bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world comparative effectiveness and cardiovascular safety of enzalutamide versus abiraterone amongst older men diagnosed with metastatic castration-resistant prostate cancer.
Authors: Gaber Charles , Okpara Ebere , Abdelaziz Abdullah , Sarker Jyotirmoy , Hanson Kent , Hassan Lubna , Lin Fang-Ju , Lee Todd , Reizine Natalie Marie 
Published: June 2024

5053 Background: Abiraterone and enzalutamide are frequently used in treating metastatic castration-resistant prostate cancer (mCRPC), and their use has expanded to castration-sensitive and non-metastatic settings. The objective of this study was to compare real-world overall survival and risk of major adverse cardiovascular events (MACE) between initiators of abiraterone and enzalutamide in a cohort of older adult men with mCRPC. Methods: The Surveillance Epidemiology and End Results-Medicare database was leveraged to design a comparative observational study. Initiators of abiraterone or enzalutamide between 2011-2017 were identified, a period when both drugs were only approved for mCRPC. Propensity scores and inverse-probability-of-treatment weighting were used to balance measured confounders. MACE was defined as a hospitalization for myocardial infarction, heart failure, or ischemic stroke or transient ischemic attack. Hazard ratios were obtained from weighted Cox proportional hazards (mortality) and Fine-and-Gray models (MACE). Results: The study population consisted of 5,633 men 66 years of age and older diagnosed with mCRPC, of which 3,720 initiated abiraterone and 1,913 enzalutamide. The median age at initiation was 77. Compared to enzalutamide initiators, the overall survival was similar in patients initiating abiraterone at both one-year (mortality hazard ratio (HR) = 1.05; 95% CI: 0.95 – 1.17) and five-years of follow up (HR= 1.01; 95% CI: 0.95 – 1.08). The one-year risk of MACE was higher in abiraterone initiators (HR = 1.30; 95% CI: 1.01 – 1.67). The agents displayed similar effects on MACE when considering a five-year follow-up period after therapy initiation (Table). Conclusions: The long-term comparative effectiveness and cardiovascular safety of abiraterone and enzalutamide were similar, though a short-term increase in MACE was seen in abiraterone initiators, highlighting the importance of considering cardiovascular risk and cancer prognosis during therapy selection.[Table: see text]
Matching-adjusted indirect comparisons (MAICs) of talazoparib plus enzalutamide (TALA+ENZA) versus olaparib plus abiraterone and prednisone/prednisolone (OLAP+AAP) for first-line (1L) therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair mutations (HRRm)/BRCAm.
Authors: Castro Elena , Wang Di , Haltner Anja , Paganelli Stefanie , Niyazov Alexander , Kirker Melissa , Thompson Allison , Samjoo Imtiaz 
Published: June 2024

5063 Background: Poly-ADP ribose polymerase inhibitors (PARPi) in combination with a novel hormonal therapy (NHT) have shown benefit for the 1L treatment of mCRPC in an all-comers population as well as HRRm and BRCAm subpopulations (TALA+ENZA [TALAPRO-2; NCT03395197] and OLAP+AAP [PROpel; NCT03732820]). In the absence of head-to-head studies, their comparative efficacy is unknown. The relative efficacy of TALA+ENZA (n=200 HRRm; n=71 BRCAm) vs OLAP+AAP (n=111 HRRm; n=47 BRCAm) in these subpopulations were estimated using MAICs for radiographic progression-free survival (rPFS) based on blinded independent central review and overall survival (OS). Methods: Unanchored MAICs were conducted using individual patient data from TALAPRO-2 Cohort 2 (data cutoff [DCO]: 03/10/22 [rPFS/OS]) and published summary level data from PROpel (DCO: 30/07/21 [rPFS]; 12/10/22 [OS]). To align across the two trials, patients from TALAPRO-2 with specific HRRm/BRCAm (co-occurring or standalone) that were not assessed in PROpel were removed from the dataset for each analysis. TALAPRO-2 patients were also matched based on PROpel’s eligibility criteria and characteristics were adjusted for key prognostic factors identified in the literature and clinical expertise including prior taxane chemotherapy in castration sensitive prostate cancer (CSPC), visceral metastasis, bone only metastasis, Eastern Cooperative Oncology Group score, prostate-specific antigen levels, Gleason score, BRCA1 and BRCA2. Results: After the removal of patients with specific gene mutations not assessed in PROpel and those who received prior NHT in CSPC, 157 and 64 patients remained in the TALA+ENZA arm for HRRm and BRCAm, respectively. The comparative effect estimates for rPFS and OS are presented in the Table. None of the results were statistically significant. Conclusions: These analyses demonstrate numerically favorable results for TALA+ENZA compared to OLAP+AAP highlighting its therapeutic potential in 1L mCRPC for patients with HRRm and BRCAm. Limitations include inability to adjust for all characteristics and biases due to unobserved trial differences. [Table: see text]
Treatment outcomes for patients with Ga68-PSMA-PET prostate cancer (PC) with or without conventional imaging correlates.
