bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of sabizabulin in phase 1b/2 clinical trials of men with metastatic castration-resistant prostate cancer who progressed on androgen receptor-targeting agents.
Authors: Markowski Mark Christopher , Eisenberger Mario A. , Pieczonka Christopher Michael , Getzenberg Robert H. , Rodriguez Domingo , Barnette K. Gary , Steiner Mitchell S. , Saltzstein Daniel R. , Antonarakis Emmanuel S. , Tutrone Ronald F. 
Published: February 2022

110 Background: Sabizabulin is a novel oral cytoskeleton disruptor being developed for use in metastatic castration resistant prostate cancer (mCRPC). A phase 1b/2 clinical study was conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC resistant to androgen receptor targeting agents (ARTAs). Methods: The phase 1b portion of the study in 39 men utilized escalating and expanding dose and duration. The phase 2 portion studied 41 men with mCRPC at the recommended phase 2 dose (RP2D) of 63 mg daily. Based upon the phase 1b/2 data, sabizabulin appears to have both cytotoxic and cytostatic activity. A analysis was conducted evaluating the best clinical response (BCR) defined as either an objective response assessed by PCWG3 criteria and/or stable disease defined as ≥5 cycles (≥15 weeks) of continuous treatment. Results: Of the combined 80 patients in the phase 1b/2 portions of the study, the BCR was 37.5% (30/80) and 5 of the responders remain on study with the longest being treated for more than 30 months. Of the patients with measurable disease at study entry, the BCR was 59% (17/29). Prior to study entry, 11/30 (37%) of those with a BCR had previously been treated with and subsequently progressed on a minimum of 2 ARTAs. The remaining 19/30 (63%) had progressed on a single ARTA agent. 11 (37%) were previously treated with enzalutamide or apalutamide and 8 (27%) with abiraterone as single agents. 8 (27%) received enzalutamide and abiraterone and 3 (10%) patients received more than two ARTAs. As described previously, the safety profile continues to be favorable with no clinically relevant neutropenia or neurotoxicity. Conclusions: In this analysis, sabizabulin has demonstrated not only cytotoxic, but also significant cytostatic activity with similar responses in men that have progressed on a single or multiple ARTA agents. Sabizabulin is a novel agent with the potential provide men with mCRPC a well-tolerated chronic treatment cytostatic option after progressing on an ARTA and is being tested in the open phase 3 VERACITY trial. Clinical trial information: NCT03752099.
Survival of patients with metastatic prostate cancer and comorbid obesity.
Authors: Cheranda Nina , Luo Suhong , Riekhof Forest , Govindan Srinivas , Sanfilippo Kristen Marie , Schoen Martin W. 
Published: February 2022

116 Background: In metastatic castrate resistant prostate cancer (mCRPC), the oral treatments of enzalutamide (ENZ) and abiraterone (AA) are used interchangeably because there are few large-scale comparative studies of the therapies. However, both drugs have different mechanisms of action, AA being an androgen biosynthesis inhibitor and ENZ being an androgen receptor inhibitor, so there may be therapeutic variance between the two drugs based on their interactions with comorbid conditions like obesity. Obesity not only increases the risk of other comorbidities, like heart disease, diabetes, and stroke, but has also been implicated in the development of CRPC. Methods: Patients treated with abiraterone or enzalutamide from September 10, 2014 to June 2, 2017 in the Veterans Health Administration were identified via pharmacy records. Among this population, patients were separated into body mass index (BMI) categories for underweight ( < 18.5), normal (18.5 to < 25), overweight (25 to < 30), and obese ( > 30). Age, Charlson Comorbidity Index and mCRPC treatments were collected and analyzed for the primary outcome of survival via the Kaplan-Meier method. A multivariate Cox proportional hazard model was performed with the following variables: BMI, Charlson Comorbidity Index, age, Black race, treatment with bone-directed therapy, and baseline PSA. Results: In patients with BMI > 25, there was a significantly improved overall survival for treatment with ENZ (n = 1623) over AA (n = 2159), with medians of 30.0 and 27.0 months respectively (p = 0.002). There was no significant difference in survival for patients with BMI < 25 (p = 0.48), with median survival of 17.7 months for ENZ (n = 589) and 16.1 months for AA (n = 860). The overall survival difference between underweight (n = 113), normal (n = 1336), overweight (n = 1879), and obese (n = 1903) groups shows significant increase in survival with increasing BMI, with the median survival durations of 9.2, 15.9, 23.9, and 29.8 months respectively (p < 0.001). This finding was corroborated by the Cox proportional hazard model, with the data indicating an increased risk of death (aHR = 1.58; 95% CI: 1.29, 1.94; p < 0.001) with the underweight group and decreased risk with the overweight (aHR = 0.75; 95% CI: 0.69, 0.81; p < 0.001) and obese (aHR = 0.64; 95% CI: 0.59, 0.70; p < 0.001) groups. Conclusions: Treatment with ENZ was associated with longer survival for mCRPC patients with overweight and obesity (BMI > 25) over AA. Otherwise, for normal and underweight patients (BMI < 25), there was no significant difference in overall survival between the two drugs. Higher BMI is associated with improved survival, suggesting a protective effect of obesity in mCRPC patients. While the reason for this finding warrants further investigation, similar findings have been seen in obese patients in some hormone driven cancers, like breast cancer and myeloma.
