bluuebunny/crossref_metadata_2025_split huggingface dataset:
Every-other-day or once-a-week: Long-term efficacy outcomes of the multicenter randomised PATRIOT prostate SBRT trial.
Authors: Ong Wee Loon , Quon Harvey Charles , Ong Aldrich , Cheung Patrick , Chu William , Chung Hans T. , Vesprini Danny , Chowdhury Amit , Panjwani Dilip , Alayed Yasir , Pang Geordi , Korol Renee , Davidson Melanie , Ravi Ananth , McCurdy Boyd , Zhang Liying , Kulasingham-Poon Meghan , Mamedov Alexandre , Deabreu Andrea , Loblaw Andrew 
Published: January 2024

325 Background: We aim to report the long-term efficacy outcomes of the PATRIOT trial, a multicenter phase 2 randomised trial of every-other-day (EOD) versus once-a-week (QW) schedule for stereotactic body radiotherapy (SBRT) for prostate cancer (NCT01423474). Methods: Between January 2012 and November 2013, 152 men with low to intermediate risk prostate cancer were randomised to prostate SBRT 40Gy in 5 fractions, delivered EOD (n=75) or QW (n=77). The oncological outcomes evaluated were biochemical failure (BF) (based on Phoenix criteria), metastases free survival (MFS), prostate cancer specific survival (PCSS) and overall survival (OS). Time-to-event was estimated from the start date of SBRT to event of interest or last follow-up. The cumulative incidence of BF was estimated using the Nelson Aalen estimates, while MFS, PCSS and OS were estimated using the Kaplan Meier method. Results: The median follow-up for the cohort was 91 months (IQR: 61-116 months). Five men in the EOD arm and eight men in the QW arm developed BF. The 8-year cumulative incidence of BF were 5.5% (SE=0.03) in the EOD arm and 9.6% (SE=0.04) in the QW arm (P=0.3). None of the men in the EOD arm developed metastases, while three men in the QW arm did. The 8-year MFS were 100% in the EOD arm and 95.9% (95%CI=91.4-100%) in the QW arm (P=0.08). Thirteen men had died at last follow-up, of which two were prostate cancer specific death. The 8-year PCSS were 100% in the EOD arm and 97.2% (95%CI=93.5-100%) in the QW arm (P=0.3), while the 8-year OS were 96.0% (95%CI=91.7-100%) in the EOD arm and 85.4% (95%CI=76.4-95.5%) in the QW arm (P=0.3). Conclusions: There are no statistically significant differences in long-term oncological outcomes between EOD and QW for five-fraction prostate SBRT in the PATRIOT trial. However, the trial was powered for acute toxicity differences, and not MFS or OS. Either prostate SBRT schedule could be safely delivered depending on patients’ preference, or for logistic reasons. We plan to combine these data with the Swiss EOD vs QW randomised trial (NCT01764646) to improve the power to detect these important outcomes. Clinical trial information: NCT01423474 .
Neoadjuvant pamiparib plus abiraterone and ADT for high-risk/very high-risk localized prostate cancer: Results of a prospective study.
