bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of progressive brain metastases in patients (pts) with relapsed germ-cell tumor (GCT) treated with salvage high-dose chemotherapy (HDCT).
Authors: King Jennifer , Abonour Rafat , Hassoun Rebecca , Althouse Sandra K. , Salous Tareq , Hanna Nasser H. , Einhorn Lawrence H. , Adra Nabil 
Published: June 2024

5036 Background: Previous data confirm that pts with relapsed GCT and progressive brain metastases (mets) can be cured with HDCT and peripheral blood stem cell transplantation (PBSCT)1. Still, there is uncertainty with the optimal management sequence of these pts prior to transplant. Here, we describe the management and outcomes of a larger cohort of these pts. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with relapsed metastatic GCT who were to undergo HDCT with PBSCT and were noted to have progressive brain mets at time of relapse. Baseline characteristics were summarized. The Kaplan-Meier method was used to analyze progression free survival (PFS) and overall survival (OS). Results: 49 pts met eligibility. Median age was 28.7yrs (16.6-51.5). Primary site was testis in 44 (90.0%), mediastinal in 4 (8.2%), and retroperitoneum in 1 (2.0%). All patients had nonseminomatous disease. Primary tumor predominant histology was choriocarcinoma (34.7%), embryonal (32.7%), mixed (18.4%), teratoma (6.1%), yolk sac tumor (4.1%), and seminoma (2.0%). IGCCCG risk at diagnosis was poor in 91.8%, intermediate in 2.1%, and good in 6.1%. 24 pts (49%) were platinum refractory at HDCT. 17 pts (34.7%) had brain mets at diagnosis; the rest developed at relapse. The table lists pt characteristics. 26 pts (53.1%) went straight to HDCT without localized treatment to progressive brain mets. 8 (16.3%) underwent craniotomy and 8 (16.3%) had radiation prior to HDCT. 3 of the pts who had radiation had stereotactic radiosurgery (SRS); 5 had whole brain radiotherapy (WBRT). 7 pts (14.3%) underwent craniotomy then radiation prior to HDCT. 5 pts (15.2%) were symptomatic from progressing brain mets at HDCT. 1 of these had mild visual symptoms and went straight to HDCT. 1 pt began having headaches the day before HDCT and given proximity to initiation, HDCT was continued. The other 3 symptomatic pts had previously failed localized treatment for brain mets. 22 pts (44.9%) progressed after HDCT. At a median follow-up of 3.8 yrs (0.6-14.8), 16 pts (32.7%) were alive with no evidence of disease, 10 (20.4%) were alive with disease, 20 (40.8%) died of disease, and 3 (6.1%) died of other causes. 2-yr PFS was 43.9%; 2-yr OS was 73.2%. Conclusions: Pts with relapsed GCT with progressive brain mets can be cured with HDCT with PBSCT. Management of progressive brain mets should be individualized for each pt, taking into account extent of brain mets and presence of symptoms. Reference: 1. Kalra M, et al. Cancer.2020; 126(6): 1202-1207.[Table: see text]
Survival associated with chemotherapy and prognostic biomarkers in penile cancer at a reference hospital in the Northeast Brazil from 2000 to 2021.
