 to 2.78, P = 0.010). The disease-free survival (DFS) in each group was 59.7 and 69.9 per cent respectively (P = 0.157), and overall survival (OS) rates at 5 years were 73.6 versus 77.9 per cent (P = 0.476). CONCLUSION Incidence of distant metastasis decreased with an interval between CRT and surgery exceeding 8 weeks, but this did not impact on DFS or OS. REGISTRATION NUMBER NCT03287843 (http://www.clinicaltrials.gov).
Collapse
Affiliation(s)
- Erhan Akgun
- Correspondence to: Erhan Akgun, Ege Universitesi Tıp Fakültesi Hastanesi, Genel Cerrahi Bornova-Izmir, Turkey (e-mail: )
| | - Cemil Caliskan
- Department of General Surgery, Ege University School of Medicine,Izmir, Turkey
| | - Osman Bozbiyik
- Department of General Surgery, Ege University School of Medicine,Izmir, Turkey
| | - Tayfun Yoldas
- Department of General Surgery, Ege University School of Medicine,Izmir, Turkey
| | | | - Serdar Ozkok
- Department of Radiation Oncology, Ege University School of Medicine,Izmir, Turkey
| | - Timur Kose
- Department of Biostatistics, Ege University School of Medicine,Izmir, Turkey
| | - Bulent Karabulut
- Department of Medical Oncology, Ege University School of Medicine,Izmir, Turkey
| | - Nevra Elmas
- Department of Radiology, Ege University School of Medicine,Izmir, Turkey
| | - Omer Ozutemiz
- Department of Gastroenterology, Ege University School of Medicine,Izmir, Turkey
| |
Collapse
|
|
27
|
Khamzina S, Lee J, Ryoo SB, Kim MJ, Park JW, Kang HC, Chie EK, Lee DW, Han SW, Kim TY, Jeong SY, Park KJ. Standard versus longer interval of radical resection after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A 20-year single-center experience & propensity-score matching. J Surg Oncol 2022; 127:119-131. [PMID: 36169163 DOI: 10.1002/jso.27105] [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: 07/12/2022] [Revised: 08/22/2022] [Accepted: 09/15/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND AND OBJECTIVES Despite the standard interval of 6-8 weeks between neoadjuvant chemoradiotherapy (nCRT) and surgery, it is debated whether an interval of >8 weeks increases the pathologic complete response (pCR) rate. We investigated the interval between nCRT and surgery, and its impact on oncological outcomes and postoperative complications in patients with locally advanced rectal cancer. METHODS We retrospectively reviewed patients with rectal cancer who underwent total mesorectal excision after long-course nCRT between 2000 and 2020. They were divided into two groups-those who underwent surgery at 6-8 and >8 weeks after nCRT. Surgical outcomes (stoma rate and postoperative complications), pCR, tumor regression grade (TRG), recurrence-free survival (RFS), and overall survival (OS) were compared. RESULTS We selected 770/1153 patients with rectal cancer, including 502 and 268 patients surgically treated at 6-8 and >8 weeks after nCRT, respectively. The pCR rates were similar between the two groups (14.7% vs. 15.3%, p = 0.836), while the TRG was significantly better in the >8 weeks group (p = 0.267). Additionally, the postoperative complications, recurrence, 5-year RFS, and OS rates were not significantly different between the two groups. CONCLUSIONS Although tumor regression increased in the >8 weeks group, the oncological benefits of surgery >8 weeks after nCRT remain uncertain.
Collapse
Affiliation(s)
- Saule Khamzina
- Department of Colorectal Surgery, Multidisciplinary City Hospital N1, Nur-Sultan, Kazakhstan.,Department of Surgery, National Research Oncology Center, Nur-Sultan, Kazakhstan
| | - Jongoh Lee
- Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Seung-Bum Ryoo
- Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.,Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.,Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Min Jung Kim
- Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.,Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.,Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Ji Won Park
- Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.,Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.,Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dae-Won Lee
- Division of Hematooncology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sae-Won Han
- Division of Hematooncology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Tae-You Kim
- Division of Hematooncology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Seung-Yong Jeong
- Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.,Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.,Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Kyu Joo Park
- Division of Colorectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.,Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea
| |
Collapse
|
|
28
|
Zhao X, Han P, Zhang L, Ma J, Dong F, Zang L, He Z, Zheng M. Prolonged neoadjuvant chemotherapy without radiation versus total neoadjuvant therapy for locally advanced rectal cancer: A propensity score matched study. Front Oncol 2022; 12:953790. [PMID: 36185248 PMCID: PMC9523158 DOI: 10.3389/fonc.2022.953790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 08/25/2022] [Indexed: 11/13/2022] Open
Abstract
Background Although neoadjvuant chemoradiotherapy (CRT) improves the local control rate of locally advanced rectal cancer (LARC), it fails to significantly improve disease-free survival (DFS) and overall survival (OS). We explored the efficacy of prolonged neoadjuvant chemotherapy (pNCT) without radiation and compared this schema with total neoadjuvant therapy (TNT). Material and methods Patients diagnosed with LARC and received TNT (4 cycles of induction CapeOX/FOLFOX followed with CRT) or pNCT (6~8 cycles of CapeOX/FOLFOX) between June 2016 and October 2021 were retrospective analyzed. All patients underwent total mesorectal excision (TME). A 1:1 propensity score match was performed to adjust baseline potential confounders. The tumor response, toxicity, recurrence-free survival (RFS) and OS were observed. Results A total of 184 patients with 92 patients in each group were finally enrolled. The median follow-up time was 35 months. TNT showed better pathological complete response (pCR) rate (25.0% vs 16.3%) and objective regression rate (73.9% vs 59.8%) than pNCT. TNT and pNCT produce similar 3-year RFS and OS rates in patients with mid-to-upper rectal cancer. TNT was associated with improved tumor responsiveness in all patients and improved 3-year RFS rates in those with low rectal cancer. Conclusion pNCT is an option for patients with mid-to-upper rectal cancer, but radiation is still necessary for low rectal cancer. To determine optimal schema for neoadjuvant therapy and patient selection, additional randomized controlled studies are needed.
