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Wang H, Zhang X, Leng B, Zhu K, Jiang S, Feng R, Dou X, Shi F, Xu L, Yue J. Efficacy and safety of MR-guided adaptive simultaneous integrated boost radiotherapy to primary lesions and positive lymph nodes in the neoadjuvant treatment of locally advanced rectal cancer: a randomized controlled phase III trial. Radiat Oncol 2024; 19:118. [PMID: 39267085 PMCID: PMC11395642 DOI: 10.1186/s13014-024-02506-6] [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: 03/14/2024] [Accepted: 08/12/2024] [Indexed: 09/14/2024] Open
Abstract
BACKGROUND In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. METHODS This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60-65 Gy in 25-28 fractions to primary lesions and positive lymph nodes; 50-50.4 Gy in 25-28 fractions to the pelvis) or intensity-modulated radiotherapy (50-50.4 Gy in 25-28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. DISCUSSION Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. TRIAL REGISTRATION The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).
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Affiliation(s)
- Haohua Wang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
- Cheeloo College of Medicine, Shandong University Cancer Center, Shandong University, Jinan, Shandong, China
| | - Xiang Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Boyu Leng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Kunli Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Shumei Jiang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Rui Feng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Xue Dou
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Fang Shi
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Lei Xu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China.
| | - Jinbo Yue
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China.
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Lee JH. Could neoadjuvant radiation dose escalation increase tumor response and recurrence-free survival in patients with locally advanced rectal cancer? Radiat Oncol J 2024; 42:167-168. [PMID: 39354818 PMCID: PMC11467481 DOI: 10.3857/roj.2024.00423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/16/2024] [Accepted: 07/22/2024] [Indexed: 10/03/2024] Open
Affiliation(s)
- Jong Hoon Lee
- Department of Radiation Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
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Soomro MY, Khan SR, Muhammad H, Ahmad S, Zehra N, Ali I, Samar MR, Hameed A, Moosajee M, Rashid YA. Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes. BMC Cancer 2024; 24:479. [PMID: 38627736 PMCID: PMC11020334 DOI: 10.1186/s12885-024-12241-6] [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: 01/13/2024] [Accepted: 04/09/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape. METHODS In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates-no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests. RESULTS We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0-1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups. CONCLUSION Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.
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Affiliation(s)
| | - Saqib Raza Khan
- Aga Khan University Hospital, Karachi, Pakistan.
- Department of Medical Oncology, Section of Oncology, Aga Khan University Hospital, Karachi, Pakistan.
| | | | - Sujjawal Ahmad
- Aga Khan University Centre for Regenerative Medicine and Stem Cell Research, Karachi, Pakistan
| | | | - Insia Ali
- Aga Khan University Hospital, Karachi, Pakistan
| | | | - Arif Hameed
- Aga Khan University Hospital, Karachi, Pakistan
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Ingle M, White I, Chick J, Stankiewicz H, Mitchell A, Barnes H, Herbert T, Nill S, Oelfke U, Huddart R, Ng-Cheng-Hin B, Hafeez S, Lalondrelle S, Dunlop A, Bhide S. Understanding the Benefit of Magnetic Resonance-guided Adaptive Radiotherapy in Rectal Cancer Patients: a Single-centre Study. Clin Oncol (R Coll Radiol) 2023; 35:e135-e142. [PMID: 36336579 DOI: 10.1016/j.clon.2022.10.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 09/01/2022] [Accepted: 10/12/2022] [Indexed: 11/06/2022]
Abstract
AIMS Neoadjuvant chemoradiotherapy followed by surgery is the mainstay of treatment for patients with rectal cancer. Standard clinical target volume (CTV) to planning target volume (PTV) margins of 10 mm are used to accommodate inter- and intrafraction motion of target. Treating on magnetic resonance-integrated linear accelerators (MR-linacs) allows for online manual recontouring and adaptation (MRgART) enabling the reduction of PTV margins. The aim of this study was to investigate motion of the primary CTV (CTVA; gross tumour volume and macroscopic nodes with 10 mm expansion to cover microscopic disease) in order to develop a simultaneous integrated boost protocol for use on MR-linacs. MATERIALS AND METHODS Patients suitable for neoadjuvant chemoradiotherapy were recruited for treatment on MR-linac using a two-phase technique; only the five phase 1 fractions on MR-linac were used for analysis. Intrafraction motion of CTVA was measured between pre-treatment and post-treatment MRI scans. In MRgART, isotropically expanded pre-treatment PTV margins from 1 to 10 mm were rigidly propagated to post-treatment MRI to determine overlap with 95% of CTVA. The PTV margin was considered acceptable if overlap was >95% in 90% of fractions. To understand the benefit of MRgART, the same methodology was repeated using a reference computed tomography planning scan for pre-treatment imaging. RESULTS In total, nine patients were recruited between January 2018 and December 2020 with T3a-T4, N0-N2, M0 disease. Forty-five fractions were analysed in total. The median motion across all planes was 0 mm, demonstrating minimal intrafraction motion. A PTV margin of 3 and 5mm was found to be acceptable in 96 and 98% of fractions, respectively. When comparing to the computed tomography reference scan, the analysis found that PTV margins to 5 and 10 mm only acceptably covered 51 and 76% of fractions, respectively. CONCLUSION PTV margins can be reduced to 3-5 mm in MRgART for rectal cancer treatment on MR-linac within an simultaneous integrated boost protocol.
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Affiliation(s)
- M Ingle
- The Royal Marsden Hospital NHS Trust, London, UK; The Institute of Cancer Research, London, UK.
| | - I White
- Guys and St Thomas NHS Trust, London, UK
| | - J Chick
- The Royal Marsden Hospital NHS Trust, London, UK
| | | | - A Mitchell
- The Royal Marsden Hospital NHS Trust, London, UK
| | - H Barnes
- The Royal Marsden Hospital NHS Trust, London, UK
| | - T Herbert
- The Royal Marsden Hospital NHS Trust, London, UK
| | - S Nill
- The Institute of Cancer Research, London, UK
| | - U Oelfke
- The Institute of Cancer Research, London, UK
| | - R Huddart
- The Royal Marsden Hospital NHS Trust, London, UK; The Institute of Cancer Research, London, UK
| | | | - S Hafeez
- The Royal Marsden Hospital NHS Trust, London, UK; The Institute of Cancer Research, London, UK
| | - S Lalondrelle
- The Royal Marsden Hospital NHS Trust, London, UK; The Institute of Cancer Research, London, UK
| | - A Dunlop
- The Royal Marsden Hospital NHS Trust, London, UK
| | - S Bhide
- The Royal Marsden Hospital NHS Trust, London, UK; The Institute of Cancer Research, London, UK
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Serra-Aracil X, Pericay C, Badia-Closa J, Golda T, Biondo S, Hernández P, Targarona E, Borda-Arrizabalaga N, Reina A, Delgado S, Vallribera F, Caro A, Gallego-Plazas J, Pascual M, Álvarez-Laso C, Guadalajara-Labajo HG, Mora-Lopez L. Short-term outcomes of chemoradiotherapy and local excision versus total mesorectal excision in T2-T3ab,N0,M0 rectal cancer: a multicentre randomised, controlled, phase III trial (the TAU-TEM study). Ann Oncol 2023; 34:78-90. [PMID: 36220461 DOI: 10.1016/j.annonc.2022.09.160] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/23/2022] [Accepted: 09/27/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND The standard treatment of T2-T3ab,N0,M0 rectal cancers is total mesorectal excision (TME) due to the high recurrence rates recorded with local excision. Initial reports of the combination of pre-operative chemoradiotherapy (CRT) and transanal endoscopic microsurgery (TEM) have shown reductions in local recurrence. The TAU-TEM study aims to demonstrate the non-inferiority of local recurrence and the improvement in morbidity achieved with CRT-TEM compared with TME. Here we describe morbidity rates and pathological outcomes. PATIENTS AND METHODS This was a prospective, multicentre, randomised controlled non-inferiority trial including patients with rectal adenocarcinoma staged as T2-T3ab,N0,M0. Patients were randomised to the CRT-TEM or the TME group. Patients included, tolerance of CRT and its adverse effects, surgical complications (Clavien-Dindo and Comprehensive Complication Index classifications) and pathological results (complete response in the CRT-TEM group) were recorded in both groups. Patients attended follow-up controls for local and systemic relapse. TRIAL REGISTRATION NCT01308190. RESULTS From July 2010 to October 2021, 173 patients from 17 Spanish hospitals were included (CRT-TEM: 86, TME: 87). Eleven were excluded after randomisation (CRT-TEM: 5, TME: 6). Modified intention-to-treat analysis thus included 81 patients in each group. There was no mortality after CRT. In the CRT-TEM group, one patient abandoned CRT, 1/81 (1.2%). The CRT-related morbidity rate was 29.6% (24/81). Post-operative morbidity was 17/82 (20.7%) in the CRT-TEM group and 41/81 (50.6%) in the TME group (P < 0.001, 95% confidence interval 42.9% to 16.7%). One patient died in each group (1.2%). Of the 81 patients in the CRT-TEM group who received the allocated treatment, 67 (82.7%) underwent organ preservation. Pathological complete response in the CRT-TEM group was 44.3% (35/79). In the TME group, pN1 were found in 17/81 (21%). CONCLUSION CRT-TEM treatment obtains high pathological complete response rates (44.3%) and a high CRT compliance rate (98.8%). Post-operative complications and hospitalisation rates were significantly lower than those in the TME group. We await the results of the follow-up regarding cancer outcomes and quality of life.
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Affiliation(s)
- X Serra-Aracil
- Coloproctology Unit, Parc Tauli University Hospital, Sabadell, Institut d'investigació i innovació Parc Tauli I3PT, Department of Surgery, Universitat Autònoma de Barcelona, Barcelona.
