bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value-based payment models and management of newly diagnosed prostate cancer.
Authors: Maganty Avinash , Kaufman Samuel , Oerline Mary , Faraj Kassem S , Caram Megan Veresh , Shahinian Vahakn B. , Hollenbeck Brent K. 
Published: January 2024

309 Background: To examine the effect of urologist participation in value-based payment models on the management of men with newly diagnosed prostate cancer. Methods: Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019 were assigned to their primary urologist, each of whom was then aligned to a value-based payment model (the Merit-based incentive payment system [MIPS], accountable care organization [ACO] without financial risk, and ACO with risk). Multivariable mixed-effects logistic regression was used to measure the association between payment model participation and treatment of prostate cancer. Additional models estimated the effects of payment model participation on use of treatment in men with very high risk (i.e.,>75%) of non-cancer mortality within 10 years of diagnosis (i.e., a group of men for whom treatment is generally not recommended) and price-standardized prostate cancer spending in the 12 months after diagnosis. Results: Treatment did not vary by payment model, both overall (MIPS— 67% [95%CI 66 to 68%], ACOs without risk—66% [95%CI 66 to 68%], ACOs with risk— 66% [95%CI 64 to 68%]). Similarly, treatment did not vary among men with very high risk of non-cancer mortality by payment model (MIPS— 52% [95%CI 50 to 55%], ACOs without risk— 52% [95%CI 50 to 55%], ACOs with risk— 51% [95%CI 45% to 56%]). Adjusted spending was similar across payment models (MIPS— $16,501 [95%CI $16,222 to $16,780], ACOs without risk— $16,140 [95%CI $15,852 to $16,429], ACOs with risk— $16,117 [95%CI $15,585 to $16,649]. Conclusions: How urologists participate in value-based payment models is not associated with treatment, potential overtreatment and prostate cancer spending in men with newly diagnosed disease.
Development of a patient-centered health-related quality of life (HRQOL) measure for metastatic renal cell carcinoma (mRCC): A three-phase study.
Authors: Bergerot Cristiane Decat , Castro Daniela V. , Bergerot Paulo Gustavo , Mercier Benjamin D. , Nally Elizabeth , Ali Adil A. , Philip Errol James , Buso Murilo , Hutson Thomas E. , Grünwald Viktor , Bex Axel , Psutka Sarah P. , Rini Brian I. , Plimack Elizabeth R. , Master Viraj A. , Albiges Laurence , Choueiri Toni K. , Pal Sumanta Kumar , Powles Thomas 
Published: January 2024

365 Background: Patients (pts) with mRCC require a tailored HRQOL assessment. Previous research (Bergerot et al. Oncologist 2023; Bergerot et al. J Clin Oncol 2023) explored FKSI-19, EORTC QLQ-C30, and EQ-5D item relevance. We aimed to develop a tailored HRQOL measure for pts with mRCC through a three-phase approach involving patient engagement, expert input, and advocacy. Methods: In Phase 1, 117 pts with mRCC (83:34 M:F, median age=64) from the US, Europe and Brazil participated in a survey study to assess the relevance of items from established measures (FKSI-19, EORTC QLQ-C30, EQ-5D). In this cohort, 88% of pts had clear cell histology and 35%, 30% and 19% received immunotherapy alone, targeted therapy alone or combination therapy, respectively. Questions identified as relevant (base on ≥66% consensus) were selected for inclusion in a preliminary survey. Phase 2 involved assembling a panel of 11 experts who rigorously reviewed and refined survey questions. In Phase 3, preliminary version were presented to 8 patient advocates (5:3 F:M; 6:2 pts:caregivers) to ensure alignment with pts' needs and experiences. Results: Phase 1 analysis identified 10 items. Pts requested the inclusion of a question about social/family issues and better coverage of emotional symptoms. An 12-item questionnaire was created, and the expert committee refined three items to incorporate patient suggestions and added one item related to functional status (Table). This questionnaire included 1 cancer-specific item, 3 cancer or treatment-specific items, 3 non-specific emotional items, and 4 non-specific physical items. Patient advocates provided feedback, agreeing with the items excluded from previous questionnaires and those included. They suggested minor edits to item wording. Conclusions: The novel approach holds the potential to replace traditional HRQOL measures that may lack relevance to specific clinical circumstances. Further validation is planned in a phase 3 trial, ensuring its applicability in clinical practice. [Table: see text]
Real-world treatment outcomes in patients with advanced renal cell carcinoma who receive axitinib plus pembrolizumab in the first-line setting in Canadian cancer centers.
