bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of HRR mutations in Indian patients with mCRPC.
Authors: Batra Atul , Menon Nandini Sharrel , Vaswani Bharat , Talwar Vineet , Bajaj Rajat , Chandrakanth MV , Hingmire Sachin Sharadchandra , Prabhash Kumar , Choudhary Priyanshu , Pathania Bhavana 
Published: January 2024

183 Background: Prostate cancer is the 12th most common cancer in India. Almost all patients with metastatic prostate cancer progress to castration-resistant prostate cancer. Ph3 studies demonstrated benefit of PARPi for patients with mutations in HRR pathway. However, the prevalence of HRR gene mutations in Indian patients with mCRPC is not known. This non-interventional multicenter study aimed to determine the prevalence of HRR gene mutations in the Indian patients with mCRPC. Methods: The study included mCRPC patients from 8 centres across India. A total of 213 patients were screened, of which 192 patients completed the study. Comprehensive molecular profiling on tumour tissue was performed using next-generation sequencing (NGS) to identify 15 HRR gene mutations. The QC-passed libraries were sequenced to a minimum depth of >250X on a validated Illumina sequencing platform. Results: NGS analysis revealed HRR gene mutations (Pathogenic, likely pathogenic and VUS) in 41/192 (21.4%, 95% CI: 15.78, 27.83)) of the patients (Table). Among the HRR gene mutations identified, BRCA2 mutations were the most prevalent.68/192 (35%) patients failed tumor testing and underwent reflex germline testing. Among patients having no known family history, 24 patients (12.5%) harboured a HRR gene mutation. Most patients (n=23, 12.0%) had Gleason score of 9 to 10. Conclusions: Pathogenic and likely pathogenic HRR gene mutations were prevalent in approximately one-fifth of the mCRPC patients in India. 64.5% patients had a successful test result on the tumor tissue sample. [Table: see text][Table: see text]
Baseline bone pain as a prognostic marker for survival for men with metastatic hormone-sensitive prostate cancer (mHSPC): Patient-level analysis of SWOG 1216 trial.
Authors: Gebrael Georges , Jo Yeonjung , Swami Umang , Plets Melissa , Hage Chehade Chadi , Narang Arshit , Gupta Shilpa , Myint Zin , Sayegh Nicolas , Tangen Catherine , Hussain Maha H. A. , Dorff Tanya B. , Lara Primo N , Lerner Seth P. , Thompson Ian M. , Agarwal Neeraj 
Published: January 2024

188 Background: Pain from bone metastasis significantly predicts overall survival (OS) in men with castration-resistant prostate cancer (PMID: 18487572). However, it has not been extensively evaluated in men with mHSPC. We hypothesized that baseline bone pain in men with mHSPC will be a significant prognostic marker for OS. Therefore, SWOG 1216 trial data which randomized men with mHSPC to androgen deprivation therapy (ADT) with orteronel vs bicalutamide was evaluated (PMID: 35446628,NCT01809691). Methods: Patient level data from SWOG 1216 were analyzed for those with documentation of baseline bone pain (yes or no). Patients were categorized into 2 cohorts: those with bone pain (BP1) vs those without bone pain (BP0). Progression-free survival (PFS) and OS were summarized by median with 95% confidence intervals (CI). Multivariable analyses on PFS and OS were done using Cox proportional hazard model, and were adjusted for treatment arm, disease burden, Gleason score, PSA (log base 2–transformed) and age (Table). All the analyses were done using R version 4.2.1. Results: Of the 1279 study participants: 301 men were in BP1 (23.5%) vs 896 were in BP0 (70.51%) cohort. Bone pain status was unavailable in 82 men (6.4%) men. Compared to BP0, BP1 cohort had lower median age (66 vs 68 years, p<0.01) and higher disease burden (70.4% vs 41.6%, p<0.001). Men in BP0 cohort had significantly better median PFS (3.7 vs. 1.3 yrs; p<0.001) and OS (NR vs 3.9 vs NR, p<0.001) then men in BP1 cohort. After adjustment for other prognostic variables including treatment, disease burden, Gleason score, log2PSA and age; bone pain was significantly associated with decreased PFS and OS (Table). Conclusions: Men with mHSPC with bone pain at baseline have worse survival outcomes despite treatment intensification and may be prioritized for enrollment in clinical trials. These data may aid patient counseling and warrant the inclusion of bone pain in the prognostic models of mHSPC. Clinical trial information: NCT01809691 . [Table: see text]
Preclinical characterization of human Kallikrein 2 (hK2) as a novel target for the treatment of prostate cancer.
