ESTRO 36 Abstract Book

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2 DKFZ, Clinical Cooperation Unit Molecular Radiooncology, Heidelberg, Germany 3 Heidelberg Ion Beam Therapy Center, HIT, Heidelberg, Germany 4 Center for Heavy Ion Research GSI, Dept. of Biophysics, Darmstadt, Germany 5 University Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg, Germany Purpose or Objective Proton therapy allows highly conformal treatments of head and neck cancer due to its inverted depth-dose profile and advanced beam delivery systems. This allows escalating the dose while still sparing the surrounding healthy tissue. For treatment planning in patients, a fixed relative biological effectiveness (RBE) of 1.1 is currently used. However, experimental in vitro studies indicate that the RBE increases at the distal edge of the spread-out Bragg peak (SOBP). This increased biological effectiveness may either lead to detrimental side effects, especially in the late responding normal central nervous system, or it may compromise dose escalation in the tumor. In this study, the potential increase of the proton RBE along the SOBP is investigated for late reactions of rat spinal cord. Material and Methods The cervical spinal cord of female Sprague Dawley rats was positioned at four different depths of a 6 cm spread-out Bragg peak (entrance region, center and two positions at the distal edge of the SOBP, linear energy transfer (LET): 1.45-5.60 keV/µm). Single proton doses of increasing dose levels were applied to the segments C1-C6 of the cervical spinal cord using a field size of 10 x 15 mm 2 . At each position, complete dose-response curves were established and the tolerance doses TD 50 (dose at 50% complication probability) were determined for the clinically relevant endpoint “development of forelimb paresis grade II within 300 days”. Based on the TD 50 -values, RBEs were calculated using the tolerance doses for photons of our previous study. Rats reaching this endpoint were sacrificed and the spinal cord was removed and processed for histological examinations. Results Preliminary evaluations of the single dose experiments showed that the minimum and mean latency time decrease with increasing LET. Preliminary data of the dose-response curves confirm an RBE of 1.1 in the entrance region (LET 1.45 keV/µm) while a further increase of the RBE was found towards the distal edge of the SOBP (LET 5.40 keV/µm). Conclusion The preliminary data of this study suggests an increased proton RBE at the distal edge of the SOBP. Further experiments with fractionated treatments are ongoing. If the finding of this study is confirmed quantitatively, it might be necessary to include the variability of the RBE in clinical treatment planning to optimize safety and effectiveness of proton therapy in patients. SP-0518 Differences between PRO and clinician reported morbidity and associations to clinical outcome K. Kirchheiner 1 1 Medical University Vienna, Dept. of Radiation Oncology, Vienna, Austria Patient-reported outcomes (PROs) describe any outcome reported directly by the patient with a subjective evaluation about disease and its treatment. PROs summarize a wide spectrum of endpoints in the framework of a holistic bio-psycho-social cancer care model, such as Symposium: Patient Reported Outcomes (PROs) in radiotherapy

reports on symptoms and side effects, as well as multi- dimensional health-related quality of life, evaluation of the perceived health and psychological status, reports about adherence to treatment, satisfaction with treatment, according to the US Food and Drug Administration (FDA) and the European Medical Agency (EMA). In contrary to the physician assessed morbidity grading, the evaluation of PROs is performed without any interpretation by a clinician, relative or anyone else and reflects the patients’ subjective experience [1]. With the development of validated questionnaires with robust psychometric properties over the last decades, PROs have been established as valuable and reliable complementary information in clinical studies [2]. Moreover, PRO assessment is recently regarded as quality indicator in routine cancer care [3]. The reporting of PROs regarding symptoms and side effects particularly in conjunction with the physician assessed morbidity following standard grading systems has been thoroughly investigated. A recently published literature review analyzed 28 high quality studies and concluded only fair to moderate associations between both assessment methods; furthermore the majority of studies demonstrated the tendency of underreporting morbidity in the physician assessed grading systems [4]. Therefore, an initiative has been started in the United States to combine both methods in a collaborative approach to enable a comprehensive and in-depth understanding of morbidity. The National Cancer Institute (NCI) has recently published a patient questionnaire version of the widely used Common Toxicity Criteria of Adverse Events (CTCAE) [5,6]. The PRO-CTCAE enables patients’ self-reporting of symptoms via paper questionnaire, touchscreen tablet computer or interactive voice response system [7]. To date, several translations and linguistic validations of the PRO-CTCAE are in progress and a widespread use in clinical cancer trials is expected in the near future [8,9]. In Europe, the Patient Reported Outcomes and Behavioral Evidence initiative (PROBE) within the European Organisation for Research and Treatment of Cancer (EORTC) [10] has recently reported on a meta-dataset pooled from different international randomized controlled clinical trials across different patient populations, disease stages and treatments, which included the EORTC quality of life assessment [11]. It has been shown that baseline EORTC quality of life assessment increases the prognostic accuracy for overall survival significantly (by 6-8%) on top of clinical and sociodemographic risk factors. For each cancer type, at least one specific quality of life domain provided prognostic information, even though no universal domain could be identified for all patients [12,13]. In conclusion, PROs add unique and highly valuable information to clinical cancer trials and should be actively promoted to complement physician assessed morbidity.