Authors: Zhuang Junlong , Zhang Shun , Qiu Xuefeng , Zhou Feng , Guo Hongqian 
Published: January 2024

327 Background: Androgen receptor (AR) signaling inhibition increases genomic instability of double-stranded DNA breaks, and co-inhibition of AR and PARP induces synthetic lethality in multiple preclinical models. In this study we tested the efficacy and safety of neoadjuvant pamiparib plus abiraterone and ADT in HRLPC/VHRLPC before radical prostatectomy (RP). Methods: In this phase II single-arm neoadjuvant trial, patients with HRLPC/VHRLPC (defined as Gleason ≥ 8 and/or cT3-4N0-1 and/or PSA≥ 20 ng/mL) were enrolled to evaluate the safety and antitumor efficacy of pamiparib before prostatectomy. Patients received pamiparib plus abiraterone and ADT for 4 months followed by prostatectomy. The primary objective was the rate of pathological complete response (pCR) or minimal residual disease (MRD). MRD was defined as ≤0.5cm of tumor or residual cancer burden ≤0.25 cm3 (RCB = tumor volume x cellularity). Secondary endpoints include PSA response, surgical staging at RP, the rate of PSA recurrence 12 months after surgery, and safety. Results: A total of 30 pts were enrolled, 29 pts (HRRm n=7) completed the full course of study treatment and underwent RP. One patient declined surgery for personal reasons and received further systemic therapy. The median age was 66 (range 41-77). Clinical characteristics were typical of high-risk disease: median PSA 34.4 ng/ml (range 10.8-204) and clinical stage cT3 (n=27), Gleason 8-10 (n=20),9 pts had enlarged pelvic lymph nodes. Following 4 months of therapy, the median pre-RP PSA was 0.103 ng/ml (range 0.006 -1.1). Final pathologic results showed that 8 pts (27.5%) achieved pCR or MRD, 3 pts (10.3%) achieved pCR, 5 patients (17.2%) achieved MRD, and 18 patients (62%) had staging downgrades, with no patients experiencing progression. Compared to patients with an HRR wild type (HRRwt), those with HRR mutations had no difference in pCR or MRD. The margin positivity rate was 6.8%(n=2) in 29 pts, all of whom were T3 stage patients. No Grade 3/4 drug-related adverse event was observed. The most common 1-2 adverse event were anaemia (48.2%), AST/ALT increased (34.4%) and hypertriglyceridemia (44.8%). Conclusions: Neoadjuvant therapy of pamiparib plus abiraterone and ADT for 4 months was effective and safe in pts with HRLPC/VHRLPC. Clinical trial information: NCT05376722 .
Temporal and regional patterns of prostate cancer positron emission tomography imaging among commercial insurance beneficiaries in the United States.
Authors: Leapman Michael , Long Jessica B. , Westvold Sarah J. , Rabil Maximilian , Sprenkle Preston , Kim Isaac Yi , Saperstein Lawrence , Fallah Jaleh , Suzman Daniel L. , Lerro Catherine , Xu Jianjin , Kluetz Paul Gustav , Karnes R. Jeffrey , Kunst Natalia , Wang Shi-Yi , Ma Xiaomei , Gross Cary Philip 
Published: January 2024

34 Background: Prostate specific membrane antigen positron emission tomography (PSMA-PET) imaging improves prostate cancer visualization and has been proposed as a tool to guide treatment decisions. As PSMA-PET imaging agents were not approved in the United States (US) until December 2020, little is known about national patterns of PET imaging utilization. Methods: We conducted a dynamic cohort study to evaluate use of PET imaging among insurance beneficiaries aged 40-89 years with a diagnosis of prostate cancer using deidentified administrative claims from Blue Cross Blue Shield Axis. We calculated the proportions of patients undergoing PET imaging in semiannual periods from January 1, 2016, through December 31, 2022, examining tracers specific to prostate cancer, including PSMA-targeted agents as well as fluciclovine, sodium fluoride, and choline tracers. Cochran-Armitage tests were used to evaluate trends in the proportion of individuals receiving PET imaging over time. We also assessed the association between regional [hospital referral region (HRR)] level contextual sociodemographic and healthcare characteristics and regional use of PSMA-PET imaging in 2022 using chi-square tests. Results: There were 410,505 beneficiaries with prostate cancer identified in the study period. The semiannual proportion of patients undergoing PET imaging increased from 4.5 [(95% confidence interval (CI) 4.1-5.0] per 1,000 in the first half of 2016 to 41.7 (95% CI 40.6-42.9) per 1,000 in the second half of 2022, p<0.001. Increases in PET imaging were driven by uptake of PSMA-PET imaging, which increased from 0.7 (95% CI 0.6-0.9) per 1000 in the second half of 2021 to 37.5 (95% CI 36.4-38.6) per 1,000 in the second half of 2022, p<0.001. Following approvals of PSMA-PET agents, other forms of PET imaging rapidly decreased – from 18.2 (95% CI 17.4-18.9) per 1000 in the second half of 2021 to 4.6 (95% CI 4.3-5.0) per 1,000 in the same period of 2022, p<0.001. Compared to HRRs in quartile 1 (Q1), HRRs in Q4 of PSMA-PET use in 2022 had higher levels of education (25.0% with college education or higher in Q1 versus 29.4% in Q4, p=0.005) and median household income ($50,200 in Q1 versus $60,900 in Q4, p<0.001). Conclusions: In this study from a large commercial US health insurer, PSMA-PET was rapidly incorporated into clinical practice and is now the dominant prostate cancer radiotracer. However, the initial uptake of PSMA-PET may be accompanied by disparity, as our data suggests less use in areas with lower income and education measures.
