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Zhou M, Huang H, Gong T, Chen M. The application of the golden-angle radial sparse parallel technique in T restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy. Abdom Radiol (NY) 2024; 49:2960-2970. [PMID: 38822854 DOI: 10.1007/s00261-024-04400-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/07/2024] [Accepted: 05/12/2024] [Indexed: 06/03/2024]
Abstract
PURPOSE To evaluate the diagnostic performance of Golden-Angle Radial Sparse Parallel (GRASP) MRI in identifying pathological stage T0-1 (ypT0-1) after neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer, compared to T2-weighted imaging (T2WI) combined with Diffusion Weighted Imaging (DWI). METHODS In this retrospective study, 168 patients were carefully selected based on inclusion criteria that targeted individuals with biopsy-confirmed primary rectal adenocarcinoma, identified via MRI as having locally advanced disease (≥ T3 and/or positive lymph node results) prior to nCRT. Post-nCRT, all MRI images obtained after nCRT were assessed by two observers independently. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying ypT0-1 based on GRASP and T2 + DWI were calculated. Multivariable regression analysis was used to explore the factors independently associated with ypT0-1 tumor. RESULTS 45 patients out of these cases were ypT0-1, and the accuracy, sensitivity, specificity, PPV, and NPV of GRASP were higher than the T2 + DWI (88% vs 74%, 93% vs 71%, 86% vs 75%, 71% vs 52% and 97% vs 88%), the AUC in identifying ypT0-1 tumor based on GRASP was 0.90 (95% CI:0.84, 0.94), which was better than the T2 + DWI (0.73; 95% CI: 0.66, 0.80). Multivariable logistic regression analysis showed that the yT stage on GRASP scans was the only factor independently associated with ypT0-1 tumor (P < 0.001). CONCLUSION The GRASP helped distinguish ypT0-1 tumor after nCRT and can select patients who may be suitable for local excision.
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Affiliation(s)
- Mi Zhou
- Department of Radiology, Sichuan Provincial Orthpaedics Hospital, Chengdu, 610041, People's Republic of China.
| | - Hongyun Huang
- Department of Radiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People's Republic of China
| | - Tong Gong
- Department of Radiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, People's Republic of China
| | - Meining Chen
- Department of MR Scientific Marketing, Siemens Healthineers, Shanghai, 200135, People's Republic of China
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2
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Lu QY, Guan Z, Zhang XY, Li XT, Sun RJ, Li QY, Sun YS. Contrast-enhanced MRI for T Restaging of Locally Advanced Rectal Cancer Following Neoadjuvant Chemotherapy and Radiation Therapy. Radiology 2022; 305:364-372. [DOI: 10.1148/radiol.212905] [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]
Affiliation(s)
- Qiao-Yuan Lu
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China
| | - Zhen Guan
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China
| | - Xiao-Yan Zhang
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China
| | - Xiao-Ting Li
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China
| | - Rui-Jia Sun
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China
| | - Qing-Yang Li
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China
| | - Ying-Shi Sun
- From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, No. 52 Fu Cheng Road, Hai Dian District, Beijing 100142, China
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3
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Park IJ. Watch and wait strategies for rectal cancer A systematic review. PRECISION AND FUTURE MEDICINE 2021. [DOI: 10.23838/pfm.2021.00177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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4
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How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement. Cancer Treat Rev 2020; 84:101964. [PMID: 32000055 DOI: 10.1016/j.ctrv.2020.101964] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 01/06/2020] [Accepted: 01/07/2020] [Indexed: 02/06/2023]
Abstract
Various methods categorize tumour response after neoadjuvant therapy, including down-staging and tumour regression grading. Response categories allow comparison of different treatments within clinical trials and predict outcome. A reproducible response categorization could identify subgroups with high or low risk for the most appropriate subsequent treatments, like watch and wait. Lack of standardization and interpretation difficulties currently limit the usability of these approaches. In this review we describe these difficulties for the evaluation of chemoradiation in rectal cancer. An alternative approach of tumour response is based on patterns of residual disease, including fragmentation. We summarise the evidence behind this alternative method of response categorisation, which explains a number of very relevant clinical discrepancies. These issues include differences between downstaging and tumour regression, high local regrowth in advanced tumours during watchful waiting procedures, the importance of resection margins, the limited value of post-treatment biopsies and the relatively poor outcome of patients with a near complete pathological response. Recognition of these patterns of response can allow meaningful development of novel biomarkers in the future.
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Cho MS, Kim H, Han YD, Hur H, Min BS, Baik SH, Cheon JH, Lim JS, Lee KY, Kim NK. Endoscopy and magnetic resonance imaging-based prediction of ypT stage in patients with rectal cancer who received chemoradiotherapy: Results from a prospective study of 110 patients. Medicine (Baltimore) 2019; 98:e16614. [PMID: 31464897 PMCID: PMC6736480 DOI: 10.1097/md.0000000000016614] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Accurate tumor response determination remains inconclusive after preoperative chemoradiation therapy (CRT) for rectal cancer. This study aimed to investigate whether clinical assessment, such as endoscopy and magnetic resonance imaging (MRI), can accurately predict ypT stage and select candidates for pelvic organ-preserving surgery in rectal cancer after preoperative CRT. A total of 110 patients who underwent preoperative CRT followed by curative resection for rectal cancer were prospectively enrolled. Magnetic resonance tumor regression grade (mrTRG) using T2-MRI, endoscopic evaluation, and combination modality (combination of endoscopy and mrTRG) were used to analyze tumor response after preoperative CRT. Endoscopic findings were categorized as 3 grades and the mrTRG was assessed into 5 grades. Twenty-nine patients (26.4%) had achieved pathologic complete response. When predicting ypT0, endoscopy showed significantly higher area under the curve (AUC 0.818) than did mrTRG (AUC 0.568) and combination modality (AUC 0.768) in differentiating good response from poor response (P < .001). Both endoscopy and combination modality showed significantly higher diagnostic performance in sensitivity (79.31%), positive predictive value (PPV 67.65%), negative predictive value (NPV 92.11%), and accuracy (84.55%) than those of MR tumor response (sensitivity 37.93%, PPV 36.67%, NPV 77.50%, and accuracy 66.36%) for the prediction of ypT0 (P < .001). Combination modality showed significantly higher diagnostic performance in sensitivity (56.92%), NPV (56.92%), and accuracy (67.27%) compared with those of mrTRG. Neither endoscopy, nor mrTRG, nor the combination modality had adequate diagnostic performances to be clinically acceptable in selecting candidates for nonoperative treatment strategies. However, endoscopy may be incorporated in clinical restaging strategy in planning the extent of surgical resection in patients with rectal cancer.
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Affiliation(s)
- Min Soo Cho
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - HonSoul Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Yoon Dae Han
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Hyuk Hur
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Byung Soh Min
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology
| | - Joon Seok Lim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
| | - Kang Young Lee
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
| | - Nam Kyu Kim
- Division of Colon and Rectal Surgery, Yonsei University College of Medicine
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Wawok P, Polkowski W, Richter P, Szczepkowski M, Olędzki J, Wierzbicki R, Gach T, Rutkowski A, Dziki A, Kołodziejski L, Sopyło R, Pietrzak L, Kryński J, Wiśniowska K, Spałek M, Pawlewicz K, Polkowski M, Kowalska T, Paprota K, Jankiewicz M, Radkowski A, Chalubińska-Fendler J, Michalski W, Bujko K. Preoperative radiotherapy and local excision of rectal cancer: Long-term results of a randomised study. Radiother Oncol 2018; 127:396-403. [PMID: 29680321 DOI: 10.1016/j.radonc.2018.04.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 03/19/2018] [Accepted: 04/02/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND PURPOSE It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established. MATERIAL AND METHODS In a phase III study, patients with cT1-2N0M0 or borderline cT2/T3N0M0 < 4 cm rectal adenocarcinomas were randomised to receive either 5 × 5 Gy plus 1 × 4 Gy boost or chemoradiation: 50.4 Gy in 28 fractions plus 3 × 1.8 Gy boost and 5-fluorouracil with leucovorin bolus. LE was performed 6-8 weeks later. Patients with ypT0-1R0 disease were observed. Completion total mesorectal excision (CTME) was recommended for poor responders, i.e. ypT1R1/ypT2-3. RESULTS Of 61 randomised patients, 10 were excluded leaving 51 for analysis; 29 in the short-course group and 22 in the chemoradiation group. YpT0-1R0 was observed in 66% of patients in the short-course group and in 86% in the chemoradiation group, p = 0.11. CTME was performed only in 46% of patients with ypT1R1/ypT2-3. The median follow-up was 8.7 years. Local recurrence incidences and overall survival at 10 years were respectively for the short-course group vs. the chemoradiation group 35% vs. 5%, p = 0.036 and 47% vs. 86%, p = 0.009. In total, local recurrence at 10 years was 79% for ypT1R1/T2-3 without CTME. CONCLUSIONS This trial suggests that in the LE setting, both local recurrence and survival are worse after short-course radiotherapy than after chemoradiation. Because of the risk of bias, a confirmatory study is desirable. Lack of CTME is associated with an unacceptably high local recurrence rate.