Collapse
Affiliation(s)
- Xuan Zhao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Peiyi Han
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Luyang Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Junjun Ma
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Feng Dong
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Lu Zang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
| | - Zirui He
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
- *Correspondence: Minhua Zheng, ; Zirui He,
| | - Minhua Zheng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Minimally Invasive Surgery Center, Shanghai, China
- *Correspondence: Minhua Zheng, ; Zirui He,
| |
Collapse
|
|
29
|
Chen M, Lin H, Zhang J, Pang X, Fan X, Luo S, Liu Z, Hu H, Lai S, Hou Y, Kang L, Huang L. Presence and clinical significance of acellular mucin pools in resected rectal cancer with pathological complete response after preoperative chemoradiotherapy. Histopathology 2022; 81:569-576. [DOI: 10.1111/his.14795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 07/25/2022] [Accepted: 08/06/2022] [Indexed: 11/26/2022]
Affiliation(s)
- Mian Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Hongcheng Lin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Jianwei Zhang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Xiaolin Pang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Xinjuan Fan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Shuangling Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Zhanzhen Liu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Huanxin Hu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Sicong Lai
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Yujie Hou
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Liang Kang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Liang Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| |
Collapse
|
|
30
|
Aref A, Abdalla A. Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Induction or Consolidation Chemotherapy? J Clin Oncol 2022; 40:2515-2519. [PMID: 35724356 DOI: 10.1200/jco.22.00506] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/22/2022] [Accepted: 05/16/2022] [Indexed: 01/12/2023] Open
Affiliation(s)
- Amr Aref
- Rectal Cancer Group, Van Elslander Cancer Center, Ascension St John Hospital, Detroit, MI
- Radiation Oncology, Van Elslander Cancer Center, Ascension St John Hospital, Detroit, MI
| | - Ahmed Abdalla
- Interdisciplinary Oncology, Mitchell Cancer Center, University of South Alabama, Mobile, AL
| |
Collapse
|
|
31
|
Yu M, Wang DC, Li S, Huang LY, Wei J. Does a long interval between neoadjuvant chemoradiotherapy and surgery benefit the clinical outcomes of locally advanced rectal cancer? A systematic review and meta analyses. Int J Colorectal Dis 2022; 37:855-868. [PMID: 35279746 DOI: 10.1007/s00384-022-04122-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/02/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE The study aims to systematically evaluate the clinical efficacy after 8 weeks (long interval, LI) between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. METHODS The PubMed database, EMBASE database, and the Cochrane Library (deadline: September 25, 2021) were searched to select clinical studies that compared two intervals between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer: after 8 weeks (long interval, LI) and within 8 weeks (short interval, SI). The included studies were screened and evaluated according to the inclusion and exclusion criteria, and meta-analysis was performed by RevMan 5.3 software. RESULTS Eighteen studies were included, with 9070 cases in the LI group and 14,207 cases in the SI group. The analysis results showed that the pathologic complete response (PCR) rate in the LI group was higher than that in the SI group (P < 0.00001). There was no significant difference in the R0 resection rate (P = 0.85), anal preservation rate (P = 0.89), morbidity rate (P = 0.60), anastomotic leakage rate (P = 0.06), operation time (P = 0.58), local recurrence rate (P = 0.56), distant metastasis rate (P = 0.32), or overall survival (OS) rate (P = 0.17) between the two groups. CONCLUSION A longer interval between neoadjuvant chemoradiotherapy and surgery can improve the PCR rate; however, it has no significant impact on the clinical efficacy or long-term prognosis. Due to some limitations in the number and quality of the studies, these findings still need to be further verified by multicenter, large-sample high-quality RCTs in the future.
Collapse
Affiliation(s)
- Miao Yu
- Department of Basic Medicine, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan, China
| | - Deng-Chao Wang
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China.
| | - Sheng Li
- Department of Basic Medicine, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan, China
| | - Li-Yan Huang
- Department of Pathology, West China Second Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jian Wei
- Department of General Surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, China
| |
Collapse
|
|
32
|
Wang L, Zhong X, Lin H, Zhang X, Shao L, Chen G, Wu J. Identifying the long-term survival beneficiary of preoperative radiotherapy for rectal cancer in the TME era. Sci Rep 2022; 12:4617. [PMID: 35301380 PMCID: PMC8931157 DOI: 10.1038/s41598-022-08541-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 03/02/2022] [Indexed: 12/19/2022] Open
Abstract
This study was to verify the long-term survival efficacy of preoperative radiotherapy (preRT) for locally advanced rectal cancer (LARC) patients and identify potential long-term survival beneficiary. Using the Surveillance, Epidemiology, and End Results (SEER) database, 7582 LARC patients were eligible for this study between 2011 and 2015 including 6066 received preRT and 1516 received surgery alone. Initial results showed that preRT prolonged the median overall survival (OS) of LARC patients (HR 0.86, 95% CI 0.75-0.98, P < 0.05), and subgroup analysis revealed that patients with age > 65 years, stage III, T3, T4, N2, tumor size > 5 cm, tumor deposits, and lymph nodes dissection (LND) ≥ 12 would benefit more from preRT (all P < 0.05). A prognostic predicting nomogram was constructed using the independent risk factors of OS identified by multivariate Cox analysis (all P < 0.05), which exhibited better prediction of OS than the 8th American Joint Cancer Committee staging system on colorectal cancer. According to the current nomogram, patients in the high-risk subgroup had a shorter median OS than low-risk subgroup (HR 2.62, 95% CI 2.25-3.04, P < 0.001), and preRT could benefit more high-risk patients rather than low-risk patients. Hence, we concluded that preRT might bring long-term survival benefits to LARC patients, especially those with high risk.
