Caleb Dulaney

Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine

Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy.

Poly(ADP-ribose) polymerase activity and inhibition in cancer.

Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination. Five PARP inhibitors are now in late-stage development in clinical trials that are seeking to expand the understanding of targeted therapies and DNA repair defects in human cancer. This review examines the cell biology of PARP, the discovery of synthetic lethality with HR deficiency, the clinical development of PARP inhibitors, and the role of PARP inhibitors in ongoing clinical trials and clinical practice.

Quality of Prostate Cancer Treatment Information on Cancer Center Websites.

Introduction Cancer center websites are trusted sources of internet information about treatment options for prostate cancer. The quality of information on these websites is unknown. The objective of this study was to evaluate the quality of information on cancer center websites addressing prostate cancer treatment options, outcomes, and toxicity. Materials and methods We evaluated the websites of all National Cancer Institute-designated cancer centers to determine if sufficient information was provided to address eleven decision-specific knowledge questions from the validated Early Prostate Cancer Treatment Decision Quality Instrument. We recorded the number of questions addressed, the number of clicks to reach the prostate cancer-specific webpage, evaluation time, and Spanish and mobile accessibility. Correlation between evaluation time and questions addressed were calculated using the Pearson coefficient. Results Sixty-three websites were reviewed. Eighty percent had a prostate cancer-specific webpage reached in a median of three clicks. The average evaluation time was 6.5 minutes. Information was available in Spanish on 24% of sites and 59% were mobile friendly. Websites provided sufficient information to address, on average, 19% of questions. No website addressed all questions. Evaluation time correlated with the number of questions addressed (R2 = 0.42, p < 0.001). Conclusions Cancer center websites provide insufficient information for men with localized prostate cancer due to a lack of information about and direct comparison of specific treatment outcomes and toxicities. Information is also less accessible in Spanish and on mobile devices. These data can be used to improve the quality and accessibility of prostate cancer treatment information on cancer center websites.

Evaluating the Role of Urinalysis for Suspected Cystitis in Women Undergoing Pelvic Radiotherapy.

PURPOSE The aims of this study were to analyze the effectiveness of urinalysis parameters in predicting positive urine culture and to characterize urinary tract infections in gynecologic cancer patients receiving pelvic radiotherapy. METHODS The records of 134 women receiving pelvic radiotherapy were retrospectively analyzed with a total of 241 urine specimens. Dipstick, urine microscopy, and urine culture data were recorded. Sensitivity, specificity, positive and negative predictive values, and diagnostic odds ratios of dipstick and microscopy components for predicting positive urine culture were calculated. Organisms isolated from positive cultures and their antibiotic resistance data were recorded. RESULTS A total of 84 urine cultures (34.9%) were positive for growth. The presence of either urine nitrites, leukocyte esterase, or both had the highest sensitivity (91.7%) of all tested parameters for predicting a positive urine culture. The presence of both urine white blood cells and urine nitrites had the highest specificity (95.5%), positive predictive value (75.0%), and diagnostic odds ratio (7.21 [2.92-17.83]), whereas the absence of urine white blood cells had the highest negative predictive value (87.0%). Escherichia coli was the most common grown in culture, isolated from 19 specimens (22.6%). When antibiotic sensitivity analysis was performed, 23.8% of pathogens were resistant to trimethoprim/sulfamethoxazole, 16.7% were resistant to ciprofloxacin, and 11.1% were resistant to nitrofurantoin. CONCLUSIONS Urinalysis may be less accurate for predicting urinary tract infection in women undergoing pelvic RT compared with the general population, but is still useful. Escherichia coli was less common than expected, and the rate of resistance to first-line antibiotics was relatively high, underscoring the importance of culture and sensitivity testing in order to confirm the efficacy of empiric antibiotic therapy.

Hospice care, cancer-directed therapy, and Medicare expenditures among older patients dying with malignant brain tumors

Background End-of-life care for older adults with malignant brain tumors is poorly understood. The purpose of this study is to quantify end-of-life utilization of hospice care, cancer-directed therapy, and associated Medicare expenditures among older adults with malignant brain tumors. Methods This retrospective cohort study included deceased Medicare beneficiaries age ≥65 with primary malignant brain tumor (PMBT) or secondary MBT (SMBT) receiving care within a southeastern cancer community network including academic and community hospitals from 2012-2015. Utilization of hospice and cancer-directed therapy and total Medicare expenditures in the last 30 days of life were calculated using generalized linear and mixed effect models, respectively. Results Late (1-3 days prior to death) or no hospice care was received by 24% of PMBT (n = 383) and 32% of SMBT (n = 940) patients. SMBT patients received late hospice care more frequently than PMBT patients (10% vs 5%, P = 0.002). Cancer-directed therapy was administered to 18% of patients with PMBT versus 25% with SMBT (P = 0.003). Nonwhite race, male sex, and receipt of any hospital-based care in the final 30 days of life were associated with increased risk of late or no hospice care. The average decrease in Medicare expenditures associated with hospice utilization for patients with PMBT was

Stereotactic Radiosurgery for Prostate Cancer Following Magnetic Resonance Imaging Directed Biopsy: A Multidisciplinary Approach with Case Examples

-12,138 (95% CI:

DNA repair deregulation in discrete prostate cancer lesions identified on multi-parametric MRI and targeted by MRI/ultrasound fusion-guided biopsy

-18,065 to

Patterns of Failure for Lymph Node-Positive Resected Pancreatic Adenocarcinoma After Adjuvant Radiotherapy or Gemcitabine-based Chemotherapy Alone

-6210) and with SMBT was

Hospital-Based End-of-Life Care and Costs for Older Patients With Malignant Brain Tumors

-1,508 (95% CI:

Gait Speed and Survival in Patients With Brain Metastases

-3,613 to