| | - C Pericay
- Medical Oncology Department, Parc Tauli University Hospital, Sabadell, Institut d'investigació i innovació Parc Tauli I3PT, Barcelona
| | - J Badia-Closa
- Coloproctology Unit, Parc Tauli University Hospital, Sabadell, Institut d'investigació i innovació Parc Tauli I3PT, Department of Surgery, Universitat Autònoma de Barcelona, Barcelona
| | - T Golda
- Colorectal Unit, General and Digestive Surgery Department, Bellvitge University Hospital, Barcelona
| | - S Biondo
- Colorectal Unit, General and Digestive Surgery Department, Bellvitge University Hospital, Barcelona
| | - P Hernández
- Colorectal Unit, General and Digestive Surgery Department, Santa Creu i Sant Pau University Hospital, Barcelona
| | - E Targarona
- Colorectal Unit, General and Digestive Surgery Department, Santa Creu i Sant Pau University Hospital, Barcelona
| | - N Borda-Arrizabalaga
- Servicio de Cirugía General y Digestiva, Hospital Universitario Donostia, Donostia, Gipuzkoa
| | - A Reina
- Unidad de Cirugía Colorrectal, Unidad de Gestión Clínica Cirugía y Area de Gestión Norte de Almería, Complejo Hospitalario Torrecárdenas, Almería
| | - S Delgado
- Colorectal Unit, General and Digestive Surgery Department, Mutua de Terrassa University Hospital, Terrassa, Barcelona
| | - F Vallribera
- Colorectal Unit, General and Digestive Surgery Department, Vall d'Hebron University Hospital, Departamento de Cirugía, Universitat Autònoma de Barcelona, Barcelona
| | - A Caro
- Colorectal Unit, General and Digestive Surgery Department, Joan XXIII University Hospital, Tarragona
| | - J Gallego-Plazas
- Medical Oncology, Hospital General Universitario de Elche (Alicante), Alicante
| | - M Pascual
- Colorectal Unit, General and Digestive Surgery Department, Del Mar University Hospital, Barcelona
| | - C Álvarez-Laso
- Colorectal Unit, General and Digestive Surgery Department, Hospital Universitario de Cabueñes, Gijón
| | - H G Guadalajara-Labajo
- Colorectal Unit, General and Digestive Surgery Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - L Mora-Lopez
- Coloproctology Unit, Parc Tauli University Hospital, Sabadell, Institut d'investigació i innovació Parc Tauli I3PT, Department of Surgery, Universitat Autònoma de Barcelona, Barcelona
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Ingle M, Blackledge M, White I, Wetscherek A, Lalondrelle S, Hafeez S, Bhide S. Quantitative analysis of diffusion weighted imaging in rectal cancer during radiotherapy using a magnetic resonance imaging integrated linear accelerator. Phys Imaging Radiat Oncol 2022; 23:32-37. [PMID: 35756883 PMCID: PMC9214864 DOI: 10.1016/j.phro.2022.06.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 05/16/2022] [Accepted: 06/02/2022] [Indexed: 11/25/2022] Open
Abstract
Background and purpose Magnetic resonance imaging integrated linear accelerator (MR-Linac) platforms enable acquisition of diffusion weighted imaging (DWI) during treatment providing potential information about treatment response. Obtaining DWI on these platforms is technically different from diagnostic magnetic resonance imaging (MRI) scanners. The aim of this project was to determine feasibility of obtaining DWI and calculating apparent diffusion coefficient (ADC) parameters longitudinally in rectal cancer patients on the MR-Linac. Materials and methods Nine patients undergoing treatment on MR-Linac had DWI acquired using b-values 0, 30, 150, 500 s/mm2. Gross tumour volume (GTV) and normal tissue was delineated on DWI throughout treatment and median ADC was calculated using an in-house tool (pyOsirix ®). Results Seven out of nine patients were included in the analysis; all demonstrated downstaging at follow-up. A total of 63 out of 70 DWI were analysed (7 excluded due to poor image quality). An increasing trend of ADC median for GTV (1.15 × 10-3 mm2/s interquartile range (IQ): 1.05-1.17 vs 1.59 × 10-3 mm2/s IQ: 1.37 - 1.64; p = 0.0156), correlating to treatment response. In comparison ADC median for normal tissue remained the same between first and last fraction (1.61 × 10-3 mm2/s IQ: 1.56-1.71 vs 1.67 × 10-3 mm2/s IQ: 1.37-2.00; p = 0.9375). Conclusions DWI assessment in rectal cancer patients on MR-Linac is feasible. Initial results provide foundations for further studies to determine DWI use for treatment adaptation in rectal cancer.
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Affiliation(s)
- Manasi Ingle
- The Royal Marsden Hospital NHS Trust, 203 Fulham Road, London SW3 6JJ, UK
- The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
| | - Matthew Blackledge
- The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
| | - Ingrid White
- Guys and St Thomas NHS Trust, Great Maze Pond, London SE1 9RT, UK
| | - Andreas Wetscherek
- The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
| | - Susan Lalondrelle
- The Royal Marsden Hospital NHS Trust, 203 Fulham Road, London SW3 6JJ, UK
- The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
| | - Shaista Hafeez
- The Royal Marsden Hospital NHS Trust, 203 Fulham Road, London SW3 6JJ, UK
- The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
| | - Shreerang Bhide
- The Royal Marsden Hospital NHS Trust, 203 Fulham Road, London SW3 6JJ, UK
- The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
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Delishaj D, Fumagalli IC, Ursino S, Cristaudo A, Colangelo F, Stefanelli A, Alghisi A, De Nobili G, D’Amico R, Cocchi A, Ardizzoia A, Soatti CP. Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature. World J Clin Cases 2021; 9:9077-9089. [PMID: 34786390 PMCID: PMC8567526 DOI: 10.12998/wjcc.v9.i30.9077] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 06/27/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2).
AIM To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques.
METHODS In December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors’ searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review.
RESULTS The main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047).
CONCLUSION Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications.
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Affiliation(s)
- Durim Delishaj
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
| | | | - Stefano Ursino
- Department of Radiation Oncology, Santa Chiara University Hospital, Pisa 56126, Italy
| | - Agostino Cristaudo
- Royal Preston Hospital, Lancashire Teaching Hospital- NHS Tust, Preston PR2 9HT, United Kingdom
| | - Francesco Colangelo
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
| | - Antonio Stefanelli
- Department of Radiation Oncology, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara 44124, Italy
| | - Alessandro Alghisi
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
| | - Giuseppe De Nobili
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
| | - Romerai D’Amico
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
| | - Alessandra Cocchi
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
| | - Antonio Ardizzoia
- Department of Clinical Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
| | - Carlo Pietro Soatti
- Department of Radiation Oncology, Alessandro Manzoni Hospital, Lecco 23900, Italy
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Gani C, Lo Russo M, Boeke S, Wegener D, Gatidis S, Butzer S, Boldt J, Mönnich D, Thorwarth D, Nikolaou K, Zips D, Nachbar M. A novel approach for radiotherapy dose escalation in rectal cancer using online MR-guidance and rectal ultrasound gel filling - Rationale and first in human. Radiother Oncol 2021; 164:37-42. [PMID: 34534612 DOI: 10.1016/j.radonc.2021.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/02/2021] [Accepted: 09/05/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Dose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling. METHODS A 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5 T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied. RESULTS Based on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four. CONCLUSION This novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation.
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Affiliation(s)
- Cihan Gani
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
| | - Monica Lo Russo
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - Simon Boeke
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - Daniel Wegener
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - Sergios Gatidis
- Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital, Eberhard Karls University, Tübingen, Germany
| | - Sarah Butzer
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - Jessica Boldt
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - David Mönnich
- Section for Biomedical Physics, Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - Daniela Thorwarth
- Section for Biomedical Physics, Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - Konstantin Nikolaou
- Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital, Eberhard Karls University, Tübingen, Germany
| | - Daniel Zips
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Marcel Nachbar
- Section for Biomedical Physics, Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
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9
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Intven M, de Mol van Otterloo S, Mook S, Doornaert P, de Groot-van Breugel E, Sikkes G, Willemsen-Bosman M, van Zijp H, Tijssen R. Online adaptive MR-guided radiotherapy for rectal cancer; feasibility of the workflow on a 1.5T MR-linac: clinical implementation and initial experience. Radiother Oncol 2021; 154:172-178. [DOI: 10.1016/j.radonc.2020.09.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 09/13/2020] [Accepted: 09/14/2020] [Indexed: 10/23/2022]
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Roeder F, Meldolesi E, Gerum S, Valentini V, Rödel C. Recent advances in (chemo-)radiation therapy for rectal cancer: a comprehensive review. Radiat Oncol 2020; 15:262. [PMID: 33172475 PMCID: PMC7656724 DOI: 10.1186/s13014-020-01695-0] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 10/21/2020] [Indexed: 12/18/2022] Open
Abstract
The role of radiation therapy in the treatment of (colo)-rectal cancer has changed dramatically over the past decades. Introduced with the aim of reducing the high rates of local recurrences after conventional surgery, major developments in imaging, surgical technique, systemic therapy and radiation delivery have now created a much more complex environment leading to a more personalized approach. Functional aspects including reduction of acute or late treatment-related side effects, sphincter or even organ-preservation and the unsolved problem of still high distant failure rates have become more important while local recurrence rates can be kept low in the vast majority of patients. This review summarizes the actual role of radiation therapy in different subgroups of patients with rectal cancer, including the current standard approach in different subgroups as well as recent developments focusing on neoadjuvant treatment intensification and/or non-operative treatment approaches aiming at organ-preservation.
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Affiliation(s)
- F Roeder
- Department of Radiotherapy and Radiation Oncology, Paracelsus Medical University, Landeskrankenhaus, Müllner Hautpstrasse 48, 5020, Salzburg, Austria.
| | - E Meldolesi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, UOC Radioterapia Oncologica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy
| | - S Gerum
- Department of Radiotherapy and Radiation Oncology, Paracelsus Medical University, Landeskrankenhaus, Müllner Hautpstrasse 48, 5020, Salzburg, Austria
| | - V Valentini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, UOC Radioterapia Oncologica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Roma, Italy
| | - C Rödel
- Department of Radiotherapy, University of Frankfurt, Frankfurt, Germany
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Hearn N, Atwell D, Cahill K, Elks J, Vignarajah D, Lagopoulos J, Min M. Neoadjuvant Radiotherapy Dose Escalation in Locally Advanced Rectal Cancer: a Systematic Review and Meta-analysis of Modern Treatment Approaches and Outcomes. Clin Oncol (R Coll Radiol) 2020; 33:e1-e14. [PMID: 32669228 DOI: 10.1016/j.clon.2020.06.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 05/15/2020] [Accepted: 06/05/2020] [Indexed: 01/10/2023]
Abstract
AIMS Improving pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy for locally advanced rectal cancer may facilitate surgery-sparing treatment paradigms. Radiotherapy boost has been linked to higher rates of pCR; however, outcomes in moderately escalated inverse-planning studies have not been systematically evaluated. We therefore carried out a systematic review and meta-analysis of radiation dose-escalation studies in the context of neoadjuvant therapy for locally advanced rectal cancer. MATERIALS AND METHODS A systematic search of Pubmed, EMBASE and Cochrane databases for synonyms of 'rectal cancer', 'radiotherapy' and 'boost' was carried out. Studies were screened for radiotherapy prescription >54 Gy. Prespecified quality assessment was carried out for meta-analysis inclusion suitability. Pooled estimates of pCR, acute toxicity (grade ≥3) and R0 resection rates were determined with random-effects restricted maximum-likelihood estimation. Heterogeneity was assessed with Higgins I2 and Cochran Q statistic. Subset analysis examined outcomes in modern inverse-planning studies. Meta-regression with permutation correction was carried out for each outcome against radiation dose, radiotherapy technique, boost technique, chemotherapy intensification and other patient- and treatment-related cofactors. RESULTS Forty-nine primary and three follow-up publications were included in the systematic review. Pooled estimates of pCR, toxicity and R0 resection across 37 eligible publications (n = 1817 patients) were 24.1% (95% confidence interval 21.2-27.4%), 11.2% (95% confidence interval 7.2-17.0%) and 90.7% (95% confidence interval 87.9-93.8%). Within inverse-planning studies (17 publications, n = 959 patients), these rates were 25.7% (95% confidence interval 21.0-31.1%), 9.8% (95% confidence interval 4.6-19.7%) and 95.3% (95% confidence interval 91.6-97.4%). Regression analysis did not identify any significant predictor of pCR (P > 0.05). CONCLUSIONS Radiotherapy dose escalation above 54 Gy is associated with high rates of pCR and does not seem to increase the risk of acute grade ≥3 toxicity events. pCR rates approaching 25% may be achievable utilising moderate escalation (54-60 Gy) with modern inverse-planning techniques; however, a clear dose-response relationship was not identified in regression analysis and additional evidence is awaited given the prevalence of heterogenous single-arm studies to date.