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Affiliation(s)
- Przemysław Wawok
- Department of Surgery, Jagiellonian Medical University College, Kraków, Poland
| | | | - Piotr Richter
- Department of Surgery, Jagiellonian Medical University College, Kraków, Poland
| | - Marek Szczepkowski
- Department of Rehabilitation, Józef Piłsudski University of Physical Education, Warsaw, Poland; Clinical Department of General and Colorectal Surgery, Bielański Hospital, Warsaw, Poland; Clinical Department of Colorectal, General and Oncological Surgery, Centre of Postgraduate Medical Education, Poland
| | - Janusz Olędzki
- Department of Colorectal Surgery, Medical University, Warsaw, Poland
| | | | - Tomasz Gach
- Department of Surgery, Jagiellonian Medical University College, Kraków, Poland
| | - Andrzej Rutkowski
- Department of Colorectal Cancer, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Adam Dziki
- Department of Colorectal Surgery, Medical University, Łódź, Poland
| | | | - Rafał Sopyło
- Department of Surgery, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Lucyna Pietrzak
- Department of Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Jacek Kryński
- Department of Colorectal Cancer, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Katarzyna Wiśniowska
- Department of Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Mateusz Spałek
- Department of Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Konrad Pawlewicz
- Department of Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Marcin Polkowski
- Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Teresa Kowalska
- Department of Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Centre, Kraków, Poland
| | - Krzysztof Paprota
- Department of Radiotherapy, St. John's Cancer Center, Lublin, Poland
| | | | | | | | - Wojciech Michalski
- Bioinformatics and Biostatistics Unit, M. Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Krzysztof Bujko
- Department of Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland.
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Skóra T, Nowak-Sadzikowska J, Martynów D, Wszołek M, Sas-Korczyńska B. Preoperative short-course radiotherapy in rectal cancer patients: results and prognostic factors. ACTA ACUST UNITED AC 2017; 7:77-84. [PMID: 29576860 PMCID: PMC5856857 DOI: 10.1007/s13566-017-0340-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 12/12/2017] [Indexed: 12/18/2022]
Abstract
Objective The purpose of this study was to evaluate the clinical outcome of preoperative short-course radiotherapy for rectal cancer patients. Methods The study group comprised 210 patients with pathologically proven resectable rectal cancer. Between 2001 and 2013, they were treated preoperatively with short-course radiotherapy (25 Gy delivered in five fractions), followed by total mesorectal excision. Adjuvant 5-fluorouracil-based chemotherapy was administered at the discretion of the treating physician, depending on the pathological stage. Results After a median follow-up of 57 months, the following 5-year survival rates were observed: overall survival-66.4%, disease-free survival-67.2%, locoregional relapse-free survival-91.7%, and distant metastases-free survival-71.5%. The local failure was observed in 15 patients. Ten patients (4.8%) achieved pathologic complete response. The multivariate analysis demonstrated the regional lymph node involvement to be statistically significant for unfavorable outcomes in terms of all estimated survival rates. Lymphovascular invasion was found to be a strong predictor of survival (HR = 1.68; 95% CI 1.29-3.55) and treatment failure (HR = 1.54; 95% CI 1.08-3.34). The presence of positive surgical circumferential margin was related to six times higher risk of locoregional recurrence. Early and late severe treatment-induced toxicity was reported in 1 and 7.6% patients, respectively. Conclusions Preoperative short-course radiotherapy followed by total mesorectal excision and adjuvant chemotherapy allows to achieve excellent local control and favorable survival rates. The treatment-induced toxicity is acceptable.
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Affiliation(s)
- Tomasz Skóra
- Krakow Branch, Department of Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, ul. Garncarska 11, 31-115 Kraków, Poland
| | - Jadwiga Nowak-Sadzikowska
- Krakow Branch, Department of Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, ul. Garncarska 11, 31-115 Kraków, Poland
| | - Dariusz Martynów
- Krakow Branch, Department of Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, ul. Garncarska 11, 31-115 Kraków, Poland
| | - Mariusz Wszołek
- Krakow Branch, Department of Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, ul. Garncarska 11, 31-115 Kraków, Poland
| | - Beata Sas-Korczyńska
- Krakow Branch, Department of Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, ul. Garncarska 11, 31-115 Kraków, Poland
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Rullier E, Rouanet P, Tuech JJ, Valverde A, Lelong B, Rivoire M, Faucheron JL, Jafari M, Portier G, Meunier B, Sileznieff I, Prudhomme M, Marchal F, Pocard M, Pezet D, Rullier A, Vendrely V, Denost Q, Asselineau J, Doussau A. Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial. Lancet 2017; 390:469-479. [PMID: 28601342 DOI: 10.1016/s0140-6736(17)31056-5] [Citation(s) in RCA: 243] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 02/28/2017] [Accepted: 03/07/2017] [Indexed: 01/22/2023]
Abstract
BACKGROUND Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy, to potentially avoid morbidity and side-effects of rectal excision. The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer. METHODS We did a prospective, randomised, open-label, multicentre, phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer. Patients aged 18 years and older with stage T2T3 lower rectal carcinoma, of maximum size 4 cm, who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour ≤2 cm) were centrally randomly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery. Randomisation, which was done via the internet, was not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was required if tumour stage was ypT2-3. The primary endpoint was a composite outcome of death, recurrence, morbidity, and side-effects at 2 years after surgery, to show superiority of local excision over total mesorectal excision in the modified intention-to-treat (ITT) population (expected proportions of patients having at least one event were 25% vs 60% for superiority). This trial was registered with ClinicalTrials.gov, number NCT00427375. FINDINGS From March 1, 2007, to Sept 24, 2012, 186 patients received chemoradiotherapy and were enrolled in the study. 148 good clinical responders were randomly assigned to treatment, three were excluded (because they had metastatic disease, tumour >8 cm from anal verge, and withdrew consent), and 145 were analysed: 74 in the local excision group and 71 in the total mesorectal excision group. In the local excision group, 26 patients had a completion total mesorectal excision. At 2 years in the modified ITT population, one or more events from the composite primary outcome occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62-2·86; p=0·43). In the modified ITT analysis, there was no difference between the groups in all components of the composite outcome, and superiority was not shown for local excision over total mesorectal excision. INTERPRETATION We failed to show superiority of local excision over total mesorectal excision, because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects, and compromised the potential advantages of local excision. Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy. FUNDING National Cancer Institute of France, Sanofi, Roche Pharma.
