An observational study of extending FOLFOX chemotherapy, lengthening the interval between radiotherapy and surgery, and enhancing pathological complete response rates in rectal cancer patients following preoperative chemoradiotherapy

Abstract

Introduction:Patients with rectal cancer who exhibit a pathologic complete response to preoperative concurrent chemoradiotherapy have excellent oncologic outcomes. In this study, we evaluated the potential advantages of adding oxaliplatin to preoperative fluoropyrimidine-based chemoradiotherapy administered in rectal cancer patients.Methods:A total of 78 patients with rectal cancer were enrolled. Patients were administered chemoradiotherapy, which comprised radiotherapy and chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Surgery was performed 10–12 weeks after radiotherapy completion. Tumor regression, adverse events, surgical complications, and short-term clinical outcomes were recorded.Results:Two patients were excluded because of incomplete radiotherapy treatment or refusal of surgery. Eventually, 76 patients underwent total mesorectal excision and no perioperative mortality was observed. Of these, 20 patients (25.6%) developed grade 3 or 4 toxicity during concurrent chemoradiotherapy. Among the 76 patients who underwent surgery, 24 (31.6%) patients achieved a pathologic complete response. The sphincter preservation rate was 96.1% (73/76) in all patients and 92.2% (39/42) in patients with tumors located less than 5 cm from the anal verge. The 2-year overall and disease-free survivals were 94% and 87.4%, respectively.Conclusion:The intensified multimodality therapy was well tolerated in our cohort and resulted in a considerably high pathologic complete response rate. Regardless of favorable short-term clinical outcomes, long-term oncologic outcomes will be closely monitored among the patients with a pathologic complete response.

Predictive Value of FOLFOX-Based Regimen, Long Interval, Hemoglobin Levels and Clinical Negative Nodal Status, and Postchemoradiotherapy CEA Levels for Pathological Complete Response in Patients with Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy

“…For patients with LARC following neoadjuvant CRT, patients achieving a pCR have had higher survival rates than those who did not [5,21]. In this study, patients who achieved a pCR had a better OS and DFS compared with those who did not.…”

“…However, the literature shows inconsistent treatment response to neoadjuvant CRT, ranging from a pathological complete response (pCR) to total resistance. A pCR to neoadjuvant CRT has been associated with a low rate of recurrence and favorable survival, but the incidence of pCR has ranged from 10% to 30% [2][3][4][5][6][7][8].…”

“…Some clinical parameters and molecular biomarkers have been reported to be predictors of a pCR to neoadjuvant CRT for patients with LARC [9][10][11]. Several clinical factors, such as pretreatment T or N stage, serum carcinoembryonic antigen (CEA), chemotherapy regimen, and radiation dose, have been associated with a pCR [5,[12][13][14][15][16]. Few studies have investigated the effect of treatment-related hematologic toxicity on a pCR.…”

Surgical treatment following neoadjuvant chemoradiotherapy in locally advanced rectal cancer

“…In 2016, a FOLFOX‐based NCRT regimen with a longer time interval (median: 76 days) between RT completion and robotic surgery in 26 LARC patients resulted in a pCR in 14 patients . An intensified FLOFOX‐based NCRT regimen with an extended interval of 10‐12 weeks between RT and surgery was well tolerated in rectal cancer patients, and it engendered improved pCR rates (31.6%) without increasing adverse events . An extended interval between RT and surgery has promising benefits for enhancing pCR rates and warrants further investigation in clinical trials.…”

“…55 An intensified FLOFOX-based NCRT regimen with an extended interval of 10-12 weeks between RT and surgery was well tolerated in rectal cancer patients, and it engendered improved pCR rates (31.6%) without increasing adverse events. 56 An extended interval between RT and surgery has promising benefits for enhancing pCR rates and warrants further investigation in clinical trials. 3,32 Considering the heterogeneity among literature reviews, the ESMO panelists did not recommend NCRT for upper rectal cancers (>12 cm from the anal verge) above the peritoneal reflection.…”