A randomized phase II trial of neoadjuvant chemokine modulation in patients with localized prostate cancer undergoing radical prostatectomy.
Authors: Jatwani Karan , Kalathil Suresh , Slomba Ronald , Farmer Bailey , Attwood Kristopher , Roy Arya Mariam , Singh Prashant , Kauffman Eric , Gopalakrishnan Dharmesh , George Saby , Levine Ellis Glenn , Guru Khurshid , Kalinski Pawel , Chatta Gurkamal S. 
Published: January 2024

340 Background: Most patients with high or very high risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). A high intra-tumoral CD8+ T lymphocyte density is associated with improved survival post-RP,1 suggesting possible clinical benefit from neoadjuvant chemokine modulation (CKM).2,3 We present the interim results of a three-arm, phase II trial where patients with localized PCa scheduled to undergo RP were randomized in 1:1:1 ratio to a 2-week regimen of neoadjuvant CKM triplet (Arm A: rintatolimod + aspirin + IFN-α: “Complete CKM regimen”) vs CKM doublet (Arm B: rintatolimod + aspirin) vs no CKM (Arm C). Methods: Thirty patients (10 per arm) are to be enrolled to assess CD8+ T cell density in the RP specimen as the primary endpoint. Pathological and PSA responses, surgical margin positivity, and safety/toxicity of the CKM combinations represent secondary endpoints. Correlative blood studies analyzed the pre- vs post-CKM changes in Granzyme B (GrB; marker of effector/cytotoxic function in CD8+ T cells and FoxP3 (Treg marker) in CD4+ T cells. Results: The trial has enrolled 11 patients thus far (N=5 Arm A, 3 Arm B, 3 Arm C). There were no clinicopathological differences between the groups. Eight patients (on Arms A and B) were analyzed for changes in cytotoxic T cell numbers (CTL-D: GrB+CD8+ T-cells) in the blood. In Arm A, the mean pre-CKM CTL-D was 35.5% (±23.2%) and post-CKM was 47.7% (± 32.5%), while in Arm B, respectively, 37.9% (±22.2%) vs 37.1% (± 21.6%). These changes were reflected in the increased CTL/Treg markers in the post-treatment samples of patients on Arm A. These data indicate the ability of the “complete CKM regimen” (Arm A) to selectively enhance the CTL effector function in circulating CD8+ T cells, without enhancing the Treg markers. CKM regimen was well tolerated with no Grade 3 or above adverse events (AEs). Conclusions: In this interim analysis, treatment in all arms was feasible and safe. CTL-D and CTL-D/Treg in Arm A (“complete CKM”) shows an increasing trend over the course of CKM treatment. The levels of CTL-D in the resected prostate tissues are being currently evaluated. The study continues recruiting patients. 1. Yang, Y et al (PMID 33085799). 2. Muthuswamy, R et al (PMID 27199259). 3. Theodoraki, MN et al (PMID 29853604). Clinical trial information: NCT03899987 .
Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial.
Authors: Bourlon Maria Teresa , Escudier Bernard , Burotto Mauricio , Powles Thomas , Apolo Andrea B. , Shah Amishi Yogesh , Porta Camillo , Suárez Cristina , Barrios Carlos H. , Richardet Martin , Gurney Howard , Kessler Elizabeth R. , Tomita Yoshihiko , Bedke Jens , Wang Fong , Wang Peter , Panzica Julie , Fedorov Viktor , Motzer Robert J. , Choueiri Toni K. 