Collapse
Affiliation(s)
- Lei Wang
- Department of Radiation Oncology, College of Clinical Medicine for Oncology, Fujian Medical University & Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China
| | - Xiaohong Zhong
- Department of Radiation Oncology, College of Clinical Medicine for Oncology, Fujian Medical University & Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China
| | - Huaqin Lin
- Department of Radiation Oncology, College of Clinical Medicine for Oncology, Fujian Medical University & Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China
| | - Xueqing Zhang
- Department of Radiation Oncology, College of Clinical Medicine for Oncology, Fujian Medical University & Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China
| | - Lingdong Shao
- Department of Radiation Oncology, College of Clinical Medicine for Oncology, Fujian Medical University & Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China
| | - Gang Chen
- Department of Pathology, College of Clinical Medicine for Oncology, Fujian Medical University & Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China.
| | - Junxin Wu
- Department of Radiation Oncology, College of Clinical Medicine for Oncology, Fujian Medical University & Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China.
| |
Collapse
|
|
33
|
Sutton TL, Wong LH, Walker BS, Dewey EN, Eil RL, Ibewuike U, Chen EY, Rocha FG, Billingsley KG, Mayo SC. Surgical timing after preoperative chemotherapy is associated with oncologic outcomes in resectable colorectal liver metastases. J Surg Oncol 2022; 125:1260-1268. [PMID: 35212404 DOI: 10.1002/jso.26832] [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: 12/02/2021] [Revised: 01/24/2022] [Accepted: 02/13/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION Preoperative chemotherapy (POC) is often employed for patients with resectable colorectal liver metastasis (CRLM). The time to resection (TTR) following the end of chemotherapy may impact oncologic outcomes; this phenomenon has not been studied in CRLM. METHODS We queried our institutional cancer database for patients with resected CRLM after POC from 2003 to 2019. TTR was calculated from date of last cytotoxic chemotherapy. Kaplan-Meier analysis and multivariable Cox proportional hazards modeling were used to analyze recurrence-free survival (RFS) and overall survival (OS). RESULTS We identified n = 187 patients. One hundred twenty-four (66%) patients had a TTR of <2 months, while 63 (33%) had a TTR of ≥2 months. Median follow-up was 36 months. On Kaplan-Meier analysis, patients with TTR ≥ 2 months had shorter RFS (median 11 vs. 17 months, p = 0.002) and OS (median 44 vs. 62 months, p < 0.001). On multivariable analysis, TTR ≥ 2 months was independently associated with worse RFS (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.06-2.22, p = 0.02) and OS (HR = 1.75, 95% CI = 1.11-2.77, p = 0.01). CONCLUSION TTR ≥ 2 months following POC is independently associated with worse oncologic outcomes in patients with resectable CRLM. We therefore recommend consideration for hepatic resection of CRLM within this window whenever feasible.
Collapse
Affiliation(s)
- Thomas L Sutton
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Liam H Wong
- School of Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Brett S Walker
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Elizabeth N Dewey
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Robert L Eil
- Division of Surgical Oncology, Department of Surgery, OHSU, Knight Cancer Institute, Portland, Oregon, USA
| | - Uchechukwu Ibewuike
- Department of Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Emerson Y Chen
- Division of Hematology and Oncology, Department of Medicine, OHSU, Knight Cancer Institute, Portland, Oregon, USA
| | - Flavio G Rocha
- Division of Surgical Oncology, Department of Surgery, OHSU, Knight Cancer Institute, Portland, Oregon, USA
| | | | - Skye C Mayo
- Division of Surgical Oncology, Department of Surgery, OHSU, Knight Cancer Institute, Portland, Oregon, USA
| |
Collapse
|
|
34
|
Zarnescu EC, Zarnescu NO, Costea R. Updates of Risk Factors for Anastomotic Leakage after Colorectal Surgery. Diagnostics (Basel) 2021; 11:diagnostics11122382. [PMID: 34943616 PMCID: PMC8700187 DOI: 10.3390/diagnostics11122382] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/06/2021] [Accepted: 12/14/2021] [Indexed: 12/13/2022] Open
Abstract
Anastomotic leakage is a potentially severe complication occurring after colorectal surgery and can lead to increased morbidity and mortality, permanent stoma formation, and cancer recurrence. Multiple risk factors for anastomotic leak have been identified, and these can allow for better prevention and an earlier diagnosis of this significant complication. There are nonmodifiable factors such as male gender, comorbidities and distance of tumor from anal verge, and modifiable risk factors, including smoking and alcohol consumption, obesity, preoperative radiotherapy and preoperative use of steroids or non-steroidal anti-inflammatory drugs. Perioperative blood transfusion was shown to be an important risk factor for anastomotic failure. Recent studies on the laparoscopic approach in colorectal surgery found no statistical difference in anastomotic leakage rate compared with open surgery. A diverting stoma at the time of primary surgery does not appear to reduce the leak rate but may reduce its clinical consequences and the need for additional surgery if anastomotic leakage does occur. It is still debatable if preoperative bowel preparation should be used, especially for left colon and rectal resections, but studies have shown similar incidence of postoperative leak rate.
