bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLATIPARP: A phase 2 study of induction docetaxel and carboplatin followed by maintenance rucaparib in treatment of patients with mCRPC with homologous recombination DNA repair deficiency.
Authors: Raychaudhuri Ruben , Gulati Roman , Schweizer Michael Thomas , Yezefski Todd , Khan Hiba M , Yu Evan Y. , Nelson Peter , Pritchard Colin C. , Montgomery Robert Bruce , Cheng Heather H. 
Published: June 2024

5052 Background: Genes involved in homologous recombination DNA repair (HR) are inactivated in ~25% of patients with metastatic castration-resistant prostate cancer (mCRPC). Inactivation of HR has been associated with sensitivity to DNA damage by platinum chemotherapy and PARP inhibitors (PARPi). While both drug classes have shown efficacy, resistance and/or cumulative dose-limiting toxicities are inevitably observed. Here, we report results from a single-center phase 2 study investigating whether induction chemotherapy (IC) with docetaxel and carboplatin followed by maintenance PARPi would provide prolonged disease control. Methods: Patients with mCRPC tumors harboring a pathogenic alteration in an HR gene, who had received prior taxane and/or androgen receptor pathway inhibitor (ARPI), but not prior PARPi were eligible. Patients received IC with 4 cycles of docetaxel 60mg/m2 with carboplatin AUC 5 IV q21 days, followed by the PARPi rucaparib 600mg BID continuously as maintenance therapy until disease progression or unacceptable toxicity. The primary endpoint was clinical/radiographic progression free survival (PFS) compared to a historical control of 9.1 months with PARPi alone without prior platinum. 20 patients provided ~90% power to determine whether this treatment lowered risk of progression with a hazard ratio of 0.5 (implying PFS of 18.2 months), based on a 1-sided 1-sample log-rank test. Secondary endpoints included PSA50 response rate, safety, and overall survival. Post-hoc subgroup analysis was performed for the BRCA complex group (alterations in BRCA1, BRCA2, and PALB2) and for those refractory to IC. Results: 18 patients were enrolled between 2018 and 2021. Under-enrollment occurred due to loss of manufacturer support for rucaparib prior to study completion. 11/18 (61%) of patients had ≥2 prior ARPI, and 9/18 (50%) had previously received docetaxel. HR genes included on study were ATM (7), BRCA1 (3), BRCA2 (8), PALB2 (1), FANCA (1) and CHD1/ SPOP (1) with three tumors harboring two alterations. Clinical outcomes for the overall cohort and key sub-groups are reported in the table. 6/18 (33%) patients experienced grade ≥3 adverse events, including one patient with grade 4 thrombocytopenia. Conclusions: IC followed by maintenance rucaparib did not significantly increase PFS in patients with HR alterations compared to historical control. Results were more encouraging in the BRCA complex group. IC refractory patients were not rescued by subsequent PARPi, suggesting overlapping mechanisms of resistance when platinum is used prior to PARPi. Clinical trial information: NCT03442556 . [Table: see text]
Real-world baseline treatment patterns and overall survival (rwOS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States.
Authors: Kariburyo-Yay Furaha , George Daniel J. , Aggarwal Himani , Tepsick Jon G. , Yu Rebekah , Li Weiyan , Orji Chinelo , Lal Lincy S. , Ghate Sameer R. 