Published: January 2024

362 Background: N+C demonstrated superior progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in patients (pts) with previously untreated aRCC in the primary analysis of the phase 3 CheckMate 9ER trial (18.1 mo median follow-up). N+C maintained efficacy benefits vs S with 44.0 mo median follow-up. Here, we report updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety with extended follow-up. Methods: Pts with aRCC were randomized to N 240 mg every 2 weeks + C 40 mg QD vs S 50 mg QD (4 weeks of 6-week cycles) until disease progression or unacceptable toxicity, with up to 2 y of N. The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Overall, 323 pts were randomized to N+C and 328 to S (ITT). With 55.6 mo median (48.1 mo min.) follow-up for OS, median PFS was 16.4 vs 8.4 mo (hazard ratio [HR] 0.58, 95% CI 0.49-0.70) and median OS was 46.5 vs 36.0 mo (HR 0.77, 95% CI 0.63-0.95) with N+C vs S. ORR (95% CI) was 55.7% (50.1-61.2) vs 27.7% (23.0-32.9); 13.6% vs 4.6% of pts achieved complete response (CR); 6.5% vs 13.7% had progressive disease (PD), respectively. Median (range) time to response (TTR) was 2.8 (1.0-22.2) vs 4.3 (1.7-30.4) mo for N+C vs S, and median (95% CI) duration of response (DOR) was 22.0 (18.0-25.2) vs 15.2 (10.9-19.3) mo. Efficacy by IMDC favorable (FAV) and intermediate/poor (I/P) risk groups is reported in the Table. Among all treated pts (320 pts each arm), any-grade (grade ≥ 3) treatment-related adverse events (TRAEs) occurred in 97.5% (67.5%) vs 93.1% (55.3%) with N+C vs S. Any-grade TRAEs led to discontinuation of N or C in 28.1% of pts (N only, 10.0%; C only, 10.3%; N+C simultaneously, 6.6%; N+C sequentially, 1.3%) and of S in 10.9% of pts. Additional analyses in subgroups of clinical interest will be presented. Conclusions: With 55.6 mo median follow-up, N+C continues to maintain meaningful long-term efficacy benefits over S. No new safety concerns were identified. These results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . [Table: see text]
Disparities in uptake of new FDA-approved therapies for metastatic clear cell renal cell carcinoma.
Authors: Hayes Mitch , Buhlmann Melanie , Gore L. Robert , Zemp Logan , Spiess Philippe E. , Manley Brandon J. , Jim Heather S.L. , Chahoud Jad 
Published: January 2024

370 Background: Multiple new therapies for metastatic clear cell renal cell carcinoma (mccRCC) have been approved in the past decade. Real-world (RW) data on access to novel therapies and the impact on health-related disparities are limited. This study assessed RW access to novel therapies along with racial and social disparities for mccRCC patients and their impact on clinical outcomes. Methods: The longitudinal Flatiron Health database was queried for adult patients with mccRCC who received systemic treatments from Jan 2011 to Dec 2022 with at least two documented clinical visits. Patients < 45 years old were excluded. Data was collected on age, gender, race, ethnicity, ECOG status, practice type, stage, smoking status, socioeconomic status (SES) defined by the Yost index, insurance status, overall survival (OS), and the first 14 treatments received. Patients were categorized as receiving a novel therapy if they received a first line mccRCC regimen during prespecified time windows starting on their first-line FDA approval date until 6 months later or when the next novel drug was approved, whichever date came later. Chi square test was used to assess variables across race. Univariable Cox proportional hazard models were used for OS analysis. R version 4.3.0 was used for programming. Results: 7,113 patients were included. 68.8% of the cohort was white, 7.1% Black, 1.4% Asian, 12.7% other, and 10.1% missing. Advanced age and receiving care in a community practice setting were associated with worse OS (CI 1.45-1.81 and CI 0.70-0.81, respectively), while SES was not (CI 0.81-1.01 for highest vs lowest group). Black race was associated with a 24% increased hazard of mortality compared to white race (CI 1.11-1.39, p=0.0003), and this was more pronounced in patients <65 years old (CI 1.17-1.63, p=0.0001). 31.4% of patients received at least one novel therapy during the study period, and there were no differences by race. Receipt of novel therapy was not statistically associated with improved OS (p=0.1660). Conclusions: This is the first study in the immunotherapy era to highlight the worse OS of Black patients with mccRCC. Access to care at an academic center was associated with improved OS. Access to novel therapies did not differ between racial groups in the US using RW data. [Table: see text]
Baseline CD8 lymph node avidity with 89-Zr-crefmirlimab in patients with metastatic renal cell carcinoma and response to IO therapy.
