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Zhou Q, Qian L, Shen C, Bei X, Liu G, Sun X. Automated VMAT planning for short-course radiotherapy in locally advanced rectal cancer. PLoS One 2025; 20:e0325567. [PMID: 40489475 DOI: 10.1371/journal.pone.0325567] [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: 02/26/2025] [Accepted: 05/14/2025] [Indexed: 06/11/2025] Open
Abstract
PURPOSE This study aims to develop a fully automated VMAT planning program for short-course radiotherapy (SCRT) in Locally Advanced Rectal Cancer (LARC) and assess its plan quality, feasibility, and efficiency. MATERIALS AND METHODS Thirty LARC patients who underwent short-course VMAT treatment were retrospectively selected from our institution for this study. An auto-planning program for neoadjuvant short-course radiotherapy (SCRT) in LARC was developed using the RayStation scripting platform integrated with the Python environment. The patients were re-planned using this auto-planning program. Subsequently, the differences between the automatic plans (APs) and existing manual plans (MPs) were compared in terms of plan quality, monitor units (MU), plan complexity, and other dosimetric parameters. Plan quality assurance (QA) was performed using the ArcCHECK dosimetric verification system. RESULTS Compared to MPs, the APs achieved similar target coverage and conformity, while providing more rapid dose fall-off. Except for the V5Gy dose level, other dosimetric metrics (V25 Gy, V23 Gy, V15 Gy, Dmean, etc.) for the small bowel were significantly lower in the AP compared to the MP (p < 0.001). Additionally, the dosimetric parameters for the bladder, pelvic marrow, and femoral head were also lower in the AP, except for the V25Gy for the bladder. The MUs of the AP were approximately 4% lower than those of the MP. The AP showed high consistency in dosimetric parameters across five organs at risk (OARs). CONCLUSION We developed a fully automated, feasible SCRT VMAT planning program for LARC. This program significantly enhanced plan quality and efficiency while substantially reducing the dose to OARs.
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Affiliation(s)
- Qiong Zhou
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ZheJiang, China
| | - Liwen Qian
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ZheJiang, China
| | - Chong Shen
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ZheJiang, China
| | - Xinyan Bei
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ZheJiang, China
| | - Gaojie Liu
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ZheJiang, China
| | - Xiaonan Sun
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ZheJiang, China
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2
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Klebaner D, Brown E, Fisher GA, Shelton A, Johnson TP, Shaheen S, Chen C, Heestand G, Holden T, Bien J, King DA, Dawes AJ, Morris AM, Kirilcuk N, Kin C, Gahagan J, Sheth V, Ghanouni P, Richter S, Vitzthum L, Rahimy E, Chang DT, Pollom EL. Phase II trial of organ preservation program using short-course radiation and FOLFOXIRI for rectal cancer (SHORT-FOX): Two-Year primary outcome analysis. Radiother Oncol 2025; 207:110884. [PMID: 40209856 DOI: 10.1016/j.radonc.2025.110884] [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: 12/16/2024] [Revised: 03/31/2025] [Accepted: 04/01/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND AND PURPOSE As patients with rectal cancer with clinical complete response (cCR) after neoadjuvant therapy may be safely spared Total Mesorectal Excision (TME), strategies to maximize cCR are needed. MATERIALS AND METHODS We conducted a single-arm phase II study to determine whether dose-escalated short-course radiotherapy (25 Gy/5 fractions + 5 Gy/1 fraction boost) followed by eight cycles of FOLFOXIRI increased cCR rates among adult patients with > T2N0M0 or low T2N0 rectal cancer. RESULTS Between 2020 and 2023, we enrolled 37 patients, of whom 27 (73 %) had at least one high-risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin, positive lateral node). At primary endpoint assessment, nine (24 %) patients had cCR on both endoscopy and MRI, and pursued organ preservation (OP). Fourteen (38 %) patients had cCR only on endoscopy, nine of whom pursued OP. Of the 18 patients who pursued OP, nine had local regrowth at two years from radiotherapy start, with two-year TME-free survival of 26 %. Baseline factors significantly associated with not achieving OP included age < 50 years and T4 disease. At mid-treatment restaging, patients who achieved OP were significantly less likely to have persistent node positivity, EMVI, and endoscopically visible tumor. Grade 3+ adverse events at least possibly attributed to chemotherapy and radiotherapy occured in 51% and 43% of patients, respectively. CONCLUSION Short-course radiotherapy with a boost followed by FOLFIXIRI results in OP in one-quarter of patients with high-risk rectal cancer, with poorer response among younger patients and T4 disease. Mid-treatment response may help guide timely decision-making regarding treatment.
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Affiliation(s)
- Daniella Klebaner
- Department of Radiation Oncology, Stanford University, Stanford, CA, United States
| | - Eleanor Brown
- Department of Radiation Oncology, Stanford University, Stanford, CA, United States
| | - George A Fisher
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, United States
| | - Andrew Shelton
- Department of Surgery, Stanford University, Stanford, CA, United States
| | - Tyler P Johnson
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, United States
| | - Shagufta Shaheen
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, United States
| | - Christopher Chen
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, United States
| | - Gregory Heestand
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, United States
| | - Thomas Holden
- Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, United States
| | - Jeffrey Bien
- Department of Oncology and Hematology, Kaiser Permanente, Santa Clara, CA, United States
| | - Daniel A King
- Department of Medical Oncology, Northwell Health, New Hyde Park, NY, United States
| | - Aaron J Dawes
- Department of Surgery, Stanford University, Stanford, CA, United States
| | - Arden M Morris
- Department of Surgery, Stanford University, Stanford, CA, United States
| | - Natalie Kirilcuk
- Department of Surgery, Stanford University, Stanford, CA, United States
| | - Cindy Kin
- Department of Surgery, Stanford University, Stanford, CA, United States
| | - John Gahagan
- Department of Surgery, Stanford University, Stanford, CA, United States
| | - Vipul Sheth
- Department of Radiology, Stanford University, Stanford, CA, United States
| | - Pejman Ghanouni
- Department of Radiology, Stanford University, Stanford, CA, United States
| | - Sara Richter
- Department of Radiation Oncology, Stanford University, Stanford, CA, United States
| | - Lucas Vitzthum
- Department of Radiation Oncology, Stanford University, Stanford, CA, United States
| | - Elham Rahimy
- Department of Radiation Oncology, Stanford University, Stanford, CA, United States
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford University, Stanford, CA, United States; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Erqi L Pollom
- Department of Radiation Oncology, Stanford University, Stanford, CA, United States.
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3
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Liu J, Xu X, Zhong H, Yu M, Abuduaini N, Fingerhut A, Cai Z, Feng B. Optimizing total neoadjuvant therapy in locally advanced rectal cancer: risk stratification should not be overlooked. Future Oncol 2025:1-10. [PMID: 40401643 DOI: 10.1080/14796694.2025.2507560] [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: 08/14/2024] [Accepted: 05/14/2025] [Indexed: 05/23/2025] Open
Abstract
Chemoradiotherapy plus total mesorectal excision has been established as the standard treatment for locally advanced rectal cancer (LARC) and can achieve satisfactory local control. However, systemic control of LARC, especially in patients with risk factors for poor prognosis, is still of concern. As application of total neoadjuvant therapy (TNT) has been proposed as a potential solution, a clearer risk stratification of LARC to guide individual treatment is needed. Combination therapy such as targeted therapy or immunotherapy can be used to increase treatment intensity for high-risk LARC. In this review, we evaluate recent trials of several treatment modalities, specifically focusing on intensified TNT regimens for high-risk LARC with the goal of summarizing optimal clinical strategies and future study designs.
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Affiliation(s)
- Jingyi Liu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ximo Xu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hao Zhong
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengqin Yu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Naijipu Abuduaini
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Abe Fingerhut
- Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Zhenghao Cai
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bo Feng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Hofheinz RD, Fokas E, Benhaim L, Price TJ, Arnold D, Beets-Tan R, Guren MG, Hospers GAP, Lonardi S, Nagtegaal ID, Perez RO, Cervantes A, Martinelli E, ESMO Guidelines Committee. Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2025:S0923-7534(25)00731-8. [PMID: 40412553 DOI: 10.1016/j.annonc.2025.05.528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 05/02/2025] [Accepted: 05/06/2025] [Indexed: 05/27/2025] Open
Affiliation(s)
- R-D Hofheinz
- TagesTherapieZentrum, Mannheim Cancer Center, University of Heidelberg, Mannheim
| | - E Fokas
- Department of Radiation Oncology, Cyberknife and Radiotherapy, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, Faculty of Medicine Cologne, University Hospital Cologne, Cologne, Germany
| | - L Benhaim
- Department of Surgical Oncology, Gustave Roussy, Villejuif, France
| | - T J Price
- Medical Oncology Unit, The Queen Elizabeth Hospital and University of Adelaide, Woodville, Australia
| | - D Arnold
- Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany
| | - R Beets-Tan
- The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - M G Guren
- Department of Oncology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - G A P Hospers
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - S Lonardi
- Oncology 3 Unit, Veneto Institute of Oncology (IOV) - IRCCS, Padua, Italy
| | - I D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - R O Perez
- Department of Colorectal Surgery, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | - A Cervantes
- Department of Medical Oncology, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, University of Valencia, Valencia; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
| | - E Martinelli
- Department of Precision Medicine, Oncology Unit, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy
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5
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Baldini EH, Gronchi A. Local Control in Soft Tissue Sarcomas. Hematol Oncol Clin North Am 2025:S0889-8588(25)00049-8. [PMID: 40374390 DOI: 10.1016/j.hoc.2025.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2025]
Abstract
Soft tissue sarcoma is a rare heterogeneous group of tumors made up of over 100 histologic types and subtypes. Expert pathology review is crucial to confirm the correct diagnosis prior to treatment. Multidisciplinary discussion and management at an expert center is strongly recommended given the many nuances of treatment. Wide resection +/- preoperative radiotherapy is recommended in most extremity and trunk wall STS patients, while a minority may also require perioperative medical therapy. Macroscopic complete resection remains the standard of care for retroperitoneal sarcoma patients, with preoperative radiotherapy recommended in selected histologic types.
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Affiliation(s)
- Elizabeth H Baldini
- Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA
| | - Alessandro Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
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Seow W, Murshed I, Bunjo Z, Bedrikovetski S, Stone J, Sammour T. Compliance and Toxicity of Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Network Meta-analysis. Ann Surg Oncol 2025:10.1245/s10434-025-17421-7. [PMID: 40325300 DOI: 10.1245/s10434-025-17421-7] [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: 01/20/2025] [Accepted: 04/21/2025] [Indexed: 05/07/2025]
Abstract
PURPOSE The individual chemotherapy- and radiotherapy-related toxicities between induction (iTNT) and consolidation total neoadjuvant therapy (cTNT) remain unclear. This network meta-analysis (NMA) comparing iTNT, cTNT, and traditional neoadjuvant chemoradiation (nCRT) evaluated the comparative treatment-related toxicities and compliance of the TNT schemas. METHODS A systematic review of randomized clinical trials and nonrandomized studies of interventions was performed as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. A Bayesian NMA was conducted, and odds ratios (OR) with 95% credible intervals (CrI) are reported for all outcomes. RESULTS Eighteen studies including 5730 patients were identified. iTNT ranked highest on rate of rectal bleeding (cTNT: OR 0.23 95% CrI 0.05-0.93; nCRT: OR 0.33, 95% CrI 0.09-0.96), proctitis (cTNT: OR 0.2, 95% CrI 0.06-0.55; nCRT: OR 0.2, 95% CrI 0.06-0.51), and postoperative diarrhea (cTNT: OR 0.37, 95% CrI 0.18-0.73; nCRT: OR 0.33, 95% CrI 0.15-0.71); cTNT ranked highest on rate of vomiting (iTNT: OR 0.24, 95% CrI 0.05-0.96; nCRT: OR 0.29, 95% CrI 0.06-0.89) and a higher rate of lymphopenia than iTNT (iTNT: OR 0.56, 95% CrI 0.34-0.99). Radiotherapy compliance was highest in cTNT (iTNT: OR 0.23, 95% CrI 0.05-0.72; nCRT: OR 0.18, 95% CrI 0.04-0.58). There was no difference in overall toxicity and mortality, chemotherapy compliance, and remaining individual system-based toxicities and postoperative complications. CONCLUSIONS Across all treatment strategies, iTNT had higher radiation-related gastrointestinal toxicities and postoperative diarrhea; cTNT had higher vomiting and lymphopenia rates. While no treatment strategy was superior in chemotherapy compliance, radiotherapy compliance was ranked highest in cTNT.