Third analysis of a randomized trial of finite abiraterone acetate (AA) plus LHRH agonist (LHRHa) versus LHRHa in biochemically recurrent, non-metastatic hormone-naïve prostate cancer (M0HNPC).
Authors: Hahn Andrew Warren , Wang Xuemei , Efstathiou Eleni , Hwang Hyunsoo , Zurita Amado J. , Spetsieris Nicholas , Boukovala Myrto A , Wang Jennifer , Araujo John C. , Pilie Patrick Glen , Siddiqui Bilal A. , Subudhi Sumit Kumar , Corn Paul Gettys , Aparicio Ana , Tu Shi-Ming , Logothetis Christopher 
Published: February 2022

135 Background: In pre-operative studies, a short duration of AA + LHRHa produced marked cytoreduction in a subset of men with high-risk prostate cancer (PCa). However, in M0HNPC, androgen signaling inhibition (ASI) is reserved for men with short PSA doubling time. We reasoned that the subset of men who experience cytoreduction with pre-operative AA + LHRHa would also benefit from a short duration of AA + LHRHa at PSA recurrence. This report is a one-year follow-up of our second analysis (ASCO Annual Meeting 2018; PMID 34536949). Methods: FINITE is a phase II trial that randomized (1:1) to two treatment groups, 8 months of LHRHa alone or LHRHa plus AA 1000 mg and prednisone 5 mg daily (NCT01786265). Eligible patients had a rising PSA after definitive therapy and no prior systemic therapy. At disease progression, men were eligible for crossover to 8 months of the alternative therapy. The primary endpoint was PSA-free survival at 12 months (≤ 0.1 ng/dL). Time to PSA progression was calculated from date of initial treatment to date of PSA progression, defined as first occurrence of a rising PSA, if PSA remained detectable after treatment, or when the PSA ≥ 1 ng/dL, if it was undetectable after treatment and confirmed 4 weeks thereafter. The probabilities of PSA progression were defined using the Kaplan-Meier method. Results: 199 men were randomized, and 197 received initial treatment (LHRHa = 99, LHRHa + AA = 98). Median age at enrollment was 65 years, median PSA was 0.95 ng/dL (range 0.1 – 33.3), and median testosterone was 342.5 ng/dL (10-986). At data cut-off (October 1, 2021), men who received LHRHa + AA were more likely to be PSA-free 12 months after completing treatment (34% vs. 19%, p = 0.02). 168 men (85%) had experienced PSA progression, and median time to PSA progression was 24.3 months for entire cohort. Receipt of LHRHa + AA was associated with longer time to PSA progression than LHRHa alone (27.2 vs. 19.9 months, p = 0.003). Conclusions: Our findings support that finite treatment with AA + LHRHa produces more durable disease-free survival than LHRHa. The finite duration of AA + LHRHa is a toxicity-sparing approach that may allow for a transition from a treatment to curative paradigm for a subset of men with M0HNPC. Further analyses will aim to link the subset of men who benefit from finite AA + LHRHa between localized high-risk PCa and M0HNPC. Clinical trial information: NCT01786265.
Characteristics of prostate cancer patients captured by facility-based versus geography-based cancer registries.
Authors: Filson Christopher Paul , Modi Parth K. , Ward Kevin C. 
