Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+rectal cancer:Istanbul R-02 phase II randomized study

Radiation therapy(RT)is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer(LARC):short-course RT(SC-RT)alone or long-course RT(LC-RT)with concurrent fluorouracil(5-FU)chemotherapy.The Phase II single-arm KROG 11-02 study using intermediate-course(IC)(33 Gy(Gray)/10 fr(fraction)with concurrent capecitabine)preoperative chemoradiotherapy(CRT)demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT.The current trial aim to compare the pathological/oncological outcomes,toxicity,and quality of life results of LC-CRT and IC-CRT in cases of LARC.The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group.Concurrent chronomodulated capecitabine(Brunch regimen)1650 mg/m2/daily chemotherapy treatment was applied in both groups.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module(EORTC QLQ-CR29)was administered at baseline and at three and six months after CRT.A total of 60 patients with LARC randomized to receive IC-CRT(n=30)or LC-CRT(n=30)were included in this phase II randomized trial.No significant difference was noted between groups in terms of pathological outcomes,including pathological response rates(ypT0N0-complete response:23.3%vs.16.7%,respectively,and ypT0-2N0-downstaging:50%for each;p=0.809)and Dworak score-based pathological tumor regression grade(Grade 4-complete response:23.3 vs.16.7%,p=0.839).The 5-year overall survival(73.3 vs.86.7%,p=0.173)rate was also similar.The acute radiation dermatitis(p<0.001)and any hematological toxicity(p=0.004)rates were significantly higher in the LC-CRT group,while no significant difference was noted between treatment groups in terms of baseline,third month,and sixth month EORTC QLQ-CR29 scores.

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase Ⅱ study

AIM To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy(HART)and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil(325 mg/m^2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS In the early phase of treatment, 6 patients had grade Ⅲ-Ⅳ gastrointestinal toxicity, 2 patients had grade Ⅲ-Ⅳ hematologic toxicity, and 1 patient had grade Ⅴ toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade Ⅳ tenesmus. Complete pathological response was achieved in 6 patients(21%), while near-complete pathological response was obtained in 9(31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively.CONCLUSION Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.