Discussion
tumor, toxicity, infraperitoneal tumors, tumors, erectile dysfunction
RECURRENCES, TUMOR, RECURRENCE, ONCOLOGY, REGRESSION, TUMORS, RECTAL CANCER, ERECTILE DYSFUNCTION
To the authors’ knowledge, the current Istanbul R-02 Phase II study is the first prospective randomized study to compare the outcomes of IC-CRT and LC-CRT with a chronomodulated capecitabine (Brunch regimen) in LARC patients. The promising long-term data on the effectiveness of IC-CRT in LARC suggest that IC-CRT is associated with a similar pathological response and sphincter preservation rate to LC-CRT, as well as a better toxicity profile.The encouraging results in sphincter preservation and R0 surgery in the current study seem to indicate that the efficacy of IC-RT is equivalent to that of long-term RT and allows for a shorter course of RT with concomitant use of chronomodulated capecitabine (Brunch regimen). A reduced dose of capecitabine (64%) could decrease toxicity.The KROG 11-02 trial was a single-arm study conducted to evaluate a short CRT treatment protocol designed to prevent tumor repopulation by completing the therapy within two weeks and to increase the sensitivity of the tumor to radiation by using concurrent capecitabine. Surgery delayed in order to maximize the pathological response [Our previous phase II brunch regimen study was based on the use of chronomodulated (morning and noon) capecitabine according to a specific time schedule as a part of neoadjuvant chemoradiation therapy in patients with LARC. Complete tumor regression was detected in 20% of the patients and no instance of grade 4 toxicity was seen [In the current study, the pCR was 24% in the LC-CRT group and 17% in the IC-CRT group. Downstaging (ypT0-2N0) was detected in 50% of the patients in both groups. The RT scheme in the current study was similar to that used in the KROG 11-02 study and, the pCR rate was 13.8% (T0N0) and 33.8% had decreased stage (ypT0-2N0). The achievement of a better pathological response rate might be associated with the use of the brunch capecitabine regimen.In the KROG 11-02 study, the median interval until surgery was reported to be 7.5 weeks [Sphincter-sparing surgery and R0 resection are important success parameters of a neoadjuvant protocol. In our study, high rates of sphincter preservation and R0 resection close to those of the KROG-11 trial were obtained in both groups (LC-CRT: 87% and 90%, respectively, and IC-CRT: 77% and 90%, respectively) in infraperitoneal tumors. Three local recurrences were observed in the LC-CRT group among patients who had positive surgical margins; the recurrence ratio was 10% for LC-CRT patients and 5% for all of the patients. The numerically higher N+, distal tumors, and greater radiological CRM involvement may have increased the likelihood of local recurrence in LC-CRT group. Several prospective studies and the Istanbul R-01 study have demonstrated similar local recurrence rates. Further subgroup analyses revealed local recurrence to be significantly more common in patients with distal tumors (0–5 cm) than those with proximal tumors (16.2% In the current study, the baseline, third month, and sixth month-CR29 scores revealed no significant difference between groups. Although erectile dysfunction was reported significantly more frequently in the IC-CRT arm in our first series, published in American Society for Therapeutic Radiation Oncology 2018 [As a result of advancing knowledge in all of these areas of discussion, the treatment approach in rectal cancer has been shifting to a total neoadjuvant protocol and an organ-preserving approach in recent years [The primary limitation of our study is the small sample size. A larger number of cases and additional substantiating data will undoubtedly increase physicians’ confidence in IC-CRT.