Published: February 2022

237 Background: Cancer registries provide valuable information related to cancer epidemiology, treatment, and outcomes. However, the sampling for inclusion can impact generalizability of findings to other settings. We use a population-based cancer registry to evaluate demographics, cancer factors, and treatment patterns based on eligibility for a facility-based cancer registry. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify men diagnosed with prostate cancer (site = C61.9) in 2018. Exposure was whether data were reported from a facility accredited by American College of Surgeons’ Commission on Cancer (CoC), providing eligibility for the National Cancer Database (NCDB) (i.e., NCDB-eligible). Outcomes of interest included demographics, tumor factors (e.g., biopsy grade), and treatment. Bivariate testing and multivariable regression analyses tested for significant associations between exposure and outcomes of interest. Results: We identified 57,713 men diagnosed with prostate cancer in 2018, of which 32,384 (61.9%) were eligible for inclusion in NCDB. NCDB-eligible men were younger (66.6 vs 67.8 years, p < 0.001), less likely to be Hispanic/Latino (8.0% vs 14.4%, p < 0.001), and more likely to reside in a county with median income over $75,000 (39.7% vs 33.3%, p < 0.001). NCDB eligibility varied widely by registry, from 96.1% in Connecticut to 44.7% in Utah. The proportion of localized cancer patients with Grade Group 1 cancer on biopsy was higher among men ineligible for NCDB (41.4% vs 26.9%, p < 0.001). The proportion of patients with more advanced disease at presentation was higher among NCDB-eligible patients (metastatic: 9.4% vs 6.8%; regional: 18.7% vs 8.7%; p < 0.001). For patients with localized or regional cancer, treatment was identified more frequently among NCDB-eligible patients for both low-risk (38.5% vs 22.7%, p < 0.001) and high-risk tumors (84.9% vs 64.2%). Among treated patients, use of radical prostatectomy was more common among NCDB-eligible patients (low risk: 58.9% vs 43.1%; high risk: 53.7% vs 43.4%, p < 0.001). Conclusions: Prostate cancer patients eligible for inclusion in the facility based NCDB have important differences in demographics, severity of cancer risk, and treatment patterns compared to those who are not eligible. Generalizations related to epidemiologic trends, practice patterns, and outcomes for prostate cancer patients in the NCDB should be interpreted with caution.
Radiation technique and outcomes following moderately hypofractionated treatment of low risk prostate cancer: A secondary analysis of the NRG oncology RTOG 0415 randomized clinical trial.
Authors: Carpenter David James , Salama Joseph Kamel , Lee W. Robert , Boyer Matthew J 
Published: February 2022

243 Background: While intensity-modulated radiotherapy (IMRT) is commonly used to deliver moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC), IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in the context of MHRT. This secondary analysis of the phase III RTOG 0415 trial compares survival outcomes and toxicity across RT technique between IMRT and 3D-CRT for low-risk PC. Methods: The phase III, non-inferiority trial RTOG 0415 randomized patients with low risk PC to either MHRT (70Gy at 2.5Gy/fraction) or conventionally fractionated radiation (CFRT; 73.8Gy at 1.8Gy/fraction) with stratification by RT technique. A secondary analysis for differences in overall (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed. For patient and tumor characteristics, continuous data were compared with Wilcoxon rank sum test and categorical data with Chi-squared test, as appropriate. Rates of BRFS and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 1079 patients received the allocated intervention with a median follow up of 5.8 years. RT technique was balanced between treatment arms, with 79.1% of patients receiving IMRT. RT protocol compliance was > 95% for both IMRT and 3D-CRT. There were no significant differences in BRFS between patients treated with 3D-CRT versus IMRT for all patients (p = 0.33), those randomized to CFRT (p = 0.78), or those randomized to MHRT (p = 0.24). Overall survival did not differ by RT technique as well. For all patients, there was no difference in acute and late GI and GU toxicity rates across RT technique. For patients treated with MHRT, late grade 2 GU toxicity was more common with IMRT than 3D-CRT (31.3% vs 23.4%; p = 0.004). On logistic regression analysis, only poor baseline urinary function, defined as an EPIC score of 90 or below, correlated with acute (p < 0.001) or late (p < 0.001) GU toxicity. Baseline bowel function did not correlate to GI toxicity. Conclusions: RT technique did not impact survival outcomes or toxicity rates following MHRT for low risk PC. Higher rates of late CTCAE grade 2+ GU and GI toxicity observed within the RTOG 0415 MHRT arm were not disproportionally observed following 3D-CRT than IMRT. These data highlight the need for careful consideration of target delineation and normal tissue constraints in the selection and delivery of appropriate RT technique.
