Simple Steps to Achieving HRCTV D90 Dose Escalation in HDR Image Guided Brachytherapy for Cervix Cancer

Total combined dose from external beam radiotherapy (EBRT) and brachytherapy (BT) >85Gy to HRCTV D90 is associated with increased local control in cervix cancer. To achieve this dose, particularly for bulky tumours, may require more complex intracavitary/interstitial (IC/IS) brachytherapy insertions. Analysis of our patient demographic was performed to establish adherence with this planning aim with our current protocol for EBRT and BT. Simple changes to EBRT and BT dose/fractionation by reducing EBRT dose and increasing the number of BT fractions were modelled to assess the potential for dose escalation and to establish the proportion of patients likely to require IC/IS insertions. Patients who completed definitive chemoradiotherapy and BT for locally advanced cervix cancer (LACC) between July 2011 and November 2014 were studied. Image guided brachytherapy plans optimised to deliver >85 Gy to HRCTV D90 whilst maintaining organ at risk (OAR) constraints (D2cc of <90Gy bladder and <70-75Gy for rectum and sigmoid) were analysed according to 1) current protocol: EBRT 50.4Gy in 28 fractions, BT 16.5 Gy in 3fractions. 2) adapted protocol: EBRT 45Gy in 25 fractions, BT 22Gy in 4 fractions. Endpoints of HRCTV D90, D98 and D100 were compared for the 2 protocols. In patients where the planning aims could not be met tumour volume at the time of BT and initial response to EBRT were examined and correlated with outcome. 62 patients with LACC were identified. 7 were excluded due to uterine perforation during BT (n=4),completed <3 fractions BT (n=2) and non-standard EBRT dose (n=1), leaving 55 patients suitable for evaluation. Using the current protocol, 37 patients (67%) received <85Gy to D90 HR-CTV (median dose 79.1Gy, SD 7.37, range 57.7 - 84.3 Gy). Following adaptation of the EBRT/BT dose fractionation 19 of 37 patients (51%) achieved D90 HR-CTV >85Gy while maintaining OAR constraints (median dose 90.3Gy, SD 2.24, range 85.1-92.5Gy). The adapted protocol also permitted dose escalation beyond 85Gy: for the entire cohort, HRCTV dose could be escalated on average by 4.05 Gy (range -10.4 - 19.7, SD 5.26) with a median dose of 90.3Gy delivered (range 55.7-94.9Gy, SD 9.85). Despite adaptation, 18 plans (32% of all patients) did not reach the planning aim. Of these, 12 patients had tumours in excess of 30cc in volume (initial FIGO stage IIB =7, Stage IIIB =5) 50% of these 12 patients had an initial partial response to EBRT, 50% had stable disease. Residual tumour volume > 30cc at brachytherapy was associated with a relapse in 7 patients (58%) 3 patients (43%) relapsed distally, 4 patients (57%) relapsed locally. The median time to relapse was 4 months from completion of treatment. Median OS in this group was 13 months (range 5-22 months, SD 6.37). Over 50% of our population not currently meeting planning aims can be dose escalated though simple changes in EBRT and BT dose fractionation. We estimate a requirement for combined IC/IS insertions in 20% of all cases to achieve HR CTV D90 > 85Gy who may be identified as those with poorly responding tumours and residual disease >30cc at time of BT. Dose escalation with these steps should result in improved local control for all groups.