Authors: Shen Fei , Kelly William Kevin , Pandit-Taskar Neeta , McDevitt Theresa , Smith Ryan , Menard Krista , Packman Kathryn , Chaudhary Ruchi , Rupnow Brent , Yu Margaret K. , Guckert Mary E. , Tian Shaozhou Ken , Chu Gerald , Xie Hong , Patricia Daniel , Max Steven I , Morris Michael J. 
Published: January 2024

202 Background: Treatment options that are durably effective for patients with metastatic (m) castration-resistant prostate cancer (CRPC) remain limited despite available therapies, highlighting a continued unmet need for novel drug development. hK2 is overexpressed in prostate cancer (PC) and has little to no expression in non-prostate tissues. Here, we use a series of preclinical experiments to evaluate hK2 as a therapeutic target in PC. Methods: hK2 expression was assessed by immunohistochemistry (IHC) in non-metastatic (nm) castration sensitive PC (CSPC; n = 100), mCSPC (n = 98), and mCRPC (n = 45) samples obtained from tumor banks and warm autopsy tumor microarrays. Multiplex immunofluorescence (IF) was used to assess hK2 expression at different mCRPC tumor sites. hK2 cell surface expression in a human prostate cancer cell model (VCaP) and fresh mCRPC patient tumor samples was assessed by flow cytometry. hK2-targeting antibody internalization over time was visualized by confocal IF microscopy in VCaP cells. VCaP xenograft models in immune-compromised NSG mice were used to evaluate anti-tumor activity, defined as change in percent of tumor growth inhibition (ΔTGI), following treatment with 3 unique hK2-targeting experimental agents (Table). Whole-body planar and SPECT/CT imaging were used to assess hK2-targeting antibody tumor uptake in patients with mCRPC. Results: IHC confirmed robust hK2 expression across different PC stages with homogenous expression in nm/mCSPC and increased heterogeneity in mCRPC. Mean percent tumor staining of hK2 in mCRPC samples was 67.6% (bone), 65.7% (lymph nodes), and 33.5% (liver) by multiplex IF. Correlation of hK2 expression across mCRPC bony lesions (r = 0.74, p < 1.6e-06) was observed, suggesting intrapatient and interlesion homogeneity. Confocal microscopy demonstrated hK2 cell surface expression in VCaP cells, with rapid antibody internalization within 3 hours. Flow cytometry confirmed hK2 cell surface expression in both VCaP cells and mCRPC samples. Robust antitumor activity was observed following treatment with each hK2-targeting agent in the xenograft mouse model (Table). Whole-body and SPECT/CT scans confirmed accumulation of the hK2-targeting antibody to PC tumors in patients with mCRPC. Conclusions: hK2 expression was homogenous in nm/mCSPC, with increased heterogeneity in mCRPC. Antitumor activity was observed across hK2-targeting agents. These data demonstrate that therapeutic strategies targeting hK2 hold promise in PC treatment and support further investigation of these agents in clinical studies. [Table: see text]
Rate of hospitalization and length of hospital stay during and post docetaxel for darolutamide in metastatic hormone-sensitive prostate cancer using ARASENS.