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Affiliation(s)
- Warren Seow
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
- JBI, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia.
| | - Ishraq Murshed
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Zachary Bunjo
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Sergei Bedrikovetski
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
- JBI, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
| | - Jennifer Stone
- JBI, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
| | - Tarik Sammour
- Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, SA, Australia
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7
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Macnair A, Adams R, Appelt A, Beavon M, Drinkwater K, Hanna CR, O'Cathail SM, Muirhead R. Neoadjuvant Treatment of Rectal Cancer: A Repeat UK-wide Survey After Implementation of National Intensity Modulated Radiotherapy Guidance. Clin Oncol (R Coll Radiol) 2025; 41:103835. [PMID: 40209514 DOI: 10.1016/j.clon.2025.103835] [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: 12/11/2024] [Revised: 03/14/2025] [Accepted: 03/19/2025] [Indexed: 04/12/2025]
Abstract
AIMS Rectal cancer management has changed significantly in the last decade with the introduction of total neoadjuvant therapy (TNT), minimally invasive surgery, brachytherapy, and organ preservation. A national survey of intensity modulated radiotherapy (IMRT) was carried out in 2020 to support the development of national Royal College of Radiologists (RCR) guidance, published in 2021. We performed a repeat survey in collaboration with the RCR, to inform iterations of the RCR Guidance and establish treatment patterns across the UK to facilitate future research and development. MATERIALS AND METHODS A web-based survey was developed and tested by the authors prior to dissemination by the RCR to all UK radiotherapy centres. The repeat survey requested details and strategies of current radiotherapy techniques, including details on setup, doses, organs at risk, peer review, and verification, and asked for the standard management of 5 clinical cases within each multidisciplinary team (MDT) serving that radiotherapy centre. Descriptive statistical analysis was carried out. RESULTS In total, 42 of 60 (70%) of the NHS centres across the UK answered the repeat IMRT rectal survey, which reflected 70 MDTs answering the clinical scenarios questions. 100% of centres that responded are routinely using IMRT, with 95% of centres using it in all patients. Variation in treatment delivery has reduced since the previous survey. The greatest difference is still in the use of simultaneous integrated boost and definition of organs at risk. The management for the clinical cases was widely different, with answers generally equally distributed between 2-4 options. The highest-scoring treatment strategies ranged from 24% to 57%. CONCLUSION RCR guidance has helped standardise the delivery of radiotherapy to treat rectal cancer in the UK. The variation in neoadjuvant treatment represents an exciting, evolving time in rectal cancer management. Clinical trials are needed to further homogenise treatment, but a degree of national variation is likely to continue.
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Affiliation(s)
- A Macnair
- Edinburgh Cancer Centre, Edinburgh, UK
| | - R Adams
- Centre for Trials Research Cardiff University and Velindre Cancer Centre, Ireland
| | - A Appelt
- Leeds Institute of Medical Research, University of Leeds, Ireland; Department of Medical Physics, Leeds Teaching Hospitals NHS Trust, UK
| | - M Beavon
- Royal College of Radiologists, London, UK
| | | | - C R Hanna
- Patrick G Johnston Centre for Cancer Research, Queen's University, Belfast, Ireland
| | | | - R Muirhead
- Oxford University Hospitals University Foundation Trust, Oxford, UK.
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Augustine A, Cecil GH, Lakhani A, Kanamathareddy HV, John R, Simon B, Eapen A, Mittal R, Chandramohan A. "Sigmoid take-off" to define recto-sigmoid junction and its impact on rectal cancer classification, staging, and management. Clin Radiol 2025; 84:106858. [PMID: 40088853 DOI: 10.1016/j.crad.2025.106858] [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: 09/18/2024] [Revised: 01/31/2025] [Accepted: 02/07/2025] [Indexed: 03/17/2025]
Abstract
AIM The primary objective of this study was to determine the clinical impact of using sigmoid take-off (STO) in the management of rectal cancer. We also evaluated the inter-observer reliability in the identification of STO. MATERIAL AND METHODS This retrospective study reviewed staging MRI of patients with mid and high-rectal cancers performed between January 2019 and December 2022. The location of the tumour was reclassified based on STO as defined by D'Souza et al. (2018) and compared with the location determined based on distance from the anal verge. The proportions of cases that show a change in tumour location from rectal cancer to sigmoid cancer and the potential change in treatment were noted. The interobserver agreement for the location of STO and the location of tumours from STO was studied among four subspecialised abdominal radiologists. RESULTS Out of 134 rectal cancer patients included, STO-based assessment resulted in the reclassification of 13.4% (n=18) cases into sigmoid cancer. There was, however, no change in the stage of cancer. Among these 18 patients, there would have been a change in management in 5 patients had the initial assessment been a sigmoid cancer. There was excellent agreement among the radiologists for measuring the distance of STO from the anal verge (ICC = 0.883, p<0.001) and determining the location of the tumour based on STO (K = 0.82, p<0.001). CONCLUSIONS Using STO changed the location of tumours in 13.4% of high- and mid-rectal cancers. There was excellent agreement among radiologists regarding determining STO and identifying tumour locations using STO.
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Affiliation(s)
- A Augustine
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - G H Cecil
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - A Lakhani
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - H V Kanamathareddy
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - R John
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - B Simon
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - A Eapen
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - R Mittal
- Department of Colorectal Surgery, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - A Chandramohan
- Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, 632004, India.
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Toda S, Inoshita N, Matoba S, Maeda Y, Hiramatsu K, Fukui Y, Hanaoka Y, Ueno M, Kuroyanagi H, Ishikawa F, Ohashi K. Lateral Pelvic Recurrence in Rectal Cancer Is Not Local Recurrence but Lymphatic Metastasis. J Anus Rectum Colon 2025; 9:225-236. [PMID: 40302858 PMCID: PMC12035336 DOI: 10.23922/jarc.2024-102] [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: 11/18/2024] [Accepted: 01/23/2025] [Indexed: 05/02/2025] Open
Abstract
Objectives Complete resection of advanced rectal cancer is challenging, with local recurrence rates ranging from 4% to 12%. Local recurrence is often categorized as central, anastomotic, or lateral, with lateral lymph node (LLN) metastasis being the primary driver of lateral recurrence. Although preoperative radiotherapy effectively manages nonlateral recurrences, it is less effective for lateral recurrences, and LLN dissection significantly reduces lateral recurrence rates. This study aimed to clarify the clinicopathological characteristics associated with lateral and nonlateral recurrences. Methods We retrospectively analyzed 232 patients (156 males and 76 females; median age, 64 years) who underwent preoperative radiotherapy followed by curative-intent surgery for clinical T3/4 rectal adenocarcinoma located below the peritoneal reflection between April 2010 and December 2017. In total, 40% of the patients underwent LLN dissection. Univariate and multivariate analyses of clinicopathological data were performed to identify the independent risk factors for lateral and nonlateral recurrences. Results Local recurrence occurred in 19 (8%) patients: 7 had lateral recurrence, 13 had nonlateral recurrence, and 1 had both. Multivariate analysis identified mesorectal lymph node metastasis as a significant risk factor for lateral recurrence, whereas positive circumferential resection margin was a significant risk factor for nonlateral recurrence. Conclusions The identification of different risk factors for lateral and nonlateral recurrence suggests that lateral recurrence is more strongly associated with lymphatic permeation than nonlateral recurrence. These findings highlight the importance of LLN dissection in minimizing the risk of lateral recurrence.
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Affiliation(s)
- Shigeo Toda
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
- Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan
| | - Naoko Inoshita
- Department of Pathology, Moriyama Memorial Hospital, Tokyo, Japan
| | - Shuichiro Matoba
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Yusuke Maeda
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Kosuke Hiramatsu
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Yudai Fukui
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Yutaka Hanaoka
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Masashi Ueno
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Hiroya Kuroyanagi
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Fumihiko Ishikawa
- Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan
| | - Kenichi Ohashi
- Department of Human Pathology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan
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10
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Horesh N, Emile SH, Garoufalia Z, Gefen R, Rogers P, Aeschbacher P, Salama E, Wexner SD. Network meta-analysis of RTCs for efficacy of neoadjuvant treatment in rectal cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:110019. [PMID: 40233522 DOI: 10.1016/j.ejso.2025.110019] [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: 01/20/2025] [Revised: 02/27/2025] [Accepted: 04/04/2025] [Indexed: 04/17/2025]
Abstract
BACKGROUND This network meta-analysis examined the efficacy of different types of neoadjuvant therapy (NAT) for rectal cancer in improving clinical and pathologic outcomes. METHODS PRISMA-compliant systematic review of PubMed and Scopus including only randomized clinical trials comparing two or more NAT regimens for rectal cancer. A network meta-analysis was undertaken for the main outcomes, including pathological complete response (pCR), disease downstaging, R0 resection, permanent stoma, and major adverse effects. Risk of bias was assessed using the ROB-2 tool. RESULTS 19 randomized controlled trials incorporating 7037 patients (62 % males) were included in the analysis. Compared to standard neoadjuvant chemoradiation (NCRT), consolidation total neoadjuvant therapy (TNT) (OR: 1.82, 95 % CI: 1.46-2.27; p < 0.001) and induction TNT (OR: 1.72, 95 % CI: 1.31-2.26; p < 0.001) had higher odds of achieving pCR. Induction TNT was also significantly associated with higher odds of major adverse effects than was NCRT (OR: 3.14, 95 % CI: 2.50-3.94; p < 0.0001). Compared to NCRT, long course chemotherapy significantly increased the odds of R0 resection (OR: 1.42, 95 % CI: 1.13-1.78; p = 0.002), while consolidation TNT significantly increased organ preservation rates (OR: 2.82, 95 % CI: 1.58-5.05; p < 0.001). Short course radiotherapy doubled the odds of positive circumferential resection margins (CRM) compared to NCRT (OR: 1.99, 95 % CI: 1.11-3.55; p = 0.02). CONCLUSIONS Consolidation and induction TNT were superior in achieving better pathological outcomes in rectal cancer, offering significant benefits over standard NCRT. However, they were associated with a higher risk of adverse effects. Conversely, short course radiotherapy was linked to higher rates of positive CRM.
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Affiliation(s)
- Nir Horesh
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Department of Surgery and Transplantations, Sheba Medical Center, Ramat Gan, Affiliated with the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sameh Hany Emile
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura, Egypt
| | - Zoe Garoufalia
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Rachel Gefen
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Department of General Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Peter Rogers
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Pauline Aeschbacher
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Ebram Salama
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Steven D Wexner
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA.
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11
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Yallala M, Krishnatry R, Shah A, Bhargava PG, Ramaswamy A, Baheti A, Saklani A, Engineer R, Ankathi SK, Kazi M, Desouza A, Ostwal V. Real-World Data on the Practice of Chemoradiation with Select Cohort Consolidation Chemotherapy in High-Risk Locally Advanced Rectal Cancers (SOLAR study). South Asian J Cancer 2025. [DOI: 10.1055/s-0045-1806957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2025] Open
Abstract
AbstractChemoradiation with capecitabine radiotherapy (Cape–RT) has been the standard of care as neoadjuvant treatment in locally advanced rectal cancer (LARC) for more than a decade. However, total neoadjuvant therapy has recently emerged as an alternative with the potential to impact survival outcomes; baseline outcomes with Cape–RT in real-world practice in the Indian context are not well known.Treatment-naive patients with adenocarcinoma on histology and clinical-radiologically diagnosed LARC who received Cape–RT from June 2014 to December 2021 after multidisciplinary discussion were included. Patients received a long course of conventionally fractionated external beam RT (45–50 Gy in 25#) with concurrent oral capecitabine at a dose of 1650 mg/m2/day. Post approximately 6 to 8 weeks of completion of Cape–RT, patients were evaluated clinically and by magnetic resonance imaging pelvis for total mesorectal excision (TME) in the multidisciplinary team meetings. The primary endpoint of the study was event-free survival (EFS), and the secondary endpoint was overall survival (OS) and pathological complete response (PCR) rates. EFS and OS were calculated using the Kaplan–Meier method.A total of 1,189 patients with a median age of 49 years (range: 15–95) were identified and included. A significant proportion of patients had high-risk characteristics, such as T3/T4 disease (94%) and node positivity (90%), and they involved circumferential resection margin (CRM) (51%) at baseline. Signet ring and mucinous histology were seen in 13 and 11% of patients. Two hundred and seventy-six patients (23%) required further consolidation chemotherapy (commonly CAPOX [capecitabine-oxaliplatin] or modified FOLFIRINOX [5-fluorouracil-leucovorin-irinotecan-oxaliplatin]) post-Cape–RT prior to attempting surgery due to either persistent CRM positivity, clinical T4 disease, prostate abutment, sphincter involvement (248 patients, 21%), or extensive bulky disease with poor response (12 patients, 1%). Overall, 14 patients (6%) had an interruption in RT and 22 (8%) in chemotherapy. Post-Cape–RT, with or without chemotherapy, 945 patients (79%) underwent TME. Chemotherapy post-TME was administered in 808 patients (78%). With a median follow-up of 54 months (range: 51.2–57.2), the 3- and 5-year EFS for the entire cohort was 73.2% (95% confidence interval [CI]: 70.6–75.8) and 64.3% (95% CI: 61.1–67.5), respectively, while the estimated 3- and 5-year OS was 81.3% (95% CI: 78.9–83.7) and 73% (95% CI: 70–76), respectively. On multivariate analysis, the presence of higher T stage (p < 0.001) and signet ring histology (p = 0.004) predicted inferior OS.Real-world data in a less-resourced setting concurs with published prospective and Western real-world data. This provides confidence in implementing consolidation chemotherapy in total neoadjuvant settings in countries with fewer resources.