Authors: Soares Joao Paulo Holanda , Cunha Maria do Perpétuo Socorro Saldanha , Hirth Carlos Gustavo , Silva Paulo Goberlânio de Barros 
Published: June 2024

5043 Background: Penile cancer is a rare neoplasm worldwide. Despite a higher incidence in the Brazilian Northeast region, data regarding chemotherapy (CHT) treatment of penile cancer in Brazil is scarce. The relationship between markers of immunosuppression in the tumor microenvironment of penile cancer and MDSCs (Myeloid Derived Suppressor Cells) is still poorly understood. Methods: 294 patients affected by Squamous Penile Cancer treated at the Haroldo Juaçaba Hospital (Ceará-Brazil) between 2000 and 2021 (82 underwent chemotherapy: 27 adjuvant, 31 neoadjuvant and 24 palliative ) were retrospectively evaluated due to their clinical and histopathological characteristics and the following immunohistochemical markers: PD-L1, CD8t (intratumoral), CD163t (intratumoral), CD84, HLA-DR II. We sought to correlate these biomarkers to clinical staging, type (neoadjuvant, adjuvant or palliative) and response to CHT, PFS post-Chemotherapy (PFS-CHT), Overall Survival by stage (OS) and OS post-Chemotherapy (OS-CHT). Results: The median age for all patients was 62,9 years (18-103). Partial penile amputation was the most common surgery (74%), followed by inguinal lymphadenectomy (56%). Platinum Doublet was administered in 95% of cases. OS at 5 years for stages I, II, III e IV was 95,3%, 93,6%, 87,4% and 14,8%, respectively. The response rate (RECIST) (PR, SD and PD) in those who underwent Neoadjuvant CT was 29% 22% and 48%, while in the Palliative group was 5%, 11% and 82% respectively. Median OS-CHT was 49 months in the adjuvant, 21 months in neoadjuvant and 12 months in palliative group (p<0.001 adjuvant vs neoadjuvant/palliative); PFS-CHT was 11 months, 4 months and 1 month in the adjuvant, neoadjuvant and palliative group, respectively (p<0.001). In the neoadjuvant group, those who underwent surgery (70%) had a PFS-CHT of 6 months versus 2 months in those who were not operated (p<0.001). In univariate analysis, PFS-CHT was significantly higher in those who had lower expression of CD8t (9 vs 5 months; p=0.02), or CD163t (7 vs 5 months; p=0.043) or CD84 (7 vs 5 months; p =0.043). Conclusions: This is the largest retrospective study on chemotherapy and survival outcomes in Brazil. Patients who underwent surgery and adjuvant CHT had the best prognosis in terms of survival followed by those operated after neoadjuvant CHT. Lower expression CD163t, or CD84 (marker of MDSCs) or CD8t correlated with greater PFS-CHT. These data may help to understand the suppressive microenvironment in penile cancer and response to chemotherapy.
Patient-reported outcomes (PROs) for rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy (ADT) in high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC): An analysis of the CHART randomized, open-label, phase 3 trial.
Authors: Ye Ding-Wei , Jiang Shusuan , Luo Hong , Zhou Fangjian , He Dalin , Ma Lulin , Guo Hongqian , Liang Chaozhao , Chong Tie , Jiang Jun , Chen Zhiwen , Wang Yong , Zou Qing , Tian Ye , Xiao Jun , Huang Jian , Chen Jinchao , Yang Xinfeng , Lian Jianpo , Wang Wenliang 
Published: June 2024

5048 Background: In the CHART trial, rezvilutamide plus ADT significantly improved radiographic PFS and OS compared with bicalutamide plus ADT in patients with high-volume mHSPC (Gu et al., Lancet Oncol 2022). Here, we report the PRO results from the CHART trial. Methods: Eligible patients were men ≥18 years old with high-volume mHSPC and without previous chemotherapy or other localized treatment for prostate cancer. Patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide (240 mg) or bicalutamide (50 mg) orally once daily. PROs were exploratory endpoints and were assessed in all randomized patients by using the Brief Pain Inventory-Short Form (BPI-SF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P). PROs were collected within 7 days prior to the first dose, on Day 1 of each cycle (28 days) in Cycles 2–12, once every 2 cycles in Cycles 13–36, once every 4 cycles afterwards, and on Day 30 after the last dose. Results: Between Jun 28, 2018, and Aug 6, 2020, a total of 654 patients were randomly assigned to receive either rezvilutamide plus ADT (n=326) or bicalutamide plus ADT (n=328). The data cutoff for this PRO analysis was Feb 28, 2022, and the median follow-up was 29.3 months (IQR 21.0–33.3). Baseline pain scores and functional status scores were comparable between the two study groups. The median time to progression of pain (both intensity and interference) was not reached in either group. The 25th percentile for the time to average pain progression was 25.8 months (95% CI 14.8–31.4) in the rezvilutamide plus ADT group and 11.7 months (95% CI 8.7–22.1) in the bicalutamide plus ADT group (HR 0.79, 95% CI 0.58–1.08; p=0.133). Patients in the rezvilutamide group exhibited a longer time to pain interference progression compared to the bicalutamide group (25th percentile, 20.2 months [95% CI 12.9–31.3] vs 10.2 months [95% CI 7.4–11.1]; HR 0.70 [95% CI 0.52–0.93]; p=0.015). Regarding functional status, the time to deterioration of the FACT-P total score was prolonged in the rezvilutamide plus ADT group compared to the bicalutamide plus ADT group (25th percentile, 12.8 months [95% CI 7.4–20.3] vs 6.0 months [95% CI 4.6–9.2]; HR 0.66, 95% CI 0.50–0.86; p=0.002). Additionally, the rezvilutamide plus ADT group exhibited delayed deterioration in all FACT-P subscale scores compared to the bicalutamide plus ADT group. Conclusions: Rezvilutamide plus ADT demonstrated superiority over bicalutamide plus ADT in delaying pain progression and functional status deterioration in high-volume mHSPC. Clinical trial information: NCT03520478 .
