Abstract Book

S132

ESTRO 37

7 Mount Vernon Hospital, Mount Vernon Centre for Cancer Treatment, Middlesex, United Kingdom Purpose or Objective The EMBRACE study (www.embracestudy.dk) includes treatment and clinical outcome data of patients with locally advanced cervical cancer from 23 centers who were treated with radiochemotherapy (EBRT and MRI- guided brachytherapy (IGBT)), between 2008 and 2016. The aim of this investigation is to study the implementation of the IGBT technique based on a variety of institutional protocols in EMBRACE, in comparison with expected dosimetric results for the future prospective dose EMBRACEII study, which applies advanced image- guided EBRT and BT through a specific prescription protocol. Material and Methods 1304 patients were included in this analysis. Total treatment dose for CTV HR and organs at risk (OARs) was calculated using the linear quadratic model for biologically equivalent dose (EQD2) using a/b=3Gy for OARs, and a/b=10Gy for CTV HR . Results were compared to specific hypotheses on technique, doses and volumes defined in the EMBRACEII protocol (Tab.1, col.1) as well as to an intermediate EMBRACE study report from the time of EMBRACEII protocol development (2014/15), cited in the study protocol. (Tab.1, col.2). Patients were grouped by volumes of CTV HR ≤/> 30cm³ for investigation of the frequency of the use of intracavitary (ic) or intracavitary+interstital (ic/is) application techqniques and the fraction of cases with CTV HR D 90 >85Gy 10 . For the whole cohort, the fraction of cases with total D 2cm³ <80Gy 3 (bladder) and <65Gy 3 (rectum) were calculated and compared to the fraction of patients expected to stay below these doses for EMBRACEII. Vaginal dose was evaluated based on the mean fraction of the total reference air kerma delivered by the vaginal applicator (ring or ovoid) and the fraction of cases with total doses to the rectovaginal ICRU point (ICRU RV) <65Gy 3 was calculated. Results The difference between the status of EMBRACE at the time of development of the EMBRACEII protocol and the current analysis of the complete EMBRACE cohort (Tab. 1), indicates an increased use (~10%) of interstitial applicators for large CTV HR volumes, to reach high prescribed D 90 doses, towards the end of the EMBRACE accrual period. The use of ic/is applicators and the fraction of patients treated with CTV D 90 >85Gy 10 was 7/10% below the aim of the EMBRACE-II protocol, for small/large volumes. EMBRACE-II dose constraints for D 2cm³ were fullfilled by nearly the same fraction of EMBRACE patients (difference 2-3%) as aimed for in the future trial. Mean vaginal loading was 13% higher in EMBRACE than the aim of EMBRACE-II. Conclusion During the last years, an increasing understanding of the correlation of dose and outcome in image-guided (adaptive) brachytherapy has emerged. This is continuously driving an evolution of the IGABT practice, and eventually the EMBRACE II protocol has been launched with hypotheses reflecting the most recent clinical evidence. During EMBRACE-I, ic/is applicators have increasingly been used, and dose to CTV HR and Organs at risk has improved over time.

Purpose or Objective Definitive concurrent chemoradiation (CRT) plus image- guided adaptive brachytherapy (IGABT) is the standard treatment for locally advanced cervical cancers (LACC). Metaanalyses examining the benefit of CRT found that the larger survival improvement was for FIGO stages Ib-IIb tumors. However, the optimal number of chemotherapy (CT) cycles is not well defined and no data is available on the benefit of an additional cycle during IGABT. These issues were assessed in a large single center cohort of patients (pts). Material and Methods Clinical records of 260 pts treated from 2004 to 2016 for a LACC were reviewed. Patients received CRT delivering 45 Gy in 25 fractions +/- lymph node boost. If not contraindicated, concurrent cisplatin 40 mg/m² was delivered weekly. Carboplatin AUC2 was preferred in case of renal function impairment. An additional cycle could be delivered during pulse dose rate (PDR) IGABT. The impact of total number of CT cycles on overall, disease-free, local relapse-free, regional relapse-free and distant metastasis -free survival (OS, DFS, LRFS, RRFS, DMFS, respectively) was examined using survival estimation model by Kaplan-Meier, log-rank tests and Cox proportional-hazards model. Results Median number of CT cycles was 5 (Interquartile 25-75 [IQ]: 4-5). A cycle was delivered concurrently with IGABT in 115 patients (44.2%). Median overall treatment time was 48 days (IQ: 44–52). With median follow-up of 5 years (4.5-5.4), estimated OS and DFS at 5 years were 72.0% (95%CI 60.6–83.4) and 63.3% (95%CI 51.0–75.6), respectively. In univariate analysis, receiving ≥ 5 cycles was associated with longer OS (p=0.000), DFS (p=.000), and improvement in time to local failure (p=.000), and distant failure (p=.000). In multivariate analysis (including nodal involvement, differentiation, neutrophilia, anemia, BMI>25), number of CT cycles ≥ 5 correlated with a longer OS (p=.000), DFS (p=.003), LRFS (p=.001), RRFS (p=.001) and DMFS (p=.004). When categorizing population according to high-risk clinical target volume (HR-CTV) (< or ≥ 30cm 3 ), number of CT cycle ≥ 5 remained correlated with DFS, LFS and DMFS for both groups, although the effect was higher in case of bulky HR-CTV. The effect on OS and RRFS was significant only in pts with bulky HR-CTV (p=0.000). In multivariate analysis, the effect of number of cycles on OS and DFS was significant only in pts with HR-CTV volume ≥ 30cm 3 (HR=0.201; 95%CI 0.09-0.452 and HR=0.238; 95%CI 0.116- 0.486, respectively). Conclusion Number of concurrent CT cycles should be ≥ 5. PDR IGABT permits to deliver an additional cycle during brachytherapy boost (52.1% of pts received their 5 th cycle during IGABT). PV-0260 On the implementation of IGBT for cervix cancer in the observational multicenter study EMBRACE N. Nesvacil 1 , K. Tanderup 2 , R. Pötter 1 , Y. Seppenwoolde 1 , A. De Leeuw 3 , J. Swamidas 4 , I. Dumas 5 , R. Hudej 6 , G. Lowe 7 , I. Jürgenliemk-Schulz 3 , J. Lindegaard 2 , C. Kirisits 1 1 Medical University of Vienna, Department of Radiotherapy- CCC- Christian Doppler Laboratory for Medical Radiation Research, Vienna, Austria 2 Aarhus University Hospital, Department of Oncology, Aarhus, Denmark 3 University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands 4 Tata Memorial Hospital, Department of Radiation Oncology, Mumbai, India 5 Gustave Roussy- University Paris-Saclay, Department of Medical Physics, Paris, France 6 Institute of Oncology, Department of Radiotherapy, Ljubljana, Slovenia