Authors: Issa Wadih , Aliru Maureen , Gunenc Damla , Zhang Song , Zhou Qinhan , Qin Qian , Wang Jue , Arafat Waddah , Courtney Kevin Dale , Yang Daniel X. , Desai Neil B , Garant Aurelie , Hannan Raquibul , Cadeddu Jeffrey A. , Gaston Kris , Woldu Solomon L. , Margulis Vitaly , Lotan Yair , Wang Andrew Zhuang , Zhang Tian 
Published: June 2024

5078 Background: The high sensitivity of PSMA PET/CT in pts with PC has created a new advanced disease space (PSMA+/CT-) with stage migration. Treatment outcomes and optimal management remain largely unstudied for these pts. Methods: Pts with metastatic castration sensitive PC identified during standard of care PMSA PET/CT imaging (Ga68 gozetotide/PSMA-11) were reviewed retrospectively at UTSW and stratified by whether a CT lesion correlates to a PSMA avid lesion (SUVmax >2.5): PSMA+/CT- vs PSMA+/CT+ groups. The primary objective was PSA Progression Free Survival (PFS) and time to castration resistance (TTCR) between cohorts. The secondary objective was TTCR in pts with PSMA+/CT- disease based on exposure to androgen deprivation therapy (ADT) alone or with AR-targeted therapy (ARTT intensification). Cohorts were compared using a two-sample t-test or a chi-square test; survival analysis was conducted using Kaplan-Meier and Cox proportional hazards regression. Results: Overall,135 pts were included; of whom 122 received ADT (PSMA+/CT- [n=73] vs PSMA+/CT+ [n=49]) and 13 PMSA+/CT- pts received localized treatment only. PSMA+/CT- and PSMA+/CT+ pts had comparable median age at diagnosis and similar racial distribution. The median follow-up was 19 months. In pts who received ADT, the PSMA+/CT- group had a lower median PSA (1.3 vs 14 ng/ml, P=0.0002), a lower rate of de-novo metastatic disease (30% vs 55%, p=0.0082) and ADT+ ARTT use (59% vs 88%, p=0.0006) compared to the PMSA+/CT+ group. Median therapy duration was similar. In pts receiving ADT, the median PSA PFS in the PSMA+/CT- group was not reached (NR) versus 37 months in the PSMA+/CT+ group. After adjusting for known prognostic factors, PSMA+/CT- lesions were significantly associated with a better PSA PFS and TTCR (Table). In pts with PMSA+/CT- receiving ADT alone (n=30) vs ADT+ARTT (n=43), only 1 patient progressed to castration resistance. After adjusting for prognostic factors, pts with PSMA+CT- disease who received ADT had a better PSA PFS [HR 0.1 (0.02-0.45)] compared to those who received localized therapy only (n=13). Conclusions: Pts with PSMA+CT- PC vs pts with PSMA+/CT+ PC have better prognosis and outcomes, with low rates of PSA progression and castration resistance. Localized therapy alone is likely insufficient for these pts, and ARTT intensification to improve longer term outcomes needs prospective studies through ongoing trials. [Table: see text]
Mutational burden among patients with metastatic prostate cancer differs by race in 3 key genes: An analysis of genomic and clinical data from the AACR Project GENIE biopharma collaborative in cBioPortal.
