bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing PSA levels as prognostic of overall survival (OS) in men with metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Halabi Susan , Roy Akash , Guo Siyuan S , Rydzewska Larysa , Godolphin Peter , Hussain Maha H. A. , Tangen Catherine , Thompson Ian , Xie Wanling , Carducci Michael Anthony , Smith Matthew Raymond , Morris Michael J. , Gravis Gwenaelle , Dearnaley David P. , Verhagen Paul , Goto Takayuki , Tierney Jayne F. , James Nicholas D. , Buyse Marc E. , Sweeney Christopher 
Published: June 2023

5070 Background: Prior data have shown that prostate specific antigen (PSA) ≤ 0.2 ng/dL at 6-7 months with androgen deprivation therapy (ADT) with testosterone suppression (TS) alone is prognostic of OS. We hypothesized that PSA ≤0.1 ng/dL at 7 months would be a stronger prognostic for OS in men with mHSPC treated with TS alone. This hypothesis was investigated by the STOPCAP M1 collaborators. Methods: Individual patient data from 13 eligible randomized trials comparing treatment regimens (TS or TS + docetaxel in the control or research arms in mHSPC trials were utilized. Landmark survival analyses were performed at 7 months after ADT initiation. Overall survival was computed as the time from 7 months after start of initial TS to death or date of last follow for patients who started TS prior to randomization or 7 months after randomization to death or date last follow-up for patients who started TS after randomization. PSA measurements between 4-7 months after ADT were selected and cut off-points of PSA ≤0.2, 0.2-4, and >4 ng/dL or PSA ≤0.1, 0.1-0.2, 0.2-4, and >4 ng/dL were considered. The proportional hazards model was utilized to explore the prognostic significance of PSA levels in predicting OS adjusting for treatment in all patients and patients who were enrolled on docetaxel trials. Results: IPD from 5,438 patients randomized 1994-2012 from 13 trials were pooled. At 7 months, the proportion of patients who had PSA≤0.1 and PSA ≤0.2 were 18.1% and 26.1%. The median OS in patients who experienced PSA ≤0.1 and PSA≤0.2 and in patients enrolled on docetaxel trials are presented in the table below. The hazard ratios (HR) for death for PSA≤0.1 and PSA≤0.2 vs. those PSA>4 at 4-7 months were 0.26 and 0.27, respectively. In patients enrolled on docetaxel, HRs for death for PSA≤0.1 and PSA≤0.2 vs. those PSA>4 at 7 months were 0.35 and 0.34, respectively. Conclusions: PSA≤0.1 and PSA≤0.2 at 7 months have similar prognostic value of OS in men with mHSPC treated with weak ADT (TS alone) without and with docetaxel. Clinical trial information: NCT00309985 ; NCT00268476 ; NCT00104715 ; NCT00079001 ; NCT00002651 ; NCT00685646 . [Table: see text]
Early results from CASCARA: A phase 2 study of cabazitaxel/carboplatin plus abiraterone in high-volume metastatic castrate-sensitive prostate cancer (mCSPC).
Authors: Ryan Charles J. , Cao Qing , De Souza Andre Luiz , VanderWeele David James , Bryce Alan Haruo , Kelly William Kevin , Jha Gautam Gopalji , Barata Pedro C. , Sartor A. Oliver , Stadler Walter Michael , Dhawan Mallika Sachdev , Morgans Alicia K. , Antonarakis Emmanuel S. 