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Affiliation(s)
- Mounika Yallala
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Rahul Krishnatry
- Department of Radiational Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Anjali Shah
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Prabhat Ghanshyam Bhargava
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akshay Baheti
- Department of Interventional Radiology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Avanish Saklani
- Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Reena Engineer
- Department of Radiational Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Suman K. Ankathi
- Department of Interventional Radiology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Mufaddal Kazi
- Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Ashwin Desouza
- Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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12
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Fang Y, Chen H, Liu Y, Jiang K, Qian Y, Wei J, Fu D, Yang H, Dai S, Jin T, Bu T, Ding K. NUPR1 Promotes Radioresistance in Colorectal Cancer Cells by Inhibiting Ferroptosis. J Cell Mol Med 2025; 29:e70519. [PMID: 40176685 PMCID: PMC11965884 DOI: 10.1111/jcmm.70519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 01/20/2025] [Accepted: 03/14/2025] [Indexed: 04/04/2025] Open
Abstract
Radioresistance is a major clinical challenge and the underlying mechanism has not been thoroughly elucidated. In this study, a radioresistant (RR) cell line is established to explore the transcriptomic signatures of radioresistance in colorectal cancer (CRC). KEGG enriched pathway analysis demonstrated that ferroptosis is inactivated in RR cells. Further detection confirmed that radiotherapy can promote ferroptosis, and ferroptosis inactivation is one of the hallmarks of radioresistance in CRC. What's more, induction of ferroptosis can restore the radiosensitivity of CRC cells. Then, we performed RNA sequencing to compare gene expression between parental and RR cells, and cells pretreated with or without RSL3. Via high-throughput screening, NUPR1 was identified as a potential candidate for ferroptosis-mediated radioresistance in CRC. CRC cells can acquire radiation resistance by NUPR1-mediated ferroptosis suppression in the NUPR1-overexpressing cell line. More importantly, ZZW-115, an NUPR1 inhibitor, can sensitise RR cells to radiotherapy. Overall, our findings identify ferroptosis inactivation linked with resistance to radiotherapy. Besides, NUPR1 can promote radiation resistance by inhibiting ferroptosis, and targeting NUPR1 may be a potential strategy to relieve radioresistance associated with ferroptosis in CRC.
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Affiliation(s)
- Yimin Fang
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Haiyan Chen
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
- Department of Radiation Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineHangzhouZhejiangChina
| | - Yunhua Liu
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Kai Jiang
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Yucheng Qian
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Jingsun Wei
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Dongliang Fu
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Hang Yang
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Siqi Dai
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Tian Jin
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Tongtong Bu
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
| | - Kefeng Ding
- Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangHangzhouChina
- Zhejiang Provincial Clinical Research Center for CANCERHangzhouChina
- Cancer Center of Zhejiang UniversityHangzhouChina
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13
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Quezada-Díaz FF, Bercz A, Escobar JL, Caire N, Díaz-Feldman LE, Manriquez E, Carvajal G. No operation after short-course radiotherapy followed by consolidation chemotherapy in locally advanced rectal cancer (NOAHS-ARC): study protocol for a prospective, phase II trial. Int J Colorectal Dis 2025; 40:69. [PMID: 40100473 PMCID: PMC11919929 DOI: 10.1007/s00384-025-04850-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2025] [Indexed: 03/20/2025]
Abstract
PURPOSE Organ preservation through a watch-and-wait (W&W) strategy has become a viable option for select rectal cancer patients with clinical complete responses (cCR) to total neoadjuvant therapy (TNT). This approach limits the morbidity associated with multimodal treatment. However, the optimal treatment strategy and predictors of treatment response are still unresolved. Rectal cancer incidence is rising, particularly in developing countries, and the disease is a major public health concern in Chile. Prior to the no operation after short-course radiotherapy followed by consolidation chemotherapy in locally advanced rectal cancer (NOAHS-ARC) trial, TNT-based treatments and W&W programs had not been implemented in Chile. METHODS/DESIGN This single-arm, multicenter, phase II prospective trial, conducted in Santiago, Chile, will enroll patients with stage II/III rectal adenocarcinoma. Treatment involves induction short-course radiotherapy (25 Gy in 5 fractions) followed by consolidation chemotherapy (FOLFOX × 9 or CAPOX × 6 cycles). The response will be assessed 4-8 weeks after chemotherapy completion. Patients achieving cCR will be offered W&W, while those with incomplete responses will undergo total mesorectal excision. The primary endpoint is the rate of complete tumor response, combining pathologic complete responses (pCR) and sustained cCR (> 1 year), compared to a matched cohort treated with neoadjuvant chemoradiation alone. The trial aims to recruit 48 patients, assuming a combined pCR/sustained cCR rate of 12%. Quality of life measures will be assessed, and a biorepository of tissue and plasma samples will be established for future research, alongside serial endoscopic and MRI images. DISCUSSION NOAHS-ARC seeks to advance organ preservation strategies in rectal cancer while pioneering TNT and W&W protocols in Chile. The study will also focus on functional outcomes and provide valuable data for improving patient care both locally and globally. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT04864067. Registered on April 28, 2021.
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Affiliation(s)
- Felipe F Quezada-Díaz
- Complejo Asistencial Doctor Sotero del Rio, Avenida Concha y Toro #3459, 8150215, Puente Alto, Chile.
| | - Aron Bercz
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jose L Escobar
- Escuela de Medicina. Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Nicole Caire
- Complejo Asistencial Doctor Sotero del Rio, Avenida Concha y Toro #3459, 8150215, Puente Alto, Chile
| | - Lucia E Díaz-Feldman
- Complejo Asistencial Doctor Sotero del Rio, Avenida Concha y Toro #3459, 8150215, Puente Alto, Chile
| | - Erik Manriquez
- Complejo Asistencial Doctor Sotero del Rio, Avenida Concha y Toro #3459, 8150215, Puente Alto, Chile
| | - Gonzalo Carvajal
- Complejo Asistencial Doctor Sotero del Rio, Avenida Concha y Toro #3459, 8150215, Puente Alto, Chile
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14
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Cotte E, Arquilliere J, Artru P, Bachet JB, Benhaim L, Bibeau F, Christou N, Conroy T, Doyen J, Hoeffel C, Meillan N, Mirabel X, Pioche M, Rivin Del Campo E, Vendrely V, Huguet F, Bouché O. Rectal cancer - French intergroup clinical practice guidelines for diagnosis, treatment, and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR, and GRECCAR). Dig Liver Dis 2025; 57:669-679. [PMID: 39694751 DOI: 10.1016/j.dld.2024.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/23/2024] [Accepted: 12/01/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND This article summarizes the French intergroup guidelines regarding rectal adenocarcinoma (RA) management published in September 2023, available on the French Society of Gastroenterology website. METHODS This work was supervised by French medical and surgical societies involved in RA management. Recommendations were rated from A to C according to the literature until September 2023. RESULTS Based on the pretreatment work-up, RA treatment was divided into four groups. T1N0 can be treated by endoscopic or surgical excision alone if there is no risk factor for lymph node involvement. For T2N0, radical surgery with total mesorectal excision is recommended, but rectal conservation is possible for small tumors (<4cm) after complete/subcomplete response following chemoradiotherapy. For T12N+ or T3+any N, total neoadjuvant treatment (TNT) followed by radical surgery is the gold standard, but rectal conservation is possible for small tumors after complete/subcomplete response following TNT. T3N2 or T+any N are an indication for TNT followed by radical surgery. Immunotherapy shows promise for dMMR/MSI RA. For metastatic tumors, recommendations are based on less robust evidence and chemotherapy plays a major role. CONCLUSION These guidelines aim at providing a personalized therapeutic strategy and are constantly being optimized. Each case should be discussed by a multidisciplinary team.
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Affiliation(s)
- Eddy Cotte
- Department of Digestive and Oncological Surgery, Lyon-Sud University Hospital, Pierre-Bénite, France.
| | - Justine Arquilliere
- Department of Digestive and Oncological Surgery, Lyon-Sud University Hospital, Pierre-Bénite, France
| | - Pascal Artru
- Department of Digestive Oncology, Jean Mermoz Private Hospital, Lyon, France
| | - Jean Baptiste Bachet
- Department of Hepato-Gastro-Enterology, Pitié-Salpêtrière Hospital Group, Assistance Publique-Hôpitaux de Paris, Pierre & Marie Curie University, Paris, France
| | - Leonor Benhaim
- Department of Visceral and Surgical Oncology, Gustave Roussy Hospital, Cancer Campus, 114 rue Edouard Vaillant, 94805 Villejuif, France
| | - Frederic Bibeau
- Department of Pathology, Besançon University Hospital, Besançon, France
| | - Niki Christou
- Department of Digestive Surgery, Limoges University Hospital, Limoges, France
| | - Thierry Conroy
- Department of Medical Oncology, Lorraine Cancer Institute, Vandoeuvre-lès-Nancy, France and Lorraine University, Inserm INSPIIRE, Nancy, France
| | - Jérome Doyen
- Department of Radiation Therapy, Antoine Lacassagne Cancer Center, University of Nice- Sophia, Nice, France
| | - Christine Hoeffel
- Department of Medical Imaging, Reims University Hospital, CRESTIC, URCA, Reims, France
| | - Nicolas Meillan
- Department of Radiation Oncology, Victor Dupouy Hospital, Argenteuil, France; Radiation Epidemiology Group, INSERM Unit 1018, Villejuif, F-94805, France
| | - Xavier Mirabel
- Academic Department of Radiation Oncology, Oscar Lambret Center, Lille, France
| | - Mathieu Pioche
- Endoscopy and Gastroenterology Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | | | - Véronique Vendrely
- Department of Radiation Oncology, Haut-Lévêque Hospital, Bordeaux University, INSERM 1218-BRIC, France
| | - Florence Huguet
- Department of Radiation Oncology, Tenon Hospital, AP-HP, Sorbonne University, Paris, France
| | - Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, Reims University Hospital, Reims, France
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15
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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.
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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
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16
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Wang F, Chen G, Zhang Z, Yuan Y, Wang Y, Gao Y, Sheng W, Wang Z, Li X, Yuan X, Cai S, Ren L, Liu Y, Xu J, Zhang Y, Liang H, Wang X, Zhou A, Ying J, Li G, Cai M, Ji G, Li T, Wang J, Hu H, Nan K, Wang L, Zhang S, Li J, Xu R. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update. Cancer Commun (Lond) 2025; 45:332-379. [PMID: 39739441 PMCID: PMC11947620 DOI: 10.1002/cac2.12639] [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: 11/27/2024] [Accepted: 12/02/2024] [Indexed: 01/02/2025] Open
Abstract
The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.