Published: June 2024

5054 Background: Olaparib is one of the first targeted therapies for pts with mCRPC. Real-world data on treatment patterns prior to receiving olaparib are limited in mCRPC pts with homologous recombination repair gene mutation (HRRm). This study describes real-world novel hormonal agent (NHA) use by clinical setting prior to receiving olaparib in mCRPC and rwOS in pts with HRRm mCRPC treated with olaparib monotherapy. Methods: HRRm+ pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy (post May 19, 2020) and prior to abiraterone or enzalutamide were abstracted from electronic medical records in the ConcertAI Oncology Dataset with PC diagnosis between 1990 and 2023. HRR genes of interest were ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L. Frequency of pts who progressed from metastatic hormone-sensitive PC (mHSPC) and from non-metastatic CRPC (nmCRPC) to mCRPC and treatment patterns prior to mCRPC were summarized. Kaplan-Meier analysis was used to describe the rwOS from the start date of earliest olaparib monotherapy treatment (index date). Results: A total of 144 mCRPC olaparib treated pts were identified [median age 73 years; any BRCAm including co-occurring HRRm 56.3%; White 73.6%; ECOG 0-1 at index 78.4%; Gleason ≥8 at index 66.7%]. Of the 144 pts, 80.5% of pts progressed from mHSPC, 11.8% of pts progressed from nmCRPC, and 7.6% of pts were identified in mCRPC setting. For pts who progressed from mHSPC, 62.1% were NHA-treated in the mHSPC setting. Overall, 43.8% initiated olaparib monotherapy in the first 2 lines of therapy after mCRPC diagnosis while 15.3% initiated olaparib in 5L+ (Table). Among pts diagnosed with mHSPC before mCRPC, olaparib was most frequently received in 2L (26.7%) and in 3L (22.4%). For mHSPC pts treated with NHA, olaparib was most frequently received in 2L (31.9%); in contrast, for mHSPC pts that were NHA-naïve, olaparib was most frequently received in the 5L+ (29.5%). The overall median rwOS from olaparib initiation was 16.5 (95% CI: 12.4, 21.1) months; and 20.3 (95% CI: 14.7, 26.8) and 12.9 (95% CI: 10.9, 16.9) months, respectively, for pts with and without any BRCA mutations. Conclusions: This real-world analysis indicates many mCRPC pts with HRRm are receiving several lines of therapy prior to olaparib, even when NHA are used prior to mCRPC. Earlier treatment with olaparib monotherapy may improve duration of therapy and overall survival. [Table: see text]
Race and decisional conflict about genetic testing in patients with advanced prostate cancer.
Authors: Purtell JP P , Ralston Avery , Rose Courtney M , McElyea Kyle , Ibrahim Farhan , Thompson Alexandra , Ghosh Sunita , Hwang Clara 
Published: June 2024

5062 Background: Guideline recommended genetic testing in advanced prostate cancer (PC) is underutilized and not always accepted by patients (pts). We assessed attitudes and decisional conflict (DC) surrounding genetic testing associated with subsequent test completion, and differences between white and nonwhite pts. Methods: Eligibility for this prospective single institution study included pts with N1 or M1 PC who had not yet completed genetic testing. Upon informed consent, pts were given a 24-question survey using a Likert scale of 0 (strongly agree) to 4 (strongly disagree) to assess attitudes toward genetic testing including a validated assessment of DC. DC and DC subscores (range 0-100, with 100 being highest DC) were calculated from subsets of survey responses. Self-identified race was obtained from the EMR. Two-group comparisons between white and nonwhite pts, and between those who completed genetic testing and who did not, were conducted with SAS v9.4 software using Fisher’s exact test for categorical variables and Wilcoxon rank sum test for Likert scale survey questions and DC score variables. Results: Of 42 enrolled pts (21 white, 17 black, 1 Asian, 3 declined), 22 (52.4%) completed genetic testing. Compared to white pts, nonwhite pts expressed more concern about test result privacy (mean = 1.72 v 2.95, p = 0.002), test results being used for non-healthcare purposes (1.78 v 3.00, p = 0.003), and trying unproven treatments (1.72 v 2.67, p = 0.01). Nonwhite pts felt more external pressure in decision-making compared to white pts (0.67 v 0.29, p = 0.04). No significant differences were appreciated in completion of testing, DC, or any subscore between racial groups. Compared to pts who did not complete testing, those who completed testing were more likely to report they knew which options were available (0.73. v 1.25, p = 0.05), knew the benefits of each option (0.77 v 1.30, p = 0.04), knew the risk and side effects of each option (0.95 v 1.50, p = 0.05), were clear about which benefits matter most to themselves (0.73 v 1.37, p = 0.02), and were clear about the best choice for themselves (0.73 v 1.35, p = 0.02). DC (28.59 v 18.11, p = 0.03) was higher in pts who did not complete testing, along with uncertainty (31.25 v 19.32, p = 0.02) and informed (31.25 v 20.45, p = 0.03) subscores. No differences were seen in values clarity, support, or effective decision subscores. Conclusions: In our study, nonwhite pts expressed greater concern about privacy, data misuse, and trying unproven treatments. Those who did not complete testing had more DC with greater uncertainty about knowledge and decision making. These findings will help direct targeted interventions to increase knowledge, trust, and decisional certainty about genetic testing in pts with advanced PC. Ongoing studies will assess the impact of these interventions on rates of testing completion at our institution.
