bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partitioned overall survival: Comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma (aRCC).
Authors: Mantia Charlene , Jegede Opeyemi , Viray Hollis , Atkins Michael B. , Rosenblatt Lisa , Yin Xin , McDermott David F. , Regan Meredith M. 
Published: June 2024

4507 Background: Immunotherapy regimens can be associated with prolonged disease control after treatment discontinuation without the need for further anticancer therapy. An integrated, comprehensive partitioned survival analysis describes how patients spend overall survival (OS) time, on/off treatment, with/without toxicity. Previous analysis of first-line (1L) nivolumab (NIVO) + ipilimumab (IPI) for aRCC in CheckMate 214 showed treatment-free survival (TFS) twice as long vs sunitinib (SUN). TFS and survival states for immune checkpoint inhibitor plus tyrosine kinase inhibitor (TKI) combination are of interest. Methods: Overall, 651 patients (pts) with aRCC were randomized to receive 1L NIVO + cabozantinib (CABO) or SUN in the CheckMate 9ER trial; treatment continued until progression or intolerance, NIVO for at most 24 months. Minimum follow-up was 4 years. We partitioned area under the Kaplan–Meier (KM) OS curve into 3 survival states, defined from randomization: time on 1L protocol therapy, TFS, and survival after subsequent systemic therapy (second line [2L]) initiation. TFS and protocol therapy were subdivided as mean times with/without reported grade 2+ treatment-related adverse events (TRAEs). Areas under and between KM curves were estimated by 48-month restricted mean times to event. Bootstrapped 95% CIs for between-group differences are reported. Results: At 4 years post randomization, KM estimates of OS were 49.2% vs 40.2% of pts assigned to NIVO+CABO vs SUN, respectively; 17.6% vs 4.7% of pts were surviving treatment-free, and 15.8% vs 8.2% were continuing on 1L protocol therapy. Over the 48-month period since randomization (Table), the mean TFS (95% CI) was 2.4 (0.8–3.9) months longer after treatment with NIVO+CABO than SUN. At least half of TFS was spent with toxicity in both treatment groups, resulting in difference in mean TFS (95% CI) without toxicity of 0.7 (−0.4 to 1.8) month. The NIVO+CABO group spent a mean (95% CI) of 8.5 (6.2–10.8) months more survival time on 1L protocol therapy, whereas the SUN group spent a mean (95% CI) of 6.5 (4.4–8.6) months more survival time after 2L therapy initiation. Conclusions: Over the 4-year period since initiation of 1L therapy for aRCC, the longer OS achieved with NIVO+CABO was accompanied by 1.5 times longer mean time surviving treatment-free before 2L therapy compared with SUN, a smaller difference than seen for NIVO + IPI vs SUN. [Table: see text]
A multi-institution analysis of outcomes with first-line systemic therapy for 99 patients with metastatic chromophobe renal cell carcinoma.
Authors: Doshi Sahil D. , Dizman Nazli , Knezevic Andrea , Touma Amina , Alaghehbandan Reza , Ged Yasser , Ornstein Moshe Chaim , Hahn Andrew Warren , Msaouel Pavlos , Voss Martin H 
Published: June 2024

4512 Background: Chromophobe renal cell carcinoma (ChRCC) represents ~5-10% of all RCCs. Given its rarity, there is limited clinical trial data to guide systemic therapy for metastatic disease. Phase 2 trials have demonstrated that targeted agents inhibiting vascular endothelial growth factor receptor and mammalian target of rapamycin have similar efficacy in ChRCC compared to conventional RCC. However, immune checkpoint inhibitor (IO) containing regimens appear less efficacious compared to other RCC subtypes. Importantly, these efforts have all enrolled < 30 ChRCC patients, and larger scale studies are needed. Methods: We conducted a retrospective study of patients with metastatic ChRCC seen at 3 academic centers. Baseline characteristics and treatment outcomes were obtained from EHR review. Patients were categorized into 4 treatment categories: 1) IO + targeted therapy doublets (e.g., lenvatinib plus pembrolizumab) 2) Pure IO monotherapy and doublets (e.g., ipilimumab plus nivolumab) 3) targeted therapy doublets (e.g., lenvatinib plus everolimus) and 4) targeted monotherapy (e.g., sunitinib). We calculated time to treatment failure (TTF) of first-line systemic therapy and overall survival (OS) by the Kaplan-Meier method. Median time-to-event was reported for each treatment category and categories compared with the log-rank test. Results: Ninety-nine patients with metastatic ChRCC treated with first-line systemic therapy were included; 62% were male, 44% had sarcomatoid features, and 33% had IMDC favorable risk. Outcomes with TTF and OS are summarized in the table below. Median TTF and 18-month OS rates were 5 months and 58% for the targeted monotherapy group, 15 months and 80% for the IO/targeted doublet group, 17 months and 65% for the targeted doublet group, and 7 months and 83% for the pure IO group. Treatment with any doublet containing a targeted agent compared to targeted monotherapy yielded a superior median TTF (15 vs 5 months, HR 0.48; 95% CI: 0.29, 0.80; p=0.005) and OS (56 vs 23 months, HR 0.56; 95% CI: 0.30, 1.04; p=0.07). Most treatment (64%) was discontinued due to progression; 25% due to toxicity. 11 patients had ongoing treatment at time of analysis. Conclusions: In this observational analysis, patients with targeted doublet regimens had a higher median TTF and OS compared to those receiving monotherapies. We continue to build on this dataset and plan to conduct progression free survival analysis. [Table: see text]
Avelumab (A) as neoadjuvant therapy in patients (pts) with muscle-invasive urothelial carcinoma (MIUC): Survival data of AURA trial, Oncodistinct 004.
