Clinical comparison of toxicity pattern of two linear quadratic model-baesd fractionation schemes of high-dose-rate intracavitary brachytherapy for cervical cancer

Introduction: Carcinoma cervix is the fourth (GLOBACON 2012) most common cancer among women worldwide, and the main cancer affecting women in Sub-Saharan Africa, Central America and south-central Asia. In India, approx. 1,23,000 (GLOBACON 2012) new cases of carcinoma cervix are diagnosed each year. Brachytherapy is an integral part of treatment of cancer cervix. In the context of a developing country like us where maximum utilization of the resource is of prime importance to provide treatment to the large patient cohort, shortening the treatment duration and number of fractions always increases efficiency. In order to maximize the logistic benefits of HDR-BT while improving patient compliance and resource sparing, various fractionation regimens are used. Fractionation and dose adjustments of the total dose are radiobiologically important factors in lowering the incidence of complications without compromising the treatment results. Aim: To compare patient outcomes and complications using two linear-quadratic model-based fractionation schemes of high-dose-rate intracavitary brachytherapy (HDR-IC) used to treat cervical cancer. Materials and Methods: A prospective randomized study on 318 patients, with histologically proven advanced carcinoma cervix (stages IIB-IIIB) was enrolled in the study. All patients received External Beam Radio Therapy (EBRT) 50 Gy in 25 fractions with concurrent chemotherapy (cisplatin 35 mg/m2) followed by IntraCavitary brachytherapy using high dose rate equipment. Patients were randomised after completion of EBRT into two arms: (1) Arm 1: HDR ICRT 6.5 Gy per fraction for 3 fractions, a week apart. (2) Arm 2: HDR ICRT, 9 Gy per fraction for 2 fractions, 1 week apart. On completion of treatment, patients were assessed monthly for 3 months followed by 3 monthly thereafter. Treatment response was assessed according to WHO criteria after one month of completion of radiotherapy. The RTOG criteria were used for radiation induced toxicities. We analyzed late toxicities in terms of Rectal, Bladder, Small Bowel toxicity and Vaginal Stenosis. Results: Acute reactions in both the groups were comparable. None of the patient developed Grade 4 toxicity in our study and no toxicity related mortality was encountered. A slightly high frequency of late toxicity was observed in 9Gy Arm patients but was not statistically significant. Conclusion: In our setup, HDR brachytherapy at 9 Gy per fraction in two fractions is safe, effective and resource saving method with good local control, survival, and manageable normal tissue toxicity.