Fractionated docetaxel (D) and radium 223 (Ra223) in metastatic castration-resistant prostate cancer (CRPC): A modular phase I trial.
Authors: Connell Brendan , Hwang Clara , Folefac Edmund , Lawlor Christian , Koethe Benjamin , Mathew Paul 
Published: June 2024

5049 Background: Disease progression following novel hormonal therapy in CRPC remains bone-dominant and D-responsive. D + Ra223 would be a logical combination but myelosuppression is dose-limiting. Prior combinations have required a reduction in dose intensity (DI) in both agents. Fractionated schedules of D Q2weekly (DQ2) have comparable activity to D 75mg/m2 Q3weekly with mitigated myelosuppression. We hypothesized that a fractionated schedule of DQ2 with standard Ra223 dosing would be feasible while preserving DI. Methods: Subjects had progressive bone-metastatic CRPC, ECOG PS 0-2, and no bulky visceral disease. Design was phase I, 6+6, dose escalation plus expansion with 28-day cycles. DQ2 was given in a 4-week lead-in, then with Ra223 every 4 weeks. Dose-level (DL) 1: D 40mg/m2; if neutropenia, then 1a: D 40mg/m2 with G-CSF on Day 16, 2a: D 50mg/m2 with G-CSF on Day 16. Up to 6 cycles of the combination were given. Primary objective was the feasibility and maximum tolerated DL explored (MTD). Secondary objectives included PSA response, ORR, PFS, OS, and quality of life. Results: 43 patients (pts) enrolled including 34.9% non-white pts and 76.7% with ≥ 4 bony mets. 8 dropped out during the D lead in (1 each neutropenia, stroke, failure to thrive, anorexia/fatigue, thrombocytopenia, infusion reaction and 2 hospitalized for other reasons). At DL1, 2 of 3 had DLT (both neutropenia). No DLT occurred at DL1a (n=5) or DL2a (n=5). MTD was DL2a. 22 subjects enrolled to expansion cohort at DL2a. Of the 35 pts treated with D + Ra223, adverse events of interest listed in the table. No febrile neutropenia, fractures, or G5 toxicity were seen. 19/35 completed all 6 cycles of combination therapy. PSA50 response was seen in 18 (51.4%) and PSA90 in 9 (25.7%) pts. Of 31 pts with evaluable data, best response (RECIST 1.1) was 1 CR, 5 PR, 23 SD, 2 PD. Median PFS was 50.0 weeks (95% CI: 37.3-86.1) and OS was 86.1 weeks (95% CI: 60.0-130.9). 10 pts progressed exclusively in nodal/visceral metastases compared to 6 in bone only. Quality of life measures remained stable on study. Conclusions: Utilizing a D lead-in strategy, combination DQ2 and Ra223 was feasible and well tolerated, with a favorable PFS and evidence of preferential control of osseous metastases. Dose-intensity for both docetaxel and Ra223 was preserved and comparable to the FDA-approved dose-schedules for each of the single agents. The lead-in design and use of G-CSF contributes significantly to the feasibility. Clinical trial information: NCT03737370 . [Table: see text]
Rapid and deep prostate-specific antigen (PSA) response to apalutamide plus ADT and survival in metastatic castration-sensitive prostate cancer (mCSPC) in real world practice in the US (OASIS Project).
