ESTRO 36 Abstract Book

S24 ESTRO 36 _______________________________________________________________________________________________

Oncology, Ljubljana, Slovenia 7 Mount Vernon Cancer Centre, Department of Radiotherapy, Northwood, United Kingdom

Comprehensive Cancer Center, Vienna, Austria 2 Aarhus University Hospital, Department of Oncology, Aarhus, Denmark 3 Gustave-Roussy, Department of Radiotherapy, Villejuif, France 4 Tata Memorial Hospital, Department of Radiation Oncology, Mumbai, India 5 University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands 6 Institute of Oncology, Department of Radiotherapy, Ljubljana, Slovenia 7 Mount Vernon Hospital, Cancer Centre, London, United Kingdom Purpose or Objective Treatment-related limb edema of the lower extremities after definitive radiochemotherapy for locally advanced cervical cancer has been reported to have a substantial impact on patients’ well-being and body image. The aim of this report is to evaluate the manifestation pattern of limb edema during the first years of follow-up within the prospective, observational, multi-center EMBRACE study (www.embracestudy.dk). Material and Methods The analysis was based on 1419 locally advanced cervical cancer patients enrolled from 2008-2015 who underwent combined external beam radiotherapy (either with 3D conformal technique or IMRT to 45-50Gy) ± concurrent chemotherapy and MRI-guided brachytherapy following the GEC-ESTRO guidelines. In case of pathological lymph nodes, a boost to 55-65Gy was applied. Limb edema was prospectively assessed with physician assessed common toxicity criteria for adverse events (CTCAE v.3) and patient reported EORTC quality of life questionnaire (module CX24, Q38) at baseline before treatment, every 3 months (1 st year), and every 6 months (2 nd and 3 rd year) and yearly thereafter. Crude incidence rates, prevalence rates and actuarial estimates using the Kaplan-Meier method were analyzed. Results Information on limb edema at baseline and follow-up was available for analysis in 1176 patients regarding CTCAE (943 patients regarding EORTC) from 22 centers with a median follow-up of 27 months (range 1-85 months). Crude incidence rates of limb edema were 18% for CTCAE G1, 4% for G2 and <1% for G3 (n=4 patients); no G4 or G5 morbidity occurred. The progressive manifestation pattern of limb edema is reflected in the gradually increasing prevalence rates as shown in in figure 1a for CTCAE and 1b for EORTC outcome. Actuarial analyses revealed a 3-year/5-year probability of 0.5%/0.5% for G≥3, 6.1%/6.6% for G≥2 and 26.5%/30.7% for G≥1. Laparoscopic lymph node staging increased the risk for the development of G≥1 limb edema significantly (p≤0.001) with an actuarial risk at 5 years of 23.8% versus 47.1% (figure 2).

Purpose or Objective Bladder morbidity is a well known side effect to radiochemotherapy of locally advanced cervical cancer (LACC). The EMBRACE study is a prospective multi- institutional study with focus on MR image guided adaptive brachytherapy (IGABT) in LACC. The study includes registration of physician assessed morbidity and patient reported outcome (PRO). This analysis evaluates bladder morbidity with both assessment methods Material and Methods Out of 1419 patients recruited for the EMBRACE study, 1176 patients with assessment of bladder morbidity were analysed. Treatment included external beam radiotherapy with prescribed dose 45-50 Gy in 25-30 fx with concomitant cisplatin in 95% of the patients. IGABT was delivered with HDR BT (57%) or PDR BT (43%). Total mean D 2cm3 to the bladder was 76.6 Gy. Median follow up (FU) was 27M (months). Morbidity and PRO was assessed according to the CTCAE v.3 and EORTC QLQ-CX24 at baseline (BL), every 3M (year 1), every 6M (year 2-3) and annually thereafter. Patients reporting ”quite a bit” or ”very much” bladder symptoms in EORTC were considered as clinically relevant endpoint analogue to CTCAE G2 and G3. Morbidity and PRO were analysed with crude incidence, prevalence rates, and actuarial estimates Results Prevalence of urinary frequency CTCAE G≥2 ranges between 4-5%, irrespectively of FU time, PRO ”frequent urination” ranges between 14-23%. Urinary incontinence CTCAE G≥2 increases gradually from 3% (BL) to 5% at 60M, PRO 'leaking of urine” increases from 5% (BL) to 11% at 60M. Prevalence of bladder bleeding CTCAE G≥1 is reported in 1% (BL) and progresses to a maximum of 5% at 36M, followed by a reduction to 2% at 60M. This manifestation pattern is also seen for bladder cystitis CTCAE G≥2 which increases from 1% (BL) to a maximum of 3% at 30M, and decreases slightly thereafter. PRO such as 'difficulty emptying the bladder” is slightly increasing during FU, while disturbance from a 'burning sensation during urination” is slightly reduced. Actuarial estimates at 5-year of CTCAE G≥2 was 16.4%, 16.2% and 11.0% for incontinence, frequency, and cystitis, respectively. Severe bladder morbidity (ureter stenosis analysed separately) CTCAE G≥3 was recorded in 39 patients (54 events), corresponding to an actuarial estimate of 4.7% risk at 5-years. G≥3 morbidity was 2.1%, 1.9%, 1.5%, and 0.7% at 5-years, for incontinence, frequency, cystitis and bladder fistula, respectively. Ureter stenosis G≥3 (19 patients) was found in 3.4% at 5- year (patients with BL ureter stenosis excluded). There was no G5 bladder morbidity Conclusion Bladder morbidity shows different manifestation patterns. Urinary frequency fluctuates during FU, while incontinence progresses. Bladder bleeding, cystitis and patient reported 'burning sensation” progress to reach a maximum prevalence followed a tendency to resolve at later FU. Further studies have to explore these findings and relate them to patient and treatment parameters in order to find strategies to reduce bladder morbidity in future radiotherapy. OC-0053 Physician assessed and patient reported limb edema after RCHT + IGABT for cervical cancer (EMBRACE) D. Najjari Jamal 1 , S. Smet 1 , N. BK Jensen 2 , L. Fokdal 2 , J.C. Lindegaard 2 , C. Kirisits 1 , C. Chargari 3 , U. Mahantshetty 4 , I.M. Jügenliemk-Schulz 5 , B. Segedin 6 , P. Hoskin 7 , K. Tanderup 2 , R. Pötter 1 , K. Kirchheiner 1 1 Medical University of Vienna / General Hospital of Vienna, Department of Radiation Oncology-