Authors: Zang Peter D. , Twardowski Przemyslaw , Chen Delphine L , Hall Evan Thomas , Hays David , Wilson Ian , Schmiedehausen Kristin , Ferris Michael , Le William , Postow Michael A. , Pal Sumanta Kumar 
Published: January 2024

375 Background: Prior studies with crefmirlimab, a 89-Zr labeled antibody with specificity for CD8+ cells, have shown a strong correlation with SUV uptake and IHC of the same lesions validating its use (Pal 2023). We predicted that responders to IO therapy would have higher CD8 lymph node avidity than non-responders. Methods: Pts enrolled had a diagnosis of mRCC and must have received IO therapy (CPI/TKI, CPI/CPI, or CPI monotherapy). Pts obtained a crefmirlimab PET/CT within 1 week before CPI infusion as baseline. PET intensity was determined using SUVMax, SUVMean, SUVPeak. Highly avid lymph nodes (SUVMax > 10) were quantified. Best overall response was determined using RECIST 1.1 criteria with SUV values and number of CD8 PET-avid lymph nodes compared using a Wilcoxon Signed Rank test in R. Results: A total of 17 pts (9 M: 8 F) were enrolled across 3 sites with 9 pts locally available for analysis. The median age of pts was 64 years old (54-71). Histology types included 12 clear cell (71%), 2 papillary (12%), and 3 indeterminate (17%). There were 3 responders (18%), 12 non-responders (71%), and 2 non-evaluable (12%). The most common treatment regimens patients received in descending order were cabozantinib + nivolumab (44.44%), nivolumab (33.33%), and ipilimumab + nivolumab (22.22%). Strong correlation was observed between CD8 cell density and SUVMean (p <0.0003 by Spearman’s correlation). The average number of CD8 PET-avid lymph nodes (defined as SUVMax > 10) in responders was 6 versus 1.17 in non-responders (p = 0.025, 95% CI [1.99,7]). SUVMax, SUVMean, SUVPeak across all CD8 PET-avid lymph nodes for responders were 15.58, 12.63, 11.44 and for non-responders were 9.86, 8.53, 7.79 respectively. The difference between SUVMax, SUVMean, SUVPeak values reached statistical significance for all three values (p = 0.023 95% CI [3.42,7.84], p = 0.023 95% CI [2.64,5.84], p = 0.029 95% CI [1.18, 5.41] respectively). Conclusions: Our results show that pts with higher number of CD8 PET-avid lymph nodes at baseline was associated with better response to IO therapy; responders also had overall higher SUV uptake in CD8 PET-avid lymph nodes than non-responders. Our findings suggest that those with a more enriched CD8 phenotype trended towards better outcomes and may be a reliable predictor for IO therapy response. Clinical trial information: NCT03802123 .
Mayo Adhesive Probability score to predict renal function following partial nephrectomy.
Authors: Nicaise Edouard , Schmeusser Benjamin , Shah Yash , Futral Cameron , Ambadi Sriram , Imtiaz Nahar , Patil Dattatraya H. , Ogan Kenneth , Master Viraj A. 