Authors: Beaulieu Carissa , Ghosh Sunita , Tajzler Camilla , Kirkpatrick McKayla , Castonguay Vincent , Wood Lori , Graham Jeffrey , Soulieres Denis , Bansal Rahul K. , Heng Daniel Yick Chin , Finelli Antonio , Tanguay Simon , Lalani Aly-Khan A. , Bhindi Bimal , Bjarnason Georg A. , Breau Rodney H. , Basappa Naveen S. 
Published: January 2024

382 Background: The landscape of management of advanced renal cell carcinoma (aRCC) in the first line setting has changed dramatically over the past decade. Axitinib with Pembrolizumab (AP) is one of the combinations which demonstrated improved outcomes in the KEYNOTE 426 study. We report real-world outcomes and safety with this combination. Methods: The Canadian Kidney Cancer information system (CKCis) is a multi-institutional prospective RCC cohort. Patients ≥18 years with aRCC and clear cell histology who received AP as first-line therapy from January 1, 2017 to June 30, 2022 were included. Descriptive and actuarial statistics were reported for the following: progression free survival (PFS), overall survival (OS) and adverse events. Results: The cohort includes 222 patients.165 (74.3%) were male with a median age of 64.5 (37.0-87.7) years. Sixty-three (28.3%) patients were IMDC favourable-risk, 69 (31.0%) intermediate-risk, 45 (20.3%) poor-risk and 45 (20.2%) unknown. Median follow-up was 26.6 (range: 0.1 – 77.2) months. Of 222 patients, 119 discontinued treatment (53.6%) due to disease progression in 45.4% or toxicity in 29.4%. Median duration of treatment was 18.5 (range 0.1 to 72.4) months. PFS probability at 12 and 24 m was 63.8% and 49.9% respectively with a median PFS of 22.6 months (95% CI: 15.9-30.1). Survival probability at 12 and 24 m was 89.1% and 80.2% respectively with a median OS of 51.5 months (95% CI 38.0-NR). By IMDC criteria, intermediate risk median OS was 44.8 m (95% CI 41.5-61.6) and poor risk 33.6 m (18.5-NR). Most patients experienced toxicity requiring dose interruption/delay or discontinuation (n=180; 81.4%) The most common toxicities were diarrhea (73.3%), fatigue (54.4%), hepatotoxicity (50.0%), anorexia (26.1%), mucositis (22.2%), nausea (21.1%), palmar plantar erythrodysesthesia (15.6%), hypertension (13.3%), weight loss (13.3%) and proteinuria (11.7%). Others included pneumonitis (8.9%), thyroid dysfunction (6.7%) and colitis (4.4%). Conclusions: The real-world experience of patients with aRCC receiving AP in Canada is similar to the KEYNOTE-426 study in both outcomes and safety. These data continue to support its position as a standard of care in the first line setting for aRCC. Longer follow up and characterization of these patients is warranted.
Real world outcomes of first line (1L) nivolumab and ipilimumab (NIVO IPI) in metastatic renal cell carcinoma (mRCC): An update from the International mRCC Database Consortium (IMDC).