Real-world evidence of patient-reported outcomes following definitive radiation therapy for prostate cancer: Findings from an Australian population-based clinical outcomes registry.
Authors: Ong Wee Loon , Evans Melanie , Papa Nathan , Millar Jeremy Laurence 
Published: February 2022

244 Background: We aimed to evaluate patient-reported functional outcomes (PRO) following definitive radiation therapy (RT) for prostate cancer (PCa) in a real-life population-based setting. Methods: The population-based Victorian Prostate Cancer Outcomes Registry (PCOR-Vic) captures approximately 90% of all PCa cases in the state. From 2015 onwards, all men in PCOR-Vic were contacted to complete the Expanded Prostate Cancer Index Composite short-form 26 (EPIC-26) at 12-month post-treatment. The EPIC-26 included urinary incontinence, urinary obstructive, bowel, sexual and hormonal function domain scores, ranging from 0 to 100, with higher score representing better outcomes. We estimated differences in the EPIC-26 domain scores between different RT techniques using linear regression, adjusting for patient, tumor, and treatment related factors, including the use of androgen deprivation therapy (ADT). The nature of recruitment methods and data collection in PCOR-Vic precluded us from measuring EPIC-26 prior to treatment, and hence this was not adjusted for in our analyses. Results: Between 2015 and 2020, there were 1,898 men treated with definitive RT who completed the EPIC-26 questionnaires and were included in this study – 1551 (82%) had external beam radiation therapy (EBRT) alone, 91 (5%) had EBRT with brachytherapy boost (EBRT+BT), 204 (11%) had low-dose-rate brachytherapy (LDR-BT) alone, and 52 (3%) had high-dose-rate brachytherapy (HDR-BT) alone. There were 1,140 (60%) men who had ADT with RT – 68% with EBRT alone, 76% with EBRT+BT, 4% with LDR-BT, and 21% with HDR-BT (P < 0.001). Compared to men who had EBRT alone, men who had LDR-BT had higher adjusted mean EPIC-26 urinary incontinence (8.6 points; 95%CI: 5.3-12.0; P < 0.001), sexual (13.5 points; 95%CI: 9.2-17.8; P < 0.001) and hormonal score (6.8 points; 95%CI: 3.5-10.1; P < 0.001) at 12-month post-treatment. Compared to men who had EBRT alone, there were no statistically significant differences in all five EPIC-26 domain scores in men who had EBRT+BT or HDR-BT alone. Conclusions: This is the first Australian real-world evidence on PRO for different RT modalities for PCa on a population-based level. We observed better urinary incontinence, sexual and hormonal function in men who had LDR-BT compared to EBRT, but no significant differences between men who had EBRT, EBRT+BT or HDR-BT.
Comparison of the medical costs between active surveillance and other treatment for early prostate cancer in Japan: From the data of PRIAS JAPAN study.