Collapse
Affiliation(s)
- Eugenia Claudia Zarnescu
- Department of General Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (E.C.Z.); (R.C.)
- Second Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Narcis Octavian Zarnescu
- Department of General Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (E.C.Z.); (R.C.)
- Second Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
- Correspondence: ; Tel.: +40-723-592-483
| | - Radu Costea
- Department of General Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (E.C.Z.); (R.C.)
- Second Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| |
Collapse
|
|
35
|
Feng W, Yu B, Zhang Z, Li J, Wang Y. Current status of total neoadjuvant therapy for locally advanced rectal cancer. Asia Pac J Clin Oncol 2021; 18:546-559. [PMID: 34818447 DOI: 10.1111/ajco.13640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 07/05/2021] [Indexed: 12/21/2022]
Abstract
Neoadjuvant chemoradiotherapy (nCRT) plus total mesorectal excision (TME) has been the standard regimen for treatment of patients with locally advanced rectal cancer (LARC), because it significantly reduces the rate of local recurrence and enables sphincter preservation. However, distant metastasis remains the major reason for treatment failure, and the value of postoperative chemotherapy is still controversial. Recent studies have examined the use of total neoadjuvant therapy (TNT), defined as induction and/or consolidation chemotherapy (CONCT) with radiotherapy (RT) or nCRT prior to surgery. The results indicated that TNT may increase the rates of chemotherapy compliance and pathological complete response (pCR), and probably improve the success rate of sphincter preservation surgery. TNT may also improve disease-free survival and overall survival, and even reduce the rate of relapse. Here, we critically appraise the existing literature on three different TNT schemes used for LARC patients.
Collapse
Affiliation(s)
- Wei Feng
- Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China.,Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Bin Yu
- The Second Department of Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, China
| | - Zhenya Zhang
- The Second Department of Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, China
| | - Juan Li
- Department of Radiation Oncology, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital & Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| | - Yuxiang Wang
- Department of Radiation Oncology, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital & Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| |
Collapse
|
|
36
|
Haak HE, Beets GL, Peeters K, Nelemans PJ, Valentini V, Rödel C, Kuo L, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Pucciarelli S, Suarez J, Theodoropoulos G, Biondo S, Lambregts DMJ, Beets-Tan RGH, Maas M. Prevalence of nodal involvement in rectal cancer after chemoradiotherapy. Br J Surg 2021; 108:1251-1258. [PMID: 34240110 PMCID: PMC8604154 DOI: 10.1093/bjs/znab194] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 04/28/2021] [Indexed: 01/14/2023]
Abstract
BACKGROUND The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.
Collapse
Affiliation(s)
- H E Haak
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
- GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
| | - G L Beets
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
- GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
| | - K Peeters
- Department of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - P J Nelemans
- Department of Epidemiology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - V Valentini
- Department of Radiation Oncology, Universita Cattolica del Sacro Cuore, Rome, Italy
| | - C Rödel
- Department of Radiation Oncology, Universitätsklinikum Frankfurt, Frankfurt, Germany
| | - L Kuo
- Department of Colorectal Surgery, Taipei Medical University Hospital, Taipei, Taiwan
| | - F A Calvo
- Department of Oncology, General University Hospital Gregorio Marañón, Madrid, Spain
| | - J Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Centre, New York, USA
| | - R Glynne-Jones
- Department of Clinical Oncology, Mount Vernon Hospital, London, UK
| | - S Pucciarelli
- Department of Surgical, Oncological and Gastroenterological Sciences, First Surgical Clinic, University of Padua, Padua, Italy
| | - J Suarez
- Department of Surgery, Hospital de Navarra, Pamplona, Spain
| | - G Theodoropoulos
- First Department of Propaedeutic Surgery, Athens Medical School, Hippocration General Hospital, Athens, Greece
| | - S Biondo
- Department of Surgery, Bellvitge University Hospital, Barcelona, Spain
- IDIBELL, University of Barcelona, Barcelona, Spain
| | - D M J Lambregts
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - R G H Beets-Tan
- GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - M Maas
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| |
Collapse
|
|
37
|
Yuval JB, Garcia-Aguilar J. Watch-and-wait Management for Rectal Cancer After Clinical Complete Response to Neoadjuvant Therapy. Adv Surg 2021; 55:89-107. [PMID: 34389102 DOI: 10.1016/j.yasu.2021.05.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Jonathan B Yuval
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
| |
Collapse
|
|
38
|
Koo K, Ward R, Smith RL, Ruben J, Carne PWG, Elsaleh H. Temporal determinants of tumour response to neoadjuvant rectal radiotherapy. PLoS One 2021; 16:e0254018. [PMID: 34191861 PMCID: PMC8244879 DOI: 10.1371/journal.pone.0254018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 06/17/2021] [Indexed: 02/01/2023] Open
Abstract
Introduction In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients. Methods A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression. Results From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery. Conclusions There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.
Collapse
Affiliation(s)
- Kendrick Koo
- Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia
| | - Rachel Ward
- Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia
| | - Ryan L. Smith
- Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia
| | - Jeremy Ruben
- Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia
| | - Peter W. G. Carne
- Colorectal Surgery Unit, Alfred Health, Melbourne, Victoria, Australia
- Cabrini Monash University Department of Surgery, Melbourne, Victoria, Australia
| | - Hany Elsaleh
- Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia
- * E-mail:
| |
Collapse
|
|
39
|
Voogt ELK, Schaap DP, van den Berg K, Nieuwenhuijzen GAP, Bloemen JG, Creemers GJ, Willems J, Cnossen JS, Peulen HMU, Nederend J, van Lijnschoten G, Burger JWA, Rutten HJT. Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study. Eur J Surg Oncol 2021; 47:2429-2435. [PMID: 34030921 DOI: 10.1016/j.ejso.2021.05.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/16/2021] [Accepted: 05/07/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. METHODS All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics. RESULTS Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). CONCLUSION Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.