Independent blinded validation of an AI-based digital histology classifier for prostate cancer recurrence and metastasis risk prediction.
Authors: Fay Magdalena , Liao Ross , Lone Zaeem M , Reddy Chandana A. , Muhammad Hassan , Xie Chensu , Jain Parag , Huang Wei , Basu Hirak S , Nguyen Jane , Nair Sujit S. , Chakravarty Dimple , Williamson Sean R. , Gupta Shilpa , Weight Christopher , Roy Rajat , Wilding George , Tewari Ashutosh K. , Klein Eric A. , Mian Omar Y. 
Published: June 2024

5098 Background: Artificial intelligence (AI) tools which identify pathology features from digitized whole slide images (WSI) of prostate cancer (CaP) generate data to predict risk of disease recurrence and metastasis. PathomIQ and ISMMS have developed an AI-enabled prognostic test, PATHOMIQ_PRAD, which predicts risk of biochemical recurrence (BCR) and distant metastasis (DM) using WSIs. The objective of this study was to evaluate the clinical validity of PATHOMIQ_PRAD using a retrospective clinical cohort at Cleveland Clinic. We also compared the test's performance to Decipher, an established genomic risk classifier. Methods: We conducted a retrospective PATHOMIQ_PRAD analysis of CaP WSIs of patients who underwent prostatectomy at Cleveland Clinic from 2009-2022 and did not receive any adjuvant therapy before BCR. 263 patients in the cohort received definitive treatment with radical prostatectomy and had a median follow-up of 50 months. Of these patients, 65 patients had BCR, and 14 patients developed DM as of last follow up. WSIs were de-identified, anonymized, and patient outcomes were blinded during the study. Patients were stratified into high-risk and low-risk categories based on pre-determined thresholds for PATHOMIQ_PRAD scores (0.45 for BCR and 0.55 for DM). The Kaplan-Meier method with log-rank was used to compare biochemical recurrence-free survival (BCRFS) and metastasis-free survival (MFS). Multivariable Cox proportional hazards regression was used to identify factors associated with BCR. Results: The rate of BCRFS and MFS were associated with both PATHOMIQ_PRAD score (BCR: >0.45 vs. <0.45, p<0.0001; DM: >0.55 vs. <0.55, p<0.0001) and Decipher score (BCR: >0.6 vs. <0.6, p=0.0009; DM: >0.6 vs. <0.6, p=0.0095). All 14 patients who had DM during the follow up time had a high PATHOMIQ_PRAD score. Univariate analysis shows that PATHOMIQ_PRAD reliably identifies patients at risk of BCR (HR: 4.19, p< 0.0001), and had comparable prognostic performance to Decipher (HR: 2.83, p=0.0013). Multivariate analysis (Table) shows that there was an increased risk of BCR in both the high-risk PATHOMIQ_PRAD (HR: 3.58, p=0.0005) and Decipher (HR: 2.20, p=0.0159) groups relative to the low-risk groups, which suggests that combining the two tests may further improve risk stratification. Conclusions: These results show that PATHOMIQ_PRAD continues to demonstrate clinical validity in predicting risk of BCR and DM with favorable performance compared to a commonly used genomic classifier. PATHOMIQ_PRAD may identify patients for early treatment intensification, as well as inform clinical trial patient selection. [Table: see text]
Nimotuzumab plus concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma: The randomized, phase 3 CC3 study.
