Manuj Agarwal

Impact of the use of an endorectal balloon on rectal dosimetry during stereotactic body radiation therapy for localized prostate cancer

PURPOSE Endorectal balloons may be of benefit during stereotactic body radiation therapy of the prostate to limit intrafraction prostatic motion and potentially minimize rectal toxicity. We evaluated the effect of the endorectal balloon (ERB) on rectal dosimetry, specifically the absolute volume of rectum receiving high dose. METHODS AND MATERIALS Eleven patients with localized prostate cancer underwent stereotactic body radiation therapy planning with computed tomography simulation with and without a RadiaDyne ERB inflated with 60 mL of water. Prescription dose was 3625 cGy in 5 fractions of 725 cGy. The V3600 (volume receiving 3600 cGy), V3440 (volume receiving 3440 cGy), and volume receiving 50% of the prescription dose were calculated for both the rectum and rectal wall. Repeat plans were generated using smaller planning target volume margins (reduced to 1 mm from 3 mm posteriorly) and after virtually replacing the water-filled ERB with air equivalent density. Comparisons were made using the Wilcoxon signed-rank test. RESULTS The rectal V3600 and V3440 were significantly lower without ERB than with water-filled ERB using standard 3-mm posterior margin (P = .003 for both V3600/V3440), water-filled ERB using reduced 1-mm posterior margin (P = .016 and .003), or air-filled ERB (P = .003 and .004). Regarding the rectal wall, V3600 and V3440 were also significantly lower without ERB than with any ERB, except when using the water-filled ERB with reduced posterior margin (P = .328). The volumes of rectum and rectal wall receiving lower dose (volume receiving 50% of the prescription dose) were not significantly greater without the ERB. CONCLUSION We found an increase in the volume of rectum and rectal wall receiving high dose radiation utilizing an ERB. Consideration in using an ERB should account for potential increased rectal dose and subsequent toxicity.

Concordance Between Prostate Needle Biopsy and Surgical Histopathology in a Primarily African-American Population

Introduction. Prior studies have revealed that the concordance between biopsy and surgical specimens has been improving over time. However, to date, this has not been analyzed in an African American population, for whom data have often shown more aggressive prostate cancer than for other races. Methods. We analyzed 250 patients who were operated on at the NY Harbor Department of Veterans Affairs for localized prostate cancer between 2003 and 2010. The clinical biopsy scores were compared with the pathological biopsy scores. We compared the concordance using the κ coefficient. Univariate and multivariate logistic regressions were used to identify predictors for poor concordance. Results. This population consisted of 59.6% African Americans, 32% Caucasians, and 8.4% Hispanics. Overall, there was a 50% exact concordance between the biopsy and surgical specimens. The κ was 0.33, indicating fair agreement. Patients with a Gleason score of 6 were found to have an exact concordance 66% of the time, and those with a score of Gleason 7 (3 + 4) had an exact concordance 50% of the time. On univariate and multivariate analyses, only an increasing prostate-specific antigen was associated with reduced concordance. Race was not a significant predictor. Conclusions. These data are in line with prior studies of concordance. Despite being a population with more aggressive prostate cancer, there does not appear to be an increase in the risk of discordance in African American men.

Checkpoint Inhibition: Will Combination with Radiotherapy and Nanoparticle-Mediated Delivery Improve Efficacy?

Checkpoint inhibition (CPI) has been a rare success story in the field of cancer immunotherapy. Knowledge gleaned from preclinical studies and patients that do not respond to these therapies suggest that the presence of tumor-infiltrating lymphocytes and establishment of immunostimulatory conditions, prior to CPI treatment, are required for efficacy of CPI. To this end, radiation therapy (RT) has been shown to promote immunogenic cell-death-mediated tumor-antigen release, increase infiltration and cross-priming of T cells, and decreasing immunosuppressive milieu in the tumor microenvironment, hence allowing CPI to take effect. Preclinical and clinical studies evaluating the combination of RT with CPI have been shown to overcome the resistance to either therapy alone. Additionally, nanoparticle and liposome-mediated delivery of checkpoint inhibitors has been shown to overcome toxicities and improve therapeutic efficacy, providing a rationale for clinical investigations of nanoparticle, microparticle, and liposomal delivery of checkpoint inhibitors. In this review, we summarize the preclinical and clinical studies of combined RT and CPI therapies in various cancers, and review findings from studies that evaluated nanoparticle and liposomal delivery of checkpoint inhibitors for cancer treatments.

Concordance of Gleason score on biopsy and after prostatectomy: A SEER database analysis.

50 Background: The Gleason score (GS) is a well-established prognostic factor and is used to guide clinical decision-making for patients with prostate cancer. Concordance between the clinical GS of the core biopsy and of the pathologic specimen after radical prostatectomy has ranged from 30% to 75% in prior single-institution studies. The objective of this study is to analyze biopsy concordance utilizing the population-based Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients diagnosed with localized prostate adenocarcinoma (cT1c-4 Nx-1 M0) who underwent prostatectomy from 2010-2011 were identified in the SEER database. Agreement between clinical and pathologic GS was analyzed using the kappa (k) statistic. Univariate and multivariate logistic regression was performed to identify factors which may impact concordance using SPSS v21. Results: A total of 34,195 patients were included in this analysis. Median age was 61 and median PSA was 5.9 ng/ml. The majority of patients had clin...