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Affiliation(s)
- Feng Wang
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
| | - Gong Chen
- Department of Colorectal SurgerySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerGuangzhouGuangdongP. R. China
| | - Zhen Zhang
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Ying Yuan
- Department of Medical OncologyThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Yi Wang
- Department of RadiologyPeking University People's HospitalBeijingP. R. China
| | - Yuan‐Hong Gao
- Department of Radiation OncologySun Yat‐sen University Cancer Centre, The State Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP. R. China
| | - Weiqi Sheng
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Zixian Wang
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
| | - Xinxiang Li
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Xianglin Yuan
- Department of OncologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanHubeiP. R. China
| | - Sanjun Cai
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Li Ren
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiP. R. China
| | - Yunpeng Liu
- Department of Medical OncologyThe First Hospital of China Medical UniversityShenyangLiaoningP. R. China
| | - Jianmin Xu
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiP. R. China
| | - Yanqiao Zhang
- Department of OncologyHarbin Medical University Cancer HospitalHarbinHeilongjiangP. R. China
| | - Houjie Liang
- Department of OncologySouthwest HospitalThird Military Medical University (Army Medical University)ChongqingP. R. China
| | - Xicheng Wang
- Department of Gastrointestinal OncologyCancer Medical Center, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Aiping Zhou
- Department of Medical OncologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Jianming Ying
- Department of PathologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Guichao Li
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Muyan Cai
- Department of PathologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP. R. China
| | - Gang Ji
- Department of Gastrointestinal SurgeryXijing HospitalAir Force Military Medical UniversityXi'anShaanxiP. R. China
| | - Taiyuan Li
- Department of General SurgeryThe First Affiliated Hospital of Nanchang UniversityNanchangJiangxiP. R. China
| | - Jingyu Wang
- Department of RadiologyThe First Hospital of Jilin UniversityChangchunJilinP. R. China
| | - Hanguang Hu
- Department of Medical OncologyThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Kejun Nan
- Department of Medical OncologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiP. R. China
| | - Liuhong Wang
- Department of RadiologySecond Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Suzhan Zhang
- Department of Colorectal SurgeryThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Jin Li
- Department of Medical OncologyShanghai GoBroad Cancer HospitalChina Pharmaceutical UniversityShanghaiP. R. China
| | - Rui‐Hua Xu
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat‐sen University, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
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17
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Wahba JF, Knight G, Husein M, Paun B, Gopaul D. Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: A Retrospective Analysis. Cureus 2025; 17:e81427. [PMID: 40296958 PMCID: PMC12037154 DOI: 10.7759/cureus.81427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2025] [Indexed: 04/30/2025] Open
Abstract
Purpose To evaluate the outcomes of patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiotherapy (CRT) at a community cancer center. Methods A retrospective chart review was conducted for patients with biopsy-proven rectal adenocarcinoma treated with CRT between January 2017 and June 2020. Patients were excluded if there was metastatic disease (stage IV) at presentation, if curative resection was not planned, or if they received additional preoperative chemotherapy. Preoperative radiotherapy was typically 50.4 Gy in 28 fractions with concurrent capecitabine chemotherapy, followed by surgery six to eight weeks later. Postoperative adjuvant FOLFOX chemotherapy was typically recommended in suitable patients. Outcomes measured included surgical margin status, pathological complete response (pCR), local recurrence rate, distant metastases, cancer-specific survival, and overall survival. Results A total of 120 patients underwent preoperative CRT during this period. Seven patients did not undergo subsequent surgical resection. The pCR rate was 14%, and R0 resection (negative margins) was achieved in 93% of cases. The cumulative incidence of local recurrence was 6%, and distant metastases developed in 23% of patients. The most common metastatic sites were the liver and lungs. With a median follow-up of 28 months, Kaplan-Meier analyses demonstrated a 78% cancer-specific survival (CSS) and 75% overall survival (OS). Conclusion Preoperative CRT resulted in a 14% pCR rate, which was associated with high R0 (93%) and low local recurrence rates (6%). Distant metastatic recurrence rate remains a concern (23%).
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Affiliation(s)
- Jacob F Wahba
- Faculty of Health Sciences, Wilfrid Laurier University, Waterloo, CAN
| | - Gregory Knight
- Department of Oncology, Grand River Regional Cancer Centre, Grand River Hospital, Kitchener, CAN
| | - Mohamed Husein
- Department of Surgery, Grand River Hospital, Kitchener, CAN
| | - Bogdan Paun
- Department of Surgery, Grand River Hospital, Kitchener, CAN
| | - Darin Gopaul
- Department of Radiation Oncology, Grand River Regional Cancer Centre, Grand River Hospital, Kitchener, CAN
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18
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Bauer PS, Gamboa AC, Otegbeye EE, Chapman WC, Rivard S, Regenbogen S, Hrebinko KA, Holder-Murray J, Wiseman JT, Ejaz A, Edwards-Hollingsworth K, Hawkins AT, Hunt SR, Balch GC, Wise PE. Short-Course TNT Improves Rectal Tumor Downstaging in a Retrospective Study of the US Rectal Cancer Consortium. J Surg Oncol 2025; 131:498-506. [PMID: 39400312 DOI: 10.1002/jso.27908] [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: 08/06/2024] [Accepted: 08/31/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND AND OBJECTIVES The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both. METHODS The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response. RESULTS Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS. CONCLUSIONS SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.
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Affiliation(s)
- Philip S Bauer
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Adriana C Gamboa
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Ebunoluwa E Otegbeye
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - William C Chapman
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Samantha Rivard
- Division of Colorectal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Scott Regenbogen
- Division of Colorectal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Katherine A Hrebinko
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jennifer Holder-Murray
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jason T Wiseman
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio, USA
| | - Aslam Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio, USA
| | - Kamren Edwards-Hollingsworth
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Alexander T Hawkins
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Steven R Hunt
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Glen C Balch
- Division of Colon & Rectal Surgery, Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Paul E Wise
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
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19
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Karahan SN, Gorgun E. Modern rectal cancer management: A review of total neoadjuvant therapy and current practices. Am J Surg 2025; 241:116145. [PMID: 39706107 DOI: 10.1016/j.amjsurg.2024.116145] [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: 08/11/2024] [Revised: 12/05/2024] [Accepted: 12/10/2024] [Indexed: 12/23/2024]
Abstract
Total Neoadjuvant Therapy (TNT) is a promising strategy for treating locally advanced rectal cancer (LARC) and has started to replace the traditional neoadjuvant chemoradiotherapy (CRT). This review combines findings from pivotal studies that helped TNT to integrate into clinical practice. It emphasizes the efficacy of TNT in improving the disease-free and metastasis-free survival, pathologic complete response and, according to recent studies, a potential improvement in overall survival when compared to standard CRT. In addition, the review analyzes increased organ preservation by TNT and explores the trend towards personalized medicine with the use of TNT. Additionally, it investigates the possibility of excluding radiotherapy in some subgroups. Future directions include integration of immunotherapy, use of TNT in early-stage disease and determining optimal components of TNT, such as type of chemotherapy and type of radiotherapy.
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Affiliation(s)
- Salih N Karahan
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Emre Gorgun
- Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
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20
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Varty GP, Patkar S, Lele S, Patel S, Deshpande G, Dhal I, Kazi M, Pawar A, Ostwal V, Ramaswamy A, Bhargava P, Goel M. Adenosquamous carcinoma of the gallbladder: a Bi-institutional experience in managing this rare entity. HPB (Oxford) 2025:S1365-182X(25)00063-2. [PMID: 40024853 DOI: 10.1016/j.hpb.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 12/21/2024] [Accepted: 02/13/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Adenosquamous Gallbladder Cancers (ASGBC) are rare variety of GBCs. Relative paucity of data with regards to the management of ASGBC exists. METHODS Patients with diagnosis of ASGBC from January 2012 to March 2022 were categorised into 'Early', 'Locally advanced (LA)' and 'Metastatic (M)' ASGBC as per the predefined 'TMH Criteria'. RESULTS A total of 196 patients included were categorised into early ASGBC (n = 19,9.7%), LA - ASGBC (n = 53,27%) and M - ASGBC (n = 124,63.3%) with median overall survival (OS) being worst for M - ASGBC (3.9 months) and best for early ASGBC (not reached). The 1-year and 3-year OS of LA-ASGBC patients who underwent surgery was significantly higher than those with non-surgical treatment (72.6%, 35.6% vs 25.1%, 0%, p <0.001). Although, the median OS of resected ASGBC was less as compared to resected gallbladder adenocarcinomas (GBACs) (40.8 vs. 56.1 months), it did not reach statistical significance (p=0.06). However, at higher stages of resected LA - ASGBC (Stage III), the median OS was significantly lower as compared to stage-matched resected GBACs (14.5 vs. 30.1 months, p= 0.006). CONCLUSION Multimodality treatment consisting of margin negative surgical resection with perioperative chemotherapy offers the best chance of long-term survival in ASGBC.
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Affiliation(s)
- Gurudutt P Varty
- Department of Gastrointestinal and Hepatopancreatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Gastrointestinal and Hepatopancreatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
| | - Sujat Lele
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Swapnil Patel
- Department of Surgical Oncology, Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Varanasi, Uttar Pradesh, India
| | - Gauri Deshpande
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Ipsita Dhal
- Department of Pathology and Molecular Biology, Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Varanasi, Uttar Pradesh, India
| | - Mufaddal Kazi
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Akash Pawar
- Department of Statistics, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mahesh Goel
- Department of Gastrointestinal and Hepatopancreatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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21
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Gandini A, Sciallero S, Martelli V, Pirrone C, Puglisi S, Cremante M, Grassi M, Andretta V, Fornarini G, Caprioni F, Comandini D, Pessino A, Mammoliti S, Sobrero A, Pastorino A. A Comprehensive Approach to Neoadjuvant Treatment of Locally Advanced Rectal Cancer. Cancers (Basel) 2025; 17:330. [PMID: 39858112 PMCID: PMC11763976 DOI: 10.3390/cancers17020330] [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: 12/10/2024] [Revised: 01/14/2025] [Accepted: 01/17/2025] [Indexed: 01/27/2025] Open
Abstract
At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2-3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Alessandro Pastorino
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (A.G.)
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22
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Lin YH, Hsu HC, Huang EY. Prognostic Value of Pretreatment Carcinoembryonic Antigen (CEA) in Rectal Cancer Treated with Preoperative Short-Course Radiotherapy with Delayed Surgery or Long-Course Radiotherapy. Onco Targets Ther 2025; 18:73-86. [PMID: 39839887 PMCID: PMC11748052 DOI: 10.2147/ott.s474855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 12/31/2024] [Indexed: 01/23/2025] Open
Abstract
Purpose To investigate the prognostic value of the pretreatment serum carcinoembryonic antigen (CEA) level in patients with rectal cancer treated by preoperative short-course radiotherapy (SCRT) followed by chemotherapy and delayed surgery. Patients and Methods Two hundred and sixty-six consecutive patients with locally advanced rectal adenocarcinoma without distant metastasis receiving preoperative radiotherapy were enrolled. Group 1 patients (n=144) received long-course radiotherapy (LCRT) with 50.4 Gy in 28 fractions using photon radiotherapy (XRT). Group 2 patients (n=122) received SCRT with 25 Gy in 5 fractions using XRT or proton beam therapy (PBT) followed by chemotherapy and delayed surgery. Pathological complete response (pCR), near pathological complete response (npCR), locoregional recurrence (LRR), distant metastasis (DM), disease-specific survival (DSS) and overall survival (OS) rates were estimated and compared to scrutinize the prognostic significance of factors including CEA level. Results In group 1, higher CEA level (≥ 7 ng/mL) was a significant negative prognostic factor of pCR (p = 0.003, OR: 0.133), OS (p = 0.011, HR: 2.999), DM (p = 0.008, HR: 2.569), LRR (p = 0.044, HR: 3.160), and DSS (p = 0.015, HR: 3.273). In group 2, higher CEA level (≥ 7 ng/mL) was a significant negative prognostic factor of pCR (p = 0.002, OR: 0.038), OS (p < 0.001, HR: 44.658), DM (p < 0.001, HR: 8.926), LRR (p = 0.028, HR: 8.570), and DSS (p = 0.001, HR: 43.918). The npCR rates for clinical T4 patients were 6.5% and 22.0% (p = 0.032), in group 1 and group 2, respectively. Conclusion This study elucidates the prognostic merit of the pretreatment serum CEA level in patients with rectal cancer treated by either preoperative LCRT or SCRT followed by chemotherapy and delayed surgery.