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Affiliation(s)
- N Hearn
- Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, Queensland, Australia; ICON Cancer Centre, Maroochydore, Queensland, Australia; University of the Sunshine Coast, Sippy Downs, Queensland, Australia.
| | - D Atwell
- Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, Queensland, Australia; ICON Cancer Centre, Maroochydore, Queensland, Australia; University of the Sunshine Coast, Sippy Downs, Queensland, Australia
| | - K Cahill
- Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, Queensland, Australia; University of the Sunshine Coast, Sippy Downs, Queensland, Australia
| | - J Elks
- University of the Sunshine Coast, Sippy Downs, Queensland, Australia
| | - D Vignarajah
- Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, Queensland, Australia; ICON Cancer Centre, Maroochydore, Queensland, Australia
| | - J Lagopoulos
- University of the Sunshine Coast, Sippy Downs, Queensland, Australia; Sunshine Coast Mind and Neuroscience - Thompson Institute, University of the Sunshine Coast, Birtinya, Queensland, Australia
| | - M Min
- Department of Radiation Oncology, Sunshine Coast University Hospital, Birtinya, Queensland, Australia; ICON Cancer Centre, Maroochydore, Queensland, Australia; University of the Sunshine Coast, Sippy Downs, Queensland, Australia
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12
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Yoon SM, Lee P, Raldow A. The Evolving Landscape of Neoadjuvant Radiation Therapy for Locally Advanced Rectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2020. [DOI: 10.1007/s11888-020-00451-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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13
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A comparative analysis between radiation dose intensification and conventional fractionation in neoadjuvant locally advanced rectal cancer: a monocentric prospective observational study. Radiol Med 2020; 125:990-998. [PMID: 32277332 DOI: 10.1007/s11547-020-01189-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 03/30/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE The potential role of neoadjuvant radiation dose intensification in locally advanced rectal cancer (LARC) is still largely debated. In the present study, a comparative analysis between radiation dose intensification and conventional fractionation was performed. MATERIALS AND METHODS In the current prospective observational study (protocol ID RT-03/2011), 56 patients diagnosed with LARC were enrolled between January 2013 and December 2016. More specifically, 25 patients underwent preoperative conventional radiation dose [i.e., 50.4 Gy in 28 fractions here defined as standard dose radiotherapy (SDR)-group 1], whereas 31 patients were candidate for radiation dose intensification (RDI) (i.e., 60 Gy in 30 fractions-group 2). The primary endpoint was the complete pathological response (pCR) rate. Secondary endpoints were postoperative complications and ChT-RT-related toxicity. RESULTS No statistical significance was observed in pCR rate (20.8% and 22.6% in SDR and RDI group, respectively, p = 0.342). Of contrast, the RDI group showed a significantly higher primary tumor downstaging in case of T3 tumor compared to SDR group (p = 0.049). Sphincter-preserving surgery was 84% and 93.5% in SDR and RDI groups, respectively (p = 0.25). All patients had R0 margins. No surgical-related death was recorded. No statistically significant difference was observed regarding surgical complications and incomplete mesorectal excision. Acute genitourinary toxicity was significantly higher in RDI group (p = 0.015). CONCLUSIONS The intensification of the neoadjuvant radiotherapy for LARC seems to produce a major pathological response in T3 tumors. The radiation dose intensification appears probably associated with a higher rate of genitourinary toxicity.
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İYİKESİCİ MS. Preliminary results of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in stage II-IV rectal cancer. ARCHIVES OF CLINICAL AND EXPERIMENTAL MEDICINE 2020. [DOI: 10.25000/acem.650341] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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15
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Kimura K, Beppu N, Doi H, Kataoka K, Yamano T, Uchino M, Ikeda M, Ikeuchi H, Tomita N. Impact of preoperative chemoradiotherapy using concurrent S-1 and CPT-11 on long-term clinical outcomes in locally advanced rectal cancer. World J Gastrointest Oncol 2020; 12:311-322. [PMID: 32206181 PMCID: PMC7081115 DOI: 10.4251/wjgo.v12.i3.311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 12/08/2019] [Accepted: 12/23/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Preoperative chemoradiotherapy regimens using a second drug for locally advanced rectal cancer are still under clinical investigation. AIM To investigate the clinical outcomes of patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy using tegafur/gimeracil/oteracil (S-1) plus irinotecan (CPT-11). METHODS This was a single-center retrospective study of 82 patients who underwent radical surgery for rectal cancer after chemoradiotherapy with S-1 (80 mg/m2/d), CPT-11 (60 mg/m2/d), and radiation (total 45 Gy) between 2009 and 2016. The median follow-up was 51 mo (range: 17-116 mo). RESULTS Twenty-nine patients (35.4%) had T3 or T4 rectal cancer with mesorectal fascia invasion, 36 (43.9%) had extramural vascular invasion, 24 (29.8%) had N2 rectal cancer and eight (9.8%) had lateral lymph node swelling. The relative dose intensity was 90.1% for S-1 and 92.9% for CPT-11. Seventy-nine patients (96.3%) underwent R0 resection. With regard to pathological response, 13 patients (15.9%) had a pathological complete response and 52 (63.4%) a good response (tumor regression grade 2/3). The 5-year local recurrence-free survival, relapse-free survival and overall survival rates were 90.1%, 72.5% and 91.3%, respectively. We analyzed the risk factors for local recurrence-free survival by Cox regression analysis and none were detected. Previously described risk factors such as T4 stage, mesorectal fascia invasion or lateral lymph node swelling were not detected as negative factors for local recurrence-free survival. CONCLUSION We demonstrated good compliance and favorable tumor regression in patients with locally advanced rectal cancer treated with preoperative S-1 and CPT-11.
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Affiliation(s)
- Kei Kimura
- Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Naohito Beppu
- Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Hiroshi Doi
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
- Department of Radiation Oncology, Kindai University Faculty of Medicine, Sayama, Osaka 589-8511, Japan
| | - Kozo Kataoka
- Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Tomoki Yamano
- Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Motoi Uchino
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Masataka Ikeda
- Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Hiroki Ikeuchi
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
| | - Naohiro Tomita
- Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
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Jin F, Luo H, Zhou J, Wu Y, Sun H, Liu H, Zheng X, Wang Y. Dose-time fractionation schedules of preoperative radiotherapy and timing to surgery for rectal cancer. Ther Adv Med Oncol 2020; 12:1758835920907537. [PMID: 32165928 PMCID: PMC7052459 DOI: 10.1177/1758835920907537] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 01/20/2020] [Indexed: 02/01/2023] Open
Abstract
Chemoradiotherapy (CRT) is extensively used prior to surgery for rectal cancer to provide significantly better local control, but the radiotherapy (RT), as the other component of CRT, has been subject to less interest than the drug component in recent years. With considerable developments in RT, the use of advanced techniques, such as intensity-modulated radiotherapy (IMRT) in rectal cancer, is garnering more attention nowadays. The radiation dose can be better conformed to the target volumes with possibilities for synchronous integrated boost without increased complications in normal tissue. Hopefully, both local recurrence and toxicities can be further reduced. Although those seem to be of interest, many issues remain unresolved. There is no international consensus regarding the radiation schedule for preoperative RT for rectal cancer. Moreover, an enormous disparity exists regarding the RT delivery. With the advent of IMRT, variations will likely increase. Moreover, time to surgery is also quite variable, as it depends upon the indication for RT/CRT in the clinical practices. In this review, we discuss the options and problems related to both the dose-time fractionation schedule and time to surgery; furthermore, it addresses the research questions that need answering in the future.
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Affiliation(s)
- Fu Jin
- Department of Radiation Oncology, Chongqing
University Cancer Hospital & Chongqing Cancer Institute & Chongqing
Cancer Hospital, Chongqing, People’s Republic of China
| | - Huanli Luo
- Department of Radiation Oncology, Chongqing
University Cancer Hospital & Chongqing Cancer Institute & Chongqing
Cancer Hospital, Chongqing, People’s Republic of China
| | - Juan Zhou
- Forensic Identification Center, Southwest
University of Political Science and Law, Chongqing, PR China
| | - Yongzhong Wu
- Department of Radiation Oncology, Chongqing
University Cancer Hospital & Chongqing Cancer Institute & Chongqing
Cancer Hospital, Chongqing, People’s Republic of China
| | - Hao Sun
- Department of Gynecologic Oncology, Chongqing
University Cancer Hospital & Chongqing Cancer Institute & Chongqing
Cancer Hospital, Chongqing, PR China
| | - Hongliang Liu
- Department of Anesthesiology, Chongqing
University Cancer Hospital & Chongqing Cancer Institute & Chongqing
Cancer Hospital, Chongqing, PR China
| | - Xiaodong Zheng
- Department of Science Education, Chongqing
University Cancer Hospital & Chongqing Cancer Institute & Chongqing
Cancer Hospital, Chongqing, PR China
| | - Ying Wang
- Department of Radiation Oncology, Chongqing
University Cancer Hospital & Chongqing Cancer Institute & Chongqing
Cancer Hospital, 181 Hanyu Road, Shapingba District, Chongqing 400030,
China
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17
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Sun XY, Cai SH, Xu L, Luo D, Qiu HZ, Wu B, Lin GL, Lu JY, Zhang GN, Xiao Y. Neoadjuvant chemoradiotherapy might provide survival benefit in patients with stage IIIb/IIIc locally advanced rectal cancer: A retrospective single-institution study with propensity score-matched comparative analysis. Asia Pac J Clin Oncol 2020; 16:142-149. [PMID: 32031326 DOI: 10.1111/ajco.13306] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 01/04/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME) are standard treatments of stage II/III locally advanced rectal cancer (LARC), currently. Here, we evaluated the oncological outcomes in LARC patients treated with NACRT compared to TME alone, and determined whether tumor regression grade (TRG) and pathologic response after NACRT was related to prognosis. METHODS This is a retrospective comparison of 358 LARC patients treated with either TME alone (non-NACRT group, n = 173) or NACRT plus TME (NACRT group, n = 185) during 2003-2013. Perioperative and oncologic outcomes, like overall survival (OS), disease-free survival (DFS) and recurrence were compared using 1:1 propensity score matching analysis. RESULTS A total of 133 patients were matched for the analysis. After a median follow-up of 45 months (8-97 months), the 5-year OS (NACRT vs non-NACRT: 75.42% vs 72.76%; P = 0.594) and 5-year DFS (NACRT vs non-NACRT: 74.25% vs 70.13%; P = 0.224) were comparable between NACRT and non-NACRT, whereas the 5-year DFS rate was higher in the NACRT group when only stage IIIb/IIIc patients were considered (NACRT vs. non-NACRT: 74.79% vs. 62.29%; P = 0.056). In the NACRT group of 185 patients, those with pCR/stage I (vs stage II/stage III disease) or TRG3/TRG4 disease (vs TRG0/TRG1/TRG2) had significantly better prognosis. CONCLUSION NACRT might provide survival benefit in patients with stage IIIb/IIIc locally advanced rectal cancer.