Authors: Maughan Benjamin L. , Liu Yanfang , Mundle Suneel , Wang Xiayi , Karsh Lawrence Ivan 
Published: June 2024

5076 Background: Apalutamide (APA) in combination with androgen-deprivation therapy (ADT) is an effective life-prolonging treatment option for mCSPC. Early and deep PSA responses are response indicators in metastatic castration-resistant PC that have been associated with improved clinical outcomes in patients with PC. APA+ADT has been shown to induce early and deep PSA responses. We evaluated correlations between PSA and long term clinical outcomes in adults with mCSPC in real world practice. Methods: This retrospective, observational cohort study used the ConcertAI RWD 360 prostate cancer dataset to evaluate correlations between PSA and long term clinical outcomes in adults with mCSPC who initiated treatment with APA+ADT. All patients with newly diagnosed mCSPC from 1 Jan 2018 to 30 Sept 2022 were enrolled and followed up until 31 Mar 2023. Correlations between time to 50% and 90% declines in PSA (PSA50 and PSA90), and time to undetectable PSA (≤0.2 ng/mL) and 24-month OS were evaluated. Adjusted Hazard ratios (aHRs) were estimated using multivariate Cox proportional hazard models adjusted for age, comorbidities, BMI, baseline PSA. Results: 183patients with mCSPC who initiated APA+ADT treatment and had monthly PSA testing were included in the analysis; mean (SD) age 73 years (8), baseline PSA 34 (81). Mean (SD) duration of follow up was 18 m (10). Overall, 116 patients (63%) reached undetectable PSA over the follow-up period and 24-month OS was 68%. OS was significantly higher when patients achieved undetectable PSA, PSA90 and PSA50 within 3 months after initiating APA+ADT (24-month survival rate, 87%, 84% and 80%, respectively) compared with patients who did not reach these levels during the follow-up period (Table). The aHR was 0.15 (95% CI 0.05–0.47; p<0.001) in patients who reached undetectable PSA within 3 months compared with not yet reached. The aHR was 0.27 (0.12–0.65; p<0.01) in patients with onset of undetectable PSA beyond 3 months compared to not reached. Conclusions: Rapid and deep PSA decline was strongly associated with better overall survivalin patients with mCSPC initiated on APA+ADT.[Table: see text]
Post-progression survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who received darolutamide or placebo: Post hoc analysis of ARASENS.
Authors: Grimm Marc-Oliver , Smith Matthew Raymond , Hussain Maha H. A. , Saad Fred , Fizazi Karim , Littleton Natasha , Paracha Noman , Srinivasan Shankar , Verholen Frank , Tombal Bertrand F. 
Published: June 2024

5083 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor pathway inhibitor (ARPI). In ARASENS (NCT02799602), the addition of DARO to androgen-deprivation therapy (ADT) and docetaxel (DOC) significantly reduced the risk of death by 32.5% in patients (pts) with mHSPC, despite most placebo (PBO) pts (75.6%) receiving subsequent therapy. DARO also delayed time to progression to metastatic castration-resistant prostate cancer (mCRPC; median, not reached vs 19.1 months for PBO), resulting in a longer time in mHSPC, which is associated with improved quality of life vs mCRPC. We report post-progression subsequent anticancer therapies and related survival from ARASENS. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or PBO in addition to ADT + DOC. After treatment discontinuation, pts entered active and long-term survival follow-up periods during which assessments included subsequent therapies and survival outcomes. Post-progression survival was defined as time from first subsequent therapy to death using Kaplan-Meier estimates. Results: Of 1305 treated pts (DARO n=651; PBO n=654), 315 receiving DARO and 495 receiving PBO entered follow-up. Of these, 57% (n=179) and 76% (n=374), respectively, received subsequent therapy; abiraterone and enzalutamide were the most frequent first subsequent therapy (Table). In the DARO arm, 90% of first subsequent therapies were ARPI or chemotherapy. Minimal difference was observed in post-progression survival between subsequent therapies, suggesting subsequent therapy with another ARPI does not provide further survival benefit vs non-ARPI options (mainly chemotherapy). In contrast, in the PBO arm where the majority (78%) received first subsequent therapy with an ARPI, a survival benefit was observed vs non-ARPI subsequent therapies (median, 23.0 vs 13.5 months). Conclusions: DARO+ADT+DOC increased overall survival vs PBO+ADT+DOC and also delayed time to progression to mCRPC. DARO pts had similar survival with all post-progression therapies. Pts receiving PBO+ADT+DOC quickly progressed to mCRPC and treatment with an ARPI in ARPI-naïve pts improved survival. Clinical trial information: NCT02799602 . [Table: see text]
EMBARK post hoc analysis of sexual activity (SA) patient-reported outcomes (PROs) in patients (pts) who were sexually active or interested in sex at baseline (BL).
Authors: Freedland Stephen J. , Mulhall John , Gleave Martin , De Giorgi Ugo , Rannikko Antti , Saad Fred , Ramirez-Backhaus Miguel , Ivanova Jasmina I. , Nasr Anchen F. , Ganguli Arijit , Kral Pavol , Reisman Arlene , Shore Neal D. 
