bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploratory analysis of predictive biomarkers for immune-related adverse events (irAEs) due to checkpoint inhibitors (CPIs) in patients with genitourinary (GU) cancers.
Authors: Vosoughi Elham , Kaakour Dalia , Chen Wen-Pin , Mar Nataliya 
Published: March 2023

569 Background: CPIs targeting PD-1/PD-L1 and CTLA-4 have transformed management of GU cancers. These agents are associated with a unique type of immune-mediated toxicities that may affect any organ, which may be severe or life-threatening. Development of irAEs may in part depend on type of CPI used, type of solid tumor, and individual patient factors including presence of subclinical inflammatory states. However, distinct biomarkers predictive of irAE development are poorly defined. This study aimed to examine possible associations between tumor mutation burden (TMB) and PD-L1 expression with occurrence of irAEs. Methods: A retrospective chart review was performed of all patients with urothelial carcinoma (UC) and renal cell carcinoma (RCC), who received therapy with CPIs from 1/2019 to 9/2022 at our institution and developed associated irAEs. Severe irAEs were defined as those necessitating initiation of immunosuppressive therapies or other supportive therapies. TMB and PDL-1 expression patterns were analyzed, if available. Given lack of standardized cutoffs for PD-L1 positivity across different GU cancer types, tumors were considered positive if a combined positive score of greater than 10 was present in UC or a total positive score of greater than 1% was present in RCC. Results: A total of 60 patients were included in this analysis - 33 with UC and 27 with RCC. Severe irAEs occurred in 19 patients with UC and 25 patients with RCC. Median TMB was 8.7 in patients with UC, while it was 2.5 in patients with RCC. PD-L1 positivity was seen in 39.3% (13/33) of UC patients and 40.7% (11/27) of RCC patients. In the UC cohort, 57.8% (11/19) had severe irAEs and TMB less than 10, while 36.8% (7/19) had severe irAEs and TMB greater than 10. Further, 47.3% (9/19) of UC patients had severe irAEs and positive PD-L1, while 42.1% (8/19) had severe irAEs and negative PD-L1. In the RCC cohort, 88% (22/25) had severe irAEs and TMB less than 10, while 8% (2/25) had severe irAEs and TMB greater than 10. Additionally, 40% (10/25) RCC patients had severe irAEs and positive PD-L1, while 56% (14/25) had severe irAEs and negative PD-L1. The incidence of TERT promoter mutations and TMB is noted in the table. Conclusions: Identification of predictive biomarkers of irAEs from CPIs is a major area of need in GU malignancies. Definitive conclusions from this dataset are limited by its small sample size. Interestingly, there appear to be differences in baseline expression of traditional immune biomarkers between UC and RCC, with lower prevalence of TMB greater than 10 and positive PD-L1 noted in the RCC cohort. As such, their utility when making treatment decisions in clinical practice may be of limited value. [Table: see text]
Penile cancer: 20 years of experience in a reference oncology center in Mexico.
Authors: Rodriguez Rosales Yuridia Evangelina , Guerra Cepeda Abraham , Najera Rubi Janday , Rivera Valdés Francisco Daniel , Hernandez Barajas David , Vidal-Gutiérrez Oscar , Zayas-Villanueva Omar Alejandro 
Published: March 2023

6 Background: Penile cancer is a rare neoplasm (<1%), being more common in underdeveloped countries, 10-20% of male neoplasms, with a mean age at diagnosis of 60 years. The number of annual cases in Mexico is only 660 cases, 0.35% of all neoplasms. Its initial symptomatology as a palpable or ulcerated lesion must be differentiated from infectious processes. From 30 to 60% of cases debut with inguinal lymphadenopathies and distant metastases in 1 to 10%. Methods: Cross-sectional, retrospective cohort study of patients diagnosed with penile cancer, who received medical care at the medical oncology service of the University Cancer Center from January 1, 1999 to December 31, 2019. Results: Of the 103 patients analyzed in this study, the mean age was 55 years (27-91 years), the highest level of schooling obtained was primary in 18.5%, being mostly from the state of Nuevo León in 61.1%. of the cases. The duration of symptoms was 17 months on average, and the time interval between diagnosis and receiving medical or surgical treatment was 97 days. Regarding the pathological characteristics of penile cancer, the average tumor size was 