Purpose To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer. Patients and Methods Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed. Results There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT. Conclusion The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.

Purpose: MDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02. Patients and Methods: Adequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Gray's regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM). Results: In multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM). Conclusion: Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.

Purpose: Two-dimensional (2D) high-dose GRID radiotherapy has shown effective tumor control in the clinical setting, and radiobiological data suggest potent bystander/abscopal effects with this technique. We present a new technical concept using modern radiation therapy instrumentation to advance traditional GRID treatment to modern three-dimensional (3D) high-dose LATTICE radiotherapy (LRT). Materials and Methods: An array of focused high-dose volumes, in essence a lattice of doses in 3D, can be generated through modern techniques resulting in highly heterogeneous dose distributions within the tumor volume, leaving adjacent and peripheral normal tissue minimally exposed. Two technical approaches were investigated for this novel concept: non-coplanar focused beams and MLC-based or aperture-modulated arc. Results: High magnitude dose oscillation is essential in traditional GRID therapy. The 3D “peak-to-valley” dose fall-off (100% to 20-30%) characteristic was attainable in test LRT cases, with a greater ability to place dose peaks within the radiation target volume and minimal dose to surrounding normal tissue. Conclusion: Modern radiotherapy methods are readily available to deliver 3D high-dose LATTICE radiotherapy with superior dosimetry compared to the 2D GRID technique. This is an easily accessible therapeutic modality that could potentially result in comparable or superior treatment outcomes than traditional 2D GRID therapy when implemented in the clinical setting.

Ethnic heterogeneity and prostate cancer mortality in Hispanic/Latino men: a population-based study Ethnic heterogeneity and prostate cancer mortality in Hispanic/Latino men: a population-based study