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      Neoadjuvant therapy and surgery in rectal adenocarcinoma: analysis of patients with complete tumor remission Translated title: Terapia neoadjuvante e cirurgia no adenocarcinoma retal: análise dos pacientes com remissão tumoral completa no reto

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          Abstract

          INTRODUCTION: the standard treatment for locally advanced extra-peritoneal rectal adenocarcinoma, consists of neoadjuvant treatment with radiotherapy and chemotherapy followed by total mesorectal excision. OBJECTIVE: evaluate, retrospectively, the patients submitted to neoadjuvant therapy and surgery that presents with total remission of the lesion in the anatomopathological examination. METHODS: between 2000 and 2010, 212 patients underwent surgery at the Coloproctology Unit at DMAD at FCM-UNICAMP. They were grouped as: rectosigmoidectomy and colorectal anastomosis (n = 54), rectosigmoidectomy with coloanal anastomosis (n = 41), 114 abdominoperineal resection of the rectum (n = 114) and other (n = 3). RESULTS: thirty (14.2%) patients (mean age 57.6 years; 60% males) showed complete remission of the rectal lesion. 4 (13.3%) had compromised lymph nodes and/or lymphatic invasion At follow-up (mean 51.9 months), 4 (13.3%) presented with local recurrence (one patient) or distant metastases (two patients had liver metastasis, one had liver and lung, and one had bone metastasis). The mean survival was 86.7%. CONCLUSION: patients with a complete tumor response show ed an increased survival rate, however, the same patients without evidence of residual tumors could develop local recurrence or distant metastases on a later follow-up.

          Translated abstract

          INTRODUÇÃO: o tratamento padrão do adenocarcinoma de reto extra-peritoneal localmente avançado consiste de neoadjuvância com radio e quimioterapia, seguida de cirurgia com excisão total do mesorreto. OBJETIVO: avaliar, retrospectivamente, os pacientes submetidos à neoadjuvância e cirurgia, que apresentaram remissão completa da lesão no reto no exame anatomopatológico. MÉTODOS: foram avaliados 212 doentes, operados no Serviço de Coloproctologia da DMAD da FCM-Unicamp, entre 2000 e 2010. As cirurgias realizadas foram: retossigmoidectomia e anastomose colorretal (n = 54), retossigmoidectomia com anastomose coloanal (n = 41), amputação abdominoperineal do reto (n = 114) e outras (n = 3). RESULTADOS: trinta (14,2%) pacientes (média de idade de 57,6 anos; 60% do sexo masculino) apresentaram remissão tumoral completa no reto; destes, 4 (13,3%) tinham acometimento linfonodal e/ou invasão linfática. No seguimento pós-operatório (médio de 51,9 meses), 4 (13,3%) apresentaram recidiva local (um doente) ou metástases à distância (dois doentes com metástases hepáticas, uma hepática e pulmonar, e um outro metástase óssea). A sobrevida média do grupo foi de 86,7%. CONCLUSÃO: os pacientes com resposta tumoral completa no reto apresentaram elevada taxa de sobrevida, mas mesmo doentes sem evidência de tumor residual, podem apresentar recidiva local ou metástases à distância no seguimento tardio.

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          Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data.

          Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0-277). 5-year crude disease-free survival was 83.3% (95% CI 78.8-87.0) for patients with pCR (61/419 patients had disease recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95% CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40-0.73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The effect of pCR on disease-free survival was not modified by other prognostic factors. Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. None. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer.