Authors: Morgans Alicia K. , Boegemann Martin , Paracha Noman , Grossman Jamie , Rodriguez Santamaria Fernando , Tyas Emma , Candish Jane , Shore Neal D. 
Published: January 2024

228 Background: ARASENS was a randomized, double-blind, Phase III trial of darolutamide (daro) + docetaxel + androgen deprivation therapy (ADT) vs. placebo (pbo) + docetaxel + ADT in patients with metastatic hormone sensitive prostate cancer (mHSPC). We sought to compare rates of hospitalizations and length of hospital stay (LoS) per patient due to any reason, and due to adverse events (AE) during or post docetaxel using data from ARASENS. Methods: We used mixed effects negative binomial regression to estimate time-varying rate of hospitalization and LoS by patient. Patients with records that began on the same start date were considered duplicates and were condensed into one visit, using the latest end date. Patients with multiple records with overlapping time periods were combined into one visit. A constant hospitalization rate assumption was considered inappropriate since docetaxel is administered for 6-cycles (~4.14 months). Hospitalizations that began within and after first 4 months of treatment were grouped together. Conversely, LoS was assumed to be time invariant. Results: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalization both due to any reason and to AE (Table 1). Daro was associated with a numerical reduction in rate of hospitalization (per year) due to any reason during docetaxel (0.75 days [95% CI: 0.61, 0.88]) vs. pbo (0.91 days [95% CI: 0.75, 1.07]) and after docetaxel (0.31 days [95% CI: 0.26, 0.37]) vs. pbo (0.38 days [95% CI: 0.31, 0.45]). A similar trend was observed for hospitalizations due to AE. Daro was associated with a marginally longer LoS per hospitalization compared with pbo (+1.90 days). Similar results were seen for LoS due to AE (+1.67 days). Conclusions: Daro was associated with a numerically lower rate of hospitalization, but marginally longer LoS compared to pbo. A lower rate of hospitalization was observed post docetaxel as opposed to during docetaxel. Clinical trial information: NCT102799602 . [Table: see text]
Individual-level social determinants of health and allostatic load/chronic toxic stress in men with prostate cancer.
Authors: Stabellini Nickolas , Cullen Jennifer , Bittencourt Marcio S , Moore Justin , Weintraub Neal L , Datta Biplab , Coughlin Steven S. , Shanahan John , Montero Alberto J. , Guha Avirup 
Published: January 2024

263 Background: Allostatic load (AL)/chronic toxic stress is linked to a higher risk of adverse cancer-specific and cardiac events in prostate cancer (PC) patients especially non-Hispanic Blacks (NHBs). We hypothesize that NHBs experience more adverse social determinants of health (SDOH) that increases this AL. Methods: We included men≥18 years diagnosed with PC (2010-2022). Individual-level SDOH with 19 covariates across 4 domains was obtained. Pre-PC diagnosis AL was calculated as an ordinal measure (0-11). Components and cutoffs for the AL score: Each measure above the cutoff add 1 point to AL. Systolic blood pressure (BP) ≥140 mmHg, diastolic BP ≥90 mmHg, heart rate >100 bpm, total cholesterol (chol) ≥240 mg/dl, high-density lipoprotein chol ≤50 mg/dl, triglycerides ≥150 mg/dl, glycated hemoglobin ≥6.5, body mass index ≥30 kg/m2, glucose ≥110 mg/dl, C-reactive protein >3 mg/L and interleukin-6 >1.8 pg/ml. A gradient-boosting Machine Learning model ranked AL predictors using SHAP scores (SS). Cubic splined from logistic regressions defined SDOH adversity cutoffs. Results: Among 4,258 patients (886 NHB), the median age was 69 (IQR 63-77). Most were former smokers (44.2%), and the median Charlson comorbidity score was 4 (IQR 2-7). In NHBs, the SDOH variables among the top 5 overall predictors of AL were annual income (SS=0.10), neighborhood murder index (SS=0.07), neighborhood median income (SS=0.06), and neighborhood car theft index (SS=0.05). Considering all the SDOH features analyzed, NHBs faced adversity in 12 of 19 SDOH features (63%; Table). Conclusions: SDOH related to the neighborhood, built environment, and economic stability, are crucial predictors of pre-PC diagnosis AL in NHBs. [Table: see text]
Prostate Cancer Foundation (PCF) screening guidelines for prostate cancer in Black men in the United States.