41.4mm, the most frequent histological type was squamous in 91.3%. Regarding the classification by clinical stages, patients in clinical stage I was 8%, II 10.6%, III 26.2% and IV 32%, not being recorded accurately in 23.3% of cases. The initial medical treatment was surgical in 81.5% of the cases, with partial phallectomy being the procedure of choice in 57.2% of the patients, with the presence of positive margins in 9.5% of the patients. Lymph node involvement was 71.2% of the cases and lymph node dissection was only performed in 31% of the patients. Those who received chemotherapy were 27.1% of the patients, the majority, 57.1% in the adjuvant setting, the most commonly used scheme was cisplatin with 5-fluoroacyl in 60.7%. Radiotherapy was used in 25.2% of the patients, being the adjuvant modality in 65.4% and in the palliative context in 34.6%, with an average dose of 46.5 Gy and 8 fractions. Conclusions: A diagnosis at an earlier age was observed in our court, being 55 years old vs 60 years old reported in the literature. A delay in diagnosis of up to 12 months has been reported in 15-50% in the literature, being higher in our population with a mean of 17.7 months. Poor adherence to treatment and clinical follow-up was observed, since one in 4 patients only goes to oncology once and loses follow-up. Penile cancer is a rare, psychologically devastating neoplasm with delayed diagnosis, advanced clinical disease, decreased survival, and high recurrence rates despite bimodal or trimodal treatment. A multidisciplinary team approach should be sought to achieve better oncological results and timely detection of cancer in earlier stages.
Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 CheckMate 9ER trial.
Authors: Burotto Mauricio , Powles Thomas , Escudier Bernard , Apolo Andrea B. , Bourlon Maria Teresa , Shah Amishi Yogesh , Suárez Cristina , Porta Camillo , Barrios Carlos H. , Richardet Martin , Gurney Howard , Kessler Elizabeth R , Tomita Yoshihiko , Bedke Jens , George Saby , Scheffold Christian , Wang Peter , Fedorov Viktor , Motzer Robert J. , Choueiri Toni K. 
Published: March 2023

603 Background: First-line nivolumab plus cabozantinib (N+C) demonstrated superiority over sunitinib (S) with 25.4 mo minimum follow-up (median, 32.9 mo) in patients (pts) with aRCC in the CheckMate 9ER trial. Here, we report survival, response per blinded independent central review (BICR), and safety after 3 y minimum follow-up in all randomized pts and by IMDC risk score. Methods: Pts were randomized 1:1 (stratified by IMDC risk score, tumor PD-L1 expression, region) to N 240 mg flat dose IV Q2W + C 40 mg PO QD vs SUN 50 mg PO for 4 wk (6-wk cycles) until disease progression or unacceptable toxicity (max N treatment, 2 y). Primary endpoint: progression-free survival (PFS) by BICR. Secondary endpoints: overall survival (OS), objective response rate (ORR) by BICR, and safety. Results: In total, 323 pts were randomized to N+C and 328 to S. With 36.5 mo minimum follow-up (median, 44.0 mo), PFS and OS benefits were maintained with N+C vs S in intent-to-treat pts. Median PFS was 16.6 vs 8.4 mo (HR 0.59 [95% CI 0.49–0.71], P < 0.0001) and median OS was 49.5 vs 35.5 mo (HR 0.70 [95% CI 0.56–0.87], P = 0.0014). ORR (95% CI) was higher with N+C vs S (56% [50–62] vs 28% [23–33]), and 13% vs 5% of pts achieved complete response (CR), respectively. Median duration of response was 22.1 vs 16.1 mo for N+C vs S. PFS, OS, and response are reported across prespecified IMDC risk groups in the table. Any-grade treatment-related adverse events (TRAEs) occurred in 97% vs 93% of pts treated with N+C vs S (grade ≥ 3 TRAE, 67% vs 55%). TRAEs led to discontinuation of C only in 10% of pts, N only in 10% of pts, N+C in 7% of pts, N or C in 28% of pts, and S in 11% of pts. Conclusions: After 3 y minimum follow-up, survival and response benefits were maintained with N+C and remained consistent with previous follow-ups. Median OS with N+C improved by 11.8 mo since the previous data cut. Responses with N+C were durable, with higher CR rates with N+C vs S regardless of IMDC risk group. No new safety signals emerged with additional follow-up in either arm. These results continue to support N+C as a first-line treatment for pts with aRCC. Clinical trial information: NCT03141177 . [Table: see text]
Outcomes by IMDC risk in the COSMIC-313 phase 3 trial evaluating cabozantinib (C) plus nivolumab (N) and ipilimumab (I) in first-line advanced RCC (aRCC) of IMDC intermediate or poor risk.