Authors: Blanc Jeremy , Carnot Aurélien , Barthelemy Philippe , Casert Vinciane , Staudacher Lionel , Van den Brande Jan , Sautois Brieuc , Vanhaudenarde Vincent , Seront Emmanuel , Debien Veronique , Ameye Lieveke , Kotecki Nuria , Fantoni Jean Christophe , Tricard Thibault , Roumeguere Thierry Andre , Awada Ahmad , Martinez Chanza Nieves 
Published: June 2024

4516 Background: Immunotherapy in the perioperative setting of MIUC appears promising. The AURA trial (NCT03674424) investigated the addition of avelumab to neoadjuvant dose-dense MVAC (ddMVAC) or cisplatin-gemcitabine (CG) respectively, followed by surgery in the cisplatin-eligible cohort. The primary endpoint was previously reported with high pathological complete response (pCR) rates with each cisplatin-based regimen. In the cisplatin-ineligible cohort, pts were randomized to neoadjuvant A alone or in combination with paclitaxel-gemcitabine (PG) followed by surgery. Avelumab monotherapy showed encouraging pCR but the addition of PG did not provide any benefit. Here, we report the survival data from cisplatin-eligible and ineligible cohorts of the AURA trial. Methods: In the cisplatin-eligible cohort, 79 pts were randomly assigned to the ddMVAC-A (n=39) or CG-A (n=40) groups. In the cisplatin-ineligible cohort, 58 pts were randomly assigned to the PG-A (n=29) or A (n=29) groups. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method at 12 months and 36 months for the overall cohort and by subgroups. Results: Median follow-up was 33 months and 45 deaths were reported. In the cisplatin-eligible cohort, 12-month DFS was 92% (95% CI, 83-96%) and 36-month DFS was 72% (95% CI, 57-83%). For ddMVAC-A group: 97% and 77%, respectively. For CG-A group: 86% and 68%. Overall, 12-month OS was 89% (95% CI, 80-95%) and 36-month OS was 73% (95% CI, 61-83%). For ddMVAC-A: 95% and 87%. For CG-A: 84% and 61%. Among the ypT0N0 pts, no events were registered within 12 months of follow-up showing a DFS rate of 100% for both arms. At 36 months no events were reported for pts treated with ddMVAC-A and two for CG-A showing DFS rates of 100% and 78% respectively. In the cisplatin-ineligible cohort, 12-month DFS was 60% (95% CI, 46-72%) and 12-month OS was 71% (95% CI, 57-81%). For PG-A: 52% and 67%. For A: 68% and 75%. Among the ypT0N0 pts, no DFS events occurred within 12 months. Data for 36-month are not yet mature. Overall, the main cause of death was disease progression (73%). Conclusions: The addition of neoadjuvant avelumab to cisplatin-based chemotherapy results in a high DFS and OS at 12 and 36 months respectively, especially in pts with complete response to neoadjuvant treatment. Combination with ddMVAC regimen offers robust activity. Cisplatin-ineligible pts had lower survival outcomes with no benefit of PG addition. Clinical trial information: NCT03674424 . [Table: see text]
Association of machine learning (ML)–derived histological features with transcriptomic molecular subtypes in advanced renal cell carcinoma (RCC).