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Affiliation(s)
- Eric Rullier
- Department of Colorectal Surgery, Haut-Lévèque Hospital, Pessac, CHU Bordeaux, France.
| | - Philippe Rouanet
- Département de Chirurgie Oncologique, ICM Val d'Aurelle, Montpellier, France
| | | | - Alain Valverde
- Service de Chirurgie Digestive, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France
| | - Bernard Lelong
- Département de Chirurgie Oncologique, Institut Paoli Calmette, Marseille, France
| | - Michel Rivoire
- Département de Chirurgie Oncologique, Centre Léon Bérard, Lyon, France
| | | | - Mehrdad Jafari
- Département de Chirurgie Oncologique, Centre Oscar Lambret, Lille, France
| | | | - Bernard Meunier
- Service de Chirurgie Viscérale, CHU Pontchaillou, Rennes, France
| | - Igor Sileznieff
- Service de Chirurgie Digestive, CHU Timone, Marseille, France
| | - Michel Prudhomme
- Département de Chirurgie Digestive et de Cancérologie Digestive, Hôpital Universitaire Carémeau, Nimes, France
| | - Frédéric Marchal
- Département de Chirurgie Oncologique, Institut de Cancérologie de Lorraine, CRAN, UMR 7039, Université de Lorraine, CNRS, Vandoeuvre les Nancy, France
| | - Marc Pocard
- Département Médico-Chirurgical de Pathologie Digestive, Hôpital Lariboisière, Paris, France
| | - Denis Pezet
- Service de Chirurgie Générale et Digestive, Hôtel Dieu, Clermont-Ferrand, France
| | - Anne Rullier
- Service d'Anatomopathologie, Hôpital Pellegrin, Bordeaux, CHU Bordeaux, France
| | - Véronique Vendrely
- Service de Radiothérapie, Haut-Lévèque Hospital, Pessac, CHU Bordeaux, France
| | - Quentin Denost
- Department of Colorectal Surgery, Haut-Lévèque Hospital, Pessac, CHU Bordeaux, France
| | - Julien Asselineau
- Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du CHU de Bordeaux, Université Bordeaux, Bordeaux, France
| | - Adélaïde Doussau
- Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du CHU de Bordeaux, Université Bordeaux, Bordeaux, France
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9
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Gollins S, Moran B, Adams R, Cunningham C, Bach S, Myint AS, Renehan A, Karandikar S, Goh V, Prezzi D, Langman G, Ahmedzai S, Geh I. Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Multidisciplinary Management. Colorectal Dis 2017; 19 Suppl 1:37-66. [PMID: 28632307 DOI: 10.1111/codi.13705] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
| | - Brendan Moran
- Basingstoke & North Hampshire Hospital, Basingstoke, UK
| | - Richard Adams
- Cardiff University and Velindre Cancer Centre, Cardiff, UK
| | | | - Simon Bach
- University of Birmingham and Queen Elizabeth Hospital, Birmingham, UK
| | | | - Andrew Renehan
- University of Manchester and Christie Hospital, Manchester, UK
| | | | - Vicky Goh
- King's College and Guy's & St Thomas' Hospital, London, UK
| | | | | | | | - Ian Geh
- Queen Elizabeth Hospital, Birmingham, UK
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Leroi N, Sounni NE, Van Overmeire E, Blacher S, Marée R, Van Ginderachter J, Lallemand F, Lenaerts E, Coucke P, Noel A, Martinive P. The timing of surgery after neoadjuvant radiotherapy influences tumor dissemination in a preclinical model. Oncotarget 2017; 6:36825-37. [PMID: 26440148 PMCID: PMC4742213 DOI: 10.18632/oncotarget.5931] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Accepted: 09/15/2015] [Indexed: 12/18/2022] Open
Abstract
Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving local tumor control and patient overall survival. The neoRT schedule and the timing of the surgical treatment (ST) are empirically based and influenced by the clinician's experience. The current study examines how the sequencing of neoRT and ST affects metastatic dissemination. In a breast carcinoma model, tumors were exposed to different neoRT schedules (2x5Gy or 5x2Gy) followed by surgery at day 4 or 11 post-RT. The impact on the tumor microenvironment and lung metastases was evaluated through immunohistochemical and flow cytometry analyses. After 2x5Gy, early ST (at day 4 post-RT) led to increased size and number of lung metastases as compared to ST performed at day 11. Inversely, after 5x2Gy neoRT, early ST protected the mice against lung metastases. This intriguing relationship between tumor aggressiveness and ST timing could not be explained by differences in classical parameters studied such as hypoxia, vessel density and matrix remodeling. The study of tumor-related inflammation and immunity reveals an increased circulating NK cell percentage following neoRT as compared to non irradiated mice. Then, radiation treatment and surgery were applied to tumor-bearing NOD/SCID mice. In the absence of NK cells, neoRT appears to increase lung metastatic dissemination as compared to non irradiated tumor-bearing mice. Altogether our data demonstrate that the neoRT schedule and the ST timing affect metastasis formation in a pre-clinical model and points out the potential role of NK cells. These findings highlight the importance to cautiously tailor the optimal window for ST following RT.
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Affiliation(s)
- Natacha Leroi
- Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Belgium.,Department of Radiotherapy-Oncology, Centre Hospitalier Universitaire (CHU) de Liège, Belgium
| | - Nor Eddine Sounni
- Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Belgium
| | - Eva Van Overmeire
- Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium.,Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
| | - Silvia Blacher
- Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Belgium
| | - Raphael Marée
- Systems and Modeling (GIGA-Systems Biology and Chemical Biology), University of Liège, Belgium.,GIGA Bioinformatics Platform, University of Liège, Belgium
| | - Jo Van Ginderachter
- Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium.,Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
| | - François Lallemand
- Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Belgium
| | - Eric Lenaerts
- Department of Radiotherapy-Oncology, Centre Hospitalier Universitaire (CHU) de Liège, Belgium
| | - Philippe Coucke
- Department of Radiotherapy-Oncology, Centre Hospitalier Universitaire (CHU) de Liège, Belgium
| | - Agnès Noel
- Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Belgium
| | - Philippe Martinive
- Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liège, Belgium.,Department of Radiotherapy-Oncology, Centre Hospitalier Universitaire (CHU) de Liège, Belgium
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11
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Bosch SL, Vermeer TA, West NP, Swellengrebel HAM, Marijnen CAM, Cats A, Verhoef C, van Lijnschoten I, de Wilt JHW, Rutten HJ, Nagtegaal ID. Clinicopathological characteristics predict lymph node metastases in ypT0-2 rectal cancer after chemoradiotherapy. Histopathology 2016; 69:839-848. [DOI: 10.1111/his.13008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 06/04/2016] [Indexed: 12/18/2022]
Affiliation(s)
- Steven L Bosch
- Department of Pathology; Radboud University Medical Centre; Nijmegen the Netherlands
| | - Thomas A Vermeer
- Department of Surgery; Catharina Hospital Eindhoven; Eindhoven the Netherlands
| | - Nicholas P West
- Pathology and Tumour Biology; Leeds Institute of Cancer and Pathology; St James's University Hospital; University of Leeds; Leeds UK
| | - Hendrik A M Swellengrebel
- Department of Gastroenterology and Hepatology; Netherlands Cancer Institute; Amsterdam the Netherlands
| | - Corrie A M Marijnen
- Department of Radiotherapy; Leids University Medical Centre; Leiden the Netherlands
| | - Annemieke Cats
- Department of Gastroenterology and Hepatology; Netherlands Cancer Institute; Amsterdam the Netherlands
| | - Cornelis Verhoef
- Department of Surgery; Erasmus MC Cancer Institute; Rotterdam the Netherlands
| | | | - Johannes H W de Wilt
- Department of Surgery; Radboud University Medical Centre; Nijmegen the Netherlands
| | - Harm J Rutten
- Department of Surgery; Catharina Hospital Eindhoven; Eindhoven the Netherlands
- Department of Surgery; Maastricht University Medical Centre; Maastricht the Netherlands
| | - Iris D Nagtegaal
- Department of Pathology; Radboud University Medical Centre; Nijmegen the Netherlands
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12
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Arezzo A, Cortese G, Arolfo S, Bullano A, Passera R, Galietti E, Morino M. Transanal Endoscopic Operation under spinal anaesthesia. Br J Surg 2016; 103:916-20. [DOI: 10.1002/bjs.10082] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2015] [Revised: 11/18/2015] [Accepted: 11/18/2015] [Indexed: 01/23/2023]
Abstract
Abstract
Background
Transanal Endoscopic Operation (TEO®) for rectal benign lesions and early rectal cancer may provide better oncological outcomes than flexible endoscopy. The major advantage of flexible endoscopy is that it does not require general anaesthesia. This prospective observational study assessed the feasibility and safety of TEO® performed under spinal anaesthesia.
Methods
The study population comprised eligible consecutive patients who underwent TEO® under spinal anaesthesia with curative or palliative intent for rectal neoplasms larger than 20 mm in diameter or for recurrent lesions of any size. The primary endpoints were feasibility and safety; secondary endpoints were postoperative pain, as measured on a visual analogue scale, heart rate, systolic and diastolic BP, opioid requested, postoperative nausea or vomiting, and urinary retention.
