PO-0858: Identifying relationships between patient-reported outcomes in multiple radiotherapy cohorts

S84 to employed beam sizes. For the manual kV planning, multiple beams and isocenters were used to cover the GTV. Moreover, covering the whole GTV while avoiding beam overlap showed to be difficult, indicated by the less homogeneous dose to GTV for the kV plans. Dose calculation times for the MV and kV plans were similar, both less than 2 minutes.

ESTRO 33, 2014 prescribed doses (adjusting for a relative biological effectiveness of 1.1 in the case of protons). The dose-volume histograms of the original 3DCRT plans and the new IMRT and IMPT plans were analyzed using radiobiological models to assess the risk of specified late effects. The relative seriality model was used to predict excess risk of cardiac mortality. The organ equivalent dose concept was used in conjunction with a modified linear quadratic model to predict the excess absolute risk for induction of lung cancer and breast cancer. Parameters for each model were derived from retrospective studies in the literature (Eriksson, Radiother Oncol 2000; Schneider, Z Med Phys 2010; Schneider, Radiat Oncol 2011). Results: Compared to the calculated risk associated with 3D-CRT, risk of radiation-induced cardiac mortality for IMRT and IMPT was 0.9 ± 0.2 and 0.7 ± 0.2 respectively. Excess absolute risk of developing lung cancer at thirty person-years of observation was on average 1.3 ±0.2 times greater for IMRT than for 3D-CRT and 0.64 ± 0.2 for IMPT as compared to 3DCRT. Excess absolute risk of developing breast cancer for female patients at thirty person-years of observation was on average 2.5 ±0.7 times greater for IMRT than for 3D-CRT and 0.4 ± 0.2 for IMPT as compared to 3D-CRT. Conclusions: IMPT had the lowest predicted risks for all late effects studied. Similar risks of cardiac mortality were exhibited by 3D-CRT and IMRT, whereas IMPT had slightly lower risks. IMRT exhibited the highest risks for induction of lung and breast cancers, greater than those of 3DCRT, while IMPT predicted significant risk reduction in the induction of these cancers. IMPT has shown the potential to reduce the risk of fatal,radiation-induced late cardiotoxicity as well as the risk of radiation-induced secondary cancers in the lungs and breasts of young patients as compared to 3D-CRT or IMRT photon radiotherapy for Hodgkin's lymphoma. PO-0858 Identifying relationships between patient-reported outcomes in multiple radiotherapy cohorts M. Thor1, C. Olsson2, S.E. Petersen3, D. Alsadius2, M. Høyer3, N. Pettersson2, L. Bentzen3, J. Deasy1, L. Muren4, G. Steineck2 1 Memorial Sloan-Kettering Cancer Centre, Department of Medical Physics, NYC, USA 2 Institute of Clinical Sciences the Sahlgrenska Academy at the University of Gothenburg, Division of Clinical Cancer Epidemiology Department of Oncology, Gothenburg, Sweden 3 Aarhus University Hospital, Department of Oncology, Aarhus, Denmark 4 Aarhus University Hospital, Department of Medical Physics, Aarhus, Denmark

Conclusions: n comparison with manually optimized kV treatment plans, MV plans using a bolus provided slightly more homogeneous GTV doses, but worse sparing of OARs for irradiation of rat flank tumors. Overall, we have shown that using manual forward planning techniques, good GTV coverage and excellent sparing of OARs can be achieved for irradiation of a rat flank tumor for kV planning in comparison with techniques available previously.

Purpose/Objective: When pooling data from different cohorts, a key challenge is how to manage endpoints assessed from different scoring systems. This can be particularly complicated for scoring systems offering several alternatives for related symptoms or a broad range of endpoints, e.g. patient-reported outcomes. In this study, we investigated if it is possible to group patient-reported gastrointestinal symptoms in two prostate cancer radiotherapy (RT) cohorts.

PO-0857 IMPT may reduce risk for cardiac mortality and secondary cancers compared to 3D-CRT and IMRT for Hodgkin's Lymphoma A. Toltz1, N. Shin1, E. Mitrou2, C. Laude3, D. Roberge2, C. Freeman3, J. Seuntjens1, W. Parker4 1 McGill University, Medical Physics Unit, Montreal, Canada 2 Centre hospitalier de l'Université de Montréal, Radio-oncologie, Montreal, Canada 3 McGill University Health Centre, Radiation Oncology, Montreal, Canada 4 McGill University Health Centre, Medical Physics Unit, Montreal, Canada

Materials and Methods: We used endpoint data from two prostate cancer cohorts: Cohort A included 213 men treated to 78 Gy@2Gy per fraction during 2005-2007 (3D-CRT: 94%; IMRT: 6%) and Cohort B included 476 men treated to 70 Gy@2Gy per fraction during 1993-2006 (3DCRT:100%). Study-specific questionnaires including questions on flatulence, frequency, leakage of blood/mucous/stools, pain, sensory symptoms, stool content and urgency were available for each cohort (27 and 34 questions in Cohort A and B, respectively). Pearson's correlation coefficients (r) were calculated between all endpoints within each cohort. Grouping of endpoints was defined at r≥I0.40I (all P≤0.05). In addition, we also studied grouping of endpoints for four different cut-off values (r≥I0.40I to r≥I0.55I, in steps of 0.05). Finally,'hub questions', the questions with the highest total sum of absolute correlation values for an endpoint group i were identified (rsum,i=∑riIri≥I0.40I; all P≤0.05).