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Affiliation(s)
- Yun-Hsuan Lin
- Department of Radiation Oncology & Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, 833, Taiwan
| | - Hsuan-Chih Hsu
- Department of Radiation Oncology & Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, 833, Taiwan
| | - Eng-Yen Huang
- Department of Radiation Oncology & Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, 833, Taiwan
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung City, 804, Taiwan
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23
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Wang F, Lai C, Lv Y, Zhang F, Shi L, Wang Y, Shen Y, Xu L, Hu P, Tang W, Xu D, Cao G, Shan L, Jia X, Chen Y, Larson DW, Wang D, Lao W, Gu H, Sun X, Huang X, Dai S. Efficacy and safety of combining short-course neoadjuvant chemoradiotherapy with envafolimab in locally advanced rectal cancer patients with microsatellite stability: a phase II PRECAM experimental study. Int J Surg 2025; 111:334-345. [PMID: 39093871 PMCID: PMC11745671 DOI: 10.1097/js9.0000000000001960] [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: 04/12/2024] [Accepted: 07/06/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. MATERIALS AND METHODS The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. RESULTS From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. CONCLUSION In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.
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Affiliation(s)
- Fei Wang
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Chuanxi Lai
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Yiming Lv
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Feixiang Zhang
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Liming Shi
- Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
| | - Yunfei Wang
- Hangzhou Shengting Medical Technology Co., Ltd
| | - Yanbin Shen
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Lingna Xu
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Peng Hu
- Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
| | - Wen Tang
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang
| | - Dengyong Xu
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Gaoyang Cao
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Lina Shan
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Xiya Jia
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Yiyi Chen
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - David W. Larson
- Department of Surgery, Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota, USA
| | - Da Wang
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Weifeng Lao
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Hongcang Gu
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, People’s Republic of China
| | - Xiaonan Sun
- Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
| | - Xuefeng Huang
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
| | - Sheng Dai
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Biotherapy of Zhejiang Province
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24
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Zhou Q, Wang Q, Li Y, Shen C, Sun X. Dosimetric comparison of VMAT plans in preoperative short-course rectal radiotherapy. Sci Rep 2024; 14:30862. [PMID: 39730522 DOI: 10.1038/s41598-024-81310-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 11/26/2024] [Indexed: 12/29/2024] Open
Abstract
Recently, neoadjuvant short-course radiation therapy (SCRT) has emerged as a valid treatment option for patients with locally advanced rectal cancer (LARC). We assessed SCRT plans using volumetric-modulated arc therapy (VMAT) with Halcyon and Infinity medical linear accelerators (Linacs) and compared the plan quality and delivery efficiency across all cases. Thirty patients who underwent preoperative SCRT for LARC at the hospital were randomly selected. Treatment plans were designed using the Halcyon and Infinity linac platforms, generating Halcyon VMAT plans (Group H) and Infinity VMAT plans (Group I). The target coverage, organ at risk (OAR) dose distribution, number of monitor units, treatment delivery time, and planning complexity of the two groups were compared and analyzed. Plan quality assurance was performed on the ArcCheck phantom. The overall plan quality regarding target volume and OARs was comparable for plans delivered on Halcyon and Infinity Agility machines, with each platform having advantages. Therefore, both radiotherapy platforms are very good options when selecting which technique to use in the clinic.
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Affiliation(s)
- Qiong Zhou
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Qi Wang
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Yongwu Li
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Chong Shen
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Xiaonan Sun
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
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25
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Pu W, Chen W, Jing H, Li J, Jiang Y, Li S, Wen W, Xu Z, Jin J. Total neoadjuvant therapy based on short-course radiotherapy versus standard long-course chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis of randomized controlled trials. Front Oncol 2024; 14:1515756. [PMID: 39801655 PMCID: PMC11718365 DOI: 10.3389/fonc.2024.1515756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/02/2024] [Indexed: 01/16/2025] Open
Abstract
Background We conducted the meta-analysis to compare the therapeutic effects of total neoadjuvant therapy (TNT) based on short-course radiotherapy followed by consolidation chemotherapy (SCRT/CCT) and long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) according to certain significant randomized controlled trials (RCTs). Methods The researchers retrieved several databases, including PubMed, Embase, Web of Science, and the Cochrane Library, to collect all the relevant literature published since the establishment of the databases until July 30, 2024, and then screened to determine the qualified literature and extracted the relevant information. Finally, RevMan 5.4 software was utilized to conduct the meta-analysis for determining the 95% confidence interval (CI) and pooled risk ratio (RR). There were 9 study indicators, including the pathologic complete remission (pCR) rate, tumor downstaging rate, R0 resection rate, sphincter preservation rate, disease-free survival (DFS), overall survival (OS), acute ≥3 grade toxicity rate, surgery complication rate, and distant recurrence rate. When moderate, even severe, heterogeneity was found, a random-effect model was applied; otherwise, a fixed-effect model was used for the analysis. Results A total of 6 eligible RCTs and 2259 participants were included in this meta-analysis. Compared with the standard LCCRT, TNT treatment on the basis of SCRT/CCT increased the pCR rate significantly [RR = 1.67, 95% CI (1.36, 2.04), P < 0.00001], especially in ≥ 4 cycles of the CCT arm [RR = 1.77, 95% CI: (1.41-2.23), p < 0.00001], and led to a similar tumor downstaging rate [RR = 0.99, 95% CI (0.85, 1.15), P = 0.92]. Moreover, survival outcomes, distant recurrence rate, and surgical indicators were comparable between the two groups. Conclusion For LARC patients, the SCRT/CCT regimen not only has a higher pCR rate, equivalent OS, and comparable additional indicators versus standard LCCRT but also shortens the treatment time, costs less, and improves patients' adherence to the innovative anti-tumor therapy; hence, with the concept of acute toxicity control, it could be further widely and safely utilized, especially in resource-limited settings. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024600180.
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Affiliation(s)
- Wenji Pu
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Medical Department of Shenzhen University, General Hospital of Shenzhen University, Academy of Clinical Medicine of Shenzhen University, Shenzhen, China
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Wenqi Chen
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Haiman Jing
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jishi Li
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Yong Jiang
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Shasha Li
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Weijie Wen
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Zhiyuan Xu
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jing Jin
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
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Baldini EH, Guadagnolo BA, Salerno KE, Chung P, Bishop AJ, Kalbasi A, Miah A, Bedi M, Harris JP, Petersen I, Gillham C, Wiltink LM, Alektiar KM, Haas RL, Kirsch DG. Hypofractionated Preoperative Radiation Should Not Yet Be Used as Standard of Care for Extremity and Truncal Soft Tissue Sarcoma. J Clin Oncol 2024; 42:4240-4245. [PMID: 39231372 DOI: 10.1200/jco.24.00238] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/01/2024] [Accepted: 07/15/2024] [Indexed: 09/06/2024] Open
Abstract
Hypofractionated radiation therapy regimens should not be used as standard of care for localized soft tissue sarcoma.
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Affiliation(s)
- Elizabeth H Baldini
- Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA
| | | | - Kilian E Salerno
- Radiation Oncology Branch, National Cancer Institute, Bethesda, MD
| | - Peter Chung
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Andrew J Bishop
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX
| | - Anusha Kalbasi
- Department of Radiation Oncology and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA
| | - Aisha Miah
- Department of Radiation Oncology, Royal Marsden Hospital, London, United Kingdom
| | - Meena Bedi
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI
| | - Jeremy P Harris
- Department of Radiation Oncology, University of California, Irvine, Orange, CA
| | - Ivy Petersen
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN
| | - Charles Gillham
- St Luke's Radiation Oncology Network, Rathgar, Dublin, Ireland
| | - Lisette M Wiltink
- Department of Radiotherapy, Leiden University Medical Center, Amsterdam, the Netherlands
| | - Kaled M Alektiar
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, NY
| | - Rick L Haas
- Department of Radiotherapy, Leiden University Medical Center, Amsterdam, the Netherlands
- Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - David G Kirsch
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada
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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.
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Affiliation(s)
| | | | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer
Center, New York, NY, United States
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28
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Bedrikovetski S, Traeger L, Seow W, Dudi-Venkata NN, Selva-Nayagam S, Penniment M, Sammour T. Oncological Outcomes and Response Rate After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Network Meta-Analysis Comparing Induction vs. Consolidation Chemotherapy vs. Standard Chemoradiation. Clin Colorectal Cancer 2024; 23:326-336.e9. [PMID: 38945765 DOI: 10.1016/j.clcc.2024.06.001] [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: 05/05/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 07/02/2024]
Abstract
TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.
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Affiliation(s)
- Sergei Bedrikovetski
- Department of Surgery, Colorectal Unit, Royal Adelaide Hospital, Adelaide, Australia; Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.
| | - Luke Traeger
- Department of Surgery, Colorectal Unit, Royal Adelaide Hospital, Adelaide, Australia; Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Warren Seow
- Department of Surgery, Colorectal Unit, Royal Adelaide Hospital, Adelaide, Australia
| | | | | | - Michael Penniment
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia
| | - Tarik Sammour
- Department of Surgery, Colorectal Unit, Royal Adelaide Hospital, Adelaide, Australia; Department of Surgical Specialties, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
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29
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Karam E, Fredon F, Eid Y, Muller O, Besson M, Michot N, Giger-Pabst U, Alves A, Ouaissi M. Review of definition and treatment of upper rectal cancer. Surg Oncol 2024; 57:102145. [PMID: 39342742 DOI: 10.1016/j.suronc.2024.102145] [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: 04/14/2024] [Revised: 08/14/2024] [Accepted: 09/19/2024] [Indexed: 10/01/2024]
Abstract
While the treatment of locally advanced lower and middle rectal cancer with total mesorectal excision (TME) after neoadjuvant therapy is now well defined, the treatment of locally advanced upper rectal cancer (LAURC) remains controversial. Although most teams and academic societies recommend upfront surgery (US) with partial mesorectal excision (PME), as this appears to be sufficient for these tumors, the literature remains conflicting regarding the additional use of neoadjuvant therapy and TME. Current recommendations for the treatment of LAURC do not reflect actual clinical practice. Notably, there is a paucity of published data specific to the treatment of LAURC since most of the data are from sub-analyses of different cohorts. Another important point responsible for the inconsistent data situation is the fact that the current definition of upper rectal cancer is based on anatomical criteria that are difficult to reproduce and therefore also differ between international professional societies. The aim of this review is to provide a deeper insight into the issues surrounding the treatment of LAURC based on an analysis of the current literature, including anatomic and embryologic data.
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Affiliation(s)
- Elias Karam
- Department of Digestive, Oncological, Endocrine, Hepatobiliary and Liver Transplant, Trousseau Hospital, University Hospital of Tours, France
| | - Fabien Fredon
- Department of Digestive Surgery, Dupuytren Hospital, University Hospital of Limoges, France
| | - Yassine Eid
- Department of Digestive Surgery, Caen Hospital, University Hospital of Caen, France
| | - Olivier Muller
- Department of Digestive, Oncological, Endocrine, Hepatobiliary and Liver Transplant, Trousseau Hospital, University Hospital of Tours, France
| | - Marie Besson
- Department of Radiology, Trousseau Hospital, University Hospital of Tours, France
| | - Nicolas Michot
- Department of Digestive, Oncological, Endocrine, Hepatobiliary and Liver Transplant, Trousseau Hospital, University Hospital of Tours, France
| | - Urs Giger-Pabst
- Fliedner Fachhochschule, University of Applied Sciences, Düsseldorf, Germany
| | - Arnaud Alves
- Fliedner Fachhochschule, University of Applied Sciences, Düsseldorf, Germany
| | - Mehdi Ouaissi
- Department of Digestive, Oncological, Endocrine, Hepatobiliary and Liver Transplant, Trousseau Hospital, University Hospital of Tours, France.
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30
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Lee PH, Kuo SH, Lin BR, Chen YH. The impact of radiation dose on chemoradiation outcomes and rectum preservation in locally advanced rectal cancer: A retrospective study. J Formos Med Assoc 2024:S0929-6646(24)00546-1. [PMID: 39613708 DOI: 10.1016/j.jfma.2024.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 09/12/2024] [Accepted: 11/12/2024] [Indexed: 12/01/2024] Open
Affiliation(s)
- Pei-Hsuan Lee
- Division of Radiation Oncology Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; National Taiwan University Cancer Center, Taipei, Taiwan
| | - Sung-Hsin Kuo
- Division of Radiation Oncology Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan; National Taiwan University Cancer Center, Taipei, Taiwan
| | - Been-Ren Lin
- Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yu-Hsuan Chen
- Division of Radiation Oncology Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; National Taiwan University Cancer Center, Taipei, Taiwan; Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
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31
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Anker CJ, Tchelebi LT, Selfridge JE, Jabbour SK, Akselrod D, Cataldo P, Abood G, Berlin J, Hallemeier CL, Jethwa KR, Kim E, Kennedy T, Lee P, Sharma N, Small W, Williams VM, Russo S. Executive Summary of the American Radium Society on Appropriate Use Criteria for Nonoperative Management of Rectal Adenocarcinoma: Systematic Review and Guidelines. Int J Radiat Oncol Biol Phys 2024; 120:946-977. [PMID: 38797496 DOI: 10.1016/j.ijrobp.2024.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 04/15/2024] [Accepted: 05/17/2024] [Indexed: 05/29/2024]
Abstract
For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values.
