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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