Neil Mariados

Comparison of Fracture Risk Assessment Tool Score to Bone Mineral Density for Estimating Fracture Risk in Patients With Advanced Prostate Cancer on Androgen Deprivation Therapy

OBJECTIVE To estimate the risk of fracture (Fracture Risk Assessment Tool [FRAX] algorithm) because of the development of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy (ADT) for patients who would otherwise not have been identified for treatment by the T score. METHODS This study includes men undergoing ADT for prostate cancer at our urology group. Clinical data were collected via chart review. Subjects were evaluated for fracture risk using country specific (for the United States of America) World Health Organizations FRAX. The FRAX calculations were then compared to fracture risk as determined by T score, for a subset of our cohort that received dual-energy X-ray absorptiometry. RESULTS Our cohort consisted of 613 patients on ADT, 94 of which had a dual-energy X-ray absorptiometry scan. The FRAX algorithm identified 61.6% patients requiring therapy without bone mass density (BMD), 46.8% with BMD, and 19.14% with T score alone. In addition, positive correlation was found between FRAX with and without BMD as well as T score and FRAX with BMD and without BMD. CONCLUSION Our data indicate that many patients who were not found at significant risk for fracture with T score were in fact found to be at risk with the FRAX calculation. The largest proportion of patients was found to be at risk through the FRAX calculation without BMD, followed by FRAX with BMD, followed by T score alone. The utility of FRAX is beneficial in identifying patients that may benefit from effective bone-tropic treatment modalities.

Re-treatment with radium-223 : first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases

Abstract Background Six radium-223 injections at 4-week intervals is indicated for patients with castration-resistant prostate cancer and symptomatic bone metastases. However, patients usually develop disease progression after initial treatment. This prospective phase I/II study assessed re-treatment safety and efficacy of up to six additional radium-223 injections. Patients and methods Patients had castration-resistant prostate cancer and bone metastases and six initial radium-223 injections with no on-treatment bone progression; all had subsequent radiologic or clinical progression. Concomitant agents were allowed at investigator discretion, excluding chemotherapy and initiation of new abiraterone or enzalutamide. The primary endpoint was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and prostate-specific antigen progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression. Results Among 44 patients, 29 (66%) received all six re-treatment injections. Median time from end of initial radium-223 treatment was 6 months. Forty-one (93%) reported ≥1 treatment-emergent adverse event. No grade 4–5 hematologic treatment-emergent adverse events occurred. Only one (2%) patient had radiographic bone progression; eight (18%) had radiographic soft tissue tumor progression (three lymph node and five visceral metastases). Median times to total alkaline phosphatase and prostate-specific antigen progression were not reached and 2.2 months, respectively. Median radiographic progression-free survival was 9.9 months (12.8-month maximum follow-up). Five (11%) patients died and eight (18%) experienced first SSEs. Median overall survival, time to first SSE, and SSE-free survival were not reached. Five (14%) of 36 evaluable patients (baseline worst pain score ≤7) had pain progression. After 2 years of follow-up, 28 (64%) patients died, and the median overall survival was 24.4 months. Conclusions Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.

eRADicAte: A Prospective Evaluation Combining Radium-223 Dichloride and Abiraterone Acetate Plus Prednisone in Patients With Castration-Resistant Prostate Cancer

Background Multiple castration‐resistant prostate cancer (CRPC) therapies are approved by the United States Food and Drug Administration. Radium‐223 dichloride (Ra‐223) with abiraterone acetate plus prednisone have different mechanisms of action and distinct off‐target side‐effect profiles. We prospectively investigated their combined safety, tolerability, and patient‐reported outcome measures. Patients and Methods eRADicAte, an investigator‐initiated, phase II trial, studied 31 patients with metastatic CRPC, from 5 United States uro‐oncology research sites. Patients completed 6 cycles of Ra‐223 with concurrent abiraterone therapy. Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy‐Prostate and the Brief Pain Inventory‐Short Form questionnaires and their subscales; we reported the number of subjects meeting standardized criteria for clinically meaningful improvements on each scale. Safety assessment included Eastern Cooperative Oncology Group performance status, laboratory changes, opioid use, radiographic responses, and adverse events (AEs). Results Twenty of 31 (65%) experienced positive clinically meaningful improvement changes on the Functional Assessment of Cancer Therapy‐Prostate, and 25 (81%) of 31 on the Prostate Cancer Subscale. Eighteen (58%) of 31 demonstrated reduced pain intensity and 12 (39%) of 31 demonstrated reduction of pain interference in their lives. At baseline, subjects averaged 11.6 ± 2.8 bone lesions; at the end of treatment, subjects averaged 5.6 ± 2.4 bone lesions (P = .0002). The most frequent AEs were diarrhea (17%), nausea (17%), and fatigue (14%). There were 6 serious AEs; 1 led to study withdrawal. Conclusions Patients experienced clinically meaningful improvements in quality of life and pain, without unexpected adverse toxicities. Phase III combination trials of Ra‐223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit. Micro‐Abstract This is the first study to prospectively evaluate the combined use of radium‐223 dichloride and a novel oral hormonal therapy, abiraterone acetate, in men with metastatic castration‐resistant prostate cancer. The eRADicAte study showed that patients with metastatic castration‐resistant prostate cancer experienced clinically meaningful improvements in quality of life with decreased pain, reduction in bone lesions, and an acceptable safety and toxicity profile.

Hydrogel Spacer Application Technique, Patient Tolerance and Impact on Prostate Intensity Modulated Radiation Therapy: Results from a Prospective, Multicenter, Pivotal Randomized Controlled Trial

Introduction We evaluate the safety, tolerability and impact on therapy of an absorbable hydrogel perirectal spacer (SpaceOAR® system) designed to reduce the rectal radiation dose during prostate cancer radiotherapy. Methods A multicenter, pivotal, randomized controlled trial was conducted in 222 men with stage T1 or T2 prostate cancer treated to 79.2 Gy with image guided intensity modulated radiation therapy in 44 fractions. Patients were randomized 2:1 to receive fiducial markers and perirectal spacer injection (spacer group) or fiducial markers alone (control group). Spacer placement, tolerability, perirectal space creation, impact on rectal dose and impact on quality of life were assessed. Results Most spacer procedures were conducted with the patient under general or local anesthesia. Procedures were rated easy or very easy in 98.7% of cases with a 99.3% success rate. Mild transient rectal events were noted in 10% of patients in the spacer group (eg pain, discomfort). Mean perirectal space was 12.6 mm after implant and 10.9 mm at 12.4 weeks with absorption at 12 months. A 25% or greater reduction in rectal V70 dose was produced in 97.3% of patients in the spacer group. The spacer group experienced a significant reduction in late rectal toxicity severity (p=0.044) as well as lower rates of decrease in bowel quality of life at 6, 12 and 15 months compared to the control group. There were no unanticipated adverse spacer effects or spacer related adverse events. Conclusions Hydrogel spacer application was straightforward and repeatable, resulting in consistent perirectal space creation and rectal dose reduction. Spacer application has the potential to improve prostate radiotherapy outcomes and enable advanced radiotherapy protocols.