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Affiliation(s)
- Xi-Yu Sun
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Song-Hua Cai
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lai Xu
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dan Luo
- National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
| | - Hui-Zhong Qiu
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bin Wu
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guo-le Lin
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun-Yang Lu
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guan-Nan Zhang
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Xiao
- Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Abstract
Gastrointestinal cancers are bordered by radiosensitive visceral organs, resulting in a narrow therapeutic window. The search for more efficacious and tolerable therapies raises the possibility that proton beam therapy's (PBT) physical and dosimetric differences from conventional therapy may be better suited to treat both primary and recurrent disease, which carries its own unique challenges. Currently, the maximal efficacy of radiation plans for primary and recurrent anorectal cancer is constrained by delivery techniques and modalities which must consider feasibility challenges and toxicity secondary to exposure of organs at risk (OARs). Studies using volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) demonstrate that more precise dose delivery to target volumes improves local control rates and reduces complications. By reducing the low-to-moderate radiation dose-bath to bone marrow, small and large bowel, and skin, PBT may offer an improved side-effect profile. The potential to reduce toxicity, increase patient compliance, minimize treatment breaks, and enable dose escalation or hypofractionation is appealing. In cases where prognosis is favorable, PBT may mitigate long-term morbidity such as secondary malignancies, femoral fractures, and small bowel obstruction.
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Affiliation(s)
| | - Jennifer Y Wo
- Harvard Medical School, Boston, MA, USA.,Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
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19
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Huang CM, Huang CW, Ma CJ, Yeh YS, Su WC, Chang TK, Tsai HL, Juo SH, Huang MY, Wang JY. Predictive Value of FOLFOX-Based Regimen, Long Interval, Hemoglobin Levels and Clinical Negative Nodal Status, and Postchemoradiotherapy CEA Levels for Pathological Complete Response in Patients with Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy. JOURNAL OF ONCOLOGY 2020; 2020:9437684. [PMID: 32411245 PMCID: PMC7204332 DOI: 10.1155/2020/9437684] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 09/12/2019] [Accepted: 11/05/2019] [Indexed: 02/01/2023]
Abstract
We aimed to identify predictors of a pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) following a multimodality therapy. We retrospectively reviewed 236 patients with LARC treated with neoadjuvant chemoradiotherapy (CRT) followed by radical resection from January 2011 to December 2017. Patients were administered CRT, which comprised radiotherapy and chemotherapy with an oxaliplatin plus 5-fluorouracil- or fluoropyrimidine-based regimen. Clinical factors were correlated with treatment response. The multivariate logistic regression revealed that a negative nodal stage (odds ratio (OR) = 3.2, P=0.0135), a high hemoglobin level (>10 g/dL) during neoadjuvant CRT (OR = 3.067, P=0.0125), an oxaliplatin-containing neoadjuvant CRT (OR = 5.385, P=0.0044), a long interval (>8 weeks) between radiotherapy and surgery (OR = 1.135, P=0.0469), and a post-CRT CEA ≤2 ng/mL (OR = 2.891, P=0.0233) were the independent predictors of increased pCR rates. The prediction nomogram was developed according to the above independent variables. The concordance index was 0.74, and the calibration curve showed good agreement. In summary, negative nodal stages, high hemoglobin levels during treatment, oxaliplatin-containing neoadjuvant therapy, a long radiotherapy-surgery interval (>8 weeks), and post-CRT CEA levels ≤2 ng/mL were favorable predictors of a pCR. This prediction nomogram might be crucial for patients with LARC undergoing a multimodality therapy.
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Affiliation(s)
- Chun-Ming Huang
- Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Wen Huang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Jen Ma
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yung-Sung Yeh
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Trauma and Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Chih Su
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Kun Chang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiang-Lin Tsai
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Suh-Hang Juo
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yii Huang
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jaw-Yuan Wang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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20
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Fanelli GN, Loupakis F, Smyth E, Scarpa M, Lonardi S, Pucciarelli S, Munari G, Rugge M, Valeri N, Fassan M. Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients' Prognosis. Int J Surg Pathol 2019; 27:816-835. [PMID: 31416371 DOI: 10.1177/1066896919869477] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.
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Affiliation(s)
| | | | | | - Marco Scarpa
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Sara Lonardi
- Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | | | | | | | - Nicola Valeri
- Royal Marsden Hospital, London and Sutton, UK
- The Institute of Cancer Research, London and Sutton, UK
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21
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Wang J, Guan Y, Gu W, Yan S, Zhou J, Huang D, Tong T, Li C, Cai S, Zhang Z, Zhu J. Long-course neoadjuvant chemoradiotherapy with versus without a concomitant boost in locally advanced rectal cancer: a randomized, multicenter, phase II trial (FDRT-002). Radiat Oncol 2019; 14:215. [PMID: 31783766 PMCID: PMC6883699 DOI: 10.1186/s13014-019-1420-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022] Open
Abstract
Background This study was designed to explore whether an intensified chemoradiotherapy (CRT) led to a better clinical outcome in locally advanced rectal cancer. Methods Patients with stage II/III rectal cancer were randomly allocated to receive either pelvic intensity-modulated radiation therapy (IMRT) of 50 Gy/25Fx concurrently with capecitabine and oxaliplatin (Arm A), or pelvic radiation of 50 Gy/25Fx with a concomitant boost of 5 Gy to the primary lesion, followed by a cycle of XELOX 2 weeks after the end of CRT (Arm B). All patients were planned to receive a definitive operation 8 weeks after the completion of CRT and a total of six perioperative chemotherapy cycles of capecitabine and oxaliplatin regardless of pathological result. Pathological complete response (ypCR) was the primary endpoint. Results From February 2010 to December 2011, 120 patients from three centers were enrolled in this study. Ninety-five percent patients completed a full-dose chemoradiotherapy as planning. Then 53 and 57 patients received a radical surgery, and 8 and 14 cases were confirmed as ypCR in two groups (P = 0.157). The other 10 patients failed to receive a definitive resection because of unresectable disease. Similar toxicities were observed between two groups and more incision healing delay were found in Arm B (3 vs.13, P = 0.011). No statistical differences were observed in local-regional control (P = 0.856), disease-free survival (P = 0.349) and overall survival (P = 0.553). Mesorectal fascia (MRF) involvement was an independent prognostic factor for survival in multivariate analysis. Conclusions A concomitant boost to oxalipatin-combined preoperative chemoradiotherapy demonstrated a slightly higher pCR rate but delayed incision healing after surgery. The impact of MRF involvement on survival merits further investigations. Trial registration NCT01064999 (ClinicalTrials.gov).
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Affiliation(s)
- Jingwen Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Yun Guan
- Cyberknife Center, Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.,Neursurgical Institute of Fudan University, Shanghai, 200040, China
| | - Weilie Gu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Senxiang Yan
- Department of Radiation Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Juying Zhou
- Department of Radiation Oncology, 1st Affiliated Hospital of Suzhou (Soochow) University, Suzhou, China
| | - Dan Huang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Tong Tong
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Chao Li
- Department of Radiation oncology, Huashan Hospital, Fudan University, Shanghai, 200040, China.,Department of Cyberknife Center, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Sanjun Cai
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Zhen Zhang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. .,Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
| | - Ji Zhu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. .,Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
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22
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Jankarashvili N, Kakhadze S, Topeshashvili M, Turkiasvili L, Tchiabrishvili M. Neoadjuvant volumetric modulated arc radiochemotherapy with a simultaneous integrated boost technique compared to standard chemoradiation for locally advanced rectal cancer. Turk J Med Sci 2019; 49:1484-1489. [PMID: 31651118 PMCID: PMC7018366 DOI: 10.3906/sag-1812-185] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 08/07/2019] [Indexed: 12/23/2022] Open
Abstract
Background/aim The present study aimed to examine whether the combination of neoadjuvant volumetric modulated arc radiotherapy (VMAT) using simultaneous integrated boost (SIB-VMAT) techniques and chemotherapy with capecitabine is associated with better clinical and dosimetric outcomes compared to the standard treatment. Materials and methods The study included 59 patients with cT2–T4 rectal cancer. In the standard arm, patients (n = 37) were treated preoperatively with image-guided VMAT plus capecitabine. In the SIB arm, patients (n = 22) were treated with the SIB-VMAT technique plus capecitabine. All patients underwent radical surgical resection after neoadjuvant radiochemotherapy. Results In the standard arm, cT0N0 was reached in 12 patients (32.4%), primary tumor clinical downstaging was observed in 22 patients (59.5%), and disease stability was achieved in 3 patients (8.1%). In the SIB arm, cT0N0 was reached in 15 patients (68.2%), primary tumor clinical downstaging was observed in 6 patients (27.3%), and disease stability was achieved in 1 patient (4.5%) (P = 0.028). Complete pathological response was observed in 11 patients (29.7%) in the standard arm and in 13 patients (59.1%) in the SIB arm (P = 0.026). In the SIB arm mild diarrhea appeared in 59.1%, moderate in 40.9%, and severe in 0% of the cases. In the standard arm mild, moderate, and severe diarrhea rates were in 54.1%, 43.2%, and 2.7%, respectively. In the SIB arm mild, moderate, and severe cystitis appeared in 63.6%, 22.7%, and 13.6%, while in the standard group mild cystitis developed in 67.6%, moderate in 24.3%, and severe in 8.1%. Mild, moderate, and severe radiation dermatitis rates were 45.5%, 45.5%, and 9.1% in the SIB group and 40.5%, 48.6%, and 10.8% in the standard group, respectively. Conclusion The SIB-VMAT technique is effective and safe for irradiating locally advanced rectal cancer. Its effectiveness is expressed in higher clinical and pathological complete response rates and safety with the same rates of acute toxicity.
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Affiliation(s)
- Natalia Jankarashvili
- Department of Radiation Oncology, Academician F. Todua Medical Center-Research Institute of Clinical Medicine, Tbilisi, Georgia
| | - Sophio Kakhadze
- Department of Radiology, Academician F. Todua Medical Center-Research Institute of Clinical Medicine, Tbilisi, Georgia
| | - Maia Topeshashvili
- Department of Radiation Oncology, Academician F. Todua Medical Center-Research Institute of Clinical Medicine, Tbilisi, Georgia
| | - Lasha Turkiasvili
- Department of Radiation Oncology, Academician F. Todua Medical Center-Research Institute of Clinical Medicine, Tbilisi, Georgia
| | - Mariam Tchiabrishvili
- Department of Radiation Oncology, Academician F. Todua Medical Center-Research Institute of Clinical Medicine, Tbilisi, Georgia
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23
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Chiloiro G, Boldrini L, Meldolesi E, Re A, Cellini F, Cusumano D, Corvari B, Mantini G, Balducci M, Valentini V, Gambacorta MA. MR-guided radiotherapy in rectal cancer: First clinical experience of an innovative technology. Clin Transl Radiat Oncol 2019; 18:80-86. [PMID: 31341981 PMCID: PMC6630154 DOI: 10.1016/j.ctro.2019.04.006] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 04/03/2019] [Accepted: 04/05/2019] [Indexed: 12/15/2022] Open
Abstract
•This study represents one of the first reports of online MRgRT.•Integrated Low-field MR provides better anatomical visualization than CBCT or MVCT.•Better visualization of the target can help to reduce the margins from CTV to PTV.•MRgRT appears a feasible option in rectal cancer treatment offering potential benefits.•MRgRT represents a promising technology for rectal cancer management.