Authors: Arigbede Olumide M. , Gbogbo David , Buxbaum Sarah 
Published: June 2024

5106 Background: Prostate cancer exhibits a range of aggressive oncological traits due to its genomic heterogeneity. The extent to which clinical and demographic variables affect cancer behaviors and increase disparities is a complex and open question. Objective: We aim to comprehensively explore the genomic and epigenetic characteristics of metastatic prostate cancer (PCa) across different racial groups to elucidate potential molecular and immune mechanisms underlying disparities in disease progression and treatment response. Methods: Data from the Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR-GENIE) registry to study men diagnosed with PCa was queried. Patients with metastatic disease (n = 1,684) were stratified into three racial groups: White (80.5%), Black (8.1%), and Asian (3.1%). cBioPortal was used to analyze the differences in genetic mutation frequencies by race and to determine the importance of these mutations. The relationships between mutation frequencies and race were examined using chi-squared test. Results: In our study, among patients with metastatic prostate cancer, the following three genes demonstrated the highest differences in frequencies of mutation: TP53, ATR, and PTEN. The most significant differences in mutation frequencies by race in metastatic PCa patients were found in TP53 (White: 3.1%; Black: 16.7%; Asian: 11.8%; P <0.005) and ATR (White: 2.39%; Black: 3.58%; Asian: 4.87%; P = 0.035). PTEN has a metastatic tumor frequency of 6.5% in Asians, 4.2% in Black men, and 7.1% in White men (P = 0.0434). Conclusions: Consistent with previous literature, our study provides new insight into the complex interplay between PCa pathogenesis and progression, paving the way for precision. In the TP53 gene, Black men were more likely than their counterparts to have a higher mutational burden. This research has significant implications for improving health equity in PCa.
Oral cyclophosphamide plus bevacizumab in recurrent ovarian, fallopian tube and primary peritoneal cancer.
Authors: Eyada Mostafa , Michael Victoria , Fellman Bryan M. , Patel Shrina , Soliman Pamela T. , How Jeffrey Andrew , Jazaeri Amir A. , Fleming Nicole D. , Sood Anil K , Westin Shannon Neville , Sims Travis T. 
Published: June 2024

5517 Background: The combination of bevacizumab, cyclophosphamide and pembrolizumab is NCCN compendium listed based on a phase 2 trial that lacked a comparison arm. The objective of this study was to assess safety and efficacy of bevacizumab plus oral cyclophosphamide in patients with recurrent high-grade ovarian, fallopian tube and primary peritoneal cancer. Methods: This retrospective analysis included patients with recurrent platinum sensitive or resistant high-grade ovarian cancer treated with oral cyclophosphamide plus bevacizumab at a single institution. Treatment consisted of bevacizumab 15 mg/kg intravenously every 3 weeks in combination with oral cyclophosphamide 50 mg daily. Patients with platinum free interval of 6 months or longer were considered to have a platinum sensitive disease. Objective response rate to chemotherapy (ORR = complete response (CR) + partial response (PR)) was calculated with 95% confidence interval (95% CI). Progression free survival (PFS) was calculated from initiation of chemotherapy to earliest date of progression or death and estimated using the methods of Kaplan and Meier. Adverse events were collected and graded using CTCAE v. 5.0. Results: One hundred patients were identified; 14 (14%) were platinum sensitive and 86 (86%) were platinum resistant. Median age was 58 (38-80). The majority of patients had high-grade serous histology (95%) and stage III or IV at diagnosis (95%). The median number of previous treatments was 3 (range 1-9). Thirty-three patients (33%) received bevacizumab in a prior regimen. A median of 5 (range 2-34) cycles of bevacizumab with daily oral cyclophosphamide were administered. ORR was 40.4% (95% CI: 30.7-50.7) with 4% CR, 36% PR, 20% SD, 39% PD. ORR among patients who received bevacizumab in a prior regimen was 12 (36%) compared to ORR of 24 (42%) among patient who never received bevacizumab in a prior regimen (P = 0.59). The median PFS was 4.6 months (95% CI: 3.42-5.9). There was no relationship between platinum status or platinum free interval and response to this regimen, although the population was predominantly platinum resistant. Seventy-six (76%) of patients had documented adverse events. Most common grade 3-4 toxicities included hypertension (3%), thrombocytopenia (3%), and hemorrhagic cystitis (1%). Conclusions: Bevacizumab in combination with oral cyclophosphamide was well tolerated and active, with a response rate of 40% in patients with recurrent platinum resistant high-grade ovarian cancer.