Collapse
Affiliation(s)
- E L K Voogt
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
| | - D P Schaap
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - K van den Berg
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | | | - J G Bloemen
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - G J Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J Willems
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J S Cnossen
- Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - H M U Peulen
- Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J Nederend
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - G van Lijnschoten
- Department of Pathology, PAMM Laboratory for Pathology and Medical Microbiology, Eindhoven, the Netherlands
| | - J W A Burger
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
| |
Collapse
|
|
40
|
Bigness A, Imanirad I, Sahin IH, Xie H, Frakes J, Hoffe S, Laskowitz D, Felder S. Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation. CA Cancer J Clin 2021; 71:198-208. [PMID: 33592118 DOI: 10.3322/caac.21661] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 12/14/2020] [Accepted: 12/17/2020] [Indexed: 01/04/2023] Open
Affiliation(s)
- Alec Bigness
- University of South Florida Morsani College of Medicine, Tampa, Florida
| | - Iman Imanirad
- Department of Gastrointestinal Oncology, Medical Oncology Section, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Ibrahim Halil Sahin
- Department of Gastrointestinal Oncology, Medical Oncology Section, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Hao Xie
- Department of Gastrointestinal Oncology, Medical Oncology Section, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Jessica Frakes
- Department of Gastrointestinal Oncology, Radiation Oncology Section, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Sarah Hoffe
- Department of Gastrointestinal Oncology, Radiation Oncology Section, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Danielle Laskowitz
- Department of Gastrointestinal Oncology, Surgical Oncology Section, H. Lee Moffitt Cancer Center, Tampa, Florida
| | - Seth Felder
- Department of Gastrointestinal Oncology, Surgical Oncology Section, H. Lee Moffitt Cancer Center, Tampa, Florida
| |
Collapse
|
|
41
|
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.
Collapse
|
|
42
|
Gani C, Lamprecht U, Ziegler A, Moll M, Gellermann J, Heinrich V, Wenz S, Fend F, Königsrainer A, Bitzer M, Zips D. Deep regional hyperthermia with preoperative radiochemotherapy in locally advanced rectal cancer, a prospective phase II trial. Radiother Oncol 2021; 159:155-160. [PMID: 33741467 DOI: 10.1016/j.radonc.2021.03.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/07/2021] [Accepted: 03/08/2021] [Indexed: 12/25/2022]
Abstract
PURPOSE The goal of the present study was to investigate the effect of deep regional hyperthermia on early and long-term oncological outcomes in the context of preoperative radiochemotherapy in rectal cancer. METHODS In this prospective phase II trial, patients with locally advanced rectal cancer were treated with 5-fluorouracil based preoperative radiochemotherapy with 50.4 Gy in 28 fractions. Deep regional hyperthermia was scheduled twice weekly. Pathological tumor regression was scored according to the Dworak regression system. The primary endpoint was pathological complete response (pCR). Further endpoints were local control (LC), distant control (DC), disease-free survival (DFS) and overall survival (OS). Hyperthermia was defined as feasible if 70% of patients received at least eight treatments. Quality of life was assessed at follow-up by the EORTC-QLQ-C30 and QLQ-CR29 questionnaires. Time to event data was analyzed according to Kaplan-Meier based on first-events. The study was registered on clinicaltrials.gov (NCT02353858). RESULTS From 2012 until 2017, 78 patients were recruited. Median follow-up was 54 months. Based on magnetic resonance imaging, the mesorectal fascia was involved or threatened in 60% of the patients. Compliance with radiotherapy was 99%, 91% received both cycles of chemotherapy and 77% had eight or more hyperthermia treatments. Median time from the end of radiotherapy to surgery was 6.7 weeks. A pathological complete response was reported in 14% of the patients, 50% had either Dworak 4 (complete regression) or Dworak 3 regression (scattered tumor cells only). Three year estimates for OS, DFS, LC and DC were 94%, 81%, 96% and 87%. Patients with higher hyperthermia related cumulative temperatures showed stronger tumor regression. Global health status based on EORTC-QLQ-C30 was comparable with data from the general population. CONCLUSION Deep regional hyperthermia was feasible, did not compromise standard treatments and resulted in promising long-term oncological outcomes and QoL.
Collapse
Affiliation(s)
- Cihan Gani
- University Hospital Tübingen, Department of Radiation Oncology, Germany; German Cancer Research Center (DKFZ) Heidelberg and German Consortium for Translational Cancer Research (DKTK), Partner Site Tübingen, Germany.