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Affiliation(s)
- Giuditta Chiloiro
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
| | - Luca Boldrini
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
| | - Elisa Meldolesi
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
| | - Alessia Re
- Unità di Radioterapia Oncologica, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy
| | - Francesco Cellini
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
| | - Davide Cusumano
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Fisica Sanitaria, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
| | - Barbara Corvari
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
| | - Giovanna Mantini
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
- Università Cattolica del Sacro Cuore, Istituto di Radiologia, Roma, Italy
| | - Mario Balducci
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
- Università Cattolica del Sacro Cuore, Istituto di Radiologia, Roma, Italy
| | - Vincenzo Valentini
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
- Università Cattolica del Sacro Cuore, Istituto di Radiologia, Roma, Italy
| | - Maria Antonietta Gambacorta
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
- Università Cattolica del Sacro Cuore, Istituto di Radiologia, Roma, Italy
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24
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Van den Begin R, Kleijnen JP, Engels B, Philippens M, van Asselen B, Raaymakers B, Reerink O, De Ridder M, Intven M. Tumor volume regression during preoperative chemoradiotherapy for rectal cancer: a prospective observational study with weekly MRI. Acta Oncol 2018; 57:723-727. [PMID: 29157069 DOI: 10.1080/0284186x.2017.1400689] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE Few data is available on rectal tumor shrinkage during preoperative chemoradiotherapy (CRT). This regression pattern is interesting to optimize timing of dose escalation on the tumor. METHODS Gross tumor volumes (GTV) were contoured by two observers on magnetic resonance imaging (MRI) obtained before, weekly during, 2-4 weeks after, and 7-8 weeks after a 5-week course of concomitant CRT for rectal cancer. RESULTS Overall, 120 MRIs were acquired in 15 patients. A statistically significant tumor volume reduction is seen from the first week, and between any two time points (p < .007). At the end of CRT, 46.3% of the initial tumor volume remained, and 32.4% at time of surgery. PTV measured 61.2% at the end of treatment. Tumor shrinkage is the fastest in the beginning of treatment (26%/week), slows down to 7%/week in the last 2 weeks of CRT, and finally to 1.3%/week in the last 5 weeks before surgery. CONCLUSIONS The main rectal tumor regression occurs during CRT course itself, and mostly in the first half, with shrinking speed decreasing over the course. This suggests that a sequential boost is preferably done after the elective fields, yielding an average PTV-reduction of 39%. A simultaneous integrated boost strategy could benefit from adaptive planning during the course.
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Affiliation(s)
| | - Jean-Paul Kleijnen
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Benedikt Engels
- Department of Radiotherapy, UZ Brussel, Vrije Universiteit Brussel, Belgium
| | - Marielle Philippens
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Bram van Asselen
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Bas Raaymakers
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Onne Reerink
- Department of Radiotherapy, Isala Clinics, Zwolle, The Netherlands
| | - Mark De Ridder
- Department of Radiotherapy, UZ Brussel, Vrije Universiteit Brussel, Belgium
| | - Martijn Intven
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
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25
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Balyasnikova S, Vuong T, Wale A, Chong I, Rutten H, Brown G. Session 3: Boosting primary and recurrent rectal cancer: how far can we push the radiotherapy envelope? Colorectal Dis 2018; 20 Suppl 1:88-91. [PMID: 29878674 DOI: 10.1111/codi.14086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Neoadjuvant pelvic radiotherapy is widely used for patients with advanced rectal cancer. The trade-off between dose and response is well-established, yet little consensus remains on the precise methods of delivery and doses given in different scenarios. Professor Vuong reviews the evidence base and trial evidence on the escalation of radiotherapy dose and the methods of achieving this.
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Affiliation(s)
| | - T Vuong
- Jewish General Hospital, Montreal, Quebec, Canada
| | - A Wale
- The Royal Marsden NHS Foundation Trust, London, UK
| | - I Chong
- The Royal Marsden NHS Foundation Trust, London, UK
| | - H Rutten
- Catharina Ziekenhuis, Eindhoven, The Netherlands
| | - G Brown
- The Royal Marsden NHS Foundation Trust, London, UK.,Imperial College London, London, UK
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26
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Corvò R, Pastrone I, Scolaro T, Marcenaro M, Berretta L, Chiara S. Radiotherapy and Oral Capecitabine in the Preoperative Treatment of Patients with Rectal Cancer: Rationale, Preliminary Results and Perspectives. TUMORI JOURNAL 2018; 89:361-7. [PMID: 14606636 DOI: 10.1177/030089160308900403] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Preoperative radiotherapy alone or combined with chemotherapy increases the chances of tumor downstaging and down-sizing and facilitates sphincter-sparing surgical procedures, thereby improving survival and quality of life. Though several innovative agents are being investigated in combination with radiotherapy, 5-fluorouracil in continuous infusion remains the common schedule used in the preoperative chemoradiation setting. However, the protracted venous infusion of 5-fluorouracil requires specialized pumps and long-term venous access, which makes patients susceptible to infections or thrombosis. To overcome the 5-fluorouracil infusion-related problems, oral 5-fluorouracil precursors and inhibitors of 5-fluorouracil degradation have been developed and explored. These include oral fluoropyrimidines such as tegafur (ftora-fur), uracil plus tegafur (UFT), S-1, eniluracil and the oral carbamate capecitabine. Phase I trials have demonstrated the feasibility of the capecitabine-radiotherapy combination with respect to the bolus or infusion 5-fluorouracil-radiation approach and have defined the optimal dose of capecitabine during radiotherapy (825 mg/m2/day through a bid administration). Severe hand-foot syndrome occurred in 7-15% of patients, representing the most commonly observed toxicity. It is noteworthy that severe diarrhea with capecitabine during radiotherapy was not common. Leukopenia frequently occurred but was mild and reversible. Phase II trials, although limited in number, have evidenced a high probability of pathological complete response (up to 31%) with capecitabine and radiation, with an increased probability of sphincter-sparing surgical procedures. Although it is too early to assess whether oral capecitabine will be able to replace iv 5-fluorouracil in combination with preoperative radiotherapy, the NSABP will address this question in a large randomized trial. Finally, phase I-II trials evaluating escalating doses of capecitabine associated with oxaliplatin or irinotecan with radiotherapy are being carried out to assess the maximum-dose tolerance and efficacy in the preoperative setting. It is likely that these new chemoradiation associations might increase rectal cancer clearance, hopefully without increasing toxicity.
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Affiliation(s)
- Renzo Corvò
- National Institute for Cancer Research, Genoa, Italy.
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27
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Grillo-Ruggieri F, Mantello G, Cardinali M, Fabbietti L, Fenu F, Montisci M, Bracci R, Delprete S, Guerrieri M, Marmorale C. Down-Staging after Two Different Preoperative Chemoradiation Schedules in Rectal Cancer. TUMORI JOURNAL 2018; 89:164-7. [PMID: 12841664 DOI: 10.1177/030089160308900211] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Aims To compare preoperative downstaging, toxicity and sphincter-saving procedures obtained with preoperative radiotherapy and two different concomitant chemotherapy schedules. Methods From February 1997 to August 2001, 68 consecutive patients were treated with external radiotherapy (5040 cGy in 28 fractions) and concomitant chemotherapy: group a) 36 patients (10T2, 19T3, 7T4, 25 adenocarcinoma and 11 mucinous histology) were treated with cis-diamminedichloroplatinum bolus + 5-fluorouracil continuous infusion; group b) 32 patients (14 T2, 18 T3, 27 adenocarcinoma and 5 mucinous histology) were treated with 5-fluorouracil bolus ± mitomycin C. The interval between the end of radiotherapy and surgery ranged from 4 to 9 weeks. Results Group a) Overall downstaging was 63.9%. Longitudinal shrinkage of the neoplasm allowed conservative surgery in 6 of 11 patients with a pre-chemoradiation tumor location ≤3 cm from the external anal ring. When patients with adenocarcinoma (25/36) were studied separately from patients with mucinous histology, 7/25 patients (28%) were found to have no microscopic evidence of residual tumor (pTO); 8/25 (32%) were found to have only rare isolated cancer cells (pTmic); only 7/25 patients (28%) were found to have no change. Overall, 72% patients had downstaging. In contrast, only 5/11 (45.5%) of mucinous tumors had partial downstaging and 6/11 (54.5%) no downstaging at all. Group b) Overall downstaging was 46.9%. When patients with adenocarcinoma (27/32) were studied separately, 7/27 (26%) were found to have pTO, 3/27 (11.1%) pTmic, and 13/27 (48.1%) no change. Only 1/5 (20%) of mucinous tumors had downstaging and 4/5 (80%) had no downstaging at all. Overall toxicity was comparable among groups a and b, except for lower hematologic and gastrointestinal G3-4 toxicity observed in group a. Conclusions The overall response allowed conservative surgery in 56 (82.3%) of the 68 patients. Continuous infusion of 5-fluorouracil and diamminedichloroplatinum as a radipsensitizer determined better results in group a than group b (63.9% downstaging vs 46.9% even with a higher incidence of mucinous histology). Mucinous histology, for a definitely lower response rate, could benefit from an even more aggressive approach.
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28
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Osti MF, Valeriani M, Masoni L, Tombolini V, Enrici RM. Neoadjuvant Chemoradiation for Locally Advanced Carcinoma of the Rectum. TUMORI JOURNAL 2018; 90:303-9. [PMID: 15315310 DOI: 10.1177/030089160409000308] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Aims and background The aim of this paper is to confirm the efficacy to reduce incidence of relapses, to increase rates of conservative radical surgery and eventually survival of concomitant neo-adjuvant chemo-radiotherapy. Methods From January 1992 to October 1999, 140 stage II (50.7%) and III (49.3%) patients with adenocarcinoma of the rectum were treated with concomitant chemoradiotherapy followed by radical surgery. Treatment consisted of 25 fractions of 180 cGy (5 days per week), for a total dose of 45 Gy on the whole pelvis. Chemotherapy consisted of 5-FU (350 mg/m2) and leucoverin (10 mg/m2) in bolus for 5 days on days 1-5 and 29-33 of radiation. After an interval of 4-6 weeks, all patients were submitted to surgery. Results The median follow-up was 48 months (median, 1-97). At 5 years the overall survival was 71.3% and relapse-free survival was 79.4%. The rate of local control was 90%. Twenty-two (15.7%) patients developed distant metastases. All patients underwent surgery: 26 (18.6%) local excision, 79 (56.4%) anterior resection, 33 (23.6%) abdomino-perineal resection, and 2 (1.4%) Hartmann resection. Consequently, 107 cases (75.4%) underwent conservative surgery. At the time of surgery, 34 patients had negative specimens (24.3%), 45 were in stage I (32.2%), 31 in stage II (22.1%), 32 in stage III (21.4%). The incidence of any grade 3 acute toxicity (WHO) was 5% diarrhea, 20% tenesmus and 11.4% myelosuppression. Conclusions The results of this study confirm good tolerance, minor surgery-related complications and efficacy of this regimen on local and distant disease control, with a high percentage of sphincter-saving surgery.