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Affiliation(s)
- Christopher J Anker
- Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, Vermont
| | - Leila T Tchelebi
- Northwell, New Hyde Park, New York; Department of Radiation Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
| | - J Eva Selfridge
- Division of Solid Tumor Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, New Jersey
| | - Dmitriy Akselrod
- Department of Radiology, University of Vermont Larner College of Medicine, Burlington, Vermont
| | - Peter Cataldo
- Department of Surgery, University of Vermont Larner College of Medicine, Burlington, Vermont
| | - Gerard Abood
- Department of Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois
| | - Jordan Berlin
- Division of Hematology Oncology, Department of Medicine Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
| | | | - Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, Washington
| | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, New Jersey
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, California
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, Pennsylvania
| | - William Small
- Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois
| | - Vonetta M Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, New York
| | - Suzanne Russo
- Department of Radiation Oncology, MetroHealth, Case Western Reserve University School of Medicine, Cleveland, Ohio
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32
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Zheng J, Liu Y, Wu J, Sun L, Zong D, He X. Dosimetric effects of the leaf positioning error of the halcyon(2.0) dual-layer multileaf collimator (MLC) on the rectal cancer radiotherapy. Med Dosim 2024; 50:120-127. [PMID: 39547897 DOI: 10.1016/j.meddos.2024.10.004] [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: 06/16/2024] [Revised: 09/27/2024] [Accepted: 10/09/2024] [Indexed: 11/17/2024]
Abstract
To study dosimetric effects of leaf positioning errors (LPEs) of the Halcyon(2.0) dual-layer MLC on the long-course chemoradiotherapy (LCCRT) with 45∼50.4 Gy in 25∼28 fractions for rectal cancer. Nine Halcyon(2.0)-based LCCRT plans of rectal cancer were retrospectively involved. Four types of LPEs were introduced: (1) Uniformly distributed dual-layer random LPEs (Dual-R); (2) Proximal-layer systemic LPEs (P-S); (3) Distal-layer systemic LPEs (D-S); (4) Dual-layer systemic LPEs (Dual-S). The sensitivities of D98%, D2% and the Equivalent Uniform Dose (EUD) of PTV to various LPEs were investigated as well as varying ranges of EUDs of OARs. The sensitivities of D98% and EUD of PTV to Dual-R was -0.65%/mm and -0.38%/mm; the sensitivities of both indices to the P-S and D-S were similar to each other, ranging from 1.92%/mm to 2.87%/mm; both indices were more sensitive to the Dual-S and values were 4.97%/mm and 3.84%/mm respectively. The EUD changes of the bladder, and left and right femoral heads were from -13.23% to 14.82%. Single-side systemic LPEs lower than 0.7 mm are acceptable for Halcyon(2.0)-based LCCRT, while dual-layer systemic LPEs lower than 0.4 mm are acceptable, considering relative changes of 2% for D98% of PTV as threshold.
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Affiliation(s)
- Jiajun Zheng
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 210009, China; School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 210024, China.
| | - Yatian Liu
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Jianfeng Wu
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Li Sun
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Dan Zong
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Xia He
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, 210009, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210024, China.
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Facondo G, Belotti F, Rotondi M, Vullo G, Fiorelli S, Mossa S, De Sanctis V, Osti MF. Long-term outcomes and prognostic factors of short-course radiotherapy (SCRT) in rectal cancer: a monocentric retrospective study. Discov Oncol 2024; 15:645. [PMID: 39531153 PMCID: PMC11557790 DOI: 10.1007/s12672-024-01529-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024] Open
Abstract
PURPOSE To evaluate efficacy and tolerance of short-course radiotherapy (SCRT) prior to possible chemotherapy (CHT) and surgery in 64 patients with locally advanced rectal cancer, in terms of acute and early late toxicity and survival outcomes with prognostic factors. METHODS Sixty-four patients affected by rectal tumor were treated from 2008 to 2023 radiation therapy, with a total dose of 25 Gy in 5 fractions. The Kaplan-Meier method was used to estimate the rates of overall survival (OS), cancer specific survival (CSS), local control (LC), disease free survival (DFS) and metastasis free survival (MFS). Univariate analysis for prognostic factors was performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios. Toxicity assessment has been considered in acute and in early late for gastrointestinal (GI), genitourinary (GU) districts. RESULTS Median follow-up was 49.6 months. The median OS was 65 months with 1-year, 2-year and 5-year OS at 90.6%, 77.7% and 60% respectively. CSS at the 1-year, 2-year and 5-year was 98.3%, 96.2% and 86.2% respectively. LC at 1-year, 2-year and 5-year was 93.4%, 89.4% and 87.2% respectively. DFS at the 1-year, 2-year and 5-year was 93.4%, 89% and 87% respectively. The status of lymph nodes at diagnosis was a prognostic factor in term of LC and DFS. Acute GI toxicity was G1 in 10 (15.6%) patients. Five (7.8%) patients had a G1 acute GU toxicity. Fifteen (23.4%) patients developed chronic GI toxicities. CONCLUSIONS SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.
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Affiliation(s)
- Giuseppe Facondo
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy.
| | - Federico Belotti
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy
| | - Margherita Rotondi
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy
| | - Gianluca Vullo
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy
| | - Silvia Fiorelli
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy
| | - Stefano Mossa
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy
| | - Vitaliana De Sanctis
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy
| | - Mattia Falchetto Osti
- Department of Medicine and Surgery and Translational Medicine, Sapienza University of Rome, Radiotherapy Oncology, St. Andrea Hospital, 00189, Rome, Italy
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Bercz A, Park BK, Pappou E, Nemirovsky D, Sarkar R, Yamner M, Omer D, Verheij FS, Alvarez J, Atri P, Reyngold M, Yaeger R, Wei IH, Wu A, Raj N, Widmar M, Hajj C, Kim MJ, Rao D, Nash GM, Williams V, Shia J, Segal NH, Diaz L, Ganesh K, Weiser MR, Gollub MJ, Paty PB, Horvat N, Zinovoy M, Roth O'Brien D, Sanchez-Vega F, Saltz LB, Crane CH, Cercek A, Gonen M, Garcia-Aguilar J, Smith JJ, Romesser PB. Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy. Ann Oncol 2024; 35:1003-1014. [PMID: 39266364 PMCID: PMC11513239 DOI: 10.1016/j.annonc.2024.07.729] [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: 04/23/2024] [Revised: 07/21/2024] [Accepted: 07/22/2024] [Indexed: 09/14/2024] Open
Abstract
BACKGROUND Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. PATIENTS AND METHODS This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. CONCLUSIONS While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.
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Affiliation(s)
- A Bercz
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - B K Park
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | - E Pappou
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA. https://twitter.com/EmmanouilPappou
| | - D Nemirovsky
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York
| | - R Sarkar
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - M Yamner
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - D Omer
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - F S Verheij
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - J Alvarez
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - P Atri
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York
| | - M Reyngold
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - R Yaeger
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York. https://twitter.com/RonaYaeger
| | - I H Wei
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - A Wu
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - N Raj
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York
| | - M Widmar
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - C Hajj
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - M J Kim
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - D Rao
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York
| | - G M Nash
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - V Williams
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - J Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York
| | - N H Segal
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York
| | - L Diaz
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York. https://twitter.com/ldiaz1971
| | - K Ganesh
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York
| | - M R Weiser
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - M J Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York
| | - P B Paty
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - N Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York
| | - M Zinovoy
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - D Roth O'Brien
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - F Sanchez-Vega
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York. https://twitter.com/fsanchezvega
| | - L B Saltz
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York
| | - C H Crane
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York
| | - A Cercek
- Department of Medicine, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York. https://twitter.com/AndreaCercek
| | - M Gonen
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York. https://twitter.com/gonen_mithat
| | - J Garcia-Aguilar
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA. https://twitter.com/DrGarciaAguilar
| | - J J Smith
- Department of Surgery, Colorectal Surgery Service, Memorial Sloan Kettering Cancer Center, New York, USA.
| | - P B Romesser
- Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York; Department of Medicine, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, USA.
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Kagawa Y, Ando K, Uemura M, Watanabe J, Oba K, Emi Y, Matsuhashi N, Izawa N, Muto O, Kinjo T, Takemasa I, Oki E. Phase II study of long-course chemoradiotherapy followed by consolidation chemotherapy as total neoadjuvant therapy in locally advanced rectal cancer in Japan: ENSEMBLE-2. Ann Gastroenterol Surg 2024; 8:1067-1075. [PMID: 39502728 PMCID: PMC11533031 DOI: 10.1002/ags3.12848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 06/13/2024] [Accepted: 07/14/2024] [Indexed: 11/08/2024] Open
Abstract
AIM To evaluate the feasibility and safety of total neoadjuvant therapy with long-course chemoradiotherapy followed by consolidation chemotherapy in Japanese patients with locally advanced rectal cancer. METHODS This prospective, multicenter, single-arm, phase II trial was conducted at 10 centers. The eligibility criteria included age ≥20 y, locally advanced rectal cancer within 12 cm of the anal verge, and cT3-4N0M or TanyN+M0 at diagnosis, enabling curative resection. The protocol treatment was capecitabine (1650 mg/m2/day)-based long-course chemoradiotherapy (50.4 Gy/28 fractions) and consolidation chemotherapy (CAPOX, four courses) followed by total mesorectal excision. Nonoperative management was allowed if a clinical complete response was achieved. The primary endpoint was the pathologic complete response rate. RESULTS Among 28 enrolled patients (19 men, 9 women; median age, 69.5 [41-79] y), the long-course chemoradiotherapy and consolidation chemotherapy completion rates were 100% and 96.4%, respectively. The clinical responses included clinical complete response, (35.7%, 10/28), near-complete response (28.6%, 8/28), and incomplete response (32.1%, 9/28). Total mesorectal excision and nonoperative management were performed in 21 and six patients, respectively. The final analysis included 21 patients. Five patients (23.8% [90% confidence interval 11.8%-41.8%]) achieved pathologic complete response, while 10 of 28 patients (35.7%) achieved a pathological complete response or a sustained clinical complete response. No treatment-related deaths occurred. Grade ≥3 adverse events included diarrhea (7.1%) and leukopenia (7.1%). CONCLUSION ENSEMBLE-2 demonstrated comparable pathologic complete response rates and well-tolerated safety of total neoadjuvant therapy with long-course chemoradiotherapy followed by consolidation chemotherapy in Japanese patients with locally advanced rectal cancer.
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Affiliation(s)
- Yoshinori Kagawa
- Department of Gastroenterological SurgeryOsaka General Medical CenterOsakaJapan
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Koji Ando
- Department of Surgery and ScienceKyushu UniversityFukuokaJapan
| | - Mamoru Uemura
- Department of Gastroenterological SurgeryOsaka UniversityOsakaJapan
| | - Jun Watanabe
- Department of Surgery, Gastroenterological CenterYokohama City University Medical CenterYokohamaJapan
- Department of Colorectal SurgeryKansai Medical UniversityOsakaJapan
| | - Koji Oba
- Department of BiostatisticsGraduate School of Medicine, the University of TokyoTokyoJapan
| | - Yasunori Emi
- Department of SurgerySaiseikai Fukuoka General HospitalFukuokaJapan
| | - Nobuhisa Matsuhashi
- Department of Gastroenterological and Pediatric SurgeryGifu University Graduate School of MedicineGifuJapan
| | - Naoki Izawa
- Department of Clinical OncologySt. Marianna University School of MedicineKawasakiJapan
| | - Osamu Muto
- Department of Clinical OncologyAkita Redcross HospitalAkitaJapan
| | - Tatsuya Kinjo
- Department of Digestive and General Surgery, Faculty of MedicineUniversity of the RyukyuOkinawaJapan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology, and ScienceSapporo Medical University School of MedicineSapporoJapan
| | - Eiji Oki
- Department of Surgery and ScienceKyushu UniversityFukuokaJapan
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Chehade L, Dagher K, Shamseddine A. Tailoring treatment for locally advanced rectal cancer. Cancer Treat Res Commun 2024; 41:100847. [PMID: 39418850 DOI: 10.1016/j.ctarc.2024.100847] [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: 07/09/2024] [Revised: 09/12/2024] [Accepted: 10/01/2024] [Indexed: 10/19/2024]
Abstract
The management of locally advanced rectal cancer (LARC) requires personalized treatment to improve outcomes and maintain quality of life. This narrative review examines the recent developments in management, focusing on non-operative management, radiotherapy choices or omission, chemotherapy sequencing, and the role of immunotherapy and brachytherapy boost. Non-operative management can be an option for select patients, and the use of long-course chemoradiation (LCCRT) with consolidation chemotherapy or brachytherapy boost has been shown to enhance rectal preservation rates. For patients requiring surgery, the choice between LCCRT and SCRT depends on the risk of local recurrence and patient preferences. MSI-high LARC patients benefit significantly from single-agent immunotherapy, and early clinical trials show promising results for the application of immunotherapy in MSS tumors. By stratifying patients based on individual and tumor risk factors, clinicians can tailor treatment plans to improve oncologic outcomes and quality of life for patients with LARC.