| | - Ulf Lamprecht
- University Hospital Tübingen, Department of Radiation Oncology, Germany
| | - Alexander Ziegler
- Department of Internal Medicine, Oncology/Hematology, Gastroenterology, Hospital Esslingen GmbH, Germany
| | - Matthias Moll
- Department of Radiation Oncology, Medical University of Vienna, Wien, Austria
| | | | - Vanessa Heinrich
- University Hospital Tübingen, Department of Radiation Oncology, Germany
| | - Svetlana Wenz
- Institute of Pathology and Neuropathology, Eberhard-Karls University, Tuebingen, Germany
| | - Falko Fend
- German Cancer Research Center (DKFZ) Heidelberg and German Consortium for Translational Cancer Research (DKTK), Partner Site Tübingen, Germany; Institute of Pathology and Neuropathology, Eberhard-Karls University, Tuebingen, Germany
| | - Alfred Königsrainer
- University Hospital Tübingen, Department of General, Visceral and Transplant Surgery, Germany
| | - Michael Bitzer
- University Hospital Tübingen, Department of Internal Medicine I, Germany
| | - Daniel Zips
- University Hospital Tübingen, Department of Radiation Oncology, Germany; German Cancer Research Center (DKFZ) Heidelberg and German Consortium for Translational Cancer Research (DKTK), Partner Site Tübingen, Germany
| |
Collapse
|
|
43
|
Total neoadjuvant therapy for rectal cancer: Making sense of the results from the RAPIDO and PRODIGE 23 trials. Cancer Treat Rev 2021; 96:102177. [PMID: 33798955 DOI: 10.1016/j.ctrv.2021.102177] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/27/2021] [Accepted: 03/01/2021] [Indexed: 02/07/2023]
Abstract
A few months ago, results from two randomised phase III trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were presented (RAPIDO and PRODIGE 23), consistently showing better short- and long-term outcomes with TNT as compared with standard neoadjuvant long-course chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). These results represent corroborating evidence in support of a practice that many centres had already implemented based on promising preliminary data. Also, they provide new, high-level evidence to endorse TNT as a new management option in the treatment algorithm of stage II-III rectal cancer in those centres where CRT and SCRT have long remained the only accepted standard neoadjuvant treatments. Having two consistently positive trials is certainly reassuring regarding the potential of TNT as a general treatment approach. Nevertheless, substantial differences between these trials pose important challenges in relation to the generalisability and applicability of their results, and translation of the same into practical clinical recommendations. In this article, we address a number of key questions that the RAPIDO and PRODIGE 23 trials have raised among the broad community of gastrointestinal oncologists, proposing an interpretation of the data that may help the decision making, and highlighting grey areas that warrant further investigation.
Collapse
|
|
44
|
Cullinane C, Shrestha A, Al Maksoud A, Rothwell J, Evoy D, Geraghty J, McCartan D, McDermott EW, Prichard RS. Optimal timing of surgery following breast cancer neoadjuvant chemotherapy: A systematic review and meta-analysis. Eur J Surg Oncol 2021; 47:1507-1513. [PMID: 33589241 DOI: 10.1016/j.ejso.2021.01.025] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/24/2021] [Accepted: 01/26/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Administration of chemotherapy before breast surgery has the potential to reduce the risk of distant recurrence by targeting micrometastasis as well as allowing a more minimalistic approach to surgical intervention. We performed a systematic review to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT). METHODS The primary outcome was to determine whether the timing of surgery post NACT impacted overall survival (OS) and disease-free survival (DFS). We compared patient outcomes between those who had surgery within 8 weeks of completion of NACT to those that had surgery after 8 weeks. An outcome comparison between <4 weeks and 4-8 weeks was also performed. Secondary outcome included complete pathological response (pCR) post NACT. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS Five studies, including 8794 patients were eligible for inclusion. Patients that had surgery within 8 weeks of completion of NACT had a statistically significant improved OS(OR 0.47, 95% c. i 0.34-0.65) and DFS(OR 0.71 (95% c. i 0.52-0.98, P = 0.04). There were no survival advantages associated with having surgery less than 4 weeks post completion of NACT (OR 0.78, 95% c. i 0.46-1.33, P = 0.37). There was no difference in pCR rate between those that had surgery <4 weeks and 4-8 weeks (OR 1.01, 95% c. i 0.80-1.28, P = 0.93). CONCLUSION This meta-analysis shows that the optimum timing of surgery post completion of NACT is 4-8 weeks as it is associated with increased OS and DFS.
Collapse
Affiliation(s)
- Carolyn Cullinane
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - Amber Shrestha
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - Ahmed Al Maksoud
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - Jane Rothwell
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - Denis Evoy
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - James Geraghty
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - Damian McCartan
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - Enda W McDermott
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| | - Ruth S Prichard
- Department of General, Breast and Endocrine Surgery, St Vincent's University Hospital, Dublin, Ireland.
| |
Collapse
|
|
45
|
Wo JY, Anker CJ, Ashman JB, Bhadkamkar NA, Bradfield L, Chang DT, Dorth J, Garcia-Aguilar J, Goff D, Jacqmin D, Kelly P, Newman NB, Olsen J, Raldow AC, Ruiz-Garcia E, Stitzenberg KB, Thomas CR, Wu QJ, Das P. Radiation Therapy for Rectal Cancer: Executive Summary of an ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2021; 11:13-25. [PMID: 33097436 DOI: 10.1016/j.prro.2020.08.004] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/12/2020] [Accepted: 08/12/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE This guideline reviews the evidence and provides recommendations for the indications and appropriate technique and dose of neoadjuvant radiation therapy (RT) in the treatment of localized rectal cancer. METHODS The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the use of RT in preoperative management of operable rectal cancer. These questions included the indications for neoadjuvant RT, identification of appropriate neoadjuvant regimens, indications for consideration of a nonoperative or local excision approach after chemoradiation, and appropriate treatment volumes and techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS Neoadjuvant RT is recommended for patients with stage II-III rectal cancer, with either conventional fractionation with concurrent 5-FU or capecitabine or short-course RT. RT should be performed preoperatively rather than postoperatively. Omission of preoperative RT is conditionally recommended in selected patients with lower risk of locoregional recurrence. Addition of chemotherapy before or after chemoradiation or after short-course RT is conditionally recommended. Nonoperative management is conditionally recommended if a clinical complete response is achieved after neoadjuvant treatment in selected patients. Inclusion of the rectum and mesorectal, presacral, internal iliac, and obturator nodes in the clinical treatment volume is recommended. In addition, inclusion of external iliac nodes is conditionally recommended in patients with tumors invading an anterior organ or structure, and inclusion of inguinal and external iliac nodes is conditionally recommended in patients with tumors involving the anal canal. CONCLUSIONS Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for rectal cancer. Future studies will look to further personalize treatment recommendations to optimize treatment outcomes and quality of life.