Published: January 2024

379 Background: Mayo Adhesive Probability (MAP) score, which measures adherent perinephric fat in renal cell carcinoma (RCC), is associated with surgical complexity and cancer progression in patients undergoing partial nephrectomy (PN). PN carries perioperative risk but preserves renal function versus radical nephrectomy (RN). We analyzed whether MAP score can predict long-term postoperative renal function in localized RCC patients who underwent PN. Methods: We reviewed our nephrectomy database to identify pT1-T3a RCC patients who underwent PN. Patients with metastatic disease, IVC thrombus, multiple masses, and prior nephrectomy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI 2021 formula and patients with values <15mL/min/1.73m2 were excluded. We calculated MAP scores from preoperative cross-sectional imaging and dichotomized patients into low (1-3) versus high (4-5) cohorts. Continuous and categorical outcomes were compared using ANOVA and chi-square tests. A hierarchical generalized linear mixed effect model was used to evaluate predictors of long-term, postoperative eGFR following PN. Results: 314 patients were identified and 97 (30.9%) were classified with a high MAP score. These patients were older (64.5 vs. 58.3 years, p<0.001), more often male (85.6% vs. 52.5%, p<0.001), and white (79.4% vs. 67.7%, p=0.016). MAP score was associated with obesity (59.8% vs. 42.9%, p=0.006), diabetes (36.1% vs. 22.6%, p=0.013), hypertension (82.5% vs. 63.1%, p<0.001), and severe CCI (5+; 35.1% vs. 23.5%, p<0.001). No difference was observed in the rate of current or former smokers. Final tumor size was greater among patients with high MAP (4.1 vs. 3.4cm, p<0.001) but no difference was noted in pT stage. Rate of acute renal failure postoperatively (dialysis or eGFR <15 within 30 days) was similar between the two cohorts (1% vs. 1.4%, p=0.797). The tablepresents the model used to evaluate postoperative eGFR predictors. Conclusions: High MAP score predicts a greater eGFR decline following PN for localized RCC. Considering the risks of PN, MAP scoring may indicate surgical complexity and inform shared decision-making when considering nephron-sparing surgery for RCC. [Table: see text]
Venous tumor thrombus destinations in patients with renal cell carcinoma.
Authors: Nabavizadeh Reza , Pessoa Rodrigo , Cheville John , Lohse Christine M. , Costello Brian Addis , Lucien Fabrice , Thompson Houston R. , Boorjian Stephen A. , Leibovich Bradley C. , Sharma Vidit 
Published: January 2024

381 Background: Venous tumor thrombus (VTT) is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). It is unknown if VTT and pulmonary embolism (PE) predispose patients to pulmonary metastasis. Methods: We queried our institutional registry for ccRCC patients undergoing radical nephrectomy (1970-2019). Cox proportional hazards regression models, adjusting for factors associated with ccRCC progression, were used to determine if VTT and PE were associated with pulmonary metastasis. Results: Of 3,410 patients studied, 1,025 (30%) had VTT, and patients with VTT were more likely to present with pulmonary metastasis at nephrectomy (20% vs 7%, p<0.001). Within the VTT subset, level of VTT was not significantly associated with pulmonary metastasis at nephrectomy (p=0.3). For all patients who had metastatic disease at nephrectomy (n=643), pulmonary metastasis was more common in those with VTT versus those without VTT (68% vs 51%, p<0.001). Excluding patients with pulmonary metastasis at nephrectomy, on multivariable analysis, VTT remained associated with post-nephrectomy pulmonary metastasis (hazard ratio (HR) 1.31, p<0.001) without a notable difference in HRs between renal vein (1.27) and caval (1.38) VTT. Presence of PE in the setting of VTT was associated with increased pulmonary metastasis post-nephrectomy (HR 2.31, p<0.001). Conclusions: VTT is associated with disproportionately increased pulmonary metastasis at presentation and post-nephrectomy in ccRCC patients. Further, the presence of PE at nephrectomy for VTT was associated with increased pulmonary metastasis post-nephrectomy. These results support a metastatic predilection of ccRCC with VTT to the lungs.