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Affiliation(s)
- Laudy Chehade
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute - NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Kristel Dagher
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute - NKBCI, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ali Shamseddine
- Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute - NKBCI, American University of Beirut Medical Center, Beirut, Lebanon..
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Scott AJ, Kennedy EB, Berlin J, Brown G, Chalabi M, Cho MT, Cusnir M, Dorth J, George M, Kachnic LA, Kennecke HF, Loree JM, Morris VK, Perez RO, Smith JJ, Strickland MR, Gholami S. Management of Locally Advanced Rectal Cancer: ASCO Guideline. J Clin Oncol 2024; 42:3355-3375. [PMID: 39116386 DOI: 10.1200/jco.24.01160] [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: 05/29/2024] [Accepted: 06/10/2024] [Indexed: 08/10/2024] Open
Abstract
ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual. ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines.Clinical Practice Guidelines and other guidance ("Guidance") provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more.PURPOSETo provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.METHODSA systematic review of the literature published from 2013 to 2023 was conducted to identify relevant systematic reviews, phase II and III randomized controlled trials (RCTs), and observational studies where applicable.RESULTSTwelve RCTs, two systematic reviews, and one nonrandomized study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.RECOMMENDATIONSFollowing assessment with magnetic resonance imaging, for patients with microsatellite stable or proficient mismatch repair locally advanced rectal cancer, total neoadjuvant therapy (TNT; ie chemoradiation [CRT] and chemotherapy) should be offered as initial treatment for patients with tumors located in the lower rectum and/or patients who are at higher risk for local and/or distant metastases. Patients without higher-risk factors may discuss chemotherapy with selective CRT depending on extent of response, TNT, or neoadjuvant long-course CRT or short-course radiation. For patients who are candidates for TNT, the preferred timing for chemotherapy is after radiation, and neoadjuvant long-course CRT is preferred over short-course radiation therapy (RT), however short-course RT may also be a viable treatment option depending on circumstances. Nonoperative management may be discussed as an alternative to total mesorectal excision for patients who have a clinical complete response to neoadjuvant therapy. For patients whose tumors are microsatellite instability-high or mismatch repair deficient, immunotherapy is recommended.Additional information is available at http://www.asco.org/gastrointestinal-cancer-guidelines.
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Affiliation(s)
| | | | | | - Gina Brown
- Imperial College London, London, United Kingdom
| | - Myriam Chalabi
- Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - May T Cho
- University of California Irvine Health, Irvine, CA
| | - Mike Cusnir
- Mount Sinai Comprehensive Cancer Center, Miami Beach, FL
| | | | - Manju George
- Paltown Development Foundation/COLONTOWN, Crownsville, MD
| | - Lisa A Kachnic
- Columbia University, Herbert Irving Comprehensive Cancer Center, New York, NY
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Lin ZY, Zhang P, Chi P, Xiao Y, Xu XM, Zhang AM, Qiu XF, Wu JX, Yuan Y, Wang ZN, Qu XJ, Li X, Nie X, Yang M, Cai KL, Zhang WK, Huang Y, Sun Z, Hou ZG, Ma C, Cheng FZ, Tao KX, Zhang T. Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial. Ann Oncol 2024; 35:882-891. [PMID: 38964714 DOI: 10.1016/j.annonc.2024.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/18/2024] [Accepted: 06/19/2024] [Indexed: 07/06/2024] Open
Abstract
BACKGROUND Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.
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Affiliation(s)
- Z Y Lin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - P Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - P Chi
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou
| | - Y Xiao
- Department of Surgery, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing
| | - X M Xu
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan
| | - A M Zhang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Hebei University, Baoding
| | - X F Qiu
- Department of Gastrointestinal Surgery, Zhongshan Hospital Xiamen University, Xiamen
| | - J X Wu
- Radiotherapy Department of Abdominal Tumors, Fujian Cancer Hospital, Fuzhou
| | - Y Yuan
- Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou
| | - Z N Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang
| | - X J Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang
| | - X Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - X Nie
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - M Yang
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - K L Cai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - W K Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Y Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou
| | - Z Sun
- Department of Surgery, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing
| | - Z G Hou
- Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China
| | - C Ma
- Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China
| | - F Z Cheng
- Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China
| | - K X Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
| | - T Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
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Williams B, Gupta A, Iype P, Woll S, Koller SE, Shin J, Cologne KG, Lee SW, Duldulao MP. Pathologic Outcomes of Short-Course and Long-Course Radiotherapy for Locally Advanced Rectal Cancers Treated With Total Neoadjuvant Therapy. Am Surg 2024; 90:2632-2639. [PMID: 38770756 DOI: 10.1177/00031348241256055] [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: 05/22/2024]
Abstract
INTRODUCTION Total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is now the standard of care. Randomized trials suggest the use of short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are oncologically equivalent. OBJECTIVE To describe pathologic outcomes after surgical resections of patients receiving SCRT versus LCRT as part of TNT for LARC. PARTICIPANTS All patients with LARC treated at a single tertiary hospital who underwent proctectomy after completing TNT were included. Patients were excluded if adequate details of TNT were not available in the electronic medical record. RESULTS A total of 53 patients with LARC were included. Thirty-nine patients (73.5%) received LCRT and 14 (26.4%) received SCRT. Forty-nine patients (92.5%) were clinical stage III (cN1-2) prior to treatment. The average lymph node yield after proctectomy was 20.9 for SCRT and 17.0 for LCRT (P = .075). Of the 49 patients with clinically positive nodes before treatment, 76.9% of those who received SCRT and 72.2% of those who received LCRT achieved pN0 disease after TNT. Additionally, there were no significant differences in rates of pathologic complete response between patients who received SCRT and LCRT, 7.1% and 12.8%, respectively (P = .565). CONCLUSION Pathologic outcomes of patients with LARC treated with SCRT or LCRT, as part of TNT, may be similar. Further prospective trials are needed to assess long-term clinical outcomes and to determine best treatment protocols.
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Affiliation(s)
- Brian Williams
- Division of Colorectal Surgery, Keck Hospital of USC, Los Angeles, CA, USA
| | - Abhinav Gupta
- Division of Colorectal Surgery, Keck Hospital of USC, Los Angeles, CA, USA
| | - Priyanka Iype
- Keck School of Medicine of USC, Los Angeles, CA, USA
| | - Sabrina Woll
- Keck School of Medicine of USC, Los Angeles, CA, USA
| | - Sarah E Koller
- Division of Colorectal Surgery, Keck Hospital of USC, Los Angeles, CA, USA
| | - Joongho Shin
- Division of Colorectal Surgery, Keck Hospital of USC, Los Angeles, CA, USA
| | - Kyle G Cologne
- Division of Colorectal Surgery, Keck Hospital of USC, Los Angeles, CA, USA
| | - Sang W Lee
- Division of Colorectal Surgery, Keck Hospital of USC, Los Angeles, CA, USA
| | - Marjun P Duldulao
- Division of Colorectal Surgery, Keck Hospital of USC, Los Angeles, CA, USA
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Giuliani J, Mandarà M, Muraro M, Rampello E, Franceschetto A, Fiorica F. "Defendit Numerus": A Pooled Analysis of 6145 Locally Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy. J Clin Med 2024; 13:5456. [PMID: 39336943 PMCID: PMC11432247 DOI: 10.3390/jcm13185456] [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: 07/25/2024] [Revised: 09/02/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
Objective: The optimal management of rectal cancer remains a subject of ongoing research. This meta-analysis of individual patient data assessed the benefit of chemoradiotherapy (fluorouracil-based) in local advanced rectal cancer: disease-free survival and overall survival. Methods: We pooled the data of 6145 patients from 24 studies of rectal cancer who received neoadjuvant radiotherapy with concomitant fluorouracil or capecitabine and surgery. The PRISMA 2020 abstract checklist was followed. Individual participant survival was reconstructed with an algorithm from published Kaplan-Meier curves. Results: The median OS was not reached; the mean survival time was 135.4 months (127.9-141.5). The median DFS was 176.9 months, and the mean disease-free survival time was 122.6 months (111.7-131.9). Conclusions: We provided a benchmark for future studies on rectal cancer treatment. The present results can be used in decision-making for locally advanced rectal cancer patients.
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Affiliation(s)
| | | | | | | | | | - Francesco Fiorica
- Department of Oncology, Azienda ULSS 9 Scaligera, 37122 Legnago, VR, Italy; (J.G.); (M.M.); (M.M.); (E.R.); (A.F.)
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Ritter AR, Prasad RN, Jhawar SR, Bazan JG, Gokun Y, Vudatala S, Diaz DA. Hypofractionated Radiation Therapy: A Cross-sectional Survey Study of US Radiation Oncologists. Am J Clin Oncol 2024; 47:434-438. [PMID: 38907597 DOI: 10.1097/coc.0000000000001114] [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: 06/24/2024]
Abstract
OBJECTIVES For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions. METHODS From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered. RESULTS A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns. CONCLUSIONS HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.
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Affiliation(s)
| | | | | | | | - Yevgeniya Gokun
- Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Sundari Vudatala
- Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH
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Emadi Torghabeh A, Aledavood SA, Soltani E, Akbari Oryani M, Akhlaghi S, Hosseini S, Fani Pakdel A, Taghizadeh Kermani A, Anvari K, Shahidsales S, Bahadorian S, Mashreghi Moghaddam S. Pathologic response evaluation of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy: a clinical trial. Front Oncol 2024; 14:1439730. [PMID: 39224811 PMCID: PMC11366607 DOI: 10.3389/fonc.2024.1439730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
Objective Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). Methods This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Results Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Conclusion Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. Clinical trial registration https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.
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Affiliation(s)
- Ali Emadi Torghabeh
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Ehsan Soltani
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahsa Akbari Oryani
- Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saeed Akhlaghi
- Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sare Hosseini
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Azar Fani Pakdel
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Kazem Anvari
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Shahrzad Bahadorian
- Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Chang CH, Chang SC, Jiang JK, Wang HS, Lan YT, Lin CC, Lin HH, Huang SC, Cheng HH, Yang YW, Lin YZ. Short-term outcomes of short- and long-course chemoradiotherapy before total mesorectal excision for locally advanced rectal tumors: A single-center study in Taiwan utilizing propensity score matching. J Chin Med Assoc 2024; 87:774-781. [PMID: 38915134 DOI: 10.1097/jcma.0000000000001127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/26/2024] Open
Abstract
BACKGROUND Locally advanced rectal tumors are typically treated with neoadjuvant chemoradiotherapy. Short-course chemoradiotherapy (SCRT, 2500 cGy in five fractions) is a convenient alternative to concurrent chemoradiotherapy with long-course radiotherapy (CCRT, 4500 cGy in 25 fractions) without sacrificing efficacy. We aimed to compare the short-term outcomes of SCRT and CCRT in patients with mid- and low- rectal tumors who underwent total mesorectal excision using real-world data. METHODS We retrospectively reviewed the data of patients with locally advanced rectal cancer who underwent radical resection after neoadjuvant chemoradiotherapy from 2011 to 2022. We analyzed the clinicopathological findings and prognostic factors for disease-free and overall survival in the SCRT and CCRT groups and compared the outcomes using propensity score matching. RESULTS Among the 66 patients in the two groups, no disparities were noted in the demographic features, pathological remission, or downstaging rates. Nonetheless, the SCRT group exhibited superior 3-year disease-free survival (81.8% vs 62.1%, p = 0.011), whereas the overall survival did not differ significantly between the two groups. The initial carcinoembryonic antigen (CEA) levels and neoadjuvant SCRT were associated with the recurrence rates [hazard ratio (HR) = 1.13-4.10; HR = 0.19-0.74], but the harvested lymph node count was not (HR = 0.51-1.97). CONCLUSION Among patients with locally advanced rectal cancer, SCRT combined with four cycles of FOLFOX was shown to enhance short-term disease-free survival. Factors impacting recurrence include the initial CEA level and SCRT, but not the harvested lymph node count.
