Abstract Book

S35

ESTRO 37

OC-0074 Image-guided brachytherapy in cervical cancer: Total Reference Air Kerma predicts bowel toxicity S. Bockel 1 , A. Escande 2 , E. Manea 1 , M. Khettab 1 , F. Busato 1 , T. Kumar 1 , L. Laurans 1 , I. Dumas 1 , R. Mazeron 1 , I. Lazarescu 1 , E. Deutsch 1 , C. Haie-Meder 1 , C. Chargari 1 1 Institut Gustave Roussy, Radiotherapy, Villejuif, France 2 Oscar Lambret Comprehensive Cancer Center, Radiotherapy, Lille, France Purpose or Objective To date, no significant dose-volume effect relationship has been demonstrated to predict late bowel or sigmoid bowel toxicity in locally advanced cervical cancer (LACC) patients (pts) receiving chemoradiation plus image guided adaptive brachytherapy (IGABT). In fact, dose volume parameters, such as the D 2cm3, are highly uncertain due to mobility of the bowel. The total reference air kerma (TRAK) is the sum of the products of the Reference Air Kerma Rate and the irradiation time for each source. It is directly proportional to the integral dose to the pts. Recent data showed that the TRAK accurately predicted isodose surface volumes in cervix cancer IGABT. This study aims to examine correlation between and late bowel toxicities in pts receiving pulse dose rate (PDR) IGABT. Material and Methods Clinical data of 260 LACC pts treated with curative intent in our institution from 2004 to 2016 were examined. Pts received external beam radiotherapy (EBRT) +/- concomitant chemotherapy and a PDR-IGABT boost. Objective was to deliver at least 60Gy to 90% of the CTV IR and 85Gy to the D90 of the CTV HR . For the sigmoid bowel, D 2cm3 was kept <70-75 Gy EQD2 . For small bowel, loops closed to CTV were delineated, but no dose constraint was applied. Bowel toxicity (including sigmoid toxicity) was examined as occurrence of late morbidity assessed using Common Terminology Criteria for Adverse event 4.03 considering following events: diarrhea, flatulence, abdominal pain, obstruction, stenosis, bowel fistula. The relationships between TRAK and toxicity were assessed using survival estimation model by Kaplan-Meier, log-rank tests and Cox proportional-hazards model on event-free periods with the exclusion of recurrences. Results With median follow-up of 5 years (Interquartile [IQ] 4.5- 5.4), late bowel toxicity Grade (Gr) ≥2 occurred in 56 pts (21.5%). Probability of survival without late bowel toxicity Gr≥2 rate for pts without recurrence (n=174) at 5 years was 82.4 (76.1–88.7). The mean TRAK was 1.7cGy at 1m (IQ: 1.51–1.88). The following variables were associated with higher probability of late bowel toxicity Gr≥ 2: smoking (p=0.029), larger CTV HR (p=0.007), higher D 2cm3 sigmoid (trend, p=0.073) and TRAK>1.8 cGy at 1m (p=0.014). Larger CTV HR volumes were correlated with higher TRAK (p<0.001). In multivariate analysis, including smoking status, a TRAK>1.8 cGy at 1m was significantly associated with more frequent bowel toxicity, with HR=6.45 (95%confidence interval: 1.22–34.19). Conclusion In this single center cohort of PDR-IGABT, TRAK was predictive of late bowel/sigmoid bowel toxicities Gr≥2. These data suggest that the integral dose (and therefore the reference isodose volume) should be considered, even in the era of IGABT, and that dose volume constraints applied to organs at risk D 2cm3 might not fully reflect the expected toxicity of treatments.

and 3 Gy (late adverse effects) using a predictive model based on Total Reference Air Kerma (TRAK). ISVs and conformity index (CI) were evaluated for IC and IC/IS BT using T&R or T&O applicators.

Results Median CTV HR

D 90%

and CTV HR

volume were 89.9 Gy and

28.4 cm 3 , respectively. The median CTV HR volume treated with IC/IS-BT was 38.0 cm 3 versus 23.6 cm 3 for IC-BT. Median EQD2 10 V85Gy , V75Gy and V60Gy were 71 cm 3 , 99 cm 3 and 230 cm 3 , respectively, and depended on CTV HR volume (Table 1). Median V85Gy was 24% smaller than in standard 85 Gy Point A prescription. 37% of patients were treated with ISVs similar to standard loading with 75 – 85 Gy Point A prescription (Figure 1). 42% of patients were treated with V85Gy smaller than with standard 75 Gy at Point A, proving volume de-escalation with IGABT (Figure 1). 21% of patients, of which two thirds had large CTV HR (> 35cm 3 ), were treated with V85Gy larger than in standard 85 Gy Point A prescription to ensure adequate target coverage (Figure 1). T&R was more conformal than T&O with CI being 23% and 16% smaller for T&R in the IC and IC/IS groups, respectively. CI was 9% and 17% smaller for IC/IS than for IC in T&R and T&O groups, respectively. For the same treated V85Gy for EQD2 10 , the corresponding V85Gy for EQD2 3 were, on average, 30% larger for HDR and 14% for PDR. Conclusion The MR-IGABT led to improved target coverage/ conformity while the irradiated volumes on average were reduced compared to standard plans. The ISVs depended strongly on CTV HR volume proving dose adaptation according to individual response. Dose conformity increased with the use of T&R and with more frequent application of IC/IS implants.