Authors: Wells Connor , Ferrier Evan , Lemelin Audreylie , Powles Thomas , Pal Sumanta Kumar , Ebrahimi Hedyeh , Agarwal Neeraj , Beuselinck Benoit , Bjarnason Georg A. , Wood Lori , Canil Christina M. , Saliby Renee Maria , de Velasco Guillermo , McKay Rana R. , Tran Ben , Suárez Cristina , Templeton Arnoud J. , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: January 2024

395 Background: NIVO IPI is one of several 1L treatment options for mRCC and is limited to intermediate and poor risk disease in many jurisdictions. We report the outcomes of 1L NIVO IPI from the IMDC. Methods: All IMDC patients who received 1L NIVO IPI were retrospectively analyzed. Key outcomes were compared between IMDC risk groups and included overall survival (OS), time to treatment discontinuation (TTD), time to next treatment (TTNT; defined as time from 1L initiation to next treatment) and response rates. Conditional OS by 6- and 12-month survival are described. Results: 1145 patients received 1L NIVO IPI, including 94 favourable, 559 intermediate, and 313 poor risk patients. 818/980 (86%) of patients had clear cell histology and 14% had sarcomatoid features. The median follow up was 20.0 months. 837/1145 (73%) patients had stopped 1L NIVO IPI and 363/1145 (32%) were deceased. Key outcomes of interest are summarized in Table 1. Subsequent 2L therapy was received by 438/727 (60%) patients and was most frequently sunitinib (37%) and cabozantinib (28%). 3L therapy was received by 160/477 (34%) patients, most often cabozantinib (29%). Immune related adverse events were documented in 48% (274/572) of patients. Conditional survival analysis showed that if a patient was alive at 6 months after starting 1L NIVO IPI, they had an 81% likelihood of being alive for an additional year and a 68% likelihood of surviving two years. If alive at 12 months, there was an 81% chance of surviving one additional year and 68% chance of surviving two additional years. If a patient remained on 1L NIVO IPI for 6 months, there was a 91% likelihood of being alive for one additional year and 76% likelihood of being alive for two years. If they remained on NIVO IPI for 12 months, there was a 94% chance of being alive for one additional year and an 84% chance of surviving two additional years. Conclusions: This large cohort of real-world patients provides benchmark data for clinical trial design and patient counselling, with a median OS surpassing 50 months for intermediate risk patients.[Table: see text]
Regulatory approvals for genitourinary (GU) cancer by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) over 20 years (2003-2023).
Authors: Khanna Sanjay , Sarwar Naveed , Caldwell Reece , Krell Jonathon , Benjamin David Joseph , Hadfield Matthew James , Khaki Ali Raza , Warner Jeremy Lyle , Lythgoe Mark 
Published: January 2024

432 Background: The past 2 decades has witnessed a transformation in the GU cancer therapy armamentarium. In this study, we analysed GU cancer therapy approvals (initial & supplemental) by the two largest global regulators (EMA and FDA) by evaluating approval timing, labels, biomarker requirements and drug withdrawal(s). Methods: A cross-sectional analysis of approved drugs and indications made for GU cancer medicines from each regulatory database from 2003-2023 was performed. We compared new approved therapies, indications and biomarker requirements. Results: The FDA approved 40 new therapies, corresponding to 57 indications, with 2 withdrawals. The EMA approved 33 new therapies, corresponding to 43 indications with 1 withdrawal. Overall, the FDA approved new GU cancer therapies 128 days earlier (table). In renal cell carcinoma (RCC), the FDA approved 14 new therapies across 18 indications, compared to 14 new therapies across 16 indications for the EMA. The FDA approved new RCC therapies 113 days earlier than the EMA. For concomitant approvals the FDA label was broader for 5 indications, more restrictive for 2 and equivocal for 9. In urothelial cancer (UC), the FDA approved 9 new therapies across 14 indications, compared to 7 new therapies across 7 indications for the EMA. The FDA approved new UC therapies 110 days earlier than the EMA. For concomitant approvals, the FDA label was broader for 4 indications and equivocal for 3. In prostate cancer (PC), the FDA approved 17 new therapies across 25 indications, compared to 12 new therapies across 20 indications for the EMA. The FDA approved new PC therapies 157 days earlier than the EMA. For concomitant approvals, the FDA label was broader for 2 indications and equivocal for 18. Across GU cancer, 8 therapies (both FDA and EMA) had biomarker-based eligibility with 3 notable differences in urothelial cancer: the EMA uniquely requires a PD-L1 combined positive score (CPS) ≥ 10 and PD-L1 ≥ 1% for pembrolizumab (platinum-ineligible) and Nivolumab (adjuvant), respectively. Although biomarker requirement was similar, the FDA has withdrawn atezolizumab in UC unlike the EMA. Conclusions: Over the past 20 years, there has been a substantial increase in new therapies to manage GU cancers. Patients in the US typically have access to more new therapies, earlier and across broader indications than those in Europe. However, a greater number of therapies are withdrawn after approval in the US. Biomarker-eligibility is broadly similar, with some discordance in UC. [Table: see text]
Impact of body mass index (BMI) on clinical and toxicity outcomes in patients with relapsed metastatic germ-cell tumor (GCT) undergoing high-dose chemotherapy (HDCT) with peripheral blood stem cell transplant (PBSCT).