Authors: Powles Thomas , Motzer Robert J. , Albiges Laurence , Suárez Cristina , Schutz Fabio A. B. , Heng Daniel Yick Chin , Chevreau Christine , Kanesvaran Ravindran , Gurney Howard , Wang Fong , Mataveli Fabio , Chang Yu-Lin , van Kooten Losio Maximiliano , Choueiri Toni K. 
Published: March 2023

605 Background: In COSMIC-313 (NCT03937219), C+N+I significantly improved progression-free survival (PFS) compared with N+I in first-line aRCC of IMDC intermediate or poor risk (Choueiri ESMO 2022). Here, outcomes are analyzed by IMDC risk group. Methods: A total of 855 patients (pts) with clear cell aRCC of IMDC intermediate or poor risk were randomized to receive C 40 mg QD or matched placebo (P), stratified by region and IMDC risk. Both treatment groups received N (3 mg/kg IV Q3W) + I (1 mg/kg IV Q3W) for 4 cycles followed by N (480 mg IV Q4W); N was administered for up to 2 years. The primary endpoint was PFS by blinded independent radiology review (BIRC) per RECIST 1.1 in the first 550 randomized pts (PITT population). The secondary endpoint was overall survival (OS) in all randomized pts; objective response rate (ORR) and safety were additional endpoints. Results: Overall, 75% of pts were IMDC intermediate and 25% were poor risk. Meaningful differences in baseline characteristics for intermediate vs poor risk in the PITT population were observed for KPS ≥90 (67% vs 47%), prior nephrectomy (71% vs 44%), and ≥2 target/non-target lesions per BIRC (68% vs 83%); characteristics were balanced across treatment arms for intermediate risk but some imbalances were seen for poor risk (42% for C+N+I vs 52% for P+N+I had KPS ≥90 and 37% vs 50% had prior nephrectomy). In intermediate risk pts, PFS was improved with C+N+I (HR 0.63, 95% CI 0.47–0.85), and ORR and DCR (PITT population) were numerically higher (Table). For poor risk pts, no difference in PFS and ORR was apparent, but DCR was numerically higher with C+N+I. PD as best response was lower with C+N+I vs P+N+I in both risk groups. Duration of response was not reached (NR) in each treatment group. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 74% with C+N+I vs 42% with P+N+I for intermediate risk and 67% vs 38% for poor risk. TRAEs led to discontinuation of all treatment components in 14% vs 5% for intermediate risk and 5% vs 4% for poor risk. Additional analyses relevant to IMDC risk group will be presented. Conclusions: In COSMIC-313, C+N+I improved PFS vs P+N+I in first-line aRCC of IMDC intermediate or poor risk; subgroup analysis suggested that the benefit was primarily in intermediate risk pts. Follow-up for OS is ongoing. Clinical trial information: NCT03937219 . [Table: see text]
CaboPoint: Interim results from a phase 2 study of cabozantinib after checkpoint inhibitor (CPI) therapy in patients with advanced renal cell carcinoma (RCC).
