Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma

Abstract

Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco- regional control with a conventional schedule.

Materials and methods: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin 40 mg/m2. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7 Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7 Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin 20 mg/m2/day was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months.

Results: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were 65±12 and 48±4 days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade≥3 toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome.

Conclusions: In the setting of concurrent chemo- radiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.