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Affiliation(s)
- Chih-Hsien Chang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shih-Ching Chang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Jeng-Kai Jiang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Huann-Sheng Wang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yuan-Tzu Lan
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Hung-Hsin Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Sheng-Chieh Huang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Hou-Hsuan Cheng
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Wen Yang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yu-Zu Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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Manriquez E, Solé S, Silva J, Hermosilla JP, Romero R, Quezada-Diaz F. Deciphering the Dilemma: Choosing the Optimal Total Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer. Curr Oncol 2024; 31:4292-4304. [PMID: 39195303 PMCID: PMC11352987 DOI: 10.3390/curroncol31080320] [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: 06/18/2024] [Revised: 07/12/2024] [Accepted: 07/27/2024] [Indexed: 08/29/2024] Open
Abstract
Rectal cancer management has evolved significantly, particularly with neoadjuvant treatment strategies. This narrative review examines the development and effectiveness of these therapies for locally advanced rectal cancer (LARC), highlighting the historical quest that led to current neoadjuvant alternatives. Initially, trials showed the benefits of adding radiotherapy (RT) and chemotherapy (CT) to surgery, reducing local recurrence (LR). The addition of oxaliplatin to chemoradiotherapy (CRT) further improved outcomes. TNT integrates chemotherapy and radiotherapy preoperatively to enhance adherence, timing, and systemic control. Key trials, including PRODIGE 23, CAO/ARO/AIO 12, OPRA, RAPIDO, and STELLAR, are analyzed to compare short-course and long-course RT with systemic chemotherapy. The heterogeneity and difficulty in comparing TNT trials due to different designs and outcomes are acknowledged, along with their promising long-term results. On the other hand, it briefly discusses the potential for non-operative management (NOM) in select patients, a strategy gaining traction due to favorable outcomes in specific trials. As a conclusion, this review underscores the complexity of rectal cancer treatment, emphasizing individualized approaches considering patient preferences and healthcare resources. It also highlights the importance of interpreting impressive positive or negative results with caution due to the variability in study designs and patient populations.
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Affiliation(s)
- Erik Manriquez
- Complejo Asistencial Doctor Sotero del Rio, Santiago 8207257, Chile;
| | - Sebastián Solé
- Clínica IRAM, Santiago 7630370, Chile; (S.S.); (J.S.)
- Radiotherapy Oncology Program, School of Medicine, Universidad Diego Portales, Santiago 8370191, Chile; (J.P.H.); (R.R.)
| | - Javiera Silva
- Clínica IRAM, Santiago 7630370, Chile; (S.S.); (J.S.)
- Radiotherapy Oncology Program, School of Medicine, Universidad Diego Portales, Santiago 8370191, Chile; (J.P.H.); (R.R.)
| | - Juan Pablo Hermosilla
- Radiotherapy Oncology Program, School of Medicine, Universidad Diego Portales, Santiago 8370191, Chile; (J.P.H.); (R.R.)
- Hospital Dipreca, Santiago 7601003, Chile
| | - Rubén Romero
- Radiotherapy Oncology Program, School of Medicine, Universidad Diego Portales, Santiago 8370191, Chile; (J.P.H.); (R.R.)
- Hospital Dipreca, Santiago 7601003, Chile
| | - Felipe Quezada-Diaz
- Complejo Asistencial Doctor Sotero del Rio, Santiago 8207257, Chile;
- Clínica Universidad de los Andes, Santiago 7620157, Chile
- Center for Cancer Prevention and Control (CECAN), Santiago 8380453, Chile
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Asare E, Venner E, Batchelor H, Sanders J, Kunk P, Hedrick T, Hoang S, Reilley M, Le T, Friel C, Janowski EM. Outcomes associated with total neoadjuvant therapy with non-operative intent for rectal adenocarcinoma. Front Oncol 2024; 14:1374360. [PMID: 39156701 PMCID: PMC11328831 DOI: 10.3389/fonc.2024.1374360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 07/15/2024] [Indexed: 08/20/2024] Open
Abstract
Purpose/objectives To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma. Methods A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 - 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios. Results Of the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1 cm from the anal verge (range, 0.0 - 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 - 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p=0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival (p=0.033). Clinical response at earlier follow up points did not predict surgery- nor permanent ostomy-free survival. Conclusion These results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy.
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Affiliation(s)
- Ebenezer Asare
- Department of Radiation Oncology, University of Virginia, Charlottesville, VA, United States
| | - Emily Venner
- University of Virginia School of Medicine, Charlottesville, VA, United States
| | - Hanna Batchelor
- University of Virginia School of Medicine, Charlottesville, VA, United States
| | - Jason Sanders
- Department of Radiation Oncology, University of Virginia, Charlottesville, VA, United States
| | - Paul Kunk
- Department of Hematology/Oncology, University of Virginia, Charlottesville, VA, United States
| | - Traci Hedrick
- Department of Colorectal Surgery, University of Virginia, Charlottesville, VA, United States
| | - Sook Hoang
- Department of Colorectal Surgery, University of Virginia, Charlottesville, VA, United States
| | - Matthew Reilley
- Department of Hematology/Oncology, University of Virginia, Charlottesville, VA, United States
| | - Tri Le
- Department of Hematology/Oncology, University of Virginia, Charlottesville, VA, United States
| | - Charles Friel
- Department of Colorectal Surgery, University of Virginia, Charlottesville, VA, United States
| | - Einsley-Marie Janowski
- Department of Radiation Oncology, University of Virginia, Charlottesville, VA, United States
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González Del Portillo E, Couñago F, López-Campos F. Neoadjuvant treatment of rectal cancer: Where we are and where we are going. World J Clin Oncol 2024; 15:790-795. [PMID: 39071468 PMCID: PMC11271721 DOI: 10.5306/wjco.v15.i7.790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 04/28/2024] [Accepted: 05/17/2024] [Indexed: 07/16/2024] Open
Abstract
Locally advanced rectal cancer requires a multidisciplinary approach based on total neoadjuvant treatment with radiotherapy (RT) and chemotherapy (ChT), followed by deferred surgery. Currently, alternatives to the standard total neoadjuvant therapy (TNT) are being explored, such as new ChT regimens or the introduction of immunotherapy. With standard TNT, up to a third of patients may achieve a complete pathological response (CPR), potentially avoiding surgery. However, as of now, we lack predictive markers of response that would allow us to define criteria for a conservative organ strategy. The presence of mutations, genes, or new imaging tests is helping to define these criteria. An example of this is the diffusion coefficient in the diffusion-weighted sequence of magnetic resonance imaging and the integration of this imaging technique into RT treatment. This allows for the monitoring of the evolution of this coefficient over successive RT sessions, helping to determine which patients will achieve CPR or those who may require intensification of neoadjuvant therapy.
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Affiliation(s)
| | - Felipe Couñago
- Department of Radiation Oncology, GenesisCare Madrid, Madrid 28010, Spain
| | - Fernando López-Campos
- Department of Radiation Oncology, Hospital Universitario Ramón Y Cajal, Madrid 28034, Spain
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47
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Noticewala SS, Das P. Current State of Neoadjuvant Therapy for Locally Advanced Rectal Cancer. Cancer J 2024; 30:227-231. [PMID: 39042772 DOI: 10.1097/ppo.0000000000000725] [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 In locally advanced rectal cancer, neoadjuvant treatment has evolved from no preoperative treatment to the addition of radiation and systemic therapy and ultimately total neoadjuvant therapy. Total neoadjuvant therapy is the completion of preoperative radiation or chemoradiation and chemotherapy before surgery in order to maximize tumor response and improve survival outcomes. This review summarizes the literature of the neoadjuvant approaches related to locally advanced rectal cancer and highlights the nuances of selecting the appropriate treatment.
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Affiliation(s)
- Sonal S Noticewala
- From the Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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48
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Chalmers ZR, Roberts HJ, Wo JY. T3N0 Rectal Cancer: Radiation for All, None, or Some? Cancer J 2024; 30:232-237. [PMID: 39042773 DOI: 10.1097/ppo.0000000000000726] [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 The optimal management of T3N0 rectal cancer is an area of active debate that has withstood multiple decades of research. In this comprehensive review, we delve into the many nuances that come with treating T3N0 rectal cancer, particularly examining the role and evolution of radiation therapy. We review both the historical paradigms and latest advances in treatment and highlight the significance of precise preoperative staging. As the field continues to evolve, this review highlights a shift toward more tailored treatments, considering both patient goals and the desire for optimal oncologic outcomes. In the current era, clinical decision-making for T3N0 rectal cancer requires a patient-centric approach that balances effective therapy while minimizing undue side effects.
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Affiliation(s)
- Zachary R Chalmers
- From the Medical Scientist Training Program, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Hannah J Roberts
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Chapman WC, Hunt SR, Henke LE. Radiotherapy for Rectal Cancer: How Much is Enough? Clin Colon Rectal Surg 2024; 37:207-215. [PMID: 38882937 PMCID: PMC11178390 DOI: 10.1055/s-0043-1770709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/18/2024]
Abstract
Though resection has been the mainstay of treatment for nonmetastatic rectal cancer over the past century, radiation has become an increasingly integral component of care for locally advanced disease. Today, two predominant radiotherapy approaches-hyperfractionated chemoradiotherapy and "short-course" radiation-are widely utilized to reduce local recurrence and, in some cases, cure disease. Both have been incorporated into total neoadjuvant therapy (TNT) regimens and achieved excellent local control and superior complete response rates compared to chemoradiation alone. Additionally, initial results of "watch and wait" protocols utilizing either radiation modality have been promising. Yet, differences do exist; though short course is cheaper and more convenient for patients, recently published data may show superior complete response and local recurrence rates with chemoradiation. Ultimately, direct comparisons of short-course radiotherapy against chemoradiation within the TNT framework are needed to identify optimal radiation regimens in the treatment of locally advanced rectal cancer.
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Affiliation(s)
- William C. Chapman
- Department of Surgery, Section of Colon Rectal Surgery, Washington University School of Medicine, St. Louis, Missouri
- Department of Colon and Rectal Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio
| | - Steven R. Hunt
- Department of Surgery, Section of Colon Rectal Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Lauren E. Henke
- Department of Radiation Oncology, University Hospitals, Cleveland, Ohio
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50
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Pollom E, Sheth VR, Dawes AJ, Holden T. Nonoperative Management for Rectal Cancer. Cancer J 2024; 30:238-244. [PMID: 39042774 PMCID: PMC11486344 DOI: 10.1097/ppo.0000000000000727] [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] [Indexed: 07/25/2024]
Abstract
ABSTRACT The treatment paradigm for rectal cancer has been shifting toward de-escalated approaches to preserve patient quality of life. Historically, the standard treatment in the United States for locally advanced rectal cancer has standardly comprised preoperative chemoradiotherapy coupled with total mesorectal excision. Recent data challenge this "one-size-fits-all" strategy, supporting the possibility of omitting surgery for certain patients who achieve a clinical complete response to neoadjuvant therapy. Consequently, patients and their physicians must navigate diverse neoadjuvant options, often in the context of pursuing organ preservation. Total neoadjuvant therapy, involving the administration of all chemotherapy and radiation before total mesorectal excision, is associated with the highest rates of clinical complete response. However, questions persist regarding the optimal sequencing of radiation and chemotherapy and the choice between short-course and long-course radiation. Additionally, meticulous response assessment and surveillance are critical for selecting patients for nonoperative management without compromising the excellent cure rates associated with trimodality therapy. As nonoperative management becomes increasingly recognized as a standard-of-care treatment option for patients with rectal cancer, ongoing research in patient selection and monitoring as well as patient-reported outcomes is critical to guide personalized rectal cancer management within a patient-centered framework.
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Affiliation(s)
- Erqi Pollom
- Department of Radiation Oncology, Stanford School of Medicine
| | - Vipul R. Sheth
- Body MRI Division, Department of Radiology, Stanford School of Medicine
| | - Aaron J. Dawes
- Section of Colon & Rectal Surgery, Department of Surgery, Stanford University School of Medicine
- Stanford-Surgical Policy Improvement Research and Education Center, Department of Surgery, Stanford University School of Medicine
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