Authors: Albiges Laurence , Powles Thomas , Sharma Anand , Venugopal Balaji , Bedke Jens , Dutailly Pascale , Qvick Bryan , Martin-Couce Lidia , Perrot Valérie , Grünwald Viktor 
Published: March 2023

606 Background: First line CPI-based therapy is the standard of care for advanced RCC. There is a lack of prospective data for cabozantinib after 1L CPI regimens, which is addressed in this study. Methods: CaboPoint (ClinicalTrials.gov identifier: NCT03945773) is an ongoing Phase 2, multicenter, open-label study of cabozantinib in adults with unresectable, locally advanced, or metastatic clear cell RCC who have progressed after 1L CPI-based therapy. Prior treatment with cabozantinib was not permitted. Patients received cabozantinib in two independent cohorts (cohort A [post nivolumab + ipilimumab] and cohort B [post CPI + vascular endothelial growth factor targeted therapy]). Both cohorts received cabozantinib (60 mg/day as starting dose) until study end (18 months after last patient’s enrollment). The primary endpoint was objective response rate (ORR) in Cohort A per RECIST 1.1 evaluated by independent central review; ORR by investigator review has been included as a secondary endpoint for both cohorts. Here we report results from the pre-planned interim analysis of ORR based on investigator assessment in both cohorts that occurred when 80% of patients in cohort A reached at least 3 months of treatment. Results: At the time of this interim analysis, 88 patients had 3 months of follow up (60 in cohort A and 28 in cohort B). Baseline characteristics were similar across cohorts. Patients had an Eastern Cooperative Oncology Group status of 0 (55.0% / 60.7%) and an intermediate or poor International Metastatic RCC Database Consortium risk (46.3% and 13.0% / 40.7% and 11.1%). The most common prior treatment in cohort B was pembrolizumab + axitinib (71.4%), followed by avelumab + axitinib (28.6%). ORR and best overall response at three months of follow-up as assessed by the Investigator are shown in the table. Conclusions: In this interim analysis, cabozantinib demonstrated preliminary efficacy in patients with advanced RCC after progression on CPI-based combination therapy, irrespective of 1L regimen. The CaboPoint trial is ongoing, with the final analysis anticipated in September 2023. Clinical trial information: NCT03945773 . [Table: see text]
Implications of ethnicity among patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (nivo/ipi).
Authors: Leong Sally , Ali Sana , Zengin Zeynep Busra , Meza Luis A , Dizman Nazli , Ebrahimi Hedyeh , Govindarajan Ameish , Castro Daniela V. , Li Xiaochen , Kim Tane , Melamed Sam , Onyshchenko Mykola , Pal Sumanta Monty , Chehrazi-Raffle Alex 
Published: March 2023

613 Background: Existing literature has reported differences in clinical outcomes by ethnicity in patients receiving immune checkpoint inhibitors (Olsen et al Front Oncol 2021). We investigated real-world outcomes between Latinx and non-Latinx mRCC patients treated with first-line nivo/ipi within a safety-net healthcare system and at a tertiary care center in Southern California. Methods: We performed a retrospective analysis of mRCC patients who received nivo/ipi within the Los Angeles County Department of Health Services (DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between Jan. 1, 2015 and Dec. 31, 2021. Patients were identified using institutional databases and clinical data were compiled from electronic health records. Patients with pathologic diagnosis of mRCC, age > 18 years and receipt of nivo/ipi as first-line therapy were included. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards model with adjustments for other covariates. Results: Of 94 patients, 66 (70%) were male, 90 (94%) had clear-cell histology, and 87 (93%) had IMDC intermediate/poor risk disease. Forty patients (43%) were Latinx. Fifty (53%) and 44 (47%) patients received their care at a tertiary care center and within a safety-net healthcare system, respectively. Most Latinx patients (95%) were treated at DHS, and most non-Latinx patients (89%) were treated at COH. Latinx patients were significantly older than non-Latinx patients (59.5 vs 55 years, p=0.008). IMDC risk classification, body mass index, history of nephrectomy, and number of comorbidities were similar between both groups. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs 25.2 months, HR 3.61, 95% CI 1.96-6.66, p= <0.01). Adjusting for age, gender, IMDC risk classification, history of nephrectomy, and number of co-morbidities, multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; p=0.01). At a median follow up of 11.0 months, the median OS was not met in either arm at the time of data cutoff (NR vs. NR, HR 1.34, 95% CI 0.44-4.11). Conclusions: Compared to non-Latinx patients,Latinx patients demonstrated shorter PFS; no difference was observed in OS although these data were immature. As the majority of Latinx patients received their care at DHS, our data suggest that disparities in access to care may significantly contribute to differences in clinical outcomes of mRCC patients receiving nivo/ipi.
Association of primary tumor radiomic phenotypes and outcomes in patients (pts) with metastatic renal cell clear cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CN).