Published: June 2023

5071 Background: Best treatment of mCSPC involves doublet therapy (ADT + novel hormonal agent) or triplet therapy (ADT + novel hormone + docetaxel); however, opportunity remains for further improvement. Studies show that homologous recombination repair (HRR) gene mutations are enriched in metastatic prostate cancer, and may portend resistance to docetaxel. CASCARA tested quadruplet therapy (ADT + cabazitaxel/carboplatin + abiraterone) in high-volume mCSPC, aiming to enhance PSA responses and decrease progression at 1 year. Methods: This phase 2 study enrolled 61 mCSPC patients with high-volume disease who received ADT plus cabazitaxel (20 mg/m2 q21d x 6) and carboplatin (AUC=4 q21d x 6) followed by abiraterone (1000 mg, plus prednisone 5 mg). Primary endpoint was freedom from PSA/radiographic progression at 1 year. Other endpoints included PSA50 response, freedom from PSA progression, and safety. Archival biopsies were retrospectively evaluated for HRR ( BRCA1/2, ATM, CHEK2, CDK12, BRIP1, RAD51B) mutations at a CLIA-certified lab. A sample size of 61 was determined using a Simon two-stage design (stage 1: 32 men, stage 2: 29 men) with a null hypothesis of a 1-year PSA/radiographic progression-free rate of 0.80 against a one-sided alternative of 0.92. Results: From 11/2019 to 06/2022, 61 men enrolled at 7 sites. Median age was 64 (range, 45–76) years; 21% were African American. Median baseline PSA was 8.9 (range, 0.1–1021) ng/mL. 44% of men had ECOG=1. 91% had Gleason sum 8–10. Prevalence of DNA alterations (50 evaluable pts) was 18% for HRR mutations, 38% for TP53 muts, 22% for ERG fusions, 10% for SPOP muts. Freedom from PSA/radiographic progression at 1 year was 77% (95% CI, 63–87%), and freedom from PSA progression at 1 year was 81% (95% CI, 67–90%). The PSA50 rate response was 97%. PSA ≤0.2 ng/mL at month-7, a surrogate for survival in other mCSPC studies, was 61%; PSA ≤4 ng/mL at month-7 was 82%. Outcomes according to mutation status are shown. AEs included 7% grade (Gr)-3/4 myelosuppression, 8% Gr-3/4 infections, 10% Gr-3 GI disorders, and 3% Gr-3 fatigue. There were 4 treatment-related discontinuations. Conclusions: Quadruplet therapy with ADT + cabazitaxel/carboplatin + abiraterone was well tolerated. At 1 year, 77% of pts were progression-free. PSA ≤0.2 ng/mL at month-7 was 61%, exceeding the historical month-7 PSA ≤0.2 ng/mL rate of 45% in CHAARTED–docetaxel arm. Further exploration of this quadruplet strategy in randomized phase III studies is warranted. Clinical trial information: NCT03934840 . [Table: see text]
The relationship between a priori defined prognostic risk groups and and overall survival (OS) in men with metastatic hormone sensitive prostate cancer (mHSPC).
Authors: Halabi Susan , Guo Siyuan S , Roy Akash , Rydzewska Larysa , Godolphin Peter , Hussain Maha H. A. , Tangen Catherine , Thompson Ian , Xie Wanling , Carducci Michael Anthony , Smith Matthew Raymond , Morris Michael J. , Gravis Gwenaelle , Dearnaley David P. , Verhagen Paul , Goto Takayuki , James Nicholas D. , Parmar Mahesh , Buyse Marc E. , Sweeney Christopher 
Published: June 2023

5073 Background: Prior analyses have shown that men who present with high volume (HV) disease and de novo metastases have shorter OS compared with other mHSPC subgroups. The objective of this analysis was to determine the prognostic relationship between a-priori defined 4-prognostic groups and OS in men with mHSPC and in a subset of trials in patients treated with androgen deprivation therapy (ADT) +docetaxel. This hypothesis was investigated by the STOPCAP M1 collaborators. Methods: We obtained individual patient data (IPD) from 13 randomized trials comparing treatment regimens (ADT or ADT + docetaxel in the control or research arms) in mHSPC. OS was defined as the time between date of randomization and date of death/or last follow-up. Patients (pts) were classified into 4 mutually exclusive groups. Poor prognostic risk-group was defined as HV (presence of visceral metastases, and/or > 4 bone metastases or presence of bone metastases beyond pelvic or vertebral bones) plus synchronous diagnosis (SYN); whereas intermediate risk groups were patients with HV and metachronous (MET; intermediate A) or low volume plus SYN (intermediate B); and lastly good risk group had LV plus MET. The proportional hazards model was used to estimate the hazard ratio (HR) and assess the prognostic significance of risk groups in predicting OS adjusting for treatment. Results: Of 6041 pts included in this analysis, 60% (3622 pts) had died. Median follow-up time=5-years. Overall 11%, 8%, 47% and 34% were in the good, intermediate A, intermediate B and poor risk groups, respectively and for trials including docetaxel (n=2627 pts) 9%, 5%, 39% and 47% respectively. HRs for risk groups are shown in the table. Conclusions: Differences in OS across the risk groups were observed. Further work is needed to investigate if more precise prognostic groups can be defined such as better characterization of patients' groupings of extent of bone metastases and visceral metastases. Clinical trial information: NCT00309985 ; NCT00268476 ; NCT00104715 ; NCT00079001 ; NCT00002651 ; NCT00685646 . [Table: see text]
Prostate-specific antigen value at 3 & 7 months (PSA-3mo, PSA-7mo) and overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation (ADT) with or without orteronel (SWOG S1216).
Authors: Parikh Mamta , Tangen Catherine , Hussain Maha H. A. , Gupta Shilpa , Jo Yeonjung , Harzstark Andrea , Paller Channing Judith , George Saby , Zibelman Matthew R. , Cheng Heather H. , Maughan Benjamin L. , Zhang Jingsong , Pachynski Russell Kent , Bryce Alan Haruo , Lin Daniel W. , Quinn David I. , Thompson Ian M , Dorff Tanya B. , Lara Primo N , Agarwal Neeraj 
Published: June 2023

5074 Background: Analysis of phase 3 studies of patients (pts) with mHSPC in the era of ADT, including in combination with docetaxel and/or androgen receptor axis targeted therapies have established PSA-7mo as a key prognostic marker. Our objective was to evaluate the association between PSA-3mo, PSA 7-mo and OS measured in the phase 3 S1216 trial in mHSPC comparing ADT + orteronel (treatment arm) vs ADT + bicalutamide (control arm) [NCT01809691]. Methods: Pts enrolled in the S1216 trial with available PSA-3mo & PSA-7mo were included in this analysis. PSA responses were defined as complete response (CR) if PSA ≤ 0.2 ng/mL, partial response (PR) for PSA >0.2 and ≤ 4ng/mL, and no response (NR) as PSA >4 ng/mL at month 3 or 7. Landmark OS was measured and Cox regression model applied adjusting for stratification (performance status, extent of disease, early vs late start of treatment, treatment arm). Results: 1251 pts were alive and evaluable for PSA-3mo and 1231 pts were evaluable at 7 mo, out of a total of 1279 pts. The median age was 67 (range: 43-92), 10% of patients were black, 96% had a Zubrod performance status of 0-1. Median PSA at baseline was 29 ng/ml (range: 2-6710). Of pts on treatment vs.control arm, PSA-3mo CR, PR, and NR occurred in 52% vs 35%; 31% vs 42%, and 17% vs 23%, respectively. Of pts on treatment vs control arm, PSA-7mo CR, PR, and NR occurred in 61% vs 46%, 20% vs 26%, and 19% vs 29%, respectively. CR or PR at either timepoint led to significantly better outcomes than those with NR. No interaction between treatment arm and PSA response was observed in terms of OS. Conclusions: PSA-3mo and PSA-7mo are strong prognostic markers for pts with mHSPC. More pts on ADT with orteronel achieved CR at 3 and 7 mo. In addition to its use in counseling patients in the clinic, PSA-3mo and PSA-7mo may be used as parameters for designing future trials in pts with mHSPC, utilizing the next generation of intensification or de-intensification treatment regimens. Clinical trial information: NCT01809691 . [Table: see text]
Comparing the efficacy of abiraterone and enzalutamide in United States veterans with metastatic castration-sensitive prostate cancer (mCSPC) by estimating rates of tumor growth (g-rate).