            Neoadjuvant chemoradiotherapy for rectal cancer can result in complete disappearance of tumor and involved nodes. In patients without residual tumor on imaging and endoscopy (clinical complete response [cCR]) a wait-and-see-policy (omission of surgery with follow-up) might be considered instead of surgery. The purpose of this prospective cohort study was to evaluate feasibility and safety of a wait-and-see policy with strict selection criteria and follow-up. Patients with a cCR after chemoradiotherapy were prospectively selected for the wait-and-see policy with magnetic resonance imaging (MRI) and endoscopy plus biopsies. Follow-up was performed 3 to 6 monthly and consisted of MRI, endoscopy, and computed tomography scans. A control group of patients with a pathologic complete response (pCR) after surgery was identified from a prospective cohort study. Functional outcome was measured with the Memorial Sloan-Kettering Cancer Center (MSKCC) bowel function questionnaire and Wexner incontinence score. Long-term outcome was estimated by using Kaplan-Meier curves. Twenty-one patients with cCR were included in the wait-and-see policy group. Mean follow-up was 25 ± 19 months. One patient developed a local recurrence and had surgery as salvage treatment. The other 20 patients are alive without disease. The control group consisted of 20 patients with a pCR after surgery who had a mean follow-up of 35 ± 23 months. For these patients with a pCR, cumulative probabilities of 2-year disease-free survival and overall survival were 93% and 91%, respectively. A wait-and-see policy with strict selection criteria, up-to-date imaging techniques, and follow-up is feasible and results in promising outcome at least as good as that of patients with a pCR after surgery. The proposed selection criteria and follow-up could form the basis for future randomized studies.
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              Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer.

              Neoadjuvant chemoradiotherapy (CRT) has been proven to increase local control in rectal cancer, but the optimal interval between CRT and surgery is still unclear. The purpose of this study was to analyse the influence of variations in clinical practice regarding timing of surgery on pathological response at a population level. All evaluable patients who underwent preoperative CRT for rectal cancer between 2009 and 2011 were selected from the Dutch Surgical Colorectal Audit. The interval between radiotherapy and surgery was calculated from the start of radiotherapy. The primary endpoint was pathological complete response (pCR; pathological status after chemoradiotherapy (yp) T0 N0). A total of 1593 patients were included. The median interval between radiotherapy and surgery was 14 (range 6-85, interquartile range 12-16) weeks. Outcome measures were calculated for intervals of less than 13 weeks (312 patients), 13-14 weeks (511 patients), 15-16 weeks (406 patients) and more than 16 weeks (364 patients). Age, tumour location and R0 resection rate were distributed equally between the four groups; significant differences were found for clinical tumour category (cT4: 17·3, 18·4, 24·5 and 26·6 per cent respectively; P = 0·010) and clinical metastasis category (cM1: 4·4, 4·8, 8·9 and 14·9 per cent respectively; P < 0·001). Resection 15-16 weeks after the start of CRT resulted in the highest pCR rate (18·0 per cent; P = 0·013), with an independent association (hazard ratio 1·63, 95 per cent confidence interval 1·20 to 2·23). Results for secondary endpoints in the group with an interval of 15-16 weeks were: tumour downstaging, 55·2 per cent (P = 0·165); nodal downstaging, 58·6 per cent (P = 0·036); and (near)-complete response, 23·2 per cent (P = 0·124). Delaying surgery until the 15th or 16th week after the start of CRT (10-11 weeks from the end of CRT) seemed to result in the highest chance of a pCR. © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                jcol
                Journal of Coloproctology (Rio de Janeiro)
                J. Coloproctol. (Rio J.)
                Sociedade Brasileira de Coloproctologia (Rio de Janeiro )
                2317-6423
                December 2013
                : 33
                : 4
                : 222-227
                Affiliations
                [1 ] Universidade Estadual de Campinas Brazil
                [2 ] Universidade Estadual de Campinas Brazil
                Article
                S2237-93632013000400222
                10.1016/j.jcol.2013.08.008
                938cb304-c627-41e4-b215-657965118b68

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=2237-9363&lng=en
                Categories
                GASTROENTEROLOGY & HEPATOLOGY
                SURGERY

                Gastroenterology & Hepatology,Surgery
                Rectal cancer,Neoadjuvant therapy,Surgery,Câncer retal,Terapia neoadjuvante,Cirurgia

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