Value of ctDNA-based molecular residual disease (MRD) in evaluating the adjuvant therapy effect in ovarian cancer.
Authors: Wang Jingjing , Chen Keyao , Guo Yu , He Ying , Cheng Shaochen , Sun Li , Teng Jiaman 
Published: June 2024

5525 Background: Ovarian carcinoma (OC) is the fifth leading cause of cancer-related mortality in women worldwide. Circulating tumor DNA (ctDNA) is a promising biomarker for ovarian cancer and can be detected using a noninvasive liquid biopsy. It reflects the status of molecular residual disease and post-surgery therapy effect in real-time. In this study, we examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding tumor specimens of different types of OC. Additionally, investigated whether mutations in plasma ctDNA can provide predictive insight into OC and provide a new perspective on the efficacy of postoperative adjuvant therapy. Methods: Stage I-IV ovarian cancer patients were recruited from 2022.11 to 2023.12. Tumor tissues were collected at excision and then subjected to whole exome sequencing(WES) for comprehensive somatic variant detection in 1000x depth. Personalized tumor-informed molecular residual disease (MRD) panel was designed for up to 40 loci including SNVs and InDELS. Plasma samples were collected at baseline and post-operation adjuvant therapy. Plasma samples performed on ctDNA-based MRD assay underwent 100,000x ultra-deep sequencing. Results: The cohort included 20 patients with high-grade serous carcinomas (HGSC), 5 with borderline tumors, 2 with clear cell carcinoma, 2 with mucinous carcinomas, 2 with endometrioid carcinoma, 1 with low-grade serous carcinomas, and 2 with other types. WES identified 2542 variants in 1906 genes, encompassing 2297 single nucleotide variants (SNVs) and 245 insertions/deletions (InDels), with missense mutations accounting for 84.5% of the major mutations. The most frequently mutated gene was TP53 (76.47%), followed by ZNF285 (44.12%), TTN (29.41%), TOPAZ1 (29.41%), THADA (23.53%), and UBE4A (20.59%). The mutation landscape showed no significant differences among subtypes. The baseline ctDNA detection rate is 88.23% for the entire cohort and 90% for HGSC patients. The consistency between plasma and tissue was verified by Pearson (p=2.7e-6) and Spearman (p=3.7e-7) correlation analyses. All HGSC patients underwent adjuvant therapy post-surgery (up to 8 cycles). 75% (15/20) of HGSC patients achieved complete response (CR), 20% (4/20) achieved partial response (PR), and 5% (1/20) showed progressive disease (PD). MRD monitoring showed a continuous decrease in postoperative ctDNA concentration, with 60% (9/15) of patients achieving MRD negativity. Among the patients with CR, 4 became MRD negative for the first time after surgery and maintained negativity after up to 6 cycles of adjuvant therapy. Conclusions: The results of this real-world study indicate that tumor-informed MRD can serve as a prognostic biomarker for OC, and would provide information about postoperative MRD status and long-term monitoring of adjuvant therapy for further precise treatment.
Molecular characterization of cervical cancer histological subtypes: The VENUS study.
Authors: Braik Dina , Alqaisi Husam , Garg Vikas , Soberanis Pina Pamela , Valente Lage Liana , Veneziani Ana , Grant Brooke , Pannu Anmol Kaur , Lajkosz Katherine , Msan Anthony , Hodgson Anjelica , Rouzbahman Marjan , Stockley Tracy , Bowering Valerie , Grant Robert C , Dhani Neesha C. , Lheureux Stephanie , Oza Amit M. 