Authors: Kato Takuma , Sugimoto Mikio , Kakehi Yoshiyuki , Tohi Yoichiro , Matsumoto Ryuji , Shinohara Nobuo , Yokomizo Akira , Fukuhara Hiroshi , Mitsuzuka Koji , Sasaki Hiroshi , Egawa Shin , Inokuchi Junichi , Eto Masatoshi ,   PRIAS-JAPAN study group
Published: February 2022

280 Background: As the number of prostate cancer patients increases, the cost of treatment is becoming an urgent issue. To compare the costs between active surveillance, robot-assisted laparoscopic prostatectomy (RALP), Brachytherapy (BT), Intensity Modulated Radiation Therapy (IMRT), and Androgen deprivation therapy(ADT). Methods: The costs of protocol biopsies in the first year of AS performed between January 2010 and June 2020, and the treatment costs of RALP, BT, and IMRT performed between May 2019 and June 2020 at Kagawa university hospital were analyzed. The cost of ADT was assumed to be the cost of the LH-RH analog over 5 years. The inpatient treatment cost for each treatment was calculated from our DPC data, and for IMRT, the treatment cost was calculated by the outpatient cost at the time of irradiation. AS-eligible patients were defined as less than 74 years old, less than T2, less than GS6, and less than two positive cores. We estimated the total number of AS-eligible patients in Japan based on the data of the J-CAP study and the data of cancer statistics in 2017 and estimated the total treatment cost of AS-eligible patients based on the data of treatment breakdown of T1/T2 patients in the J-CAP study. In addition, we used the data from PRIAS-JAPAN to calculate the AS continuation rate, protocol biopsy acceptance rate, and the breakdown of secondary treatments. We simulated the 5-year treatment cost for AS patients using the system. Results: The median treatment costs for AS (n = 45), RALP (n = 68), BT (n = 27), and IMRT (n = 44), and ADT were US$1.24 thousand, US$ 14.6 thousand, US$14.8 thousand, US$ 12.9 thousand, and US$8.16, respectively. The number of AS-eligible patients in Japan was estimated to be 5414, and the total cost of AS, RALP, BT, IMRT, HT, and ADT over 5 years was estimated to be US$3.07 million, US$34.8 million, US$8.46 million, US$11.09 million, and US$14.05 million, respectively. If 50% and 100% of the patients in each treatment group chose AS as their first treatment, the total cost of treatment would be reduced by US$18.6 million and US$38.5 million, respectively. Conclusions: The prevalence of AS will contribute to reducing the cost of prostate cancer treatment.
Healthcare resource utilization (HRU) and costs among patients with Von Hippel-Lindau disease (VHL)-associated renal cell carcinoma (RCC): A retrospective administrative claims analysis.
Authors: Jonasch Eric , Song Yan , Freimark Jonathan , Berman Richard , Nguyen Ha , Signorovitch James , Sundaram Murali 
Published: February 2022

305 Background: VHL disease is an inherited condition characterized by the formation of benign and malignant tumors in multiple organs, and RCC affects up to 40-70% of patients with VHL disease. However, real-world evidence on HRU and direct healthcare costs related to VHL-RCC is lacking. This study sought to address the gap in the literature by evaluating HRU and healthcare costs associated with the disease. Methods: Patients with VHL disease were identified from the Optum Clinformatics claims data using an algorithm based on combinations of manifestations of the disease. Among the patients identified, those with at least 1 diagnosis of RCC were further selected. The index date was defined as the date of first observed RCC diagnosis in the data, and the study period extends up to 5 years after index date or the end of continuous enrollment, whichever was earlier. A minimum continuous enrollment of 12 months prior to and 3 months after the index date was required. All-cause and RCC-related HRU and healthcare costs were evaluated among eligible patients with VHL-RCC. HRU was expressed as events per person-month and cost was expressed as average monthly cost. HRU and healthcare costs related to other VHL disease-related tumors were also assessed, including central nervous system (CNS) hemangioblastomas (Hb), retinal Hb, and pancreatic neuroendocrine tumors (pNETs). Results: 160 patients with VHL-RCC were included in the analyses. Mean age of the patients was 51.5 years and 89 (56%) were male. During the study period, patients with VHL-RCC incurred 0.10 hospitalizations (0.52 inpatient days), 1.49 outpatient visits, 0.09 emergency department (ED) visits, and 0.17 other medical visits per person-month on average. This translated to a monthly all-cause healthcare cost of $4,276, which included $2,222 inpatient, $1,318 outpatient, $188 ED, $63 other medical visits, and $485 pharmacy costs. $1,627 out of the all-cause cost per month was RCC-related, which was mainly driven by inpatient costs for RCC ($1,184/month). There were also notable costs associated with other tumor types: $2,159/month for CNS Hb, $601/month for retinal Hb, and $3,306/month for pNETs on average. Among patients with VHL-RCC who received surgical procedures for different tumors, the average hospitalization or outpatient visit costs were $28,356 for nephrectomies, $70,515 for CNS Hb surgeries, $2,887 for laser therapy of retinal Hb, and $81,825 for pNET surgeries. Conclusions: VHL-RCC is associated with significant HRU and healthcare costs due to the needs of managing RCC as well as tumors in other organs caused by VHL disease. This highlights the multi-disciplinary nature of VHL disease and the need for novel effective therapies to prevent or delay the recurrence of VHL-related tumors in order to mitigate the economic burden related to the disease.