Authors: Leuva Harshraj , Zhou Mengxi , Stamatov Rumen , Teply Benjamin A. , Rosenberg Ta-Chueh Melody , Luhrs Carol A. , Mundi Prabhjot Singh , Park Yeun-Hee Anna , Bates Susan Elaine , Faiena Izak , Fojo Antonio Tito 
Published: June 2023

5076 Background: The choice of 1st line novel hormonal therapy in mCSPC is often based on comorbidities/physician preference due to the lack of data comparing abiraterone (Abi) and enzalutamide (Enza) in clinical trials and in real-world settings; especially in Black American (BA) patients. We have developed a novel method to estimate rates of tumor growth ( g-rate) and have shown that the g-rate is a robust biomarker of drug efficacy and overall survival in prostate cancer (Wilkerson, 2017; Leuva, 2019). We performed a 1:1 matched analysis to compare Abi and Enza outcomes in 1st line mCSPC, using g-rate and median overall survival (mOS) estimates. Methods: All patients with mCSPC diagnosis in national VA Corporate Data Warehouse were eligible for comparison. The cohort date range was from 7/2017 to 6/2022. Drug efficacy was established by estimating g-rates using PSA values while on therapy via the TUMGr package for R. For the matched analyses, we created 1:1 comparison cohorts for Abi and Enza, matched on age (±10 years), race, total number of therapies received (1/≥2), drug start year (<2020/≥2020), PSA at diagnosis (<20/≥20), Gleason score (GS) (<8/≥8), Charlson comorbidity index excluding cancer diagnosis (<5/≥5) and therapy setting (urban/rural). Results: We identified a total of 1712 and 464 Veterans with mCSPC who received Abi and Enza as 1st line, with median follow-ups of 19 and 12 mo, respectively. Fewer Veterans and shorter duration of follow up with Enza than Abi reflect Abi’s earlier approval in mCSPC. The Abi and Enza cohorts had similar median g-rates 0.000114/d and 0.000110/d, respectively (p=0.76). The mOS was 43 mo for Abi versus not reached (NR) for Enza (p=0.33). Our cohort had 425(25%) and 119(26%) BA veterans who received Abi and Enza, respectively. Compared to Caucasians, mOS was similar with Abi (42.7 vs 41.9 mo, HR-0.96, p=0.6) and Enza (NR, HR-0.85, p=0.4) for BA. In 1:1 matched analysis, the Abi and Enza arms had 391 patients and both had median follow-ups of 13 mo. We did not observe a statistically significant difference in median g-rate and mOS for either the whole matched cohort or BA subgroup when comparing Abi to Enza. The matched cohort had 203 (52%) with GS ≥8 and 228 (58%) Veterans with PSA ≥20 at diagnosis; there was no significant mOS difference in these subgroups. Conclusions: Real-world data from 2176 Veterans show comparable efficacy for Abi and Enza as 1st line for mCSPC, with similar g-rates and mOS, even when matched on various factors, including comorbidities, and in aggressive/high volume matched cohorts. BA patients also had similar g-rates and mOS. [Table: see text]
Phase 2 study of olaparib (without ADT) in men with biochemically recurrent prostate cancer (BCR) after prostatectomy.
Authors: Marshall Catherine Handy , Teply Benjamin A. , Lim Su Jin , Wang Hao , Mao Shifeng S. , Kelly William Kevin , Paller Channing Judith , Markowski Mark Christopher , Denmeade Samuel R. , Carducci Michael Anthony , Eisenberger Mario A. , King Serina , Sullivan Rana , Lotan Tamara L. , Antonarakis Emmanuel S. 