Purpose/Objective: To evaluate the potential risk reduction of radiation-induced late effects for young patients with Hodgkin's lymphoma planned with intensity modulated proton therapy (IMPT) as compared to involved-field 3D conformal photon radiotherapy (3D-CRT) or intensity modulated radiotherapy (IMRT). The late effects considered were cardiac mortality and secondary cancer in the lungs and breasts (for female patients). Materials and Methods: The study cohort comprised twenty patients who were under thirty years of age and were treated with thoracic irradiation for Hodgkin's lymphoma in Quebec in 2010. All patients were originally treated with 3D-CRT at 6, 10, or 18 MV using an AP/PA beam configuration and multileaf collimation for field shaping. The original CT simulation images were used to re-plan the patients for IMRT (applied as helical arc therapy) and IMPT using commercially-available treatment planning software to the original planning target volumes at the

Results: For the highest cut-off values (r≥I0.55I) two and four distinct groups of endpoints were observed corresponding to urgency and leakage of stools in Cohort A and urgency, leakage of mucus/stools and pain in Cohort B. For lower cut-off values additional endpoints were added to these groups (r≥I0.50I), correlations were seen between them (r≥I0.45I) and new groups of endpoints were formed (r≥I0.40I) (Table). For r≥I0.40I two and three groups of endpoints were identified in Cohort A and B, respectively. The hub questions in Cohort A were sensory (clustering of stool) with rsum,1=3.75 and stool content (strain to defecate) with rsum,2=1.27 (directly linked to 8/14 and 3/3 endpoints, respectively). In Cohort B, the hub questions were leakage (stools awake) with rsum,1=4.42, pain (abdominal) with rsum,2=1.51, and urgency with rsum,3=0.62 (directly linked to 8/14, 3/4 and 1/1 endpoints, respectively).

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Conclusions: We have shown that it is feasible to group simultaneously occurring symptoms related to gastrointestinal toxicity following RT. This may assist in confirming intuitive translations between scoring systems and potentially opens up for the possibility of pooling endpoints from different cohorts. The usefulness of the identified groups of endpoints and endpoint hub questions as surrogates for radiation-induced injuries will be studied in subsequent normal tissue complication probability modelling. XXX is acknowledged for excellent support in the statistical analyses. PO-0859 Estimated effect of overall treatment time on the risk of late rectal toxicity M.C. Aznar1, S.M. Bentzen2, P.M. Pedersen3, I.R. Vogelius1 1 The Finsen Center - Rigshospitalet, Department of Radiation Oncology, Copenhagen, Denmark 2 University of Maryland School of Medicine, Division of Biostatistics and Bioinformatics, Baltimore, USA 3 The Finsen Center - Rigshospitalet, Department of Oncology, Copenhagen, Denmark Purpose/Objective: Recent data suggest that prostate cancer has a low α/β ratio and, consequently, hypofractionated treatment regimens are being tested in clinical trials. Most of these studies are expected to increase the effective dose to the target according to a recent metaanalysis of the α/β ratio for prostate cancer [1]. It is generally assumed that overall treatment time does not have an effect on late toxicity. In this study, we estimate the dose equivalent per day of acceleration, dProlif, from published randomized fractionation trials. We then illustrate the impact of dProlif on the patient-specific risk of developing grade 2 rectal toxicity using two published hypofractionated schemes. Materials and Methods: We collected rectal toxicity (grade 2 or higher) data from published randomized hypofractionationtrials (see table 1). The equieffective dose in 2-Gy fractions in the presence of an effect of overall treatment time is

, where Tref is a reference time. For each randomized study, we use the control arm as reference and the steepness of the dose response curve for late rectal injury from the QUANTEC report and estimated the effective dose of the experimental arm with the prescription as dose metric. Once the effective dose of the experimental arm is estimated, a relation between assumed α/β value and the corresponding dProlif can be derived from the equation above. An average relation is found by weighting the studies by number of patients and taking the average dProlif for each α/β value. In addition, we collected dose plans for 20 patients treated for locally advanced prostate cancer with intensity modulated arc therapy and with a standard (2Gyx39) scheme. The risk of rectal toxicity (NTCP) is modelled with the QUANTEC model using per-bin fractionation correction and dProlif. Finally, we estimate the impact of dProlif on each patient's risk of developing rectal toxicity using two illustrative schedules (3Gyx20 in 28 days; 7.6Gyx5 in 7 days) compared to a standard fractionation schedule (2 Gy x39 over 53 days). Results: The relation between α/β and dProlif is shown in the Figure (top). For the most commonly assumed α/β values (3-5 Gy) the estimated value of dProlif is very low (0 to 0.16). Only one of the tested scenarios (7.6Gy x5, α/β=3, dProlif=0) lead to an increased NTCP compared to standard fractionation, cf. Figure (bottom). Varying the probable combinations of dProlif and α/β had a much larger impact on the profound hypofractionated schedule (NTCP values vary by up to 400%) than on the mildly hypofractionated schedule (up to 40%).

Conclusions: The published randomized studies support the assumption of little or no effect of overall treatment time for late rectal injury. However, for profoundly hypofractionated schedules, a time factor may still add substantially to the uncertainty of predictions of rectal toxicity. 1. Vogelius et al. 2012 IJROBP 85:89-94 PO-0860 Disregarding RBE variation in treatment plan comparisonmay lead to bias in favor of proton therapy M. Wedenberg1, I. Toma-Dasu2 1 Raysearch Laboratories AB, Oncology-Pathology, Stockholm, Sweden 2 Karolinska Institutet and Stockholm University, Medical Radiation Physics, Stockholm, Sweden Purpose/Objective: When comparing treatment plans of photons and protons, biologically equivalent doses should be used. The conversion from a physical proton dose to an equivalent photon dose is usually made by assuming a constant relative biological effectiveness (RBE) equal to 1.1. The aim of this study is to evaluate how the comparison of photon and proton treatment plans is affected by accounting for a variable RBE.