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Affiliation(s)
- Mattia F Osti
- Institute of Radiology, University La Sapienza, Rome, Italy
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29
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Serra-Aracil X, Pericay C, Golda T, Mora L, Targarona E, Delgado S, Reina A, Vallribera F, Enriquez-Navascues JM, Serra-Pla S, Garcia-Pacheco JC. Non-inferiority multicenter prospective randomized controlled study of rectal cancer T 2-T 3s (superficial) N 0, M 0 undergoing neoadjuvant treatment and local excision (TEM) vs total mesorectal excision (TME). Int J Colorectal Dis 2018; 33:241-249. [PMID: 29234923 DOI: 10.1007/s00384-017-2942-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/28/2017] [Indexed: 02/04/2023]
Abstract
PURPOSE The standard treatment of rectal adenocarcinoma is total mesorectal excision (TME), in many cases requires a temporary or permanent stoma. TME is associated with high morbidity and genitourinary alterations. Transanal endoscopic microsurgery (TEM) allows access to tumors up to 20 cm from the anal verge, achieves minimal postoperative morbidity and mortality rates, and does not require an ostomy. The treatment of T2, N0, and M0 cancers remains controversial. Preoperative chemoradiotherapy (CRT) in association with TEM reduces local recurrence and increases survival. The TAU-TEM study aims to demonstrate the non-inferiority of the oncological outcomes and the improvement in morbidity and quality of life achieved with TEM compared with TME. METHODS Prospective, multicenter, randomized controlled non-inferiority trial includes patients with rectal adenocarcinoma less than 10 cm from the anal verge and up to 4 cm in size, staged as T2 or T3-superficial N0-M0. Patients will be randomized to two areas: CRT plus TEM or radical surgery (TME). Postoperative morbidity and mortality will be recorded and patients will complete the quality of life questionnaires before the start of treatment, after CRT in the CRT/TEM arm, and 6 months after surgery in both arms. The estimated sample size for the study is 173 patients. Patients will attend follow-up controls for local and systemic relapse. CONCLUSIONS This study aims to demonstrate the preservation of the rectum after preoperative CRT and TEM in rectal cancer stages T2-3s, N0, M0 and to determine the ability of this strategy to avoid the need for radical surgery (TME). TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01308190. Número de registro del Comité de Etica e Investigación Clínica (CEIC) del Hospital universitario Parc Taulí: TAU-TEM-2009-01.
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Affiliation(s)
- X Serra-Aracil
- Coloproctology Unit, General and Digestive Surgery Department, Parc Tauli University Hospital, Universitat Autònoma de Barcelona, Parc Tauli s/n. 08208, Sabadell, Spain.
| | - C Pericay
- Medical Oncology Department, Parc Tauli University Hospital, Universitat Autònoma de Barcelona, Sabadell, Spain
| | - T Golda
- Coloproctology Unit, General and Digestive Surgery Department, Bellvitge University Hospital, Barcelona, Spain
| | - L Mora
- Coloproctology Unit, General and Digestive Surgery Department, Parc Tauli University Hospital, Universitat Autònoma de Barcelona, Parc Tauli s/n. 08208, Sabadell, Spain
| | - E Targarona
- General and Digestive Surgery Department, Santa Creu and Sant Pau University Hospital, Barcelona, Spain
| | - S Delgado
- General and Digestive Surgery Department, Clinic University Hospital, Barcelona, Spain
| | - A Reina
- Coloproctology Unit, General and Digestive Surgery Department, Torrecardenas University Hospital, Almeria, Spain
| | - F Vallribera
- Coloproctology Unit, General and Digestive Surgery Department, Vall d'Hebron University Hospital, Barcelona, Spain
| | | | - S Serra-Pla
- Coloproctology Unit, General and Digestive Surgery Department, Parc Tauli University Hospital, Universitat Autònoma de Barcelona, Parc Tauli s/n. 08208, Sabadell, Spain
| | - J C Garcia-Pacheco
- Coloproctology Unit, General and Digestive Surgery Department, Parc Tauli University Hospital, Universitat Autònoma de Barcelona, Parc Tauli s/n. 08208, Sabadell, Spain
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30
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Definitive chemoradiotherapy with low-dose continuous 5-fluorouracil reduces hematological toxicity without compromising survival in esophageal squamous cell carcinoma patients. Clin Transl Radiat Oncol 2017; 9:12-17. [PMID: 29594245 PMCID: PMC5862669 DOI: 10.1016/j.ctro.2017.12.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 11/28/2017] [Accepted: 12/20/2017] [Indexed: 12/19/2022] Open
Abstract
Background and purpose To compare chemoradiotherapy (CRT) with low-dose continuous 5-fluorouracil (5FU) to CRT with 5FU+cisplatin (CDDP) for esophageal squamous cell carcinoma (ESCC) in a retrospective cohort study. Methods and materials We reviewed the cases of Stage I–IV ESCC patients who underwent definitive CRT in 2000–2014. Concomitant chemotherapy was one of the three regimens: (1) high-dose intermittent 5FU and CDDP (standard-dose FP: SDFP), (2) low-dose continuous 5FU and CDDP (LDFP), or (3) low-dose continuous 5FU (LD5FU). The general selection criteria for chemotherapy were: SDFP for patients aged <70 yrs; LDFP for those aged 70–74 yrs; LD5FU for those aged ≥75 yrs or with performance status (PS) ≥3. Propensity scores were derived with chemotherapy (LD5FU vs. 5FU+CDDP) as the dependent variable. Results In a multivariate analysis, chemotherapy (LD5FU vs. SDFP, p = .24; LDFP vs. SDFP, p = .52) did not affect the overall survival (OS). LD5FU caused significantly less grade 3–4 leukopenia (9%) compared to SDFP (47%) and LDFP (44%) (p < .001). In a propensity-matched analysis, LD5FU affected neither OS (HR 1.06; 95%CI 0.55–2.05; p = .87) nor progression-free survival (HR 0.95, 95%CI 0.50–1.81; p = .87). Conclusion CRT with low-dose continuous 5FU may be a less toxic option for elderly ESCC patients.
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Abstract
Colorectal cancer is one of the major leading causes of death in both men and women. The successful management of colon or rectal cancer demands a multidisciplinary approach. In the last few years, significant improvement has been noticed in the management of localized rectal cancer to reduce local recurrence and obtain complete pathological response following appropriate surgical steps, if necessary. Implementation of neoadjuvant therapy not only enhances disease control, it may also ensure sphincter preserving procedures or organ-preserving options. This article principally concentrates on the current neoadjuvant treatment for locally advanced rectal cancer and the prognostic outcomes of such therapy, including a discussion on the historical perspective.
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Affiliation(s)
- Shahab Ahmed
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Cathy Eng
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Van Wickle JD, Paulson ES, Landry JC, Erickson BA, Hall WA. Adaptive radiation dose escalation in rectal adenocarcinoma: a review. J Gastrointest Oncol 2017; 8:902-914. [PMID: 29184696 DOI: 10.21037/jgo.2017.07.06] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Total mesorectal excision (TME) after neoadjuvant chemoradiotherapy (CRT) has offered superior control for patients with locally advanced rectal cancer, but can carry a quality of life cost. Fortunately, some patients achieve a complete response after CRT alone without the added morbidity caused by surgery. Efforts to increase fidelity of radiation treatment planning and delivery may allow for escalated doses of radiotherapy (RT) with limited off-target toxicity and elicit more pathological complete responses (pCR) to CRT thereby sparing more rectal cancer patients from surgery. In this review, methods of delivering escalated RT boost above 45-50.4 Gy are discussed including: 3D conformal, intensity-modulated radiotherapy (IMRT), and brachytherapy. Newly developed adaptive boost strategies and imaging modalities used in RT planning and response evaluation such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are also discussed.
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Affiliation(s)
| | - Eric S Paulson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Jerome C Landry
- Department of Radiation Oncology, Emory University, Atlanta, GA, USA
| | - Beth A Erickson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - William A Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
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Serra-Aracil X, Pericay C, Mora-Lopez L, Garcia Pacheco JC, Latorraca JI, Ocaña-Rojas J, Casalots A, Ballesteros E, Navarro-Soto S. Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0 rectal tumors. Local recurrence, complete clinical and pathological response. Cir Esp 2017; 95:199-207. [PMID: 28411888 DOI: 10.1016/j.ciresp.2017.03.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 01/22/2017] [Accepted: 03/20/2017] [Indexed: 01/14/2023]
Abstract
INTRODUCTION The association of preoperative chemoradiotherapy and transanal endoscopic surgery in T2 and superficial T3 rectal cancers presents promising results in selected patients. The main objective is to evaluate the long-term loco-regional and systemic recurrence and, as secondary objectives, to provide results of postoperative morbidity and the correlation between complete clinical and pathological response. METHODS This is a retrospective observational study including a consecutive series of patients with T2-T3 superficial rectal cancer, N0, M0 who refused radical surgery (2008-2016). The treatment consisted of preoperative chemotherapy (5-fluorouracil or capecitabine) combined with radiotherapy (50, 4Gy) and transanal endoscopic surgery after 8weeks. Preoperative, surgical, pathological and long-term oncologic results were analyzed. RESULTS Twenty-four patients were included in the study. Two of them required rescue radical surgery for unfavorable pathological results. A local recurrence (4.5%) was observed and 2patients presented systemic recurrence (9%), with a median follow-up of 45 months. A complete clinical tumor response was achieved in 12 patients (50%), and complete pathological tumor response in 9 patients (37.5%). Postoperative complications were observed in 5 patients (20.8%), and they were mild except one. There was no postoperative mortality. CONCLUSIONS In this stage of rectal cancer, our results seem to support this strategy, mainly when a complete pathological response is achieved. The complete clinical tumor response does not coincide with the pathological tumor response. Randomized prospective studies should be performed to standardize this treatment.
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Affiliation(s)
- Xavier Serra-Aracil
- Unidad de Coloproctología, Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España.
| | - Carlos Pericay
- Servicio de Oncología Médica, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona , Sabadell (Barcelona), España
| | - Laura Mora-Lopez
- Unidad de Coloproctología, Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España
| | - Juan Carlos Garcia Pacheco
- Unidad de Coloproctología, Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España
| | - José Isaac Latorraca
- Unidad de Coloproctología, Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España; Servicio de Oncología Médica, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona , Sabadell (Barcelona), España; Servicio de Anatomía-Patológica, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España; Servicio de Radiología, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España
| | - Julio Ocaña-Rojas
- Servicio de Oncología Médica, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona , Sabadell (Barcelona), España
| | - Alex Casalots
- Servicio de Anatomía-Patológica, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España
| | - Eva Ballesteros
- Servicio de Radiología, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España
| | - Salvador Navarro-Soto
- Unidad de Coloproctología, Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Parc Taulí, Universidad Autónoma de Barcelona, Sabadell (Barcelona), España
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An update on the multimodality of localized rectal cancer. Crit Rev Oncol Hematol 2016; 108:23-32. [PMID: 27931837 DOI: 10.1016/j.critrevonc.2016.10.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 07/12/2016] [Accepted: 10/12/2016] [Indexed: 12/15/2022] Open
Abstract
New strategies have reduced the local recurrence (LR) rate and extended the duration of overall survival (OS) in patients with localized rectal cancer (RC) in recent decades. The mainstay of curative treatment remains radical surgery; however, downsizing the tumor by neo-adjuvant chemo-radiotherapy and adjuvant cytotoxic therapy for systemic disease has shown significant additional benefit. The standardization of total mesorectal excision (TME), radiation treatment (RT) dose and fractionation, and optimal timing and sequencing of treatment modalities with the use of prolonged administration of fluoropyrimidine concurrent with RT have significantly decreased the rates of LR in locally advanced rectal cancer (LARC) patients. This review focuses on the optimization of multi-modality therapies in patients with localized RC.