Published: June 2023

5087 Background: The natural history of BCR after prostatectomy is variable and current treatment approaches include observation, salvage radiation, or androgen deprivation therapy (ADT), although many men wish to defer such therapy. We hypothesized that olaparib, now approved for use in certain men with metastatic castration resistant prostate cancer, might be an alternative option for men with high-risk BCR. Methods: This was a single arm, phase 2 trial (NCT03047135) conducted at 4 US sites. Subjects with biochemically recurrent (M0) prostate cancer, post prostatectomy, with a PSA doubling time of ≤6 months and an absolute PSA of ≥1.0 ng/mL were eligible. Patients were NOT selected based on the presence of homologous recombination repair (HRR) mutations. 51 patients were treated with olaparib 300mg twice per day, until radiographic or symptomatic progression, PSA doubling from baseline value, or drug-related toxicity. The primary endpoint was PSA50 response (50% PSA decline from baseline). Secondary endpoint was PSA progression free survival (PFS). Patients were required to undergo tissue-based next generation sequencing on the radical prostatectomy specimen to determine the presence of mutations in HRR genes ( ATM, BARD1, BRCA1/2, BRIP1, CDK12, CHEK1/2, FANCA/E/L, PALB2, RAD51B/C/D). A prespecified endpoint was to assess PSA responses in HRR[+] and HRR[–] cohorts separately. Results: Mean age was 64 years (SD 7), and 92% (47/51) of patients were White. Mean baseline PSA doubling time was 2.9 (SD 1.5) months. 55% (28/51) of pts had Gleason 6-7, 14% (7/51) had Gleason 8, and 31% (16/51) had Gleason 9-10. 86% (44/51) of patients had previously received salvage radiation. 27 patients harbored HRR mutations, the most common of which were BRCA2 (n=11), CHEK2 (n=6), and ATM (n=6). The overall PSA50 response rate was 24% (12 of 51)(95% CI 0.13, 0.38), with no responses in the HRR[–] group and 44% (12/27) PSA50 responses in the HRR[+] group (95%CI 0.26, 0.65). All 11 of the participants with a BRCA2 mutation achieved a PSA50 response. The median PSA PFS was 22 months in the HRR[+] group and 13 months in the HRR[–] group (HR 0.71; 95% CI 0.31, 1.63). Most AEs were low grade. The most common all-grade AEs were fatigue, nausea, leukopenia, anemia, and dysgeusia. Grade-3 AEs were leukopenia (9.8%), ALT/AST increase (3.9%), and anemia (2.0%). There were no grade 4–5 AEs. Conclusions: Olaparib, in the absence of ADT, can be safely administered and demonstrated activity in men with BCR prostate cancer and HRR mutations, especially for BRCA2 mutations. Additional studies to further evaluate olaparib in these patients are indicated. Clinical trial information: NCT03047135 .
Assessment of risk of overall and late distant recurrence by Breast Cancer Index in postmenopausal women with early-stage, HR+ breast cancer in the TEAM trial.