Collapse
Affiliation(s)
- Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Christopher J Anker
- Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, Vermont
| | | | | | - Lisa Bradfield
- American Society for Radiation Oncology, Arlington, Virginia
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford University, Stanford, California
| | - Jennifer Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals, Cleveland, Ohio
| | - Julio Garcia-Aguilar
- Department of Colorectal Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - David Goff
- Patient Representative, Las Cruces, New Mexico
| | - Dustin Jacqmin
- Department of Human Oncology, University of Wisconsin, Madison, Wisconsin
| | - Patrick Kelly
- Department of Radiation Oncology, Orlando Health, Orlando, Florida
| | - Neil B Newman
- Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jeffrey Olsen
- Department of Radiation Oncology, University of Colorado, Aurora, Colorado
| | - Ann C Raldow
- Department of Radiation Oncology, University of California, Los Angeles, California
| | - Erika Ruiz-Garcia
- Department of Medical Oncology, Instituto Nacional de Cancerologia, Mexico City, Mexico
| | - Karyn B Stitzenberg
- Department of Surgery, University of North Carolina, Chapel Hill, North Carolina
| | - Charles R Thomas
- Department of Radiation Oncology, Oregon Health & Science University, Portland, Oregon
| | - Q Jackie Wu
- Department of Radiation Oncology, Duke University, Durham, North Carolina
| | - Prajnan Das
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.
| |
Collapse
|
|
46
|
Wang Y, Liu Z, Shan F, Ying X, Zhang Y, Li S, Jia Y, Li Z, Ji J. Optimal Timing to Surgery After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer. Front Oncol 2020; 10:613988. [PMID: 33392098 PMCID: PMC7773852 DOI: 10.3389/fonc.2020.613988] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 11/17/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The relationship between time to surgery (TTS) and survival benefit is not sufficiently demonstrated by previous studies in locally advanced gastric cancer (LAGC). This study aims to assess the impact of TTS after neoadjuvant chemotherapy (NACT) on long-term and short-term outcomes in LAGC patients. METHODS Data were collected from patients with LAGC who underwent NACT between January 2007 and January 2018 at our institution. Outcomes assessed were long-term survival, pathologic complete response (pCR) rate, and postoperative complications. RESULTS This cohort of 426 patients was divided into five groups by weeks of TTS. Under cox regression, compared to other groups, the 22-28 days and 29-35 days groups revealed a better OS (≤21 vs. 22-28 days: HR 1.54, 95% CI = 0.81-2.93, P = 0.185; 36-42 vs. 22-28 days: HR 2.20, 95% CI = 1.28-3.79, P = 0.004; 43-84 vs. 22-28 days: HR 1.83, 95% CI = 1.09-3.06, P = 0.022) and PFS (≤21 vs. 22-28 days: HR 1.54, 95% CI = 0.81-2.93, P = 0.256; 36-42 vs. 22-28 days: HR 2.20, 95% CI = 1.28-3.79, P = 0.111; 43-84 vs. 22-28 days: HR 1.83, 95% CI = 1.09-3.06, P = 0.047). Further analysis revealed a better prognosis in patients with TTS within 22-35 days (OS: HR 1.78 95% CI = 1.25-2.54, P = 0.001; PFS: HR 1.49, 95% CI = 1.07-2.08, P = 0.017). Postoperative stay was significantly higher in the ≤21 days group, while other parameters revealed no statistical significance (P > 0.05). Restricted cubic spline depicted the nonlinear relationship between TTS and OS/PFS. CONCLUSION Patients who received surgery within 3-5 weeks experienced the maximal survival benefit without an increase in postoperative complications or lowering the rate of pCR. Further investigations are warranted.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | | |
Collapse
|
|
47
|
Sutton TL, Schlitt A, Gardiner SK, Johnson N, Garreau JR. Time to surgery following neoadjuvant chemotherapy for breast cancer impacts residual cancer burden, recurrence, and survival. J Surg Oncol 2020; 122:1761-1769. [PMID: 33125715 DOI: 10.1002/jso.26216] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/10/2020] [Accepted: 09/04/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND The impact of length of time to surgery (TTS) on oncologic outcomes following neoadjuvant chemotherapy (NAC) in breast cancer patients is unclear. We investigated the relationship between TTS on residual cancer burden (RCB) score and oncologic outcomes. METHODS Patients with breast cancer receiving NAC from 2011 to 2017 were identified. The association of TTS with recurrence-free survival (RFS), overall and disease-specific survival (OS, DSS), and RCB score was examined with Kaplan-Meier and Cox proportional hazards analysis, adjusting for relevant clinicopathologic factors. RESULTS We identified 463 patients. Median TTS was 29 days (range 11-153). Median follow-up was 57 months (range, 2-93 months). Five-year local recurrence-free survival, locoregional RFS, OS, and DSS was 86%, 96%, 89%, and 91%, respectively. On multivariate analysis, TTS >6 weeks was independently associated with worse RFS (HR [hazard ratio] 3.45; p < .001) and DSS (HR 2.82; p < .05), while TTS >6 weeks was independently associated with a positive size of the effect on RCB score of 0.59 (p < .0001). CONCLUSION Prolonged TTS is a modifiable risk factor for adverse oncologic outcomes following NAC for breast cancer, possibly mediated by increasing RCB score overtime after NAC. In the absence of contraindications, surgery should be performed within 6 weeks following NAC for optimal oncologic outcomes.