Authors: Cunha Mateus Trinconi , Stangler Lucas , Freire Pedro , Pinto Paulo Victor Alves , Coelho Fernando Morbeck Almeida , Viana Públio , Cordeiro Mauricio , Nahas William Carlos , Mota Jose Mauricio 
Published: March 2023

622 Background: Despite the advances in systemic therapy for mRCC, CN may benefit a subset of pts. We investigated the correlation of clinical outcomes with primary tumor radiomics and radiology measurements of primary and metastatic lesions in mRCC pts treated with CN. Methods: We searched our institutional database for mRCC pts referred for CN from July 2011 to October 2019. Key eligibility criteria included clear cell histology, measurable metastatic disease, and OS >60 days from CN, to avoid surgery-related deaths. Demographics and IMDC risk strata were collected from medical charts. Volumetry and radiomic features (first and second order) were assessed in the arterial phase abdominal computerized tomography (CT) of the primary lesion. Metastatic disease foci were segmented from venous phase CT and measured. Bone disease and <1cm visceral metastases were disregarded for 3-axial measurement. After dimensionality reduction of the radiomic features with Uniform Manifold Approximation and Projection, an unsupervised Gaussian Mixture Model (GMM) clustering was performed. Characteristics of different clusters were compared with Mann-Whitney U test and univariate Cox regression estimated the effect on outcomes. Results: From 54 mRCC pts treated with CN, 39 were included. Median age was 60 years-old. Most patients were male (74%) and intermediate-risk by IMDC (64%). Sites of metastasis included lung (44%), bone (38%), and adrenal (21%). GMM identified 4 distinct clusters from radiomic features, which were grouped according to median OS relative to all pts (2.8 years): Group A (below mOS) and Group B (above mOS). The table shows the association of different factors with OS. Group B had longer median OS (3.4 vs. 1.8 years, p=0.009), progression-free survival (16.8 vs. 9.8 months, p=0.024), systemic treatment-free survival (9.5 vs. 3.8 months, p=0.028), and survival during first-line tyrosine kinase inhibitor (2.2 vs. 0.9 years, p=0.016). Group men had a lower primary-to-whole-body burden ratio compared to Group A (median 0.83 vs. 0.99, p<0.01). Only IMDC risk criteria (HR 1.97, p<0.01) and radiomic group B (HR 0.35, p=0.01) correlated with OS in univariate Cox analysis. Conclusions: Our study suggests that radiomics of the primary lesion may predict OS in mRCC pts after CN, despite limited by its retrospective nature and small sample size. Further validation in larger datasets is warranted. Univariate Cox proportional hazards of prognostic factors on OS. [Table: see text]
Patient and physician preferences for adjuvant treatment of renal cell carcinoma: A discrete-choice experiment.
Authors: Calhoun Shawna R , Vass Caroline , Myers Kelley , Imai Kentaro , Bussberg Cooper , Bhattacharya Rituparna , Pinto Cathy Anne , Poulos Christine 
Published: March 2023

635 Background: Although a handful of studies have elicited treatment preferences in renal cell carcinoma (RCC), most focused on advanced disease. This study elicited United States patients’ and physicians’ preferences for adjuvant treatment characteristics. Methods: Patients with physician-confirmed RCC and (physician-defined) intermediate high or high risk of recurrence and physicians who treat such patients completed online surveys in Q1-Q2 2022 with a discrete-choice experiment. Hypothetical treatments were described by median disease-free survival (DFS); 5-year overall survival (OS) rate; mode and frequency of administration; need for concomitant daily pill; treatment duration; and the risks of severe diarrhea, fatigue, and dizziness. Preference weight estimates from random parameter logit analysis were used to calculate the conditional relative importance of attributes and risk tolerance measures. Results: 250 patients (50% post-nephrectomy) and 250 physicians (64% oncologists; 36% urologists) completed the survey. OS was the most important attribute to both patients and physicians, but DFS was also important (Table). OS had a greater influence on physicians’ choices than on patients’ choices. On average, OS was 3.2 and 2.5 times as important as DFS and 5.8-9.1 and 2.4-3 times more important than the evaluated risks for physicians and patients, respectively. Further, DFS was 1.8-2.9 times more important to physicians than the evaluated risks, while the importance of DFS and risks were nearly equivalent for patients. The need for concomitant oral medication was the least important attribute to patients and physicians. Both groups were willing to accept more than a 25-percentage-point increase in the risks of severe diarrhea, fatigue, and dizziness for improvements (from 45% to 60% or 85%) in OS. Conclusions: While both patients and physicians weighted OS improvements more than the other treatment attributes, including risks, physicians tended to place lower importance on changes in risk and administration than patients. Physicians and patients should discuss potential benefits and harms when considering adjuvant RCC therapies. [Table: see text]