Authors: Bartlett John MS , Xu Keying , Wong Jenna , Pond Gregory Russell , Zhang Yi , Spears Melanie , Salunga Ranelle C. , Mallon Elizabeth , Taylor Karen J , Hasenburg Annette , Markopoulos Christos , Dirix Luc Yves , Seynaeve Caroline M. , Van De Velde Cornelis J.H. , Rea Daniel William , Schnabel Catherine A , Treuner Kai , Bayani Jane 
Published: June 2023

509 Background: Individual risk assessment of distant recurrence (DR) is particularly relevant for early-stage HR+ breast cancer patients, as they face a prolonged risk of recurrence even after adjuvant endocrine therapy. Previously, we have shown that the Breast Cancer Index (BCI) and BCIN+ risk groups are significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence in N0 and N1 breast cancer patients, respectively, enrolled in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. Here, the prognostic performance of BCI and BCIN+ as a continuous risk score for overall and late distant recurrence was evaluated in the TEAM trial. Methods: BCI testing was performed blinded to clinical outcome with BCI/BCIN+ risk scores calculated as previously described. Cox proportional hazard models adjusted for age, tumor size, grade and treatments were used to estimate hazard ratios (HRs) and the associated 95% confidence intervals (CIs) for BCI/ BCIN+ continuous risk scores. The 10y risk of overall and late DR were estimated as a function of risk scores from the Cox models using Breslow estimates. Results: Continuous risk curves for overall and late DR were obtained in patients who did not receive adjuvant chemotherapy and those who remained DR-free at 5 years regardless of chemotherapy, respectively, to reflect the two key time points for breast cancer treatment decision-making. InN0 patients not treated with chemotherapy (N = 1197), BCI was significantly prognostic for overall DR with a HR of 1.39 (95% CI 1.25-1.54; p < 0.001), while BCIN+ was significantly prognostic in N1 patients who did not receive chemotherapy (N = 1319) with a HR of 4.29 (95% CI 2.93-6.28; p < 0.001). Among patients who remained DR-free at 5 years, in the N0 subset (N = 1285), BCI was significantly prognostic for late DR with a HR of 1.23 (95% CI 1.07-1.42; p < 0.001), while BCIN+ remained to be significantly prognostic in the N1 subset (N = 1762) with a HR of 2.78 (95% CI 1.75-4.43; p < 0.001). Similar results were observed in the HER2- subset for both overall and late DR. Continuous risk curves for BCI and BCIN+ for overall and late DR showed an increasing risk of DR with higher BCI/BCIN+ scores. Conclusions: Results from this largest BCI study to date further support the use of BCI to provide individualized risk estimates for both overall and late DR in women with HR+ breast cancer to aid in personalized decision-making for adjuvant therapy. [Table: see text]
Racial differences in the utilization of MRI-guided biopsy before prostate cancer diagnosis.
Authors: Lu-Yao Grace L. , Gandhi Krupa , Nikita Nikita , Shaver Amy L , Sharma Swapnil , Keith Scott W. , Freedland Stephen J. 
Published: June 2023

5093 Background: Most low-risk prostate cancer (PCa) patients undergo active surveillance (AS). Compared with Whites, Blacks are more likely to opt for AS and suffer a higher risk of cancer progression while on AS. A primary concern of AS is the likelihood of missing clinically significant cancer. Transrectal ultrasound-guided biopsy is the most common method for diagnosing and grading PCa; however, this method often misses anterior PCa. Magnetic resonance imaging (MRI) allows clinicians to identify better and detect PCa; however, current guidelines on MRI-guided biopsy (MRI-GB) are inconsistent. This population-based study aimed to examine the utilization of MRI-GB 6 months before PCA diagnosis over time by race in the US. Methods: We used SEER-Medicare data to identify men diagnosed with PCa between January 1, 2012, to December 31, 2017, and excluded patients missing the date of diagnosis, being diagnosed at death, enrolled in HMO, or having no continuous A and B coverage six months before diagnosis. We used the CPT codes to identify prostate biopsy and MRI use. Multivariable logistic regression was used to evaluate racial disparity in MRI use six months before PCa. The model included covariates age, race, SEER region, marital status, state buy-in for Medicare (a poverty indicator), education, income, Charlson comorbidity index, and procedure (MRI) year. Results: Among 38,612 eligible men, MRI use six months before PCa diagnosis increased from 2012 to 2017 (3.2% to 24.3% among Whites, 1.8% to 14.2% among Blacks). Compared with Whites, Blacks were 38% less likely to receive pre-diagnosis MRI (OR=0.62, 95% CI 0.52-0.74). Besides race, having state buy-in for Medicare (OR=0.44; 95% CI 0.30-0.65) and geographic regions (Central vs. West OR=0.40; 95% CI 0.34-0.45) were strong predictors of lower utilization of MRI. Conclusions: The gap in the utilization of MRI may exacerbate racial disparities in PCa. Future studies are needed to identify potential barriers to adopting MRI for PCa workups.