Authors: Wang Jun jie , Jiang Ping , Qu Ang , Wei Lichun , Zou Lijuan , Li Xiaofan , Wang Chunyan , Sun Xiaoge , Ding Li , Yuan Xiangkun , Cheng Huijun , Wu Dehua , Cai Rong , Yin Rutie , Zhang Jidong , Qiu Hui , Wang Tiejun , Gao Kun , Zhuo Yanhong , Zhang Yun Yan 
Published: June 2024

5514 Background: Cervical cancer is the fourth common malignancy in women, with a 5-year overall survival rate of 24%-76.1%. At present, there are few studies on targeted drugs combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) and the survival results were not satisfactory. This CC3 study is the first randomized, controlled, multicenter phase 3 trial of EGFR combined with CCRT for advanced cervical cancer, aims to evaluate the efficacy and safety of nimotuzumab (humanized EGFR) in combination with CCRT for LACC. (NCT04678791). Methods: All patients with locally advanced cervical squamous cell carcinoma were randomized (1:1) to receive nimotuzumab (400mg, iv, weekly, for 6 weeks) combined with CCRT (cisplatin: 40 mg/m2, weekly, for 6 weeks; IMRT/VMAT: 45-50.4 Gy/25-28f; high-dose rate brachytherapy: 30-40 Gy, in 8 weeks) or CCRT alone. The primary endpoint was 3-year progression free survival (PFS) per RECIST 1.1. The secondary endpoints were 3-year overall survival (OS), objective response rate (ORR), complete response (CR) rate per RECIST v1.1, and safety per CTCAE v5.0. Results: Totally 286 patients were enrolled. 142 patients in the Nimo group (nimotuzumab combined with CCRT) and 144 in the CCRT group (CCRT alone). The baseline characteristics were balanced between the two groups. The 1-year PFS rate of the Nimo group was longer than that of CCRT group (96.1% vs. 92.1%, P=0.506). There was no significant difference in the risk ratio between the two groups (HR=0.76, 95% CI: 0.33-1.72, P=0.507), the 3-year PFS and 3-year OS were not reached. A total of 62 (43.99%) patients achieved partial response (PR) and 57 (40.14%) achieved CR in the Nimo group, 50 (34.72%) and 57 (39.58%) in the CCRT group, respectively. The ORR was 83.80% vs. 74.31% (P=0.049). The most common AEs were graded 1-2 as reported before. Follow-up is ongoing. Conclusions: Nimotuzumab combined with CCRT showed significant ORR improvement, longer trend in PFS and good safety in the treatment of LACC patients. Clinical trial information: NCT04678791 . [Table: see text]
Assessing the risk of uterine serous carcinoma in survivors of triple-negative breast cancer: Is BRCA1 the link?
Authors: Manning William , Li Siguo , Bregar Amy , Gockley Allison Ann , Clapp Mark C. , Wilke Roni Nitecki , Dioun Shayan , Rauh-Hain Jose Alejandro , Melamed Alexander 
Published: June 2024

5602 Background: Uterine serous carcinoma (USC) is a rare and deadly form of endometrial cancer. It is unclear whether BRCA1 pathogenic variants (PV) are associated with an increased risk of USC. Because patients with triple-negative breast cancer (TNBC) have a high prevalence of BRCA1 PV, we hypothesize that if BRCA1 PV are causally related to the development of USC, survivors of TNBC would be at an increased risk of subsequent USC. This cohort study compares USC incidence rates in TNBC survivors with population-based controls. We estimate the magnitude of the association between BRCA1PV and USC that must exist if the excess risk of USC among TNBC survivors is attributable to differences in the prevalence of BRCA1 PV between TNBC survivors and controls. Methods: Using the Surveillance, Epidemiology, and End Results 17 registry data, we identified patients with TNBC diagnosed between Jan 2010 and Dec 2020 and population-based controls. Due to limited data on BRCA1 PV prevalence among non-white TNBC survivors, we restricted this analysis to White women. We estimated the probability of having a BRCA1 PV based on reported age-based prevalence for the general population and cohorts of patients with TNBC. We fit Poisson regression models to estimate age-specific incidence rates and age-adjusted relative risk of USC among TNBC survivors compared with controls and to estimate the relative risk of USC among BRCA1 PV carriers. Results: We identified 48,082 patients with TNBC accounting for 202,074 person-years. The median age at diagnosis was 61 years. The control population contributed 215,813,524 person-years of follow-up. There were 19 incident diagnoses of USC among TNBC survivors and 8,056 among controls, corresponding to crude rates of 9.4 and 3.7 cases per 100,000 person-years, respectively (Figure). After adjusting for age, TNBC survivors had a 59% increase in rate of developing USC (incidence rate ratio 1.59; 95% CI 1.02 to 2.50) compared to controls. We attributed the excess risk of USC among TNBC survivors to differences in BRCA1 PV prevalence. Given this, we estimated that BRCA1 PV was associated with an approximately 30-fold increase in the incidence of TNBC (95% CI 1.1 to 790). Conclusions: Survivors of TNBC, a population with a high prevalence of BRCA1 mutations, are at increased risk of USC compared with population-matched controls. This observation is concordant with an association between pathologic BRCA1 mutations and USC.
Exploring genetic ancestry and tumor mutation profiles in renal clear cell carcinoma: A comprehensive analysis using The Cancer Genetic Ancestry Atlas.