Authors: Khalid Ahmed Bilal , Pham Phillip , Hassoun Rebecca , Althouse Sandra K. , Abonour Rafat , Abu Zaid Mohammad Issam , Hanna Nasser H. , Adra Nabil , Einhorn Lawrence H. , King Jennifer 
Published: January 2024

517 Background: ASCO guidelines recommend full weight-based dosing of cytotoxic chemotherapy for all pts regardless of BMI. The regimen for HDCT in relapsed GCT at our institution uses actual body weight (ABW) dosing for carboplatin and etoposide. There is limited data on the implications of using ABW to dose HDCT in pts with GCT. We describe clinical and toxicity outcomes based on pre-transplant BMI in pts with relapsed metastatic GCT undergoing HDCT with PBSCT. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with relapsed GCT treated between 1990-2023 with HDCT and PBSCT. Pts were classified by pre-transplant BMI as BMI <25 (normal weight), BMI 25-29.9 (overweight), or BMI ≥30 (obese). Grade 3 or higher (≥G3) toxicities were assessed using CTCAE. Comparisons between groups were done using Chi-square tests for categorical variables or Wilcoxon test for continuous variables. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). The log rank test was used to compare groups. Results: 597 pts met inclusion criteria. Median age at initiation of HDCT was 32.4 (range, 16.7-70.1). Primary site was testis in 85%, retroperitoneum in 8%, and mediastinum in 7%. 76% of patients had non-seminoma. IGCCCG risk was good in 40%, intermediate in 11%, and poor in 48%. HDCT was the 2nd line treatment for 83% of pts and ≥3rd line for 17%. 90% of pts completed both cycles of HDCT. 202 pts (34%) had normal BMI, 223 (37%) were overweight and 172 (29%) were obese. Median carboplatin dose was 2100mg/m2 and median etoposide dose 2250mg/m2 for all pts in both cycles. 63% of obese pts experienced at least 1 G≥3 non-hematologic adverse event vs. 43% of overweight pts vs. 44% of pts with normal weight (p=0.0001). The rate of G≥3 renal toxicity was higher in obese pts at 17% vs. 7% in overweight pts vs. 5% in normal weight pts (p= 0.0001). G≥3 GI toxicity was higher in obese pts at 50% compared to 36% in overweight pts and 37% in normal weight pts (p=0.0079). The table lists toxicity and survival outcomes by pre-transplant BMI. Conclusions: Obese pts with relapsed GCT undergoing HDCT had higher incidence of overall G≥3 toxicity specifically renal and GI toxicity. Treatment-related mortality and survival was not impacted by differences in BMI. [Table: see text]
Plasma DNA and deoxyribonuclease in testicular germ cell tumors.
Authors: Mego Michal , Vlkova Barbora , Kalavska Katarina , Cierna Zuzana , Rejlekova Katarina , Udvorkova Natalia , Majtanova Kristina , Lesko Peter , Obertova Jana , Orszaghova Zuzana , Palacka Patrik , Sycova-Mila Zuzana , Mardiak Jozef , Chovanec Michal , Kucerova Lucia , Celec Peter 
Published: January 2024

518 Background: Despite high cure rate, small proportion of patients with germ cell tumors (GCTs) experience relapse and eventually die as a consequence of their disease. Tumor-derived DNA, but also total extracellular DNA (ecDNA) in plasma were found to be associated with the prognosis in different types of cancer. Deoxyribonuclease (DNase) catalyzes the cleavage of ecDNA and is likely the main metabolic pathway of ecDNA degradation. We hypothesized that DNase activity might modulate the association between ecDNA and prognosis. This study aimed to determine the prognostic value of ecDNA of different subcellular origin and plasma DNase activity in GCTs. Methods: This study included 117 patients with testicular GCTs starting a new line of therapy and 19 healthy controls. Plasma ecDNA was quantified using fluorometry (total ecDNA) and using PCR (nuclear – ncDNA and mitochondrial DNA – mtDNA). DNase activity was assessed using the single radial enzyme diffusion method in a DNA-containing gel. An in vivo experiment in mice was conducted to evaluate the effect of DNase I treatment alone and in combination with cisplatin on the xenografts derived from the human embryonal carcinoma cell line variant NTERA-2 CisR. Results: Plasma ecDNA was higher in patients with GCTs compared to healthy controls (mean ng/ml ± SEM: 6.2 ± 0.6 vs.1.2 ± 2.2). Patients with high total ecDNA, ncDNA but not mtDNA had inferior PFS and OS compared to patients with low ecDNA (all p < 0.05). There was an inverse relationship between plasma DNase and ecDNA as well as between plasma DNase and clinical outcome (HR=2.96, 95%CI 1.39-6.32, P = 0.01 for PFS and HR=4.88, 95%CI 2.06-11.53, p = 0.005 for OS, respectively). Our experiments on selected model human GCT cell lines confirmed the lack of cytotoxic or inhibitory effects of DNase I in vitro. The animal experiment showed that the combination treatment with DNase I and cisplatin substantially reduced the growth of the NTERA-2 cisplatin-resistant xenografts (by 30%). Conclusions: We confirmed the prognostic value of ecDNA and proved it for the first time for DNase in patients with GCTs. We suggest that based on the animal experiment there is strong rationale to add DNase to cisplatin in refractory GCTs. Although the mechanisms are unclear and could involve reduced inflammatory response to ecDNA, we hypothesize that degradation of ecDNA by DNase might contribute to a better control of the tumor progression by cisplatin in patients with progressing or relapsing GCTs.