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Li J, Liu H, Hu J, Liu S, Yin J, Du F, Yuan J, Lv B. New tumor regression grade for rectal cancer after neoadjuvant therapy and radical surgery. Oncotarget 2016; 6:42222-31. [PMID: 26540466 PMCID: PMC4747220 DOI: 10.18632/oncotarget.6008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Accepted: 10/09/2015] [Indexed: 11/25/2022] Open
Abstract
In this retrospective study, we defined a new tumor regression grade (NTRG), which we used to evaluate the prognosis of patients with locally advanced rectal cancer who received neoadjuvant therapy and then underwent radical surgery between June 2004 and October 2011. Calculated as the TRG plus a lymph node score, the NTRG was determined for 347 patients: NTRG 0, 46 patients (13.3%); NTRG 1, 63 (18.2%); NTRG 2, 183 (52.7%); NTRG 3, 30 (8.6%); NTRG 4, 25 (7.2%). Among this group, 45 (97.8%) NTRG 0, 56 (88.9%) NTRG 1, 148 (80.9%) NTRG 2, 24 (66.7%) NTRG 3, and 10 (40.0%) NTRG 4 patients experienced 5-year disease-free survival. We also found that NTRG is significantly associated with 5-year local recurrence, distant metastasis and disease-free survival (P = 0.004, 0.007 and 0.039, respectively). The NTRG may thus be an independent prognostic factor for oncologic outcomes in rectal cancer patients after neoadjuvant therapy and radical surgery, but this conclusion must be validated in randomized trials.
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Affiliation(s)
- Jun Li
- General Surgery Department, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, People's Republic of China
| | - Hao Liu
- General Surgery Department, 2nd Affiliated Hospital of Jilin University, Changchun, People's Republic of China
| | - Junjie Hu
- Gastrointestinal Tumor Surgery, Hubei Cancer Hospital, Wuhan, People's Republic of China
| | - Sai Liu
- Surgical Department of Gastrointestinal Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Jie Yin
- General Surgery Department, Xuzhou Central Hospital, Xuzhou, People's Republic of China
| | - Feng Du
- Internal Medicine-Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Jiatian Yuan
- General Surgery Department, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, People's Republic of China
| | - Bo Lv
- General Surgery Department, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, People's Republic of China
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Cui J, Fang H, Zhang L, Wu YL, Zhang HZ. Advances for achieving a pathological complete response for rectal cancer after neoadjuvant therapy. Chronic Dis Transl Med 2016; 2:10-16. [PMID: 29063019 PMCID: PMC5643745 DOI: 10.1016/j.cdtm.2016.06.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Indexed: 12/21/2022] Open
Abstract
Neoadjuvant therapy has become the standard of care for locally advanced mid-low rectal cancer. Pathological complete response (pCR) can be achieved in 12%–38% of patients. Patients with pCR have the most favorable long-term outcomes. Intensifying neoadjuvant therapy and extending the interval between termination of neoadjuvant treatment and surgery may increase the pCR rate. Growing evidence has raised the issue of whether local excision or observation rather than radical surgery is an alternative for patients who achieve a clinical complete response after neoadjuvant therapy. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for pCR of rectal cancer in the modern era.
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Affiliation(s)
- Jian Cui
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Hui Fang
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Lin Zhang
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Yun-Long Wu
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Hai-Zeng Zhang
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
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Pericay C, Serra-Aracil X, Ocaña-Rojas J, Mora-López L, Dotor E, Casalots A, Pisa A, Saigí E. Further evidence for preoperative chemoradiotherapy and transanal endoscopic surgery (TEM) in T2-3s,N0,M0 rectal cancer. Clin Transl Oncol 2015; 18:666-71. [DOI: 10.1007/s12094-015-1415-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 09/23/2015] [Indexed: 12/21/2022]
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Issa N, Murninkas A, Schmilovitz-Weiss H, Agbarya A, Powsner E. Transanal Endoscopic Microsurgery After Neoadjuvant Chemoradiotherapy for Rectal Cancer. J Laparoendosc Adv Surg Tech A 2015; 25:617-24. [PMID: 26258267 DOI: 10.1089/lap.2014.0647] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Radical rectal resection following neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer is accompanied by relatively high morbidity. Local excision of rectal cancer may be more appropriate for some frail patients with severe comorbidities. Transanal endoscopic microsurgery (TEM), consisting of local excision of selected rectal cancers, has been associated with low rates of postoperative complications. Because neoadjuvant CRT for rectal cancer may be associated with increased complications, the suitability of TEM following CRT is still unclear. In this study we aimed to assess the clinical outcomes of patients undergoing TEM following neoadjuvant CRT. PATIENTS AND METHODS This study retrospectively analyzed all patients undergoing TEM for malignant rectal tumor in our institution between 2004 and 2010. They were divided into those who received CRT (CRT group) and those without CRT (non-CRT group). Demographics and clinical data were compared. RESULTS Forty-four of 97 patients who underwent TEM were included: 13 CRT and 31 non-CRT. Age, comorbidities, and the duration of the procedure were similar for both groups. There were no significant group differences in tumor diameter (2.1 cm [range, 0.5-3.5 cm] and 2.9 cm [range, 0.5-4.2 cm], respectively; P=.125) or distance of the lower part of the tumor from the anal verge (6.7 cm [range, 5-10 cm] and 7.7 cm [range, 5-15 cm], respectively; P=.285). Two non-CRT patients had peritoneal entry, and 1 of them underwent protective ileostomy because of insecure rectal defect closure. One non-CRT patient underwent a re-operation for postoperative bleeding. The other perioperative complications were minor and included urinary retention requiring catheter placement (2 patients in each group), pulmonary edema (1 non-CRT patient), and pneumonia (1 non-CRT patient). All complications were managed conservatively. There was no wound disruption, major complication, or mortality in either group. CONCLUSIONS With proper patient selection, TEM can be performed safely following CRT, without major complication or increased postoperative morbidity.
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Affiliation(s)
- Nidal Issa
- 1 Department of Surgery B, Rabin Medical Center , Petah-Tikva, Israel .,2 Sackler School of Medicine, Tel-Aviv University , Tel Aviv, Israel
| | - Alejandro Murninkas
- 1 Department of Surgery B, Rabin Medical Center , Petah-Tikva, Israel .,2 Sackler School of Medicine, Tel-Aviv University , Tel Aviv, Israel
| | - Hemda Schmilovitz-Weiss
- 2 Sackler School of Medicine, Tel-Aviv University , Tel Aviv, Israel .,3 Department of Gastroenterology, Hasharon Hospital, Rabin Medical Center , Petah-Tikva, Israel
| | - Abed Agbarya
- 4 Oncology Community Unit, Northern District, Clalit Health Services , Nazareth, Israel
| | - Eldad Powsner
- 1 Department of Surgery B, Rabin Medical Center , Petah-Tikva, Israel .,2 Sackler School of Medicine, Tel-Aviv University , Tel Aviv, Israel
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Abstract
Multimodality therapy for gastrointestinal (GI) cancers carries considerable risk for toxicity; even single-modality radiation therapy in this population carries with it a daunting side effect profile. Supportive care can certainly mitigate some of the morbidity, but there remain numerous associated acute and late complications that can compromise the therapy and ultimately the outcome. Gastrointestinal cancers inherently occur amid visceral organs that are particularly sensitive to radiotherapy, creating a very narrow therapeutic window for aggressive cell kill with minimal normal tissue damage. Radiation therapy is a critical component of locoregional control, but its use has historically been limited by toxicity concerns, both real and perceived. Fundamental to this is the fact that long-term clinical experience with radiation in GI cancers derives almost entirely from 2-dimensional radiation (plain x-ray-based planning) and subsequently 3-dimensional conformal radiation. The recent use of intensity-modulated photon-based techniques is not well represented in most of the landmark chemoradiation trials. Furthermore, the elusive search for efficacious but tolerable local therapy in GI malignancies raises the possibility that proton radiotherapy's physical and dosimetric differences relative to conventional therapy may make it better suited to the challenge. In many sites, local recurrences after chemoradiation pose a particular challenge, and reirradiation in these sites may be done successfully with proton radiotherapy.
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Predictors of Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer: A Multicenter Study. Clin Colorectal Cancer 2015; 14:291-5. [PMID: 26433487 DOI: 10.1016/j.clcc.2015.06.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2015] [Revised: 05/29/2015] [Accepted: 06/08/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) for rectal cancer is associated with better long-term outcomes, and is used as an early indicator of response to novel agents. To assess the rate and predictors of pCR, we performed a retrospective multicenter study involving 5 Canadian cancer centers. PATIENTS AND METHODS Cancer registries identified consecutive patients with locally advanced rectal adenocarcinoma from the Tom Baker Cancer Centre, Cross Cancer Institute, British Columbia Cancer Agency, Ottawa Hospital Cancer Centre, and the Dr H. Bliss Murphy Cancer Centre who received fluoropyrimidine-based CRT and had curative intent surgery from 2005 to 2012. Patient, tumor, and therapy characteristics were correlated with response. RESULTS Of the 891 patients included, 885 patients had pCR data available. Of the included patients, 161 (18.2%) had a pCR to CRT, and 724 (81.8%) did not. Patients with a pCR had a lower pretreatment carcinoembryonic antigen (CEA) level, and higher hemoglobin level in univariate analysis. In multivariable analysis, statin use at baseline (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.02-2.92; P = .04), lower pretreatment CEA level (OR, 1.03; 95% CI, 1.01-1.06; P = .03), and distance closer to anal verge (OR, 1.07; 95% CI, 1.01-1.15; P = .04) were significant predictors of pCR. The 3-year disease-free survival was 86% in those with a pCR versus 62.5% in those without a pCR (P < .0001) and pCR was associated with improved overall survival (hazard ratio, 0.29; 95% CI, 0.17-0.51; P < .0001). CONCLUSION Lower pretreatment CEA level, proximity to anal verge, and statin use are predictors of pCR in our large retrospective cohort. Clinical trials to investigate statins combined with neoadjuvant CRT might be warranted.
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Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer. Cancer Genet 2015; 208:319-26. [PMID: 25963525 DOI: 10.1016/j.cancergen.2015.03.010] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 01/23/2015] [Accepted: 03/11/2015] [Indexed: 12/24/2022]
Abstract
Neoadjuvant chemoradiotherapy (nCRT) may lead to complete tumor regression in rectal cancer patients. Prediction of complete response to nCRT may allow a personalized management of rectal cancer and spare patients from unnecessary radical total mesorectal excision with or without sphincter preservation. To identify a gene expression signature capable of predicting complete pathological response (pCR) to nCRT, we performed a gene expression analysis in 25 pretreatment biopsies from patients who underwent 5FU-based nCRT using RNA-Seq. A supervised learning algorithm was used to identify expression signatures capable of predicting pCR, and the predictive value of these signatures was validated using independent samples. We also evaluated the utility of previously published signatures in predicting complete response in our cohort. We identified 27 differentially expressed genes between patients with pCR and patients with incomplete responses to nCRT. Predictive gene signatures using subsets of these 27 differentially expressed genes peaked at 81.8% accuracy. However, signatures with the highest sensitivity showed poor specificity, and vice-versa, when applied in an independent set of patients. Testing previously published signatures on our cohort also showed poor predictive value. Our results indicate that currently available predictive signatures are highly dependent on the sample set from which they are derived, and their accuracy is not superior to current imaging and clinical parameters used to assess response to nCRT and guide surgical intervention.