Authors: Lee Michelle J , Vemuru Shalini , Rhee Christopher H , Moses Marcus , Patel Deven , Nazha Bassel , Bilen Mehmet Asim , Brown Jacqueline T 
Published: June 2024

e16512 Background: Addressing health disparities in renal cell carcinoma (RCC) has been an enduring challenge globally, with notable variations in incidence and outcomes among different racial groups. Genomic ancestry serves as a valuable tool in capturing biological variations among diverse populations and offers insights into clinical, histopathological, and molecular distinctions. We utilized The Cancer Genetic Ancestry Atlas (TCGAA) to investigate tumor mutation profiles of RCC with focus on the influence of genetic ancestry on the intricate genomic landscape of this malignancy. Methods: Genomic and clinical data of TCGA PanCancer Atlas KIRC were downloaded through the GDC Data Portal. We utilized The Cancer Genome Ancestry Atlas (TCGAA) and the STRUCTURE algorithm for estimation of genetic ancestry. Primary ancestry was specified as comprising greater than or equal to 50% of genetic ancestry from a single reference population. Statistical analyses were performed using chi-square, Cox proportional hazards models, and Kaplan-Meier methods. Results: 64.5% were male and 41% were locally advanced or metastatic (stage III-IV). Genomic analysis revealed 438 individuals with European ancestry (mean European ancestry of 95.78%), 50 patients with African ancestry (mean African ancestry of 77.7%), and 8 patients with Asian ancestry (mean Asian ancestry of 92.5%). The mean age of patients was 61.0, 58.5, and 49.5 for the European, African, and Asian ancestry groups, respectively. African ancestry correlated with a trend towards reduced overall survival (OS) compared to European ancestry (median OS 62.89 vs 90.48 months). African ancestry patients harbored lower frequency of VHL and PBRM1 alterations, but with significant enrichment in MTOR, FREM2, UNC80, LRP2 alterations compared with European ancestry group. Conclusions: This study reveals genetic heterogeneity in RCC across diverse ancestry groups, indicating presence of distinct oncogenic genes and pathways in African American populations.These findings suggest potential contributions to racial disparities in clinical presentation, outcomes, and treatment responses. Future research should include exploring the role of genetic ancestry in tumorigenesis and disease progression, alongside developing targeted therapies to mitigate health inequities and enhance outcomes for all populations. [Table: see text]
The prognostic value of Meet-URO score in patients with metastatic clear cell renal cell carcinoma receiving second or third-line tyrosine kinase inhibitors/immune checkpoint inhibitors combination therapy: A real-world study.
Authors: He Sike , Liu Haoyang , Chen Junru , Sun Guangxi , Liu Zhenhua , Zeng Hao 
Published: June 2024

e16516 Background: A novel prognostic predictive model based on inflammatory indices and clinical factors; Meet-URO Score has been validated in patients with metastatic clear cell renal cell carcinoma (mccRCC) receiving immunotherapy. Here we investigate its prognostic value in Clear Cell Renal Cell Carcinoma (ccRCC) patients receiving second and third-line tyrosine kinase inhibitors-immune checkpoint inhibitors (TKIs-IOs) combination treatment. Methods: Baseline and follow up data from patients with mccRCC were obtained retrospectively from a single institution. Neutrophil-to-lymphocyte ratio (NLR), the International Metastatic RCC Database Consortium (IMDC) score and bone metastases were assessed before treatment. The primary outcomes were overall survival (OS). Harrell’s c-index was estimated to compare the accuracy of the prediction ability of the two models and Cox proportional hazard-regression model was used for univariable and multivariable analyses. Results: A total or 72 patients received TKIs-IOs combination treatment as second- and third-line therapy (88.89% and 11.11%) were included in this study. A significant shorter median overall survival (mOS) was observed in the IMDC poor risk group. Applying Meet-URO score, four groups were found and stratified (p=0.0016). The c-index in Meet-URO was higher than in IMDC (0.676 vs 0.585) and indicated that Meet-URO score had a higher discriminative ability than the IMDC score. In the Cox regression model, nephrectomy was found to be a protective factor (HR=0.21, 95% confidence interval: 0.05 - 0.93, p=0.04). Conclusions: Meet-URO score presents more accurate prognostic stratification than the IMDC score in mccRCC patients receiving TKIs-IOs combination treatment as second or further line therapy. More research is necessary to validate these findings in the future.