Authors: Beig Niha , Nofallah Shima , McDermott David F. , Motzer Robert J. , Powles Thomas , Rini Brian I. , Koeppen Hartmut , Banchereau Romain , Markey Miles , Finberg Isaac , Singh Geetika , Yu Limin , Egger Robert , Parmar Chintan , Conway Jake , Hennek Stephanie , Ruderman Daniel , Vilchez Samuel , Huseni Mahrukh A , Giltnane Jennifer Margaret 
Published: June 2024

4519 Background: Metastatic RCC (mRCC) is a molecularly heterogeneous disease. Transcriptomic analysis in the Phase 3 IMmotion 151 (Im151) trial identified 7 molecular subtypes that showed differential outcomes to Atezolizumab+Bevacizumab (A+B) vs Sunitinib (S) treatment (Motzer, Cancer Cell 2020). Here, we present histological correlates of these subtypes as identified in whole slide images (WSI) of hematoxylin and eosin (H&E) stained tumors. Methods: ML models identified 922 H&E derived, human interpretable histological features (ML HIFs) in RCC associated with tumor and stromal (including vessels, immune cells, fibroblasts) cell and tissue morphologies, and nucleus shape. These ML HIFs were then extracted from WSI in 2 mRCC trials – Im151 (n=797) and IMmotion150 (Im150, n=203). Previously described 7 molecular subtypes were combined into 4 subgroups (Angiogenic [comprised of Angiogenic/Stromal and Angiogenic], Complement/OmegaOxidation, T-effector, and Proliferative [comprised of Proliferative and Stromal Proliferative]) for computational power. Due to low prevalence, snoRNA subset was excluded. Univariate analysis with FDR correction was applied to identify positively associated ML HIFs in each of the 4 subgroups in the Im151 WSI and then validated in Im150 subgroups. Representative ML HIFs that showed uniquely higher abundance in each molecular subgroup in both studies were dichotomized by tertiles as ‘high’ or ‘low/intermediate’ and associated with progression free survival (PFS) to fit Cox proportional hazard models in Im151 study. Results: 169 ML HIFs were differentially enriched across 3 molecular subgroups in both Im151 and Im150 data sets. Angiogenic subgroup had higher prevalence of 40 ML HIFs associated with density of endothelial cells in cancer epithelium. T-effector subtype showed higher abundance of 64 ML HIFs associated with immune cell presence in stroma. Proliferative subgroup showed higher prevalence of 40 ML HIFs associated with nuclear morphologies. No ML HIFs were uniquely associated with the Complement/OmegaOxidation subgroup. Consistent with transcriptional findings in Im151, ML HIFs that were enriched in T-effector and Proliferative subgroups showed improved PFS benefit to A+B vs S (Table). Conclusions: We identified unique histological features of RCC tumors that correlate with previously defined molecular subtypes. Our results suggest that clinically relevant RCC subtypes may be extracted directly from H&E-stained WSI and may complement gene expression based patient stratification and selection strategies. [Table: see text]
Clinical utility of transcriptomic signatures to identify androgen receptor and neuroendocrine signaling in prostate cancer.
Authors: Chen Yu-Wei , Xiu Joanne , Poorman Kelsey Anne , Ryan Charles J. , Gilg Brady , Oberley Matthew James , Sledge George W. , Beltran Himisha , McKay Rana R. 
Published: June 2024

5015 Background: Neuroendocrine prostate cancer (NEPC) is a relatively androgen receptor (AR)-independent and aggressive variant of PC that can arise from adenocarcinoma with varied degrees of adenocarcinoma and high-grade neuroendocrine histologic features seen during its progression. This study evaluated the clinical and molecular features of histologic subtypes of prostate tumors (adenocarcinoma, NEPC, mixed adeno-NE) based on previously validated AR signaling and NEPC transcriptomic signatures of PC. Methods: Whole exome (WES) and whole transcriptome sequencing (WTS) were performed on PC tumors. Molecular subsets were defined by AR signaling signature [AR score positive (+) vs negative (-)] and NEPC gene signature [NE score positive (+) vs negative (-)]. The prevalence of key molecular alterations (RB1, TP53, PTEN, AR, FANC, SLFN11 expression) were investigated. Genes encoding cell surface antigens with potential therapeutic implications were described across signature groups. Overall survival (OS) was obtained from claims data and analyzed with Kaplan-Meier estimator. Results: A total of 4,476 prostate tumors were analyzed in this study including: 3,623 prostate adenocarcinoma, 56 NEPC, and 25 tumors with mixed adeno-NE. Tissue from 2,641 (67%) tumors were collected from prostate and 1,326 (33%) were metastatic tumors [lymph node (14%), bone (9%), liver (7%), lung (2%), CNS (2%)]. The four AR/NEPC signature-defined subtypes were AR+/NE+ (N=649, 14%), AR+/NE- (N=1614, 36%), AR-/NE+ (N=875, 20%), and AR-/NE- (N=1358, 30%). AR+/NE- was most common in prostate (39%), LN (42%) and lung metastasis (35%); AR-/NE+ was most common in bone (34%) and liver metastasis (43%); AR-/NE- was most common in CNS metastasis. The most common gene alterations in each molecular subtype are defined in Table. AR-/NE+ tumors had the lowest mRNA expression of FOLH1(PSMA), STEAP1, TACSTD2 (Trop-2), CD276 (B7-H3), and PSCA among the four groups. DLL3 expression was higher among NE+ subtypes. FOLH1 and PSCA expression were higher among NE- subtypes. The median OS (months) was longer in NE- than NE+ subtypes [AR+/NE- (78.3), AR-/NE- (78.7) vs AR+/NE+ (70.7), AR-/NE+ (69.1)]. In the platinum-treated subgroup (N=146), the median OS was numerically longer among tumors with SLFN11 overexpression (17.6 vs 12.0) although this was not statistically significant (p-value: 0.99). Conclusions: Molecularly distinct subtypes of PC can be further characterized by AR signaling signature, NEPC gene expression signature, and co-occurring molecular alterations. The phase II biomarker-driven PREDICT trial will integrate the above signatures/molecular alterations to allocate treatment regimens in metastatic castration-resistant PC. [Table: see text]
PHAROS, a real-world multi-country European study on patients with high-risk localised and locally advanced prostate cancer receiving radical treatment.
Authors: Eiber Matthias , Aebersold Daniel M. , Valcarcel diaz Alfonso , Wetterauer Christian , Bach Michael , Camarrone Flavio , Herkommer Kathleen , Li Honghao , Campos Fernando Lopez , Mathieu Thomas , Olivier Jonathan , Pissart Geneviève , Robinson Paul , Shelan Mohamed , Stitou Hind , Thiriez Céline , Touzot Maxime , Villers Arnauld 
Published: June 2024

5027 Background: Primary radical therapy with curative intent is standard of care for patients diagnosed with high risk (HR) localised (LPC) and locally advanced prostate cancer (LAPC). However, many patients relapse and detailed epidemiological data on natural history, routine management, and clinical outcomes in this setting are sparse. We aimed to explore real world data (RWD) to gain insights into the understanding of the disease pathway. Methods: PHAROS is a retrospective, observational study conducted in five academic centres across four European countries from 1989 to 2022 (France, Germany, Switzerland, Spain). All patients with HR LPC and LAPC, according to EAU guidelines, and treated by primary radical prostatectomy (RP) or radiotherapy (RT) (alone or with ADT) were eligible. Data were structured and analysed to describe the patient characteristics at the time of radical therapy, subsequent treatment patterns and clinical events including biochemical recurrence (BCR), event-free survival (EFS) [defined by loco-regional relapse, BCR, metastasis or death] and overall survival (OS) that were estimated by Kaplan-Meier method. Results: The table summarizes baseline characteristics and intermediate endpoints for a total of 2303 patients, mostly diagnosed between 2005 and 2020, with a mean follow-up of 6.8 years. RP patients were younger and more likely to be node-positive (N+) as compared to RT patients. EFS at 5 years was 48 % [0.43-0.54] in the RP cohort (N=1539), and 74% [0.66-0.81] in the RT cohort (N=764). At 5 years after radical treatment, 21% of the RP cohort developed distant metastases and rates were higher (30%) in centres with routine access to PSMA PET. The rate was lower (12%) in the RT cohort potentially because of extended hormonal treatment. The principal reported treatment after the first BCR in the RP cohort was salvage RT ±ADT and ADT for the RT cohort. Only 249 and 311 deaths were observed in the RP and RT cohort with an estimated 10-year OS of 73 % [0.66-0.80] and 69% [0.57-0.80], respectively. Conclusions: In this large RWD cohort of HR LPC & LAPC, initial results suggest that a significant proportion of patients fail after primary curative treatment within 5 years, indicating an unmet medical need to improve outcomes. Further analysis of the PHAROS dataset will bring better understanding of the real-world patient pathway in this setting and the role of intermediate endpoints. [Table: see text]
Association between body mass index and physical activity among prostate cancer survivors.
