Published online Jan 15, 2018. doi: 10.4251/wjgo.v10.i1.40
Peer-review started: September 7, 2017
First decision: October 9, 2017
Revised: November 26, 2017
Accepted: December 4, 2017
Article in press: December 4, 2017
Published online: January 15, 2018
Currently, preoperative chemoradiation (CRT) is the preferred treatment regimen in locally advanced rectal cancer patients, owing to low local recurrence rates and higher chance of sphincter-sparing surgery. Besides conventional radiotherapy consisting of 45-50 Gy/1.8-2 Gy/5-6 wk, other radiotherapy schemes are also used. The hyperfractionated accelerated radiotherapy (HART) scheme reduces the risk of repopulation in tumor cells by shortening the treatment time and increases the repair capacity of normal tissues. In this background, a HART scheme and the combination of infusional 5-fluorouracil (5-FU) was examined in this study to augment the pathological complete response.
Local recurrence is still a substantial problem for locally advanced rectal cancers. Investigating tolerability and the effect of different radiotherapy schemes on local control other than conventional and hypofractionated radiotherapy can be a solution.
This study was mainly designed to observe the early and late effects of HART regimen in combination with neoadjuvant chemotherapy in patients diagnosed with locally advanced rectal cancer. The primary aim of this study was to search for possible therapeutic strategies that may help increase the rate of pathological tumor response and to decrease late side effects.
Previously untreated locally advanced rectal cancer patients with histological confirmation were included in the study. The patients were clinically staged according to positron emission-computed tomography and pelvic-diffusion magnetic resonance imaging. All patients received preoperative HART (42 Gy/1.5 Gy/18 d/bid) and concurrent continuous infusion of 5-FU (325 mg/m2) and were hospitalized during treatments to observe the possible acute side effects. Total mesorectal excision was performed 4-8 wk after the completion of chemoradiotherapy. Four cycles of 5-FU (400 mg/m2, D1-5, q 28 d) plus folinic acid (20 mg/m2, D1-5, q 28 d) were administered postoperatively. The primary endpoint was pathological response rate after CRT, and secondary endpoints included the local control rate, surgical margin positivity, survival and toxicity.
Thirty patients were included between October 2007 and March 2009. The median age was 53 years. Most of the patients clinically staged as T3N+ disease (90%). Surgery was performed at week 4 in half of the patients. Twelve patients (41%) underwent sphincter-sparing surgery. The Dworak total regression scoring system was used to evaluate pathological response, and grade IV (total) regression was found in 6 of 29 (21%) patients; nine patients (31%) had grade III (near total) regression. Positive margins were found in 2 patients (6.6%). One (3.3%) patient had local recurrence during a median follow-up of 60 mo. The 5-year disease-free survival rate was 53%, while the 5-year overall survival rate was 53.1%. There were no interruptions in RT due to toxicity, while in 4 patients chemotherapy was interrupted for 1 wk. Sixteen (53%) patients underwent adjuvant chemotherapy.
Improved local control rates and tumor regression may be achieved with HART but with higher acute toxicity. Toxicity could be reduced by giving chronomodulated concomitant chemotherapy or reducing the dose of 5-FU. Surgery timing has no effect on survival but still should be considered because of increased acute side effects due to HART fractionation. Besides an increased pathological response rate, this study showed no survival benefit.
Different HART schemes can be examined with concomitant chemotherapy in the future studies. Because of the high incidence of acute toxicity, fraction dose and chemotherapy doses should be designed properly for new studies.