Authors: Garraway Isla , Carlsson Sigrid V. , Nyame Yaw A. , Vassey Jason , Chilov Marina , Fleming Mark T. , Frencher Stanley K , George Daniel J. , Kibel Adam S. , King Sherita A , Kittles Rick , Mahal Brandon A , Pettaway Curtis Alvin , Rebbeck Timothy , Rose Brent S. , Vince Randy , Winn Robert A. , Yamoah Kosj , Oh William K. 
Published: January 2024

264 Background: Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer. Few guidelines have outlined specific recommendations for prostate-specific antigen (PSA)-based prostate cancer screening among Black men. We performed a comprehensive literature search and assembled a diverse, interdisciplinary panel of experts to establish practical consensus guidelines addressing PSA screening in Black men. Methods: A comprehensive literature search was conducted in April 2023 in PubMed and Embase. A total of 287 studies were reviewed utilizing Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Of these, 265 were relevant. The panel’s expertise included fields of primary care, urology, medical and radiation oncology, translational science, and patient advocates. Results: Six guideline statements were developed. Three randomized controlled trials provided Level 1 evidence that regular PSA screening of men aged 50-74 of average risk reduces metastasis and prostate cancer death at 16-22 years. The best available evidence for Black men, who are considered higher than average risk for prostate cancer metastasis and death, comes from observational (Level 3) and modeling (Level 4) studies that consider the age to obtain a baseline PSA, the frequency of testing, and the age when screening should end. Cohort studies suggest that discussions with health care providers about baseline PSA testing should begin by the time Black men are in their early 40s and modeling data suggests prostate cancer develops 3-9 years earlier in Black men compared to their peers. Lowering the age for baseline PSA testing from 50-55 years to 40-45, followed by regular screening intervals until the age of 70 (when to stop is determined by age, PSA values, and health factors) would reduce prostate cancer mortality in Black men (~30% relative reduction) without significantly increasing the rate of overdiagnosis. Conclusions: Black men should obtain information about PSA screening for prostate cancer. Among Black men who elect screening, baseline PSA testing should occur between ages 40-45. Depending on the PSA value and health status, annual screening should be strongly considered. Personalized prostate cancer surveillance and/or treatment can prevent potential harms from overdiagnosis.
Influential factors impacting treatment (tx) decision making (TDM) and decision regret (DR) in patients (pts) with localized or locally advanced prostate cancer (LPC/LAPC).
Authors: Gartrell Benjamin Adam , Phalguni Angaja , Mundle Suneel , McCarthy Sharon , Brookman-May Sabine D. , De Solda Francesco , Jain Ruhee , Ploussard Guillaume , Hadaschik Boris A. 