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Rectal Cancer. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Burbach JPM, den Harder AM, Intven M, van Vulpen M, Verkooijen HM, Reerink O. Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: a systematic review and meta-analysis. Radiother Oncol 2014; 113:1-9. [PMID: 25281582 DOI: 10.1016/j.radonc.2014.08.035] [Citation(s) in RCA: 115] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 08/25/2014] [Accepted: 08/31/2014] [Indexed: 02/07/2023]
Abstract
PURPOSE We conducted a systematic review and meta-analysis to quantify the pathological complete response (pCR) rate after preoperative (chemo)radiation with doses of ⩾60Gy in patients with locally advanced rectal cancer. Complete response is relevant since this could select a proportion of patients for which organ-preserving strategies might be possible. Furthermore, we investigated correlations between EQD2 dose and pCR-rate, toxicity or resectability, and additionally between pCR-rate and chemotherapy, boost-approach or surgical-interval. METHODS AND MATERIALS PubMed, EMBASE and Cochrane libraries were searched with the terms 'radiotherapy', 'boost' and 'rectal cancer' and synonym terms. Studies delivering a preoperative dose of ⩾60 Gy were eligible for inclusion. Original English full texts that allowed intention-to-treat pCR-rate calculation were included. Study variables, including pCR, acute grade ⩾3 toxicity and resectability-rate, were extracted by two authors independently. Eligibility for meta-analysis was assessed by critical appraisal. Heterogeneity and pooled estimates were calculated for all three outcomes. Pearson correlation coefficients were calculated between the variables mentioned earlier. RESULTS The search identified 3377 original articles, of which 18 met our inclusion criteria (1106 patients). Fourteen studies were included for meta-analysis (487 patients treated with ⩾60 Gy). pCR-rate ranged between 0.0% and 44.4%. Toxicity ranged between 1.3% and 43.8% and resectability-rate between 34.0% and 100%. Pooled pCR-rate was 20.4% (95% CI 16.8-24.5%), with low heterogeneity (I2 0.0%, 95% CI 0.00-84.0%). Pooled acute grade ⩾3 toxicity was 10.3% (95% CI 5.4-18.6%) and pooled resectability-rate was 89.5% (95% CI 78.2-95.3%). CONCLUSION Dose escalation above 60 Gy for locally advanced rectal cancer results in high pCR-rates and acceptable early toxicity. This observation needs to be further investigated within larger randomized controlled phase 3 trials in the future.
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Affiliation(s)
| | | | - Martijn Intven
- Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands
| | - Marco van Vulpen
- Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands
| | | | - Onne Reerink
- Department of Radiation Oncology, University Medical Center, Utrecht, The Netherlands
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Battersby NJ, Moran B, Yu S, Tekkis P, Brown G. MR imaging for rectal cancer: the role in staging the primary and response to neoadjuvant therapy. Expert Rev Gastroenterol Hepatol 2014; 8:703-19. [PMID: 24954622 DOI: 10.1586/17474124.2014.906898] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Pre-operative staging is an essential aspect of modern rectal cancer management and radiological assessment is central to this process. An ideal radiological assessment should provide sufficient information to reliably guide pre-operative decision-making. Technical advances allow high-resolution imaging to not only provide prognostic information but to define the anatomy, helping the surgeon to anticipate potential pitfalls during the operation. The main imaging modality for local staging of rectal cancer is Magnetic Resonance Imaging (MRI), as it defines the tumour and relevant anatomy providing the most detail on the important prognostic factors that influence treatment choice. In addition, there is an emerging role for MRI in the assessment of the response to neoadjuvant therapy. This article is an evidence-based review of rectal cancer staging focusing on post-treatment assessment of response using MRI. The discussion extends into the implications for reliably assessing response and how this may influence future rectal cancer management.
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Affiliation(s)
- Nick J Battersby
- Pelican Cancer Foundation, Colorectal Research Unit, Basingstoke, UK
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Fokas E, Liersch T, Fietkau R, Hohenberger W, Beissbarth T, Hess C, Becker H, Ghadimi M, Mrak K, Merkel S, Raab HR, Sauer R, Wittekind C, Rödel C. Tumor Regression Grading After Preoperative Chemoradiotherapy for Locally Advanced Rectal Carcinoma Revisited: Updated Results of the CAO/ARO/AIO-94 Trial. J Clin Oncol 2014; 32:1554-62. [DOI: 10.1200/jco.2013.54.3769] [Citation(s) in RCA: 284] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months. Patients and Methods TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS). Results Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026). Conclusion Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.
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Affiliation(s)
- Emmanouil Fokas
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Torsten Liersch
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Rainer Fietkau
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Werner Hohenberger
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Tim Beissbarth
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Clemens Hess
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Heinz Becker
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Michael Ghadimi
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Karl Mrak
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Susanne Merkel
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Hans-Rudolf Raab
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Rolf Sauer
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Christian Wittekind
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
| | - Claus Rödel
- Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria
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Glimelius B. Optimal Time Intervals between Pre-Operative Radiotherapy or Chemoradiotherapy and Surgery in Rectal Cancer? Front Oncol 2014; 4:50. [PMID: 24778990 PMCID: PMC3985002 DOI: 10.3389/fonc.2014.00050] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Accepted: 03/02/2014] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND In rectal cancer therapy, radiotherapy or chemoradiotherapy (RT/CRT) is extensively used pre-operatively to (i) decrease local recurrence risks, (ii) allow radical surgery in non-resectable tumors, and (iii) increase the chances of sphincter-saving surgery or (iv) organ-preservation. There is a growing interest among clinicians and scientists to prolong the interval from the RT/CRT to surgery to achieve maximal tumor regression and to diminish complications during surgery. METHODS The pros and cons of delaying surgery depending upon the aim of the pre-operative RT/CRT are critically evaluated. RESULTS Depending upon the clinical situation, the need for a time interval prior to surgery to allow tumor regression varies. In the first and most common situation (i), no regression is needed and any delay beyond what is needed for the acute radiation reaction in surrounding tissues to wash out can potentially only be deleterious. After short-course RT (5Gyx5) with immediate surgery, the ideal time between the last radiation fraction is 2-5 days, since a slightly longer interval appears to increase surgical complications. A delay beyond 4 weeks appears safe; it results in tumor regression including pathologic complete responses, but is not yet fully evaluated concerning oncologic outcome. Surgical complications do not appear to be influenced by the CRT-surgery interval within reasonable limits (about 4-12 weeks), but this has not been sufficiently explored. Maximum tumor regression may not be seen in rectal adenocarcinomas until after several months; thus, a longer than usual delay may be of benefit in well responding tumors if limited or no surgery is planned, as in (iii) or (iv), otherwise not. CONCLUSION A longer time interval after CRT is undoubtedly of benefit in some clinical situations but may be counterproductive in most situations. After short-course RT, long-term results from the clinical trials are not yet available to routinely recommend an interval longer than 2-5 days, unless the tumor is non-resectable at diagnosis.
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Affiliation(s)
- Bengt Glimelius
- Department of Radiology, Oncology and Radiation Science, Uppsala University , Uppsala , Sweden
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Biagioli MC, Herman JM. Preoperative endorectal brachytherapy in the treatment of locally advanced rectal cancer: Rethinking neoadjuvant treatment. SEMINARS IN COLON AND RECTAL SURGERY 2014. [DOI: 10.1053/j.scrs.2013.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Kim D. More Treatment is not Necessarily Better - Limited Options for Chemotherapeutic Radiosensitization. COLORECTAL CANCER 2014. [DOI: 10.1002/9781118337929.ch12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Saglam S, Bugra D, Saglam EK, Asoglu O, Balik E, Yamaner S, Basaran M, Oral EN, Kizir A, Kapran Y, Gulluoglu M, Sakar B, Bulut T. Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0+ rectal cancer: Istanbul R-01 study. J Gastrointest Oncol 2014; 5:9-17. [PMID: 24490038 PMCID: PMC3904022 DOI: 10.3978/j.issn.2078-6891.2013.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Accepted: 04/17/2013] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND AND PURPOSE The optimum duration between neoadjuvant radiochemotherapy and transmesorectal excision in locally advanced rectal cancer has not been defined yet. This randomized study was designed to compare the efficacy of four-week versus eight-week delay before surgery. METHODS One-hundred and fifty-three patients with locally advanced low- or mid-rectum rectal adenocarcinoma were included in this single center prospective randomized trial. Patients were assigned to receive surgical treatment after either four weeks or eight weeks of delay after chemoradiotherapy. Patients were followed for local recurrence and survival, and surgical specimens were examined for pathological staging and circumferential margin positivity. RESULTS 4-week and 8-week groups did not differ with regard to lateral surgical margin positivity (9.2% vs. 5.1%, P=0.33, respectively), pathological tumor regression rate (P=0.90), overall survival (5-year, 76.5% vs. 74.2%, P=0.60) and local recurrence rate (11.8% vs. 10.3%, 0.77). Overall survival was better in patients with negative surgical margins (78.8% vs. 53.0%, P=0.04). Local recurrence rate was significantly higher among patients with positive surgical margin (28.5% vs. 9.3%, P=0.02). CONCLUSIONS Intentional prolongation of the chemoradiotherapy-surgery interval does not seem to improve clinical outcomes of patients with locally advanced rectal cancer. Surgical margin positivity seems to be more important with this regard.
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Affiliation(s)
- Sezer Saglam
- Istanbul Bilim University Medical Faculty, Department of Medical Oncology, Turkey
| | - Dursun Bugra
- Koc University, School of Medicine, Department of General Surgery, Turkey
| | - Esra K. Saglam
- Istanbul University, Istanbul Medical Faculty, Department of Radiation Oncology, Turkey
| | - Oktar Asoglu
- Istanbul University, Istanbul Medical Faculty, Department of General Surgery, Turkey
| | - Emre Balik
- Istanbul University, Istanbul Medical Faculty, Department of General Surgery, Turkey
| | - Sumer Yamaner
- Istanbul University, Istanbul Medical Faculty, Department of General Surgery, Turkey
| | - Mert Basaran
- Istanbul University Oncology Institute, Department of Medical Oncology, Turkey
| | - Ethem N. Oral
- Istanbul University, Istanbul Medical Faculty, Department of Radiation Oncology, Turkey
| | - Ahmet Kizir
- Istanbul University, Istanbul Medical Faculty, Department of Radiation Oncology, Turkey
| | - Yersu Kapran
- Istanbul University, Istanbul Medical Faculty, Department of Pathology, Turkey
| | - Mine Gulluoglu
- Istanbul University, Istanbul Medical Faculty, Department of Pathology, Turkey
| | - Burak Sakar
- Istanbul Bilim University Medical Faculty, Department of Medical Oncology, Turkey
| | - Turker Bulut
- Istanbul University, Istanbul Medical Faculty, Department of General Surgery, Turkey
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Boostrom SY, Nelson H. Current treatment of rectal cancer: The watch-and-wait method. Are we there yet? SEMINARS IN COLON AND RECTAL SURGERY 2013. [DOI: 10.1053/j.scrs.2013.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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