Estimating the impact of adjuvant treatment with nivolumab on long-term survivorship rates compared with surveillance: Analyses of disease-free survival (DFS) from the phase 3 CheckMate-274 trial.
Authors: Geynisman Daniel M. , Yates Georgia , Chepynoga Kateryna , Teitsson Siguroli , Kurt Murat , Patel Miraj Y. , Mamtani Ronac 
Published: January 2024

528 Background: Durable DFS and cure are the ultimate goals for the treatment of muscle invasive urothelial carcinoma (MIUC) with radical cystectomy. This analysis employed mixture cure models (MCMs) to estimate the underlying cure fraction among high-risk MIUC patients following radical resection in the Phase 3 CheckMate-274 study. Methods: MCMs were applied to patient-level DFS data from the trial (minimum follow-up: 31.6 months). Intention-to-treat (ITT) population and the subpopulation with tumor PD-L1 expression ≥1% were analyzed separately for nivolumab (NIVO) and placebo (PBO) arms. In MCMs, the patient populations were assumed to consist of two exclusive subgroups as cured and uncured. Cured subgroup was assumed to be free of disease recurrence and disease-related mortality risks. The uncured subgroup was at the risk of both disease recurrence and all-cause mortality. DFS for the cured subgroup was estimated using background mortality rates published by WHO matched to the trial’s demographic characteristics. DFS for the uncured subgroup was modelled using parametric distributions, which were characterized along with the cure fraction by maximum likelihood methods. Model selection was primarily based on clinical plausibility of estimated DFS for the uncured subgroup. Visual comparison of the fits from the MCMs to the reported DFS data from the trial and goodness-of-fit statistics also assisted model selection. Results: In the trial, 353 patients were treated with NIVO (mean age: 65.3; male: 75.1%; PD-L1≥1%: 39.7%) and 356 patients were in PBO control (mean age: 65.9; male: 77.2%; PD-L1≥1%: 39.9%). Selected models estimated almost all uncured patients to experience recurrence within 5 years. The estimated cure fraction in the ITT population ranged from 43.1%-45.1% in the NIVO arm (95% CI: 36.7%-51.6%), and 36.4%-37.0% in the PBO arm, (95% CI: 30.9%-43.0%) for clinically plausible models. Projected range of 10-year mean DFS for the ITT patients was 4.38-4.47 years in the NIVO arm and 3.61-3.64 years in the PBO arm. Estimated cure fractions in the PD-L1≥1% subpopulation ranged from 59.1%-61.0% in the NIVO arm (95% CI: 48.9%-72.0%), and 35.9%-36.9% in the PBO arm, (95% CI: 27.5%-45.9%). Projected range of 10-year mean DFS for the PD-L1≥1% subpopulation was 5.54-5.65 years in the NIVO arm and 3.54-3.57 years in the PBO arm. Conclusions: In the adjuvant treatment of MIUC, relative to radical resection only, systemic therapy with NIVO is associated with a 6-9 percentage points higher cure fraction in the ITT population. Tumor PD-L1≥1% expression was associated with higher cure fractions in the NIVO arm but had only negligible impact on the underlying cure fraction in the PBO arm. Clinical trial information: NCT02632409 .