Authors: Haiderbhai Shabbir , Sahmoun Abe Eric 
Published: June 2024

5029 Background: Prostate cancer (PCa) has become a chronic disease due to advances in treatment and earlier detection. Therefore, factors that modify survival post‐diagnosis are important. Obesity is associated with increased PCa recurrence and mortality. Thus, interventions that reduce obesity, e.g., physical activity (PA) may prolong survival. We assessed the association between body mass index (BMI) and PA among prostate cancer survivors as well as other modifiable predictors of PA. Methods: We conducted a cross-sectional analysis of data from the 2018-22 Behavioral Risk Factor Surveillance System, an ongoing national population-based telephone survey conducted in the U.S. The outcome variable is PA after PCa diagnosis. We classified BMI (exposure) using standard cut points defined by the WHO. Multivariable weighted logistic regression was used to examine the association between BMI and PA adjusting for confounders. All significance tests were two-sided and p-value < 0.05 was significant. The data were analyzed accounting for the complex sample survey design. Results: Of the 4,944 prostate cancer respondents, 78% were 65 years or older and 69% were White. 23% were obese class I and 11% were obese class II & III. Obese class I and obese class II & III respondents were significantly less likely to report PA (OR=0.48; 95% CI: 0.28-0.84 and OR=0.37; 95% CI: 0.20-0.67; respectively). Men who received a summary of their cancer treatment were significantly more likely to report PA (OR=1.53; 95% CI: 1.03-2.28). Current smokers were less likely to report PA (OR=0.50; 95% CI: 0.26-0.96). Conclusions: Obese men and current smokers were less likely to report PA. Men who received a summary of their cancer treatment were more likely to report PA. Healthcare providers should talk to their patients about the benefit of exercising and refer patients to available exercise programs. Key words: Prostate Cancer Survivorship; Body Mass Index; BRFSS; Quality of Care, Healthy Behaviors.
Utilization patterns and outcomes of radiotherapy for patients with germ cell tumor relapsing with brain metastases, with a focus on stereotactic radiosurgery.
Authors: Gui Chengcheng , Funt Samuel A , Yu Yao , Zinovoy Melissa , Chen Linda , Yamada Yoshiya , Pike Luke R. G. , Feldman Darren R. , Imber Brandon S. 
Published: June 2024

5032 Background: Brain metastases (BM) from germ cell tumors (GCT) are a poor-prognostic feature. Nonetheless, many patients (pts) relapsing with BM achieve long-term disease control. Radiotherapy (RT) is a key component of GCT BM management, alongside salvage chemotherapy (CT), but minimal data are available to guide its use. Outcomes of stereotactic radiosurgery (SRS) alone, without whole brain RT (WBRT), are seldom reported. We describe treatment patterns and outcomes of pts with GCT who received RT for BM relapse. Methods: Male pts with extracranial GCT who received RT for BM relapse between 2005 and 2023 were included. Four subgroups were defined based on incorporation of RT into the broader BM treatment strategy: RT without concurrent salvage CT (Group 1), RT with salvage conventional-dose CT (CDCT) (Group 2), RT with high-dose CT (HDCT) (Group 3), and salvage RT for progressing BM initially treated with CT alone (Group 4). RT approach included WBRT and SRS. Primary outcomes were overall survival (OS) and intracranial progression (IP) from RT completion. Local progression (LP) after SRS was also assessed. Associations with outcomes were modeled with Cox regression and competing risk regression, accounting for death. Results: Sixty pts were included. Median age at BM diagnosis was 28 years. Median follow-up among those alive was 87 months. At 3 years after RT, OS was 39%, and IP was 44%. Groups 1, 2, 3, and 4 included 20, 17, 13, and 10 pts, respectively. Groups were not significantly associated with other baseline features, including RT approach. Outcomes by Group are reported (Table). OS was not significantly different in any Group. There was a trend for worse IP in Group 4, compared with all other groups (HR 2.2, 95% CI 0.99-5.1, p = 0.05). WBRT and SRS alone were used in 32 and 27 pts, respectively. RT approach was not significantly associated with other baseline features. Outcomes by RT approach are reported (Table). OS and IP were not significantly different. Among 53 BM treated with SRS, LP was 8% at 3 years. Among 27 pts treated with SRS, ≥ 2 BM (13 pts) predicted increased risk of death (HR 4.9, 95% CI 1.5-16, p = 0.01) and IP (HR 3.6, 95% CI 1.2-11, p = 0.02). This was not observed after WBRT. Conclusions: We found heterogeneous patterns of RT use for BM relapse: RT alone, RT with CDCT, RT with HDCT, and salvage RT after initial CT alone. Long-term survival and intracranial control are achievable with each strategy and with both WBRT and SRS. This analysis includes the largest reported series of GCT BM treated with SRS; local control after SRS is excellent, but caution is advised for pts with multiple BM, given elevated risk of IP and death. [Table: see text]