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

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.

Detecting the Research Trends and Hot Spots in External Irradiation Therapy for Rectal Cancer

“…Michael J O'Connell et al reported that the addition of oxaliplatin to capecitabine combined with preoperative radiotherapy did not further improve the efficacy but significantly increased the toxicity [26]. However, data from Claus Rödel et al showed that adding oxaliplatin to fluorouracil-based neoadjuvant radiotherapy and adjuvant chemotherapy significantly increased disease-free survival in rectal cancer patients (clinically staged cT3-4 or cN1-2) and could be a new treatment option for locally advanced rectal cancer [25,45]. Regarding the exploration of adding adjuvant chemotherapy after neoadjuvant radiotherapy, a multicenter, phase 2 trial conducted by Julio Garcia-Aguilar et al showed that mFOLFOX6 administered after neoadjuvant radiotherapy may increase the rate of patients achieving pathologic complete response, and a phase 3 clinical trial is currently underway [27].…”

Predictive and Prognostic Factors Related to Chemoradioresistance in Neoadjuvant Treatment of Locally Advanced Rectal Cancer at Panama

“…Identification of factors that influence histological response can help predict prognosis and propose organ preservation for good responders. Multiple studies have correlated pathological complete response with disease-free survival and overall survival [4][5][6]. It is essential to increase complete pathological responses, but it is unclear what clinical factors are involved.…”

Exome and Tissue-Associated Microbiota as Predictive Markers of Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer

“…Several studies have evaluated the importance of clinical and pathological markers potentially associated with nCRT response. For instance, the pathological grade, tumor size, clinical stage determined by imaging techniques, pre-treatment levels of the carcinoembryonic antigen (CEA), nCRT and surgery intervals, and tumor budding, among others, may impact the nCRT response ( 1 , 9 – 11 ). More recently, molecular approaches such as the identification of gene mutations, gene expression profiles ( 12 ), genomic instability ( 13 ), and DNA methylation ( 14 ) have been evaluated in pCR prediction and some frequently mutated genes were identified ( 15 ).…”