Collapse
Affiliation(s)
- Thomas L Sutton
- Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Alexander Schlitt
- College of Osteopathic Medicine of the Pacific-Northwest, Western University Of Health Sciences, Lebanon, Oregon, USA
| | - Stuart K Gardiner
- Devers Eye Institute, Legacy Research Institute, Legacy Health, Portland, Oregon, USA
| | - Nathalie Johnson
- Legacy Cancer Institute, Legacy Medical Group Surgical Oncology, Portland, Oregon, USA
| | - Jennifer R Garreau
- Legacy Cancer Institute, Legacy Medical Group Surgical Oncology, Portland, Oregon, USA
| |
Collapse
|
|
48
|
Healey Bird BRJ. Total neoadjuvant therapy for locally advanced rectal cancer: the fuse is lit. Br J Surg 2020; 107:1705-1707. [PMID: 33104240 DOI: 10.1002/bjs.12014] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 07/29/2020] [Indexed: 12/20/2022]
Abstract
Explosively disrupting
Collapse
Affiliation(s)
- B R J Healey Bird
- Department of Medical Oncology, Bon Secours Hospital Cork, Cork, T12 DV56, Ireland
| |
Collapse
|
|
49
|
Shamseddine A, Zeidan YH, Kreidieh M, Khalifeh I, Turfa R, Kattan J, Mukherji D, Temraz S, Alqasem K, Amarin R, Al Awabdeh T, Deeba S, Jamali F, Mohamad I, Elkhaldi M, Daoud F, Al Masri M, Dabous A, Hushki A, Jaber O, Khoury C, El Husseini Z, Charafeddine M, Al Darazi M, Geara F. Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma. BMC Cancer 2020; 20:831. [PMID: 32873251 PMCID: PMC7466814 DOI: 10.1186/s12885-020-07333-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 08/24/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.
Collapse
Affiliation(s)
- Ali Shamseddine
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon.
| | - Youssef H Zeidan
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Malek Kreidieh
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ibrahim Khalifeh
- Department of pathology and laboratory medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rim Turfa
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Joseph Kattan
- Department of Medical Oncology, Hôtel Dieu de France, Beirut, Lebanon
| | - Deborah Mukherji
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Sally Temraz
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Kholoud Alqasem
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Rula Amarin
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Tala Al Awabdeh
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Samer Deeba
- Department of General Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Faek Jamali
- Department of General Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Issa Mohamad
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Mousa Elkhaldi
- Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Faiez Daoud
- Department of Surgical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Mahmoud Al Masri
- Department of Surgical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Ali Dabous
- Department of Surgical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Ahmad Hushki
- Gastroenterology Department, King Hussein Cancer Center, Amman, Jordan
| | - Omar Jaber
- Pathology Department, King Hussein Cancer Center, Amman, Jordan
| | - Clement Khoury
- Department of Radiation Oncology, Hotel-Dieu de France Hospital, Beirut, Lebanon
| | - Ziad El Husseini
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maya Charafeddine
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Monita Al Darazi
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fady Geara
- Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
| |
Collapse
|
|
50
|
Mei SW, Liu Z, Wei FZ, Chen JN, Wang ZJ, Shen HY, Li J, Zhao FQ, Pei W, Wang Z, Wang XS, Liu Q. Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients. World J Gastroenterol 2020; 26:4624-4638. [PMID: 32884221 PMCID: PMC7445870 DOI: 10.3748/wjg.v26.i31.4624] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 06/07/2020] [Accepted: 08/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Epidemiologically, in China, locally advanced rectal cancer is a more common form of rectal cancer. Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival (DFS) and pathologic response after surgery. At present, this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers, but the optimal time for surgery after neoadjuvant therapy is still controversial. AIM To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer. METHODS A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study. The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery: 139 (60.2%) patients were in group A (≤ 9 wk), and 92 (39.2%) patients were in group B (> 9 wk). DFS and pathologic response were analyzed as the primary endpoints. The secondary endpoints were postoperative complications and sphincter preservation. RESULTS For the 231 patients included, surgery was performed at ≤ 9 wk in 139 (60.2%) patients and at > 9 wk in 92 (39.8%). The patients' clinical characteristics, surgical results, and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis. The overall pathologic complete response (pCR) rate was 27.2% (n = 25) in the longer time interval group (> 9 wk) and 10.8% (n = 15) in the shorter time interval group (≤ 9 wk, P = 0.001). The postoperative complications did not differ between the groups (group A, 5% vs group B, 5.4%; P = 0.894). Surgical procedures for sphincter preservation were performed in 113 (48.9%) patients, which were not significantly different between the groups (group A, 52.5% vs group B, 43.5%; P = 0.179). The pCR rate was an independent factor affected by time interval (P = 0.009; odds ratio [OR] = 2.668; 95%CI: 1.276-5.578). Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval (> 9 wk) was a significant independent prognostic factor for DFS (P = 0.032; OR = 2.295; 95%CI: 1.074-4.905), but the time interval was not an independent prognostic factor for overall survival (P > 0.05). CONCLUSION A longer time interval to surgery after neoadjuvant therapy may improve the pCR rate and DFS but has little impact on postoperative complications and sphincter preservation.
Collapse
Affiliation(s)
- Shi-Wen Mei
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fang-Ze Wei
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jia-Nan Chen
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhi-Jie Wang
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hai-Yu Shen
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Juan Li
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fu-Qiang Zhao
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wei Pei
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zheng Wang
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xi-Shan Wang
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qian Liu
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| |
Collapse
|