Published: January 2024

294 Background: Pts newly diagnosed with LPC/LAPC must contemplate many factors to make tx decisions that may later lead to regret. We conducted literature reviews exploring factors associated with pt TDM and DR. Methods: Databases (Ovid Medline, Ovid Embase, Cochrane Library), select congress proceedings and gray literature were searched (12 Sept 2022). Publications (pubs) on pt TDM and tx DR in LPC/LAPC were included following systematic literature review methods and selected based on the following criteria: 2012 onward, ≥100 pts, journal article, and quantitative data. Study quality was assessed by risk of bias tools (NICE STA guidance; Newcastle-Ottawa). Influential factors were those with p<0.05; for TDM, factors described as “a decision driver,” “associated,” “influential,” or “significant” were also included. Key factors were determined under consideration of number of studies, consistency of evidence, and study quality. Results: 75 pubs (68 studies) reported TDM (12 countries; 68% North America [NA] 25% Europe [E]). Pt TDM participation was reported in 34 pubs; overall, pts preferred an active/shared role. Of 39 influential TDM factors, those related to baseline demographics, health and disease, external factors (doctor recommendation most common), and tx goals/attributes were key (Table). 49 pubs reported DR (12 countries; 59% NA, 29% E). DR was assessed at 2 weeks to 6 years post-tx. Not tx specific DR (23 studies), was felt by 8-48% of pts. Regret associated with specific tx (18 studies) was felt by 7-43% (active surveillance), 12-57% (radical prostatectomy), 1-49% (radiotherapy), 28-49% (androgen deprivation therapy), and 21-47% (combination therapy) of pts. Of 42 significant DR factors, tx toxicity (sexual/urinary/bowel dysfunction), pt role in TDM, and making an informed tx decision were key (Table). Conclusions: DR is common in pts with LPC/LAPC. To help pts navigate factors influencing TDM and limit risk of DR, a shared consensual TDM approach between pts, caregivers, and healthcare professionals is needed. [Table: see text]
Selection of active surveillance in Medicaid patients: Results from the Michigan Urological Surgery Improvement Collaborative.
Authors: Srivastava Arnav , Daignault-Newton Stephanie , Meah Sabir , Faraj Kassem S , Ginsburg Kevin , Goh Keow , Hollenbeck Brent K. , Shahinian Vahakn , Herrel Lindsey A. , Borza Tudor 
Published: January 2024

302 Background: Active surveillance (AS) is the preferred treatment for low-risk prostate cancer. Insurance coverage and cost sharing often influence treatment choices for providers and patients. The impact of insurance payer, specifically Medicaid, on treatment selection in prostate cancer remains understudied. Methods: We identified patients with biopsy-proven prostate cancer from the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry, a statewide quality improvement collaborative, from 2016-2021. We captured risk category, insurance payer (Medicaid vs. private insurance), and treatment (AS vs. primary treatment). Watchful waiting rates were under 2% in both payer groups; these patients were excluded from analysis. We used logistic regression to assess the correlation between payer status and treatment choice by prostate cancer risk group. Results: We identified 38,663 patients. Most patients had private insurance (51%), followed by Medicare (45%) and Medicaid (3%). Median age was 62 (IQR 58 – 66) for privately insured patients and 60 (IQR 56 – 63) for Medicaid patients. Among patients with low-risk disease, 65% of privately insured patients and 67% of Medicaid patients elected for AS. AS for favorable intermediate-risk prostate cancer was also similar across the payer groups (private 20%, Medicaid 19%). In an adjusted analysis Medicaid and privately insured patients did not demonstrate different odds of AS (OR 0.99 (95%CI 0.71 – 1.40), p > 0.9). No significant differences in treatment selection were noted in favorable or unfavorable intermediate-risk patients (Table). Conclusions: Our analysis, from a granular statewide registry, suggests that Medicaid patients undergo similar treatment patterns to commercially insured patients. This suggests that insurance status may not drive AS selection in our cohort. Our work points towards not only the increased adoption of AS, but also its adoption across payers. [Table: see text]
Clinical and patient-reported outcomes of fully adaptive MR-guided stereotactic radiotherapy to prostate: Real-world experience from the UK.
