S247 ______________________________________________________________________________________________________fractions against 69.1 Gy/32 fractions in the IMRT group.Endpoints were local control, acute and late toxicity.Results A. Interim analysis (n = 150) showed low rates of moist desquamation, mostly located in the infra-mammary fold (5/75 WBI-SeqB vs 3/75 WBI-TDP-SIB, p =0.5).Trends in favor of WBI-TDP-SIB were observed for breast edema (p=0.08) and pruritus (p = 0.1).B. 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 a pain response of 80% compared to 53% and 60% for Conv-8Gy and DP-16Gy.Quality of life analysis suggests better outcome for patients treated in the DP-8Gy arm with the scores 'painful characteristic', 'insomnia' and 'appetite loss' reaching significance (p<0.05).C. Local control at 5 y was 83.4% and 75.2% in the DP-and IMRT-treated patients, respectively (p=0.28).Grades of acute dysphagia and mucositis were higher for the DP-than for the IMRT-treated group (p=0.03 and p=0.08, respectively) but differed according to DP-technique and -prescription.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 all DPtreated patients showed that DP-planning using a linear relation between 18F-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-fraction schedules (OTT = 6 weeks).Discussion and conclusions The term DP covers a variety of techniques that open a vast spectrum of applications.The use of TDP after breastconserving surgery allows to integrate boost treatment in WBI without increasing toxicity.In bone metastasis, DP-8Gy was selected as a candidate experimental arm to test the hypothesis of improved palliation by reducing the irradiated volume.A confirmatory phase III trial is underway.In locoregionally advanced head&neck cancer, DP may open a window for improving local control.However, the safety margin for dose-escalation is narrow.Poorly healing mucosal ulcers at the peak-dose regions are DLT of DP.The dose/volume/DLT relationship casts doubt on the safety of linear 18F-FDG voxel-intensity based DP.A phase III trial using non-linear DP is underway.Tumor heterogeneityknown for decades-supports DP and refutes the use of homogeneous dose distributions.Dose escalation to radioresistant regions in the tumor or decreasing the irradiated volume may be a conceptually naive way to use DP.The insight that ionizing radiation can enhance vascular and immunogenic mechanisms of cell death opens a new field for DP characterized by large fraction doses to small subvolumes of tumor.In these applications, direct cancer cell kill might be subordinate to other goals of DP including amplifying bystander and abscopal effects or breaking immune tolerance.Combination of DP with immunomodulating drugs or drugs that target vasculature or immune checkpoints are investigated to validate these concepts.

Conclusion:This study did not show that heart V5 or MHD had a negative effect on survival for NSCLC patients treated with definitive radiotherapy.This study differs from recently reports by having a longer follow-up.On the other hand, concomitant chemotherapy was only used in 12% of the patients in this study.The main goal for NSCLC patients is still to achieve better loco-regional control.However, if dose escalation is performed with doses significant above those in the present study, strict dose constraints to the heart might still be advisable based on experience from patients with breast cancer.

Purpose: The work aims to 1) prove the feasibility of dose painting by numbers (DPBN) in proton therapy with usual contour-driven plan optimization and 2) compare the achieved plan quality to that of rotational IMRT. Methods: For two patients with head and neck cancers, voxel-by-voxel prescription to the target volume (PTV-PET) was calculated from 1 8 FDG-PET images and converted to contour-based prescription by defining several sub-contours. Treatments were planned with RayStation (RaySearch Laboratories, Sweden) and proton pencil beam scanning modality. In order to determine the optimal plan parameters to approach the DPBN prescription, the effect of the number of fields, number of sub-contours and use of range shifter were tested separately on each patient. The number of sub-contours were increased from 3 to 11 while the number of fields were set to 3, 5, 7 and 9. Treatment plans were also optimized on two rotational IMRT systems (TomoTherapy and Varian RapidArc) using previously published guidelines. Results: For both patients, more than 99% of the PTV-PET received at least 95% of the prescribed dose while less than 1% of the PTV-PET received more than 105%, which demonstrates the feasibility of the treatment. Neither the use of a range shifter nor the increase of the number of fields had a significant influence on PTV coverage. Plan quality increased when increasing number of fields up to 7 or 9 and slightly decreased for a bigger number of sub-contours. Good OAR sparing is achieved while keeping high plan quality. Finally, proton therapy achieved significantly better plan quality than rotational IMRT. Conclusion: Voxel-by-voxel prescriptions can be approximated accurately in proton therapy using a contour-driven optimization. Target coverage is nearly insensitive to the number of fields and the use of a range shifter. Finally, plan quality assessment confirmed the superiority of proton therapy compared to rotational IMRT.

Purpose/Objective: To report outcomes for patients treated with salvage surgical resection and intraoperative radiotherapy (IORT) for residual or recurrent squamous cell carcinoma (SCC) of the anus after primary chemoradiotherapy (CRT).Materials and Methods: The prospective radiation oncology department IORT database was searched for patients treated with surgery and IORT for anal SCC.Thirty-two patients treated between 1993 and 2012 were identified.All patients had previously received primary concurrent CRT and had residual or recurrent disease based on clinical findings and/or tissue confirmation.All patients with recurrent disease received pre-operative, limited field external beam re-irradiation (median dose 30 Gray) and concurrent chemotherapy.IORT was utilized due to concern that salvage surgery alone would be unlikely to remove all gross and/or microscopic disease.Treatmentrelated adverse events were classified according to the National Cancer Institute -Common Toxicity Criteria Adverse Events (AEs).Overall survival (OS), disease-free survival (DFS), central failure (CF; within the IORT field), local-regional failure (LRF; tumor bed or draining lymphatics), and distant failure (DF) were estimated using the Kaplan-Meier technique.Results: Median age at IORT was 53 years (range 34-87).Twenty-six patients (81%) were female.Salvage treatment was performed for residual disease after CRT (n=9), 1st recurrence after CRT (n=17), or 2nd recurrence after CRT and salvage abdominal-perineal resection (APR, n=6).APR was a component of the multimodality salvage attempt in 22 patients.Extent of surgical resection was R0 (negative margins, n=16), R1 (microscopic residual, n=13), or R2 (macroscopic residual, n=3).IORT was delivered with electron beams (n=31) or highdose rate brachytherapy (n=1).Median IORT dose was 12.5 Gray (range 7.5 -20).Median length of hospital stay was 9 days.Nine patients (28%) were alive at last follow-up.The median follow-up duration was 1.6 years for all patients and 6.3 years for living patients.Mortality at 30 days after surgery and IORT was 0%.Fifteen patients (47%) experienced a total of 16 grade 3 treatment-related AEs.The most common Grade 3 AEs were wound complications (n=6), bowel obstruction (n=5), and ureteral obstruction (n=3).There were no grade 4 or 5 AEs.The 5-year estimates of OS and DFS were 23% and 17%, respectively.The 5-year estimates of CF, LRF, and DF were 26%, 64%, and 48%, respectively.Conclusions: In this heavily pre-treated, high-risk patient population, aggressive salvage surgery and IORT was associated with long-term survival in a small, but significant subset of patients.