K.R. Jethwa

Prostate cancer–specific PET radiotracers: A review on the clinical utility in recurrent disease

Prostate cancer-specific positron emission tomography (pcPET) has been shown to detect sites of disease recurrence at serum prostate-specific antigen (PSA) levels that are lower than those levels detected by conventional imaging. Commonly used pcPET radiotracers in the setting of biochemical recurrence are reviewed including carbon 11/fludeoxyglucose 18 (F-18) choline, gallium 68/F-18 prostate-specific membrane antigen (PSMA), and F-18 fluciclovine. Review of the literature generally favors PSMA-based agents for the detection of recurrence as a function of low PSA levels. Positive gallium 68/F-18 PSMA positron emission tomography/computed tomography scans detected potential sites of recurrence in a median 51.5% of patients when PSA level is <1.0 ng/mL, 74% of patients when PSA level is 1.0 to 2.0 ng/mL, and 90.5% of patients when PSA level is >2.0 ng/mL. Review of carbon 11/fludeoxyglucose 18 (F-18) choline and F-18 fluciclovine data commonly demonstrated lower detection rates for each respective PSA cohort, although with some important caveats, despite having similar operational characteristics to PSMA-based imaging. Sensitive pcPET imaging has provided new insight into the early patterns of disease spread, which has prompted judicious reconsideration of additional local therapy after either prostatectomy, definitive radiation therapy, or postprostatectomy radiation therapy. This review discusses the literature, clinical utility, availability, and fundamental understanding of pcPET imaging needed to improve clinical practice.

Predictors of prostate volume reduction following neoadjuvant cytoreductive androgen suppression

Purpose Limited duration cytoreductive neoadjuvant hormonal therapy (NHT) is used prior to definitive radiotherapeutic management of prostate cancer to decrease prostate volume. The purpose of this study is to examine the effect of NHT on prostate volume before permanent prostate brachytherapy (PPB), and determine associated predictive factors. Material and methods Between June 1998 and April 2012, a total of 1,110 patients underwent PPB and 207 patients underwent NHT. Of these, 189 (91.3%) underwent detailed planimetric transrectal ultrasound before and after NHT prior to PPB. Regression analysis was used to assess predictors of absolute and percentage change in prostate volume after NHT. Results The median duration of NHT was 4.9 months with inter quartile range (IQR), 4.2-6.6 months. Prostate-specific antigen (PSA) reduced by a median of 97% following NHT. The mean prostate volume before NHT was 62.5 ± 22.1 cm3 (IQR: 46-76 cm3), and after NHT, it was 37.0 ± 14.5 cm3 (IQR: 29-47 cm3). The mean prostate volume reduction was 23.4 cm3 (35.9%). Absolute prostate volume reduction was positively correlated with initial volume and inversely correlated with T-stage, Gleason score, and NCCN risk group. In multivariate regression analyses, initial prostate volume (p < 0.001) remained as a significant predictor of absolute and percent prostate volume reduction. Total androgen suppression was associated with greater percent prostate volume reduction than luteinizing hormone releasing hormone agonist (LHRHa) alone (p = 0.001). Conclusions Prostate volume decreased by approximately one third after 4.9 months of NHT, with total androgen suppression found to be more efficacious in maximizing cytoreduction than LHRHa alone. Initial prostate volume is the greatest predictor for prostate volume reduction.

Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool

Background Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985-2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors. Methods A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively. Results The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0-1.0, 1.5-2.0, 2.5-3, and 3.5-4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively. Conclusion The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com.

Increased utilization of external beam radiotherapy relative to cystectomy for localized, muscle-invasive bladder cancer: a SEER analysis

OBJECTIVE To assess recent utilization patterns of radiotherapy (RT) relative to cystectomy for muscle-invasive bladder cancer (MIBC) and evaluate survival trends over time in patients receiving RT. MATERIALS AND METHODS The surveillance, epidemiology, and end results program (SEER) was used to identify patients diagnosed between 1992 and 2013 with localized MIBC. Patients with a prior history of non-bladder malignancy, who received no treatment, or did not have available treatment information, were excluded. Treatment utilization patterns were assessed using Cochran-Armitage tests for trend, and patient characteristics were compared using chi-square tests. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan-Meier method. All-cause (ACM) and cause-specific mortality (CSM) were evaluated with multivariable Cox proportional hazards regression. RESULTS Of 16175 patients analyzed, 11917 (74%) underwent cystectomy, and 4258 (26%) were treated with RT. Patients who received RT were older (median age 79 vs. 68, P < 0.01). Over time, the proportion of patients receiving RT relative to cystectomy increased (24% 1992–2002 vs. 28% 2003–2013, P < 0.01), despite median patient age throughout the study period remaining unchanged (71 for each 1992–2002 and 2003–2013, P = 0.41). For RT, compared with patients diagnosed earlier, those diagnosed from 2010–2013 showed improved OS (64% vs. 60% at 1 year, P < 0.01; 38% vs. 29% at 3 years, P < 0.01) and CSS (71% vs. 67% at 1 year, P = 0.01; 51% vs. 40% at 3 years, P < 0.01). On multivariable analysis, diagnosis from 2010–2013 was associated with a lower estimated risk of ACM (hazard ratio 0.77; 95% confidence interval 0.66–0.89, P < 0.001) and CSM (hazard ratio 0.81; 95% confidence interval 0.67–0.97, P = 0.02). CONCLUSION Utilization of RT for localized MIBC increased relative to cystectomy from 1992 to 2013, despite the median age of treated patients remaining unchanged. More recent survival outcomes for patients receiving RT were improved, supporting continued use of bladder preservation strategies utilizing RT.

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes

Purpose Pencil-beam scanning intensity modulated proton therapy (IMPT) may allow for an improvement in the therapeutic ratio compared with conventional techniques of radiation therapy delivery for pancreatic cancer. The purpose of this study was to describe the clinical implementation of IMPT for intact and clinically localized pancreatic cancer, perform a matched dosimetric comparison with volumetric modulated arc therapy (VMAT), and report acute adverse event (AE) rates and patient-reported outcomes (PROs) of health-related quality of life. Methods and materials Between July 2016 and March 2017, 13 patients with localized pancreatic cancer underwent concurrent capecitabine or 5-fluorouracil-based chemoradiation therapy (CRT) utilizing IMPT to a dose of 50 Gy (radiobiological effectiveness: 1.1). A VMAT plan was generated for each patient to use for dosimetric comparison. Patients were assessed prospectively for AEs and completed PRO questionnaires utilizing the Functional Assessment of Cancer Therapy-Hepatobiliary at baseline and upon completion of CRT. Results There was no difference in mean target coverage between IMPT and VMAT (P > .05). IMPT offered significant reductions in dose to organs at risk, including the small bowel, duodenum, stomach, large bowel, liver, and kidneys (P < .05). All patients completed treatment without radiation therapy breaks. The median weight loss during treatment was 1.6 kg (range, 0.1-5.7 kg). No patients experienced grade ≥3 treatment-related AEs. The median Functional Assessment of Cancer Therapy-Hepatobiliary scores prior to versus at the end of CRT were 142 (range, 113-163) versus 136 (range, 107-173; P = .18). Conclusions Pencil-beam scanning IMPT was feasible and offered significant reductions in radiation exposure to multiple gastrointestinal organs at risk. IMPT was associated with no grade ≥3 gastrointestinal AEs and no change in baseline PROs, but the conclusions are limited due to the patient sample size. Further clinical studies are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.