Results
The study included 50 patients (median age 70 years; 29 men and 21 women). No intraoperative complications occurred. The median duration of operation was 60 (range 20–165) min. No opioids were requested during the perioperative or postoperative period. The median postoperative pain score was 0 at 4, 8, 24 and 48 h after surgery. There were no significant fluctuations in heart rate, systolic and diastolic BP up to 48 h after the procedure (P = 0·379, P = 0·386 and P = 0·617 respectively). Postoperative nausea and vomiting occurred in one patient, and urinary retention in four.
Conclusion
TEO® under spinal anaesthesia was safe and feasible with no conversions to general anaesthesia.
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Affiliation(s)
- A Arezzo
- General Surgery I, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - G Cortese
- Anaesthesia, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - S Arolfo
- General Surgery I, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - A Bullano
- General Surgery I, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - R Passera
- General Surgery I, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - E Galietti
- Anaesthesia, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - M Morino
- General Surgery I, Department of Surgical Sciences, University of Turin, Turin, Italy
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13
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Habr-Gama A, São Julião GP, Perez RO. Nonoperative management of rectal cancer: identifying the ideal patients. Hematol Oncol Clin North Am 2015; 29:135-51. [PMID: 25475576 DOI: 10.1016/j.hoc.2014.09.004] [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] [Indexed: 01/10/2023]
Abstract
Neoadjuvant chemoradiation (CRT) is considered one of the preferred treatment strategies for patients with locally advanced rectal cancer. This strategy may lead to significant tumor regression, ultimately leading to a complete pathologic response in up to 42% of patients. Assessment of tumor response following CRT and before radical surgery may identify patients with a complete clinical response who could possibly be managed nonoperatively with strict follow-up (watch-and-wait strategy). The present article deals with critical issues regarding appropriate selection of patients for this approach.
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Affiliation(s)
- Angelita Habr-Gama
- Angelita and Joaquim Gama Institute, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil; University of São Paulo School of Medicine, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil.
| | | | - Rodrigo O Perez
- Angelita and Joaquim Gama Institute, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil; Colorectal Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, Rua Manoel da Nóbrega 1564, Paraiso, São Paulo 04001-005, Brazil
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14
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Arezzo A, Arolfo S, Allaix ME, Munoz F, Cassoni P, Monagheddu C, Ricardi U, Ciccone G, Morino M. Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer. Int J Radiat Oncol Biol Phys 2015; 92:299-306. [DOI: 10.1016/j.ijrobp.2015.01.024] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 01/07/2015] [Accepted: 01/20/2015] [Indexed: 10/23/2022]
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15
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Rullier E, Denost Q. Transanal surgery for cT2T3 rectal cancer: Patient selection, adjuvant therapy, and outcomes. SEMINARS IN COLON AND RECTAL SURGERY 2015. [DOI: 10.1053/j.scrs.2014.10.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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16
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Habr-Gama A, São Julião GP, Perez RO. Pitfalls of transanal endoscopic microsurgery for rectal cancer following neoadjuvant chemoradiation therapy. MINIM INVASIV THER 2014; 23:63-9. [PMID: 24635719 DOI: 10.3109/13645706.2014.893891] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Transanal endoscopic microsurgery has become a very useful surgical tool for the management of selected cases of rectal cancer. However, the considerably high local recurrence rates led to the introduction of neoadjuvant therapies including radiation with or without chemotherapy. This treatment strategy may result in significant rates of tumor regression allowing the procedure to be offered to a significant proportion of cases. On the other hand, neoadjuvant chemoradiation (CRT) may also determine wound-healing difficulties with significant postoperative pain. In addition, salvage total mesorectal excision in the case of local recurrence may also be a challenging task. Finally, accurate selection criteria for this minimally invasive approach are still lacking and may be influenced by baseline staging, post-treatment staging and final pathology information. Ultimately, selection of patients for this treatment modality remains a significant challenge for the colorectal surgeon who should be aware of the pitfalls of this procedure in the setting of neoadjuvant CRT.
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Affiliation(s)
- Angelita Habr-Gama
- Angelita & Joaquim Gama Institute/Hospital Alemão Oswaldo Cruz , São Paulo , Brazil
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17
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Hompes R, McDonald R, Buskens C, Lindsey I, Armitage N, Hill J, Scott A, Mortensen NJ, Cunningham C. Completion surgery following transanal endoscopic microsurgery: assessment of quality and short- and long-term outcome. Colorectal Dis 2014; 15:e576-81. [PMID: 24635913 DOI: 10.1111/codi.12381] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Accepted: 04/21/2013] [Indexed: 12/16/2022]
Abstract
AIM Patients with unfavourable pathology after transanal endoscopic microsurgery (TEM) should be offered completion surgery (CS) if appropriate. The aim of this retrospective cohort study was to assess the short-term outcome and long-term oncological results of CS and identify factors compromising the quality of resection specimens. METHOD Data were retrieved and analysed on patients who underwent CS from a comprehensive national TEM database (1992-2008) and the institutional prospective database from the Oxford University Hospitals (2008-2011). RESULTS There were 36 patients eligible for analysis. Postoperative complications occurred in 19 and were minor (grade I-II) in 13 and major (grade III-V) in six patients. The quality of the resected specimen was graded as good in 23 (64%), moderate in six (16.6%) and poor in seven (19.4%). Full-thickness excision by TEM (P = 0.03), an interval to CS greater than 7 weeks (P = 0.05) and distally located lesions (P = 0.04) were associated with increased risk for an inferior surgical specimen. Overall survival after CS was 91% at 1 year and 83% at 5 years. Patients with a 'good' TME specimen had significantly improved disease-free survival compared with patients with an 'inferior' specimen (100 vs 51%, P = 0.001). CONCLUSION Patients having full-thickness TEM excision, distally placed lesions and a long interval (> 7 weeks) to CS were likely to have an inferior TME specimen. The results confirm that CS after TEM does not negatively influence local recurrence and survival, but the reduced disease-free survival in patients with an inferior specimen is of concern.
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Affiliation(s)
- R Hompes
- Department of Colorectal Surgery, Oxford University Hospitals, Oxford, UK
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18
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Baatrup G, Qvist N. Local resection of early rectal cancer. APMIS 2014; 122:715-22. [PMID: 25046201 DOI: 10.1111/apm.12292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Accepted: 06/14/2014] [Indexed: 12/15/2022]
Abstract
The introduction of the National Danish screening programme for colorectal cancer will result in the detection of more early rectal cancers (ERC), which may be considered for local excision. For the low risk≤T1 cancer, the oncological outcome at local excision in smaller patient series has shown similar results to conventional surgery, but with a significantly lower rate of serious complications, morbidity and mortality. The challenge is correct preoperative staging, and a meticulous systematic histopathological staging of the excised specimen to distinguish the low risk from high-risk cases, where rescue surgery may be considered. The establishment of a regional or national clinical database is necessary to improve the local treatment of ERC.
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Affiliation(s)
- Gunnar Baatrup
- Institute of Regional Health, Medical Faculty, University of Southern Denmark, Svendborg, Denmark; Department of Surgery A, Odense University Hospital, Svendborg, Denmark
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19
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Park IJ, Yu CS. Current issues in locally advanced colorectal cancer treated by preoperative chemoradiotherapy. World J Gastroenterol 2014; 20:2023-2029. [PMID: 24587677 PMCID: PMC3934472 DOI: 10.3748/wjg.v20.i8.2023] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/26/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
In patients with locally advanced rectal cancer, preoperative chemoradiotherapy has proven to significantly improve local control and cause lower treatment-related toxicity compared with postoperative adjuvant treatment. Preoperative chemoradiotherapy followed by total mesorectal excision or tumor specific mesorectal excision has evolved as the standard treatment for locally advanced rectal cancer. The paradigm shift from postoperative to preoperative therapy has raised a series of concerns however that have practical clinical implications. These include the method used to predict patients who will show good response, sphincter preservation, the application of conservative management such as local excision or “wait-and-watch” in patients obtaining a good response following preoperative chemoradiotherapy, and the role of adjuvant chemotherapy. This review addresses these current issues in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy.
