A prospective randomised study comparing three-fraction regiments of HDR

Abstract

ABSTRACT Purpose Cancer of uterine cervix is one of the leading malignancies affecting the South African female population. In recent years, High Dose Rate (HDR) brachytherapy in combination with External Beam Radiotherapy (EBRT) has been popular in the management of cancers of uterine cervix. Various fractionations regimens of HDR are used in different centres. This randomized prospective study reports the treatment results and incidence of bladder and rectal complications following radical treatment of carcinoma of cervix with standard EBRT and 2, 3 or 4 fractions of HDR brachytherapy. Methods and Materials Sixty-six patients with biopsy proven stage IIB and stage IIIB cancer of cervix were recruited. All patients were treated radically and received EBRT 50 Gy in 25 fractions at 2 Gy per fraction. Almost all patients received concomitant Cisplatin 80 mg/m2 3 weekly. Patients were then randomized into one of the three-fractionation regimens of HDR: 6.5 Gy x 4; 8 Gy x 3; and 9 Gy x 2. Each HDR application wasevaluated separately. AP and lateral radiographs were taken. ICRU rectum, bladder, and PSW reference point were identified. Using the linear quadratic formula, the biologically effective dose to the tumour using an a/β ratio of ten (Gy10) was calculated at point A in order to determine a dose response relationship for local control. The biologically effective dose to organs at risk was calculated using an a/b ratio of 3 and this was used to assess the complication rates of the treatment. Patients were evaluated using SOMA Lent toxicity criteria during the treatments, at 6 weeks and finally at 6 months when Pap-smears were performed to assess local control. Results Sixty-six patients were entered in this study. Fifty-nine completed chemoradiotherapy and attended both 6 weeks and 6 months follow up and evaluations. The mean age of the patients was 51.6 years and the mean duration of the treatment was 47.2 days. Of the 59 patients who completed treatment and had six months follow up, 29 patients were stage IIB and 30 were stage IIIB. The overall complete response rate for the whole group was 88%. The response rate was 90% in arm I, 85.7% in arm II, and 88.8 in arm III, which was not statistically significant (p=0.463). The following prognostic factors were analysed to assess their influence on local control and found to be not significant: stage (IIB vs. IIIB) (p=0.995), age above and below 50 years (p=0.532), treatment duration (p=0.6508), and number of fields used (p=0.603). The adverse effects of radiation-induced toxicity depended on age group (p=0.01), number of fields (p=0.001), and BED Gy3 dose to organ at risk were statistically significant (p=0.001). The rectal, grade 3 and 4 radiation induced toxicity were observed to be increased when the BED Gy3 dose was above 105 Gy3. Similarly, bladder grade 3 & 4 toxicity rate were increased with BED Gy3 dose of 120 Gy3 (p=0.001). Conclusion Limiting the number of HDR brachytherapy applications from 4 or 3 to 2 fractions has the potential benefit of improving patient compliance. Two HDR applications of 9 Gy each is most cost effective and resource sparing to the institution compared to 3 or 4 insertions. This study showed that 9 Gy  2 fractionations HDR brachytherapy with concomitant chemo-radiotherapy was equally effective in short term local control and incidence of treatment related complications compared to other 2 fractionation regimens during 6 months follow up.