Published: June 2024

5084 Background: In EMBARK (NCT02319837), enzalutamide (ENZ) + leuprolide (L) or ENZ (ENZ mono) delayed metastasis-free survival vs placebo (P) + L while maintaining high quality of life (QoL) in high-risk biochemically recurrent nonmetastatic hormone-sensitive prostate cancer. SA (a composite score from European Organization for Research and Treatment [Tx] of Cancer QoL Questionnaire-Prostate 25 [QLQ-PR25]) was better preserved with ENZ mono vs P + L with no difference between ENZ + L vs P + L. To better understand effect on SA in relevant subgroups, we examined SA in pts who were sexually active or interested in sex at BL. Methods: QoL was assessed (BL, every 12 weeks) until metastasis/death. Cox regression was used to examine time to confirmed deterioration (TTCD) (confirmed at next visit) defined by one category change for sexual interest, activity, satisfaction, erectile function, and feeling like a man using QLQ-PR25 and FACT-P items (Table).Intent-to-treat analysis was applied. Results: Among pts interested in sex (n=694) or sexually active (n=437) at BL, TTCD in QLQ-PR25 SA domain, items 50 (interest), 51 (activity), GS7 (satisfaction), and BL5 (erectile function) were significantly delayed with ENZ mono vs P + L. In contrast, TTCD in BL5 (erectile function) was shorter with ENZ + L vs. P + L (Table). Conclusions: Among pts who were interested in sex or sexually active at BL, ENZ mono better preserved SA vs P + L in terms of SA domain, interest, activity, satisfaction, and maintaining erection. Adding ENZ to L had no impact on interest, activity, or satisfaction but may adversely affect erectile function, though differences in the median TTCD were clinically non-significant (0.06 months [1.8 days] and 0.09 months [2.7 days] in pts interested in sex and sexually active at BL, respectively). Clinical trial information: NCT02319837 . [Table: see text]
Comparison of outcomes with docetaxel or ARPI combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) by volume of disease.
Authors: Schoen Martin W. , Etzioni Ruth Douglas , Luo Suhong , Candelieri Danielle , Fedele Nicholas , Baxi Priya , Pickett Carley , Riekhof Forest , Ingram Kara , Karunanandaa Krishny , Govindan Srinivas , Cheranda Nina , Knoche Eric Marshall , Montgomery Robert Bruce 
Published: June 2024

5092 Background: Combination therapy has improved treatment of metastatic hormone sensitive prostate cancer (mHSPC). Doublets include androgen deprivation therapy (ADT) plus docetaxel (DOC) or the androgen receptor pathway inhibitors (ARPIs) abiraterone, enzalutamide, apalutamide, or darolutamide. There have been no large clinical trials that compare DOC to ARPIs in mHSPC. This study evaluates overall survival and time to castration-resistance in patients with de novo (synchronous) mHSPC in the Veterans Health Administration treated with combination therapy. Methods: Veterans were identified with initial diagnosis of ‘distant’ prostate cancer. All veterans had ADT initiated within 4 months of diagnosis and followed until September 2023. First combination therapy with DOC from 7/2016-6/2021 or ARPI from 7/2017-6/2021 were included if initiated within 4 months after ADT. Volume of disease was determined from chart review and castration-resistance (mCRPC) by a combination of natural language processing and administrative data. Real-world progression-free survival (rwPFS) was determined as time to mCRPC or death. Kaplan-Meier time to event analyses and Cox proportional hazard modeling with age, Black race, Charlson comorbidity index, prostate specific antigen, body mass index, and weight change in the year prior was used for analyses. Results: 1,226 patients with de novo mHSPC were identified with median age of 71.5 years and 349 (28.6%) were Black. High volume disease was identified in 929 (76.0%) and low volume in 293 (24.0%). DOC was used in 341 (27.9%) and ARPIs in 881 (72.1%). Veterans with high volume disease had shorter overall survival (OS) than low volume (23.8 vs. 64.1 months, p<0.001). Overall, there was no difference in OS between DOC and ARPI (36.4 vs. 38.9 months, p=0.68), however DOC was associated with a shorter rwPFS (16.5 vs 22.1 months, p<0.001). In high volume disease, there was no difference in OS between DOC and ARPI (33.8 vs. 32.5 months, p=0.68), however DOC was associated with a shorter rwPFS (14.9 vs 19.2 months, p=0.002). In a multivariable model of patients with high volume disease, there was no difference in OS observed between initial treatment with DOC and ARPIs (aHR 0.83, 95% CI 0.69-1.00). Conclusions: In veterans with de novo mHSPC, no difference in OS were observed between combination treatment with DOC or ARPI in patients with low or high-volume mHSPC. ARPIs were associated with longer progression free survival. Due to a lack of clinical trials comparing DOC and ARPI therapy, these data may guide selection of combination therapy for mHSPC.[Table: see text]