Authors: Das Prantik , Nugent Killian , Dallas Nicola Louise , Perna Carla , Sabharwal Ami , Ford Daniel , Camilleri Philip 
Published: January 2024

303 Background: Stereotactic MR-guided adaptive radiotherapy (SMART) brings several advancements including enhanced soft tissue definition, adaptation of individual fractions based on daily anatomy, real time tracking of prostate coupled with beam gating that prevents treatment delivery if the prostate is outside the treatment boundary and negating the need for invasive fiducial markers. Here we evaluate treatment response and acute and intermediate patient adverse events amongst prostate cancer patients who underwent SMART. Methods: A total of 197 patients with localised prostate cancer were treated with SMART. Patients were assessed for eligibility against robust institutional criteria. SMART consisted of MR- and computed tomography (CT) simulation scan, inverse intensity-modulated radiotherapy (IMRT) treatment planning and daily plan re-optimization prior to treatment delivery with editing CTVs (as per daily variation) and OAR recontouring within the first 3 cm outside the PTV. Prescription dose was 36.25 Gy in 5 fractions delivered on alternate days. Patients who completed a baseline 12 item PRO-CTC AE, before treatment, were subsequently followed up with the same graded questionnaire at set time points. Results: Median follow up was 12 months (inter quartile range 6 – 36). Patients included low (6%), intermediate (86%) and high risk (8%). Median pre-treatment PSA was 7.09 ng/ml (interquartile range IQR 1 – 133.2). At first follow up at 6 months, median drop in PSA was 97.09 % from base line (range 27.7– 99.9 %, SD 15.04). At second follow up at 12 months, median change in PSA was 96.92% (range 5.88– 233.3%, SD 12.41). At 24 months median PSA was 0.28 ng/ml (IQR 0.03 -3.26) with a median drop from baseline of 95.98%. ADT was used in 88% of patients and median duration of ADT was 6 months (IQR 3-30). 69 patients, who completed baseline and subsequent PRO CTC AE questionnaires in different time frames were included in analysis. More than 80% of men reported no change from baseline urinary toxicity during follow up apart from urinary urgency. Regarding GI toxicities, new ≥ frequent/severe patient reported adverse events were diarrhoea (9%), constipation (3%) and pain on opening bowels (6%) in the first 3 months but were all absent after 33 months. No patient reported frequent GI bleeding. No grade ≥4 toxicity was seen. Conclusions: SMART shows low acute and intermediate toxicities and excellent short-term outcomes.
Impact of a rash management guide on incidence and severity of rash with apalutamide: Experience from the Apa-RP study in high-risk localized prostate cancer.
Authors: Shore Neal D. , Hafron Jason , Saltzstein Daniel , Bhaumik Amitabha , Aggarwal Pankaj , Potdar Rushikesh , Phillips Jennifer , McGowan Tracy 
Published: January 2024

316 Background: Apa-RP is a multicenter, open-label, single-arm Phase 2 study of adjuvant treatment with apalutamide and androgen deprivation therapy (ADT) in treatment-naïve patients with high-risk localized prostate cancer who underwent radical prostatectomy (NCT04523207). A rash management guide was implemented to improve dermatologic adverse events (AEs) that included proactive patient education on appropriate skin care and monitoring for rash, and frequent outreach through patient phone calls. We present rash-related safety data from Apa-RP compared with data from 2 Phase 3 apalutamide registrational studies. Methods: 108 patients were treated with apalutamide 240 mg once daily with ADT for 12 28-day cycles. Rash occurrence was monitored and skin-related AEs were defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading scale. These factors were collated and compared with data from the North American population from SPARTAN (non-metastatic castration-resistant prostate cancer; NCT01946204) and TITAN (metastatic castration-sensitive prostate cancer; NCT02489318). Results: Of 108 patients in Apa-RP, 21.3% developed rash vs 28.3% in SPARTAN and 33.3% in TITAN. Information on rash severity, median time to onset of first rash, the proportion of patients with rash resolution, median time to resolution and the treatment administered for rash are provided in the Table. Conclusions: The Apa-RP rash management protocol demonstrates a proactive and patient-empowered approach to monitoring and managing patients on apalutamide who develop skin rash. With increased vigilance from the care team and appropriate patient education, it may be possible to reduce the incidence, severity and median time to resolution of skin rash. Clinical trial information: NCT04523207 . [Table: see text]