Predictive factors for tumour response after the neoadjuvant-treatment of rectal adenocarcinoma

Journal of Coloproctology - Tập 40 - Trang 112-119 - 2020
Carolina De la Pinta1, Margarita Martín1, Asunción Hervás1, Luis Cristian Perna1, Eva Fernández-Lizarbe1, Fernando López1, Víctor Jose Duque1, Sonsoles Sancho1
1Radiation Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain

Tóm tắt

Abstract Purpose Standard of care for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. This study identified predictive factors for tumour response in our series. Patients and methods Between January 2005 and December 2018, 292 patients with locally advanced rectal cancer treated by preoperative chemo-radiation before surgery were retrospectively analyzed. The radiation dose was 50.4 Gy with fluoropyrimidine-based chemotherapy regimens. Patients-tumour and treatment-factors were tested for influence on tumour down staging and regression grade using Mandard scoring system on surgical specimens (TRG). Results Median age was 69 years (range 39–87); 33.9% of patients was Stage II and 54.5% Stage IIIB. Tumour down staging occurred in 211 patients (73%), including 63 patients (21.6%) with ypT0 (documented T0 at surgery) and 148 patients (50.7%) with a satisfactory tumour regression grade defined as TRG2–3. Upper rectal tumours were identified to predictive factors for pathologic complete response by univariate analysis (p = 0.002). TRG1–3 was associated with intervals from chemo-radiation to surgery (p = 0.004); TRG1–3 rates were higher with longer intervals: 1.71% in ≤ 5 weeks, 23.63% in 6–8 weeks and 46.9% in ≥ 9 weeks; and PTV 50.4 ≥ 800cc (p = 0.06); 3 and 5 years survivals were 85% and 90% for the group as a whole. Among ypT0 cases, the overall survival was 91.1% without significantly different (p = 0.25) compared with the remaining group, 87.2%. Among ypT0 cases, the relapse-free survival was 94.5%, with significantly different (p = 0.03) compared with the remaining group 78.2%. There were no treatment-associated fatalities. Thirty-two patients (10.96%) experienced Grade III/IV toxicities (proctitis, ephitelitis and neutropenia). Conclusions Tumour localization was identified as predictive factors of pathologic complete response for locally advanced rectal cancer treated with preoperative chemo-radiation. Upper rectal tumours are more likely to develop complete responses. Delay in surgery was identified as a favorable predictive factor for TRG1–3. The relapse-free survival in pathologic complete response group was higher compared with non-pathologic complete response.

Tài liệu tham khảo

Globocan database: http://gco.iarc.fr. Sauer, 2004, German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer, N Engl J Med, 351, 1731, 10.1056/NEJMoa040694 Mandard, 1994, Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma, Clinicopathol Correl Cancer, 73, 2680 Maas, 2010, Long term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data, Lancet Oncol, 11, 835, 10.1016/S1470-2045(10)70172-8 de Campos-Lobato, 2011, Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence, Ann Surg Oncol, 18, 1590, 10.1245/s10434-010-1506-1 Park, 2012, Neoadjuvant treatment response as an early response indicator for patients with rectal cancer, J Clin Oncol., 30 Yeo, 2010, Pathologic complete response of primary tumor following preoperative chemoradiotherapy for locally advanced rectal cancer: long-term outcomes and prognostic significance of pathologic nodal status (KROG 09-01), Ann Surg., 252, 10.1097/SLA.0b013e3181f3f1b1 Glimelius, 2013, ESMO Guidelines Working Group. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up, Ann Oncol, 248, 81, 10.1093/annonc/mdt240 Diaz-Gonzalez, 2007, Rectal cancer treatment: improving the picture, World J Gastroenterol, 13, 5805, 10.3748/wjg.v13.i44.5805 Agarwal, 2013, Quantified pathologic response assessed as residual tumor burden is a predictor of recurrence-free survival in patients with rectal cancer who undergo resection after neoadjuvant chemoradiotherapy, Cancer, 119, 10.1002/cncr.28331 Habr-Gama, 2006, Assessment and management of the complete clinical response of rectal cancer to chemoradiotherapy, Colorectal Dis, 8, 21, 10.1111/j.1463-1318.2006.01066.x Maas, 2011, Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer, J Clin Oncol, 29, 4633, 10.1200/JCO.2011.37.7176 De La Pinta, 2019, Magnetic resonance imaging value to predict pathologic staging in Locally Advanced Rectal Cancer after neoadjuvant chemoradiation, Turk J Colorectal Dis, 29, 39, 10.4274/tjcd.galenos.2018.36024 Das, 2007, Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer, Cancer, 109, 1750, 10.1002/cncr.22625 Huang, 2018, Comparison of efficacy and safety of preoperative chemoradiotherapy in locally advanced upper and middle/lower rectal cancer, Radiat Oncol, 13, 53, 10.1186/s13014-018-0987-0 You, 2015, Tailored selection of the interval between neoadjuvant chemoradiotherapy and Surgery for locally advanced rectal cancer: analysis based on the pathologic stage or chemoradiation response, J Cancer Res Clin Oncol, 141, 719, 10.1007/s00432-014-1843-8 Tulchinsky, 2008, An interval & 7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease- free survival in patients with locally advanced rectal cancer, Ann Surg Oncol, 15, 2661, 10.1245/s10434-008-9892-3 Du, 2018, Optimal interval to surgery after neoadjuvant chemoradiotherapy in rectal cancer: a systematic review and meta-analysis, Clin Colorectal Cancer, 17, 13, 10.1016/j.clcc.2017.10.012 Ryan, 2019, Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer, Br J Surg, 106, 1298, 10.1002/bjs.11220 Huntington, 2016, Optimal timing of surgical resection after radiation in locally advanced rectal adenocarcinoma: an analysis of the National Cancer Database, Ann Surg Oncol, 23, 877, 10.1245/s10434-015-4927-z Liu, 2019, The relationship between primary gross tumor volume and tumor response of locally advanced rectal cancer: pGTV as a more accurate tumor size indicator, J Invest Surg, 22, 1 Patel, 2016, Distance to the anal verge is associated with pathologic complete response to neoadjuvant therapy in locally advanced rectal cancer, J Surg Oncol, 114, 637, 10.1002/jso.24358 Restivo, 2013, Elevated CEA levels and low distance of the tumor from the anal verge are predictors of incomplete response to chemoradiation in patients with rectal cancer, Ann Surg Oncol, 20, 864, 10.1245/s10434-012-2669-8 Sun, 2017, A nomogram predicting pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer: implications for organ preservation strategies, Oncotarget, 8, 67732, 10.18632/oncotarget.18821 Aschele, 2011, Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial, J Clin Oncol, 29, 2773, 10.1200/JCO.2010.34.4911 Gérard, 2010, Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2, J Clin Oncol, 28, 1638, 10.1200/JCO.2009.25.8376 O’Connell, 2014, Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04, J Clin Oncol, 32, 1927, 10.1200/JCO.2013.53.7753 Rödel, 2015, Lancet Oncol, 16, 979, 10.1016/S1470-2045(15)00159-X