Published: June 2024

5537 Background: While the landscape of cervical cancer treatment has undergone considerable advances, systemic treatment options following recurrence remain limited. There is paucity of data on predictive and prognostic molecular alterations within distinct histologic subtypes. Methods: In this prospective, translational, single-institution study (NCT03420118), patients diagnosed with cervical cancer were enrolled. Tumor tissue samples (biopsy or archival) were obtained at different time points from initial histological diagnosis to each progression, when feasible. Genomic DNA was extracted and analyzed, using the UHN Hi5 Panel and the Illumina TruSight Oncology 500 assays, to detect molecular alterations. Variant annotations were obtained from OncoKB database. In addition, clinical data for each patient, including histopathologic subtype, stage at diagnosis, and lines of treatment were collected. Results: 124 patients (median age 48 years; range 24-80) with a pathologic diagnosis of cervical cancer were enrolled. Clinical characteristics of patients with available tumor tissue samples (n=112) are detailed in the table. In 99 of the 112 (88.4%) available tumor tissue samples, 243 validated molecular alterations were identified across 88 different genes. Seven tumors had ≥ 5 alterations detected per sample; one squamous cell carcinoma (SCC) and one poorly differentiated adenocarcinoma (AC) had 14 alterations each. PIK3CA, the most frequently detected alteration (41/243; 16.8%), was identified in 22 of 58 (37.9%) SCC samples vs 8 of 38 (21.1%) AC samples (p-value 0.11). Other commonly detected alterations included TP53 (18/243; 7.4%) and KRAS (13/243; 5.3%), both identified more frequently in AC compared to SCC tumor samples (28.9% vs 3.4%; p-value < 0.001, and 23.7% vs 3.4%; p-value 0.006, respectively). KRAS alterations were predominantly G12D or G12V. No G12C variants were detected. All tumors were MSI-stable. Among rare histologic subtypes, unique alterations were detected. Adenosquamous subtypes had alterations of TET2, BARD1, BRAF, in addition to CCND3 and CCNE1amplifications, while neuroendocrine subtypes showed alterations of ATM, MYC, SDHB, TSC1, FANCE, and FGFR1. Overall survival did not show a significant correlation with molecular alterations among different subtypes. Conclusions: Genomic analysis of histologic subtypes of cervical cancer reveals distinctive molecular features which may allow the development of genomic biomarkers of resistance and sensitivity. [Table: see text]
Differences in physical and emotional distress amongst patients undergoing neoadjuvant chemotherapy versus surgery for advanced ovarian cancer: Patient-reported outcomes at diagnosis.
Authors: Mokshagundam Shilpa , McGree Michaela E , Fought Angela J , Ishitani Karen P , Lee Minji K , Kumar Amanika 
Published: June 2024

5546 Background: Advanced ovarian cancer (OC) is managed with cytoreductive surgery and platinum-based chemotherapy. Prehabilitation is a multimodal intervention to improve physical and mental health prior to oncologic surgery. This study evaluates baseline differences in clinical characteristics, functional status, and patient-reported outcomes (PROs) between patients undergoing primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy (NACT) who enrolled in a prospective prehabilitation trial. Methods: This was a single-institution, non-randomized prospective behavioral intervention trial of patients with suspected advanced stage (IIIC/IV) OC. Baseline functional testing included the Short Physical Performance Battery (SPPB), Fried Frailty Index (FFI), gait speed, and grip strength. Patient-Reported Outcomes Measurement Information System (PROMIS) metrics, the Mindfulness Attention Awareness Scale (MAAS), and the Perceived Stress Scale (PSS-10) were used to evaluate PROs. Comparisons between cohorts utilized two-sample t-test or Kruskal Wallis test for continuous variables and chi-square or Fisher’s exact test for categorical variables. T-scores were obtained for PROMIS data using the HealthMeasures Scoring Service; validated cut points for PROMIS, MAAS, and PSS-10 were used for categorization. Results: Amongst the 53 enrolled patients, physical and emotional distress was higher amongst OC patients compared to population means. When compared to PCS patients, NACT patients were more likely to report “severe” in at least one PROMIS domain (emotional distress and anxiety, pain interference, physical function, and fatigue, p<0.01). NACT patients reported significantly higher levels of perceived stress (p<0.01). NACT patients were more likely to have stage IV disease, albumin <3.5 g/dL, and lower gait speed and grip strength (all p<0.01). Despite differences in clinical variables and PROs including physical function, there were no measurable differences in physical function based on SPPB and FFI. Conclusions: Advanced OC patients have high psychosocial needs, with NACT patients reporting severe perceived symptoms on PRO measures. The PSS-10 may be a valuable screening tool for patients undergoing NACT to prioritize supportive care services. Clinical trial information: NCT05047926 . [Table: see text]