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20
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Pinkney TD, Bach SP. Neoadjuvant Therapy Without Surgery for Early Stage Rectal Cancer? COLORECTAL CANCER 2014. [DOI: 10.1002/9781118337929.ch7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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21
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Intven M, Reerink O, Philippens MEP. Repeatability of diffusion-weighted imaging in rectal cancer. J Magn Reson Imaging 2013; 40:146-50. [PMID: 24127172 DOI: 10.1002/jmri.24337] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Accepted: 07/10/2013] [Indexed: 11/08/2022] Open
Abstract
PURPOSE Serial diffusion-weighted MRI (DW-MRI) measurements of the apparent diffusion coefficient (ADC) of rectal tumors are used for rectal cancer response evaluation after neo-adjuvant treatment. In this study, we determined the repeatability of DW-MRI to distinguish therapy-related response from measurement variations. MATERIALS AND METHODS In 18 patients with rectal cancer on five consecutive days, 1.5 Tesla (T) MR imaging was performed including two identical DW-MRI sequences. The repeatability of the tumor ADC measurements and the intraobserver ADC variation were depicted in a Bland-Altman plot. The repeatability coefficient was calculated as the range of ADC values of two identical DWI measurements for 95% of subjects. It was expressed as percentage of the mean ADC value. RESULTS Three females and 15 males were included. The mean tumor ADC value was 1.15 × 10(-3) mm(2)/s (SD 0.07 × 10(-3) mm(2)). The repeatability coefficient of the ADC value was 9.8% and for the intraobserver repeatability 4.7%. CONCLUSION In serial DW-MRI for rectal cancer treatment response evaluation, a repeatability coefficient of 9.8% has to be considered to account for measurement variations in rectal tumor ADC. These variations represent observer judgement and patient and MR spectrometer induced variations.
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Affiliation(s)
- Martijn Intven
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
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22
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Abstract
Rectal resection with total mesorectal excision is the standard treatment for rectal cancers. Local excision represents an alternative with less post-operative mortality and morbidity and preservation of intestinal and bladder function. However, local excision cannot provide adequate nodal staging. Presently, endorectal ultrasound and magnetic resonance imaging are used to select the appropriate patients for local excision, those with limited T1 rectal tumors. There is general agreement that the ideal tumors for local excision are less or equal to 3 cm in diameter, superficial (usTis and/or usT1N0), infra-peritoneal, located below the middle rectal valve, and involving no more than 40% of the rectal circumference. Transanal tumor excision is suitable for distal tumors and transanal endoscopic microsurgery for mid and upper lesions. The principles of adequate resection margin, non-fragmentation, and full-thickness excision are similar to those for any cancer resection. Unfavorable pathologic criteria, as assessed on the fixed rectal specimen, include depth of tumor invasion (submucosal [T1sm3] or muscular [T2]), positive resection margins, vascular and/or lymphatic invasion, and poor differentiation. Further radical surgery is required in case of unfavorable criteria. Simple surveillance may be advised for superficial tumors (T1sm1) without any unfavorable criteria. Management of T1sm2 tumors without any unfavorable criteria should be discussed on a case-by-case basis.
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Affiliation(s)
- C Lartigau
- Service de chirurgie digestive, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex, France
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Bujko K, Nasierowska-Guttmejer A, Wyrwicz L, Malinowska M, Krynski J, Kosakowska E, Rutkowski A, Pietrzak L, Kepka L, Radziszewski J, Olszyna-Serementa M, Bujko M, Danek A, Kryj M, Wydmanski J, Zegarski W, Markiewicz W, Lesniak T, Zygulski I, Porzuczek-Zuziak D, Bebenek M, Maciejczyk A, Polkowski W, Czeremszynska B, Cieslak-Zeranska E, Toczko Z, Radkowski A, Kolodziejski L, Szczepkowski M, Majewski A, Jankowski M. Neoadjuvant treatment for unresectable rectal cancer: an interim analysis of a multicentre randomized study. Radiother Oncol 2013; 107:171-7. [PMID: 23590986 DOI: 10.1016/j.radonc.2013.03.001] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2012] [Revised: 02/18/2013] [Accepted: 03/03/2013] [Indexed: 01/08/2023]
Abstract
PURPOSE To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer. METHODS Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 × 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II). Surgery in both groups was performed 12 weeks after the beginning of radiation and 6 weeks after neoadjuvant treatment. RESULTS 49 patients were treated according to schedule I and 48 according to schedule II. Grade III+ acute toxicity was observed in 26% of patients in group I and in 25% in group II. There were two toxic deaths, both in group II. The microscopically radical resection (primary endpoint) rate was 73% in group I and 71% in group II. Overall and severe postoperative complications were recorded in 27% and 9% of patients vs. 16% and 7%, respectively. Pathological complete response was observed in 21% of the patients in group I and in 9% in group II. CONCLUSIONS The interim analysis revealed no major differences in acute toxicity and local efficacy between the two evaluated strategies.
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Affiliation(s)
- Krzysztof Bujko
- Department of Radiotherapy II, M. Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland.
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Is tailoring treatment of rectal cancer the only true benefit of long-course neoadjuvant chemoradiation? Another view. Dis Colon Rectum 2013; 56:267-70. [PMID: 23303158 DOI: 10.1097/dcr.0b013e318277e8fc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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25
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Bujko K, Richter P, Smith FM, Polkowski W, Szczepkowski M, Rutkowski A, Dziki A, Pietrzak L, Kołodziejczyk M, Kuśnierz J, Gach T, Kulig J, Nawrocki G, Radziszewski J, Wierzbicki R, Kowalska T, Meissner W, Radkowski A, Paprota K, Polkowski M, Rychter A. Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: a prospective multicentre study. Radiother Oncol 2013; 106:198-205. [PMID: 23333016 DOI: 10.1016/j.radonc.2012.12.005] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2012] [Revised: 12/13/2012] [Accepted: 12/13/2012] [Indexed: 12/12/2022]
Abstract
PURPOSE To assess local control after preoperative radiation and local excision and to determine an optimal radiotherapy regimen. METHODS Eighty-nine patients with G1-2 rectal adenocarcinoma <3-4 cm; unfavourable cT1N0 (23.6%), cT2N0 (62.9%) or borderline cT2/cT3N0 (13.5%) received 5 × 5 Gy plus 4 Gy boost (71.9%) or 55.8 Gy in 31 fractions with 5-FU and leucovorin (28.1%). Local excision (traditional technique 56.2%, transanal endoscopic microsurgery 41.6%, Kraske procedure 2.2%) was performed 6-8 weeks later. If patients were downstaged to ypT0-1 without unfavourable factors (good responders), this was deemed definitive treatment. Immediate conversion to radical surgery was recommended for remaining patients. RESULTS Good response to radiation was seen in 67.2% of patients in the short-course group and in 80.0% in the chemoradiation group, p = 0.30. Local recurrence at 2 years (median follow-up) in good responders was 11.8% in the short-course group and 6.2% in the chemoradiation group, p = 0.53. In the total group, a lower rate of local recurrence at 2 years was observed in elderly patients (>69 years, median value) when compared to the younger patients; 8.3% vs. 27.7%, Cox analysis hazard ratio 0.232, p = 0.016. A total of 18 patients initially managed with local excision required conversion to abdominal surgery but either refused it or were unfit. In this group, local recurrence at 2 years was 37.1%. CONCLUSIONS This study suggests an acceptable local recurrence rate after preoperative radiotherapy and local excision of small, radiosensitive tumours in elderly patients.
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Affiliation(s)
- Krzysztof Bujko
- Department of Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland.
