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Purpose Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by IMRT with FDR-G, freedom from local progression (FFLP) and overall survival (OS). Methods and Materials Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status (PS) of 0–2, ANC of ≥1500/mm3, platelets ≥100,000/mm3, creatinine <2 mg/dl, bilirubin <3 mg/dl and ALT/AST ≤2.5 x ULN. FDR-G (1000 mg/m2/100-minutes I.V.) was given on days −22 and −15, 1, 8, 22, and 29. IMRT started day 1. Dose levels were escalated from 50 to 60 Gy in 25 fractions. DLT was defined as gastrointestinal toxicity ≥Grade (G)3, neutropenic fever, or deterioration in PS to ≥3 between day 1 and 126. Dose level was assigned using TITE-CRM with the target DLT rate set to 0.25. Results Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% CI: 32–79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6–22.2) and 30% (95% CI 17–45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions High dose radiotherapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

New lower bounds for the quadratic assignment problem QAP are presented. These bounds are based on the orthogonal relaxation of QAP. The additional improvement is obtained by making e cient use of a tractable representation of orthogonal matrices having constant row and column sums. The new bound is easy to implement and often provides high quality bounds under an acceptable computational e ort.

Purpose Study the impact of daily rotations and translations of the prostate on dosimetric coverage during RT. Methods and Materials Real–time tracking data for 26 patients were obtained during RT. IMRT plans meeting RTOG0126 dosimetric criteria were created with 0, 2, 3, and 5 mm PTV margins. Daily translations and rotations were used to reconstruct prostate delivered dose from the planned dose. D95 and V79 are computed from the delivered dose to evaluate target coverage and the adequacy of PTV margins. Prostate equivalent rotation is a new metric introduced in this study to quantify prostate rotations by accounting for prostate shape and length of rotational lever-arm. Results Large variations in prostate delivered dose were seen among patients. Adequate target coverage was met in 39%, 65%, and 84% of the patients for plans with 2, 3, and 5 mm PTV margins, respectively. While no correlations between prostate delivered dose and daily rotations are seen, the data shown clear correlation with prostate equivalent rotation. Conclusions Prostate rotations during RT could cause significant underdosing even if daily translations were managed. These rotations should be managed with rotational tolerances based on prostate equivalent rotations.

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Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined.

This work investigates the increase in surface dose caused by thermoplastic masks used for patient positioning and immobilization. A thermoplastic mask is custom fit by stretching a heated mask over the patient at the time of treatment simulation. This mask is then used at treatment to increase the reproducibility of the patient position. The skin sparing effect of mega‐voltage X‐ray beams can be reduced when the patient's skin surface is under the mask material. The sheet of thermoplastic mask has holes to reduce this effect and is available from one manufacturer with two different sizes of holes, one larger than the other. This work investigates the increase in surface dose caused by the mask material and quantifies the difference between the two samples of masks available. The change in the dose buildup was measured using an Attix parallel plate chamber by measuring tissue maximum ratios (TMRs) using solid water. Measurements were made with and without the mask material on the surface of the solid water for 6‐MV and 15‐MV X‐ray beams. The effective thickness of equivalent water was estimated from the TMR curves, and the increase in surface dose was estimated. The buildup effect was measured to be equivalent to 2.2 mm to 0.6 mm for masks that have been stretched by different amounts. The surface dose was estimated to change from 16% and 12% for 6 MV and 15 MV, respectively, to 27% to 61% for 6 MV and 18% to 40% for 15 MV with the mask samples.PACS number: 87.53.Dq