Abstract Book

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treatments. The increase in TCP correlated with the heterogeneity of the functional images in the target, times the size of tumor. The patients with highest TCP for conventional treatment were found to benefit the least from dose painting prescription, see fig 1, thus providing selection criteria for design of clinical trials. Also, the formalisms enabled inclusion of dose limits to facilitate safe escalation routes in study design. Robustness studies were made to investigate implications from uncertainties in the learning data sets, showing very limited impact on the resulting dose prescription, but with offsets in predicted TCP levels. The limited impact on prescriptions is a result the mean dose constraint; the optimization uses the available freedom in a similar pattern, but end with different TCP depending on the learning set data. Conclusions The formalism for derivation of empirically based dose painting functions from learnings set data of patients treated with conventional RT was found to give prescriptions, robust with respect to input data uncertainties. Optimization constrained to equal mean dose was found to increase the predicted patient TCP correlated to the size and functional image heterogeneity of the tumor. Figure 1. The increase in dose painted TCP for prostate cancer versus the TCP predicted with conventional treatment, based on Gleason dose responses and ADC mapping. SP-0692 From prescription to delivery - optimisation, robustness and quality assurance E. Sterpin 1 1 Katholieke Universiteit Leuven, Oncology, Leuven, Belgium Abstract text Dose painting by numbers is the delivery of a voxel-by- voxel heterogeneous dose distribution according to the spatial distribution of some biological feature of the tumor (e.g. tumor burden, hypoxia, proliferation…). This biological feature can hypothetically be quantified by some imaging modality, for instance a PET-scan. Ideally, such treatment strategy would enable dose escalation to radioresistant parts of the tumor without causing significant secondary effects. Although appealing, the aim of dose painting – the spatial correlation between a given phenotype and the delivered dose – is jeopardized by the uncertainties that affect all steps of the preparation and execution of the treatment. In a typical dose painting by numbers workflow with 18 FDG-PET, the tracer is injected in the patient. The FDG uptake is imaged by the PET scan. The PET image is then segmented to determine the external contour of the tumor. The spatial distribution of the PET image inside the tumor contour is converted to a dose prescription, generally using a linear relationship from a minimum to a maximum dose value defined by the physician. The planned dose distributions must match the non- homogeneous prescription. Finally, treatment delivery accuracy is verified by quality assurance. This lecture will review the uncertainties associated to dose painting from the point-of-view of the radiation physicist working in a radiotherapy department, that is, going backwards in the workflow from treatment delivery to the biology of the tumor. Intuitively, the radiation physicist will first focus on the feasibility of delivering complex, non-uniform dose distributions. The radiation physicist should also ensure that geometric errors (patient setup, morphological modifications) are minimized and incorporated in the treatment planning and delivery processes. These two aspects will be covered in detail. After this review, the radiation physicist should have a better insight about his role in the development of a dose

painting by numbers strategy but also about the present clinical relevance of dose painting. A large uncertainty at one single step of the workflow makes it globally ineffective, no matter the efforts performed elsewhere to improve it. SP-0693 Dose painting: conclusions from clinical trials W. De Neve 1 1 De Neve Wilfried, Radiotherapy UZ-Gent, Gent, Belgium Abstract text The term dose painting (DP) is used for radiotherapy (RT) techniques that use dose distributions which are function of intra-target or intra-organ-at-risk variations of radiosensitivity [1-5]. During the last decade, clinical studies were started with the aims of enhancing tumor control, improve palliation or reduce toxicity. The main application scenarios are A) longitudinal or B) single imaging in fractionated RT and C) DP in single-fraction or oligo-fractionated RT. A) Patients (n = 72) with loco-regionally advanced head&neck cancer, enrolled in DP dose-escalation studies were matched with standard IMRT-treated patients (n=72) irradiated during the same time period [6]. Median dose in the DP-group was 70.2-85.9 Gy/32-30 fractions (F) against 69.1 Gy/32F in the IMRT group [6]. Local control at 5 y was 82.3% and 73.6% in the DP- and IMRT-treated patients, respectively (p=0.36). Five-year overall and disease-specific survival rates were 36.3% versus 38.1% (P = .50) and 56.5% versus 51.7% (p = .72), respectively. Rates of acute dysphagia and mucositis were higher for the DP- than for the IMRT-treated group (p=0.03 and p=0.08, respectively). Poorly healing mucosal ulcers at the locations of the highest doses were observed in 9 DP- and 3 IMRT-treated patients (p=0.07) and reflect dose- limiting toxicity (DLT). Analysis of DP-treated patients showed that DP-planning using a linear relation between 18 F-FDG voxel-intensity and dose was associated with high risk of DLT if peak-doses were >84 Gy or the volume receiving >80 Gy was >1.75 cc in 30-F schedules (OTT = 6 weeks) [7]. Patients who continue smoking or drinking alcohol had highly increased risk to develop mucosal ulcers. B) Pathological investigations [8] and clinical relapse patterns indicate that subclinical disease concentrates nearby primary breast tumors. Topographical DP (T-DP) distributes dose as function of the spatial distribution of subclinical cancer in the breast. Patients (n=167) were randomized after breast-sparing surgery between prone whole breast irradiation (WBI) followed by a boost (SeqB: OTT=4 weeks) and WBI with simultaneous integrated boost using T-DP (T-DP: OTT=3 weeks) [9]. Acute moist desquamation rate was the primary endpoint. In both arms, 6/83 patients developed moist desquamation. Grade 2/3 dermatitis was significantly more frequent in the SeqB arm (38/83 vs 24/83 patients, p=0.037). In the T-DP and SeqB arm, respectively, 36 patients (43%) and 51 patients (61%) developed pruritus (p=0.015). A trend towards lower edema was observed in the T-DP arm (59 vs 68 patients. p=0.071). C) No dose-response relationship above 8 Gy single dose was demonstrated for pain control of uncomplicated bone metastases. This observation triggered the hypothesis that cytokine cascades counteracting palliation are activated by radiation in a dose- and volume-dependent way. DP was employed to reduce integral dose. Patients (n=45) were randomly assigned (1:1:1) to receive a single fraction of either 8 Gy with conventional prescriptions (Conv-8Gy) or 8 Gy with DP (range 6-10 Gy) (DP-8Gy) or 16 Gy with DP (range 14-18 Gy) (DP-16Gy) [10]. The trial was designed for selection of the experimental arm worthwhile of continuing in phase III. The volume of normal tissue receiving 4 Gy, 6 Gy and 8 Gy was at least 3, 6 and 13 times smaller in the DP-8Gy arm compared to Conv-8Gy and DP-16Gy (p<0.05). DP-8Gy resulted in 80%