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Transanal endoscopic microsurgery for residual rectal cancer (ypT0-2) following neoadjuvant chemoradiation therapy: another word of caution. Dis Colon Rectum 2013; 56:6-13. [PMID: 23222274 DOI: 10.1097/dcr.0b013e318273f56f] [Citation(s) in RCA: 90] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Significant tumor downstaging among patients with rectal cancer following neoadjuvant chemoradiation has raised the issue of offering patients with small residual cancers restricted to the bowel wall an alternative treatment strategy to total mesorectal excision. Transanal endoscopic microsurgery may allow proper primary tumor resection with promising oncological outcomes, less postoperative morbidity, and minimal long-term sexual, urinary, and fecal continence disorders in comparison with radical resection. OBJECTIVE The aim of this study was to determine the oncological outcomes of patients with residual rectal cancers restricted to the rectal wall (ypT0-2) following neoadjuvant chemoradiation and transanal endoscopic microsurgery. DESIGN This study considered a prospective cohort of patients with residual rectal cancers following neoadjuvant chemoradiation treated by transanal endoscopic microsurgery and no additional systemic therapy. SETTINGS This study was a single-institution experience. PATIENTS Patients with adenocarcinoma of the rectum located no more than 7 cm from the anal verge and endorectal ultrasound- or magnetic resonance-staged cT2-4N0-2M0 treated by neoadjuvant chemoradiation (50.4-54 Gy and 5-fluorouracil-based chemotherapy) were eligible for the study. Patients with small residual tumors (≤3 cm) radiologically staged ycT0-2N0 were treated by transanal endoscopic microsurgery. INTERVENTIONS Transanal endoscopic microsurgery was performed. MAIN OUTCOME MEASURES The primary outcome measured was local recurrence. RESULTS Of the 27 patients treated by transanal endoscopic microsurgery, 3 had ypT0, 6 had ypT1, and 18 had ypT2 cancers. All patients underwent R0 transanal endoscopic microsurgery excision. Local recurrence was observed in 4 (15%) patients after a median follow-up of 15 months. Only lymphovascular invasion was an independent predictive factor for local failure (p = 0.04). Tumor size, ypT status, T-status downstaging, lateral/radial margins, and tumor regression grade were not predictors of local failure. LIMITATIONS This study was limited by the small sample size and limited follow-up. CONCLUSIONS A local failure rate of 15% after transanal endoscopic microsurgery for patients with residual rectal cancers restricted to the bowel wall (ypT0-2) may limit the indication of this procedure to highly selected patients as an alternative to standard radical total mesorectal excision.
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27
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de Manzini N, Leon P, Tarchi P, Giacca M. Surgical Strategy: Indications. Updates Surg 2013. [DOI: 10.1007/978-88-470-2670-4_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Intven M, Reerink O, Philippens M. Diffusion-weighted MRI in locally advanced rectal cancer. Strahlenther Onkol 2012; 189:117-22. [DOI: 10.1007/s00066-012-0270-5] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Accepted: 11/08/2012] [Indexed: 12/29/2022]
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29
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Milgrom SA, Garcia-Aguilar J. Organ-preserving therapy for rectal cancer. COLORECTAL CANCER 2012. [DOI: 10.2217/crc.12.63] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Total mesorectal excision has resulted in low local recurrence rates in rectal cancer patients; however, it is associated with a significant impairment in quality of life. The operation may be disfiguring and cause permanent effects on gastrointestinal, genitourinary and sexual function. Recently, researchers have identified subgroups of rectal cancer patients who may be able to forgo total mesorectal excision without compromising their oncological outcomes. Two groups of patients are candidates for organ preservation: those with early-stage disease that may be adequately addressed by a more limited resection, and those with locally advanced disease that has responded completely to neoadjuvant therapy. Additionally, radiation alone may be curative in both early and locally advanced disease. This article reviews the data regarding these approaches.
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Affiliation(s)
- Sarah A Milgrom
- Department of Radiation Oncology, Memorial Sloan–Kettering Cancer Center, NY, USA
| | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, NY 10065, USA
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Rödel C, Trojan J, Bechstein WO, Woeste G. Neoadjuvant short- or long-term radio(chemo)therapy for rectal cancer: how and who should be treated? Dig Dis 2012. [PMID: 23207941 DOI: 10.1159/000342038] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
There are two general approaches to preoperative radiotherapy (RT) in rectal cancer: short-course (25 Gy in 5 fractions) radiation with immediate surgery and long-course 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT; 50.4 Gy in 28 fractions) with surgery scheduled 6-8 weeks thereafter. While it is clear that downsizing and downstaging effects are more pronounced with long-course CRT and delayed surgery, a Polish randomized trial and, more recently, an Australian phase III trial demonstrated no significant differences in long-term oncologic outcomes and late toxicity rates between either preoperative concept. Ongoing studies currently address short-course preoperative RT with a longer interval to surgery (Stockholm III trial), and short-course RT with sequential combination chemotherapy in patients with synchronous distant metastasis. With respect to the long-course CRT approach, newer-generation chemotherapeutics as well as molecularly targeted agents have been tested within phase I-III studies, both as induction/adjuvant chemotherapy as well as during concomitant CRT. Evidently, the monolithic approaches to either apply the same schedule of preoperative 5-FU-based CRT to all patients with TNM stage II/III rectal cancer or to give preoperative short-course RT for all patients with resectable rectal cancer irrespective of tumor stage and location need to be questioned. The inclusion of different multimodal treatments into the surgical oncological concept, adapted to tumor location, stage, and individual patient risk factors and preferences is upcoming. Clearly, future developments will aim at identifying and selecting patients for ideal treatment alternatives.
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Affiliation(s)
- Claus Rödel
- Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany.
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Smith FM, Sheahan K, Hyland J, O'Connell PR, Winter DC. Authors' reply: The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy (Br J Surg 2012; 99: 993–1001). Br J Surg 2012. [DOI: 10.1002/bjs.8947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- F M Smith
- Surgical Professorial Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - K Sheahan
- Surgical Professorial Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - J Hyland
- Surgical Professorial Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - P R O'Connell
- Surgical Professorial Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - D C Winter
- Surgical Professorial Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
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Ceelen WP. Progress in rectal cancer treatment. ISRN GASTROENTEROLOGY 2012; 2012:648183. [PMID: 22970381 PMCID: PMC3437282 DOI: 10.5402/2012/648183] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/24/2012] [Accepted: 08/08/2012] [Indexed: 12/17/2022]
Abstract
The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a "wait and see" approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer.
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Affiliation(s)
- Wim P Ceelen
- Department of Surgery, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium
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Hingorani M, Hartley JE, Greenman J, Macfie J. Avoiding radical surgery after pre-operative chemoradiotherapy: a possible therapeutic option in rectal cancer? Acta Oncol 2012; 51:275-84. [PMID: 22150079 DOI: 10.3109/0284186x.2011.636756] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND In this modern era of multi-modality treatment there is increasing interest in the possibility of avoiding radical surgery in complete responders after neo-adjuvant long-course chemoradiotherapy (LCPRT). In this article, we present a systematic review of such treatments and discuss their therapeutic applicability for the future. METHODS We searched the PubMed online libraries to identify studies that reported on the long-term surgical and pathological outcomes after local excision together with those that explored the possibility of clinical observation only in patients achieving a complete clinical response after LCPRT. RESULTS Several retrospective (n = 10), one single-arm prospective, and one small randomised series have reported on the use of local excision after LCPRT and demonstrated acceptably low levels of local recurrence with survival comparable to patients progressing to conventional surgery. One prospective series allocated patients to observation or radical surgery based on histological parameters after local excision (ypT0 and ypT1) and showed no differences in outcomes. Two retrospective series from the same group on a Brazilian cohort of patients reported excellent long-term outcomes after "wait and watch" in complete clinical responders. However, other reports have shown no direct correlation between clinical and pathological response. CONCLUSION Local excision may be an appropriate option for selected patients developing good clinical response after LCPRT. In our opinion, a policy of clinical observation in complete clinical responders after LCPRT may not be a safe strategy, unless we had robust predictive models for accurate identification of pathological complete response. In order to identify patients that may be potentially appropriate for such an approach we propose a clinical algorithm incorporating important clinical, radiological, and pathological parameters. The proposed model will require validation in a prospective study. Finally, we need randomised data for demonstrating the non-inferiority of clinical observation compared to conventional surgery before this can be considered as standard possible therapeutic option.
