Interfractional Variations in the Setup of Pelvic Bony Anatomy and Soft Tissue, and Their Implications on the Delivery of Proton Therapy for Localized Prostate Cancer

Purpose To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and set-up approaches employed in proton therapy. Methods We used series of CT data, which included the pre-treatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription iso-dose were evaluated. Results In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7–3.6 mm for individual patients, variations of over 5 mm from the planning CT observed in all series), and femur rotation angle (standard deviation between 1.3–4.8°, with the maximum excursion exceeding 10° in 6 out of 10 datasets). Shifts in the position of treated volume (98% iso-dose) were correlated with the variations in the lateral tissue thickness. Conclusions Analysis suggests that, combined with image-guided set-up verification, the range compensator expansion technique prevents loss of dose to target due to femur rotation and soft tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer

The association of very low PSA with increased cancer-specific death in men with high-grade prostate cancer

62 Background: It has been hypothesized that very low PSAs in men with high-grade prostate cancer could reflect dedifferentiation and a poorer prognosis, but clinical evidence to support this is limited. We sought to determine whether a very low-presenting PSA was associated with greater prostate cancer-specific mortality (PCSM) among men with Gleason score (GS) 8-10 disease. Methods: The Surveillance, Epidemiology and End Results Program was used to identify a national cohort of 328,904 men diagnosed with cT1-4N0M0 prostate cancer between 2004 and 2010. Multivariable Fine-Gray competing-risks regression analysis was used to determine PCSM as a function of PSA level (40ng/mL) and GS (8-10 vs. 40 was 3.19 (2.83-3.59; P<0.001), suggesting a U-shaped distribution. There was a significant interaction between PSA level and GS (Pinteraction<0.001) such that PSA <2.5 only significantly predicted for poorer PCSM among patients with high grade GS 8-10 disease. Conclusions: Among patients with high grade GS 8-10 disease, patients with PSA <2.5 and 2.6-4 appear to have a higher risk for cancer-specific death compared to patients with a 10.1-20 PSA level, supporting the notion that low PSA in GS 8-10 disease may be a sign of underlying aggressive and extremely poorly differentiated or anaplastic low PSA-producing tumors. Patients with low PSA GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents in very-high risk prostate cancers