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Smith FM, Chang KH, Sheahan K, Hyland J, O'Connell PR, Winter DC. The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy. Br J Surg 2012; 99:993-1001. [PMID: 22351592 DOI: 10.1002/bjs.8700] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Local excision of rectal cancer after neoadjuvant chemoradiotherapy (CRT) has been proposed as an alternative to radical surgery in selected patients. However, little is known about the significance of the morphological and histological features of residual tumour. METHODS Patients who had undergone CRT at the authors' institution between 1997 and 2010 were identified. Multiple features were assessed as putative markers of pathological response. These included: gross residual disease, diameter of residual mucosal abnormalities, tumour differentiation, presence of lymphovascular/perineural invasion and lymph node ratio. RESULTS Data from 220 of 276 patients were suitable for analysis. Diameter of residual mucosal abnormalities correlated strongly with pathological tumour category after CRT (ypT) (P < 0·001). Forty of 42 tumours downstaged to ypT0/1 had residual mucosal abnormalities of 2·99 cm or less after CRT. Importantly, 19 of 31 patients with a complete pathological response had evidence of a residual mucosal abnormality consistent with an incomplete clinical response. The ypT category was associated with both pathological node status after CRT (P < 0·001) and lymph node ratio (P < 0·001). Positive nodes were found in only one of 42 patients downstaged to ypT0/1. The risk of nodal metastases was associated with poor differentiation (P = 0·027) and lymphovascular invasion (P < 0·001). CONCLUSION In this series, the majority of patients with a complete pathological response did not have a complete clinical response. In tumours downstaged to ypT0/1 after CRT, residual mucosal abnormalities were predominantly small and had a 2 per cent risk of positive nodes, thus potentially facilitating transanal excision. The presence of adverse histological characteristics risk stratified tumours for nodal metastases.
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Affiliation(s)
- F M Smith
- Section of Surgery and Surgical Specialties, University College Dublin, Ireland.
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Glynne-Jones R. The Future of Rectal Cancer: Let's Do the Right Trials. J Clin Oncol 2011; 29:4057-9; author reply 4059-61. [DOI: 10.1200/jco.2011.37.1609] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Rob Glynne-Jones
- Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom
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Bujko K, Bujko M. Point: short-course radiation therapy is preferable in the neoadjuvant treatment of rectal cancer. Semin Radiat Oncol 2011; 21:220-7. [PMID: 21645867 DOI: 10.1016/j.semradonc.2011.02.008] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
There are 2 types of neoadjuvant radiation regimens accepted as standard for resectable rectal cancer: short-course (5 × 5 Gy) radiation therapy alone with immediate surgery and long-course combined chemoradiation therapy with delayed surgery. A Polish randomized study (n = 312) and an Australian randomized study (n = 326) compared these 2 schedules. Both trials showed a lower rate of early adverse effects using a short-course radiation regimen and no differences in long-term oncologic outcomes and late toxicity rates between groups. The small number of fractions makes short-course radiation less expensive and more convenient than chemoradiation therapy. These facts indicate that short-course radiation is preferable to chemoradiation for resectable cancers. Additionally, short-course preoperative radiation with a long interval to surgery is a valuable option for patients unfit for chemotherapy, with unresectable cancer or with a small tumor that is amenable to local excision. Moreover, short-course radiation enables the intensification of both radiotherapy and chemotherapy in patients with metastatic rectal cancer with potentially resectable synchronous metastatic disease.
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Affiliation(s)
- Krzysztof Bujko
- Department of Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland.
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Overgaard J. Advancing radiation oncology through scientific publication – 100 volumes of Radiotherapy and Oncology. Radiother Oncol 2011; 100:1-6. [DOI: 10.1016/j.radonc.2011.07.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Moraes RDS, Losso GM, Matias JEF, Mailaender L, Telles JEQ, Malafaia O, Coelho JCU. Microcirurgia endoscópica transanal e tratamento adjuvante no câncer retal precoce. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2011. [DOI: 10.1590/s0102-67202011000200005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
RACIONAL: A excisão total do mesorreto é considerada a operação padrão no tratamento dos tumores do reto, apesar de não existir comprovação científica de que ela deva ser usada para todos os estádios da doença. Tem sido demonstrado que em casos escolhidos de tumores retais, resultados promissores podem ser conseguidos com tratamento local por microcirurgia endoscópica transanal. Tais tumores, denominados de câncer retal precoce, são tumores T1 - menores do que 4 cm -, bem diferenciados sem invasão angiolinfática pT1 Sm1. Como o risco de comprometimento linfonodal nesses tumores é de aproximadamente 3%, a ressecção local teria grande chance de ser curativa. OBJETIVO: Apresentar os resultados de uma série prospectiva não randômica de pacientes portadores de câncer retal precoce submetidos ao tratamento local por microcirurgia endoscópica transanal. MÉTODOS: Entre 2002 e 2010, 38 pacientes avaliados por protocolo pré-operatório como portadores câncer retal precoce foram submetidos à ressecção local endoscópica microcirúrgica de toda a parede retal com o tumor quando localizado entre 2 e 8 cm da linha pectínea. A avaliação pré-operatória consistiu de toque retal, retossigmoidoscopia rígida para macrobiópsias, enema opaco e/ou colonoscopia, ultrassonografia endoretal e abdominal, tomografia axial computadorizada do abdome, radiografia do tórax e dosagem sérica do CEA. Realizou-se seguimento pós-operatório endoscópico e ultrassonográfico endoretal a cada três meses nos dois primeiros anos, e a cada seis nos próximos três anos, além de dosagem do CEA a cada seis meses nesse mesmo período de cinco anos. Avaliou-se a recidiva tumoral, morbidade e mortalidade. RESULTADOS: Após avaliação anatomopatológica da lesão, 29 cânceres retais precoces foram categorizados como de baixo risco e nove sendo de alto. O seguimento na série variou de um a sete anos. Recidiva tumoral foi confirmada em dois casos dos 38 (5,26%), uma lesão considerada de alto e a outra de baixo risco. CONCLUSÃO: Microcirurgia endoscópica transanal, associada ou não à quimioradioterapia, pode ser considerada atualmente o padrão-ouro na ressecção retal local, apresentando resultados animadores em casos escolhidos de tumores retais precoces de baixo risco.
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Preoperative intensified radiochemotherapy for rectal cancer: experience of a single institution. Int J Colorectal Dis 2011; 26:153-64. [PMID: 21107849 DOI: 10.1007/s00384-010-1064-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/04/2010] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of our study was to evaluate the feasibility and the effectiveness of an intensified neoadjuvant protocol with the addition of weekly oxaliplatin in the preoperative strategy of rectal cancer treatment. PATIENTS AND METHODS Patients with locally advanced rectal cancer received continous infusion 5-Fluorouracil (5-FU) 200 mg/m(2)/day in combination with weekly oxaliplatin at a dose of 50 mg/m(2). Doses of radiotherapy were 45 Gy to the whole pelvis plus 5.4-9 Gy to the tumour mass. The primary end-points of the study were evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response (pCR) and the rate of sphincter preservation for distal cancers. Secondary end-points were relapse-free and overall survival. RESULTS From November 2006 to June 2009, 51 patients were enrolled into the study. Compliance with chemotherapy was 80%. The incidence of G3 diarrhoea and proctitis were 17.6% and 21.5%, respectively. Surgery was performed in 48 patients with 100% R0 resection. 76.4% of low-lying tumours underwent conservative treatment. Seventy-nine percent of patients were downstaged: T and N downstaging were observed in 71% and 75% of patients, respectively. A pCR was obtained in 11 (22.9%) patients. CONCLUSIONS Intensification of neoadjuvant treatment for rectal cancer with the addition of weekly oxaliplatin is feasible, with remarkable rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. Phase III trials with a longer follow-up will establish whether this good outcome in terms of surrogate end-points will translate into better rates of disease-free and overall survival.
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Smith FM, Waldron D, Winter DC. Rectum-conserving surgery in the era of chemoradiotherapy. Br J Surg 2010; 97:1752-64. [PMID: 20845400 DOI: 10.1002/bjs.7251] [Citation(s) in RCA: 124] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND A complete pathological response occurs in 10-30 per cent of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy (CRT). The standard of care has been radical surgery with high morbidity risks and the challenges of stomata despite the favourable prognosis. This review assessed minimalist approaches (transanal excision or observation alone) to tumours with a response to CRT. METHODS A systematic review was performed using PubMed and Embase databases. Keywords included: 'rectal', 'cancer', 'transanal', 'conservative', 'complete pathological response', 'radiotherapy' and 'neoadjuvant'. Original articles from all relevant listings were sourced. These were hand searched for further articles of relevance. Main outcome measures assessed were rates of local recurrence and overall survival, and equivalence to radical surgery. RESULTS Purely conservative 'watch and wait' strategies after CRT are still controversial. Originally used for elderly patients or those who refused surgery, the data support transanal excision of rectal tumours showing a good response to CRT. A complete pathological response in the T stage (ypT0) indicates < 5 per cent risk of nodal metastases. CONCLUSION Rectal tumours showing an excellent response to CRT may be suitable for local excision, with equivalent outcomes to radical surgery. This approach should be the subject of prospective clinical trials in specialist centres.
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Affiliation(s)
- F M Smith
- Department of Surgery, Mid-Western Regional Hospital, Limerick, Ireland
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Lambrecht M, Deroose C, Roels S, Vandecaveye V, Penninckx F, Sagaert X, van Cutsem E, de Keyzer F, Haustermans K. The use of FDG-PET/CT and diffusion-weighted magnetic resonance imaging for response prediction before, during and after preoperative chemoradiotherapy for rectal cancer. Acta Oncol 2010; 49:956-63. [PMID: 20586658 DOI: 10.3109/0284186x.2010.498439] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate the use of FDG-PET/CT before, during and after chemoradiotherapy (CRT) and diffusion-weighted magnetic resonance imaging (DW-MRI) before CRT for the prediction of pathological response (pCR) in rectal cancer patients. MATERIAL AND METHODS Twenty-two rectal cancer patients treated with long course CRT were included. An FDG-PET/CT was performed prior to the start of CRT, after 10 to 12 fractions of CRT and five weeks after the end of CRT. The tumor was delineated using a gradient based delineation method and the maximal standardized uptake values (SUV(max)) were calculated. A DW-MRI was performed before start of CRT. Mean apparent diffusion coefficients (ADC) were determined. The ΔSUV(max) during and after CRT and the initial ADC values were correlated to the histopathological findings after total mesorectal excision (TME). RESULTS ΔSUV(max) during and after CRT significantly correlated with the pathological response to treatment (during CRT: ΔSUV(max) = 59% ± 12% for pCR vs. 25% ± 27% if no pCR, p=0.0036; post-CRT: 90% ± 11 for pCR vs. 63% ± 22 if no pCR p=0.013). ROC curve analysis revealed an optimal threshold for ΔSUV(max) of 40% during CRT and 76% after CRT. The initial ADC value was also significantly correlated with pCR (0.94 ± 0.12 × 10(-3) mm(2)/s for pCR vs. 1.2 ± 0.24 × 10(-3) mm(2)/s, p=0.002) and ROC curve analysis revealed an optimal threshold of 1.06 × 10(-3) mm(2)/s. Combining the provided ΔSUV(max) thresholds during and after CRT increased specificity of the prediction (sensitivity 100% and specificity 94%). The combination of the thresholds for the initial ADC value and the ΔSUV(max) during CRT increased specificity of the prediction to a similar level (sensitivity of 100% and specificity of 94%). CONCLUSIONS The combination of the different time points and the different imaging modalities increased the specificity of the response assessment both during and after CRT.
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Affiliation(s)
- Maarten Lambrecht
- Department of Radiation Oncology, Leuvens Kankerinstituut, University Hospitals Leuven, Leuven, Belgium
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Wygoda M, Rottenberg Y, Kadouri L, Pikarsky A, Hubert A. Preoperative Radiotherapy and Concurrent Chemotherapy with Bolus 5-Fluorouracil for Rectal Cancer: A Prospective Analysis of 98 Patients. TUMORI JOURNAL 2010; 96:709-12. [DOI: 10.1177/030089161009600512] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aims and background Surgical resection of rectal cancer is associated with a high pelvic recurrence rate. Preoperative large-fraction radiotherapy (RT) with a short interval after local excision has been associated with a significant improvement in locoregional recurrence rates and overall survival, but with high rates of toxicity. We here present the results of our combined-modality treatment protocol for patients with locally advanced rectal cancer. Methods Between September 1999 and June 2005, 98 patients were prospectively entered into the protocol. Eligibility criteria included any of the following: cT3-4 disease, clinically positive lymph nodes, or tumor located less than 6 cm from the anal verge. RT was delivered with a three-field technique to a dose of 45 Gy, plus an optional 5.4–9 Gy boost. Chemotherapy, administered concomitantly with RT, consisted of bolus 5-fluorouracil (5-FU) 500 mg days 1–5 followed by 5-FU 600 mg/m2 and leucovorin 50 mg on days 16, 23, 30 and 37. Surgery was performed 6–8 weeks after RT completion and was followed by 8 courses of 5-FU 900 mg/m2 and leucovorin 100 mg/m2 every 14 days. Results Low anterior resection was performed in 64.5% of the patients and in 38.8% of those with tumors located less than 6 cm from the anal verge. All patients except one had clear pathological margins, 68.8% had negative nodes, and pathological complete response was seen in 13.5%. With a median follow-up of 31.5 months, 3 patients (3.0%) had locoregional recurrence, 19 (19.3%) developed distant metastasis, and 10 patients (10.1%) died. The estimated median disease-free survival was 70.6 months. Grade 3 or 4 gastrointestinal toxicity was seen in 24.5% of the patients and 3.0% had neutropenic fever. One fatal toxicity occurred during treatment. Conclusions Our results suggest that our combined-modality treatment protocol is well tolerated and achieves high locoregional control in this unselected population. The overall survival results are also encouraging. Further studies are required to confirm the toxicity profile and survival results of this regimen. Free full text available at www.tumorionline.it
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Affiliation(s)
- Marc Wygoda
- Department of Oncology, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel
| | - Yakir Rottenberg
- Department of Oncology, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel
| | - Luna Kadouri
- Department of Oncology, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel
| | - Alon Pikarsky
- Department of Surgery, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel
| | - Ayala Hubert
- Department of Oncology, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel
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Clinical evidence on PET-CT for radiation therapy planning in gastro-intestinal tumors. Radiother Oncol 2010; 96:339-46. [DOI: 10.1016/j.radonc.2010.07.019] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2010] [Revised: 07/26/2010] [Accepted: 07/27/2010] [Indexed: 12/29/2022]
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Yeo SG, Kim DY, Kim TH, Kim SY, Chang HJ, Park JW, Choi HS, Oh JH. Local excision following pre-operative chemoradiotherapy-induced downstaging for selected cT3 distal rectal cancer. Jpn J Clin Oncol 2010; 40:754-60. [PMID: 20457724 DOI: 10.1093/jjco/hyq062] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE To investigate the long-term outcomes of selected patients with cT3 distal rectal cancer treated with local excision following pre-operative chemoradiotherapy. METHODS Between January 2003 and February 2008, 11 patients with cT3 distal rectal cancer received a local excision following pre-operative chemoradiotherapy. The median age of the patients was 61 years (range, 42-71). The median tumor size was 3 cm (range, 2-5), and the median distance of the caudal tumor edge from the anal verge was 3 cm (range, 1-4). Clinical lymph node status was positive in five patients. Pre-operative chemoradiotherapy consisted of a 50.4 Gy in 28 fractions with concurrent chemotherapy. A transanal full-thickness local excision was performed after a median of 54 days (range, 31-90) from chemoradiotherapy completion. Ten patients received post-operative chemotherapy. RESULTS Pathologically complete responses occurred in eight patients, ypT1 in two and ypT2 in one. The pathologic tumor size for three ypT1-2 tumors was 0.9, 1.1 and 2.2 cm. The follow-up period was a median of 59 months (range, 24-85). One patient (ypT0) developed recurrence at the excision site 14 months after surgery, but was successfully salvaged with an abdominoperineal resection and adjuvant chemotherapy. Another patient (ypT2) developed bone metastasis after 8 months and died of the disease. The 5-year local recurrence-free, disease-free and overall survival rates were 90.9%, 81.8% and 88.9%, respectively. No Grade 3 or worse gastrointestinal toxicity was detected. CONCLUSIONS Full-thickness local excision following chemoradiotherapy may be an acceptable option for cT3 distal rectal cancer that responds well to chemoradiotherapy.
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Affiliation(s)
- Seung-Gu Yeo
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea
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Hughes R, Corner C, Glynne-Jones R. Are there alternatives to radical surgery in rectal cancer? CURRENT COLORECTAL CANCER REPORTS 2009. [DOI: 10.1007/s11888-009-0033-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Rectal cancer multidisciplinary management: evidences and future landscape. Radiother Oncol 2009; 92:145-7. [PMID: 19596463 DOI: 10.1016/j.radonc.2009.06.026] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2009] [Accepted: 06/25/2009] [Indexed: 01/08/2023]
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