bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of care and treatment outcomes in locoregional squamous cell carcinoma of the prostate.
Authors: Weil Christopher , Hutten Ryan , Tward Jonathan David , Lloyd Shane , Johnson Skyler B 
Published: March 2021

260 Background: Primary pure prostate squamous cell carcinoma (PSCC) is a rare, aggressive disease accounting for less than 0.5-1% of prostate cancer diagnoses. PSCC is a distinct entity from adenocarcinoma with historically poor outcomes, often presenting in younger patients with lower urinary tract symptoms and normal PSA. There are currently no established treatment guidelines. Case reports are limited but describe multiple treatment approaches including various combinations of surgery, platinum and non-platinum-based chemotherapy, radiotherapy and androgen deprivation therapy, with selected reports showing longer survival times with a combined modality approach. Methods: Seeking to identify practice patterns and treatment outcomes, we performed a retrospective analysis of the United States National Cancer Database to identify 66 males with locoregional, nonmetastatic primary pure squamous cell carcinoma of the prostate and treated with surgery, chemotherapy, and/or radiotherapy between 2004 and 2015. Clinical factors in analysis included pretreatment PSA, clinical T-stage, histology, treatment modality and demographic factors including age, comorbidity index, race, insurance status and treatment facility type. Patients were stratified into treatment groups consisting of local therapy alone (n = 40, 60%), local therapy and chemotherapy (n = 13, 20%), chemotherapy alone (n = 7, 11%), and observation (n = 6, 9%). Survival analysis was estimated using the Kaplan-Meier method and analyzed with log-rank testing. A Cox proportional hazards model was used to evaluate the association between patient characteristics and survival. Univariable and multivariable logistic regression was performed to identify covariates associated with receipt of each treatment modality. Results: With an overall median follow-up of 21.9 months, median survival was 19.7 months for patients treated with local therapy alone, 10.9 months with chemotherapy alone, and 36.5 months with combined local therapy and chemotherapy. Overall survival was not statistically significant between treatment groups. Statistically significant predictors of death included age (HR 1.1, 95% CI [1.03-1.17]) and clinical stage ≥T3a (HR 4.05, 95% CI [1.35-12.2]). Statistically significant predictors of receipt of chemotherapy were clinical stage T3a or greater (OR 34.6, 95% CI [2.65-364]) and age (OR 0.91, 95% CI [0.82-99]). Conclusions: This analysis represents the largest reported cohort analysis of locoregional pure PSCC. Unfortunately, due to the rarity of this disease, prospective or randomized trials to determine the optimal treatment strategy are not feasible. Despite limitations in sample size, and in the absence of prospective data, this analysis suggests the addition of chemotherapy to local therapy is a reasonable treatment approach in appropriately selected patients and may result in improved survival.
Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: Oncologic implications in the COVID-19 era and beyond.
Authors: Srivastava Arnav , Patel Hiren V. , Kim Sinae , Shinder Brian , Sterling Joshua , Tabakin Alexandra L. , Polotti Charles , Saraiya Biren , Mayer Tina M. , Kim Isaac Yi , Ghodoussipour Saum , Patel Hiten Dilip , Jang Thomas L , Singer Eric A. 
Published: March 2021

283 Background: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined, RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival (OS). Methods: We retrospectively abstracted cT1b-cT2bN0M0 RCC patients from the National Cancer Database (NCDB), stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within <1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed OS. Results: 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR=0.90; 95%CI: 0.77–1.05, p = 0.170), cT2a (OR=0.90; 95%CI: 0.69–1.19, p=0.454), or cT2b (OR=0.96; 95%CI:0.62–1.51, p=0.873) masses (Table). In all clinical stage strata, non-clear cell RCCs were significantly less likely to be upstaged (p<0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk. Conclusions: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered. [Table: see text]
Outcomes and prognostic factors in metastatic renal cell carcinoma patients with brain metastases.
Authors: Dogan İzzet , Iribas Ayca , Paksoy Nail , Ekenel Meltem , Vatansever Sezai , Basaran Mert 
Published: March 2021

289 Background: The study aimed to evaluate the outcomes and prognostic factors in patients with brain metastatic renal cell carcinoma (bmRCC). Methods: The data of 322 patients with renal cell carcinoma, between 2012 and 2020, were retrospectively reviewed. The clinicopathological features and treatments of the patients with bmRCC were recorded. Overall survival (OS) and prognostic factors were evaluated with Kaplan-Meier analysis and Cox-regression analysis. Results: Forty (12.4%) of the patients had bmRCC. The median follow-up period was 7.3 months (range, 0.2-55.5). The male/female ratio was 2.3, and the median age at diagnosis was 62 years (range, 25-84). Seventeen (42.5%) of the patients were de-novo metastatic, and nine (22.5%) of the patients had brain metastases at presentation. The most common extracranial metastatic sites of the disease were lung (72.5%), bone (47.5%), lymph node (27.5%), and liver (12.5%). Twenty-four (60%) patients previously had received various therapies (tyrosine kinase inhibitor, checkpoint inhibitors, or palliative radiotherapy). After brain metastases developed, 92% of the patients received brain radiotherapy (whole-brain radiotherapy or stereotactic radiosurgery), and twenty-five (62.5%) patients received different therapies. Nine patient received sunitinib, nine patient pazopanib, five patient nivolumab, and two patient axitinib. A total of 32 (80%) patients died during the study period. The median OS was 8.8 months (range, 2.9-14.6) for all patients with bmRCC. Six months- and one-years overall survival ratios were 60% and 40%, respectively. In univariate analysis, the number of brain metastasis (p = 0.352), the localization of brain metastasis (p = 0.790), the longest size of brain metastasis (p = 0.454), the number of extracranial metastatic sites (p = 0.812), de-novo metastatic disease (p = 0.177), primary tumor localization (left or right) (p = 0.903), and tumor grade (p = 0.093) were not statistically significant factors on OS. However, age (p = 0.02), a history of nephrectomy (p < 0.001), receiving brain radiotherapy (p = 0.005), and type of treatment (p = 0.044) was statistically significant. Only, the effect of brain radiotherapy on OS (p = 0.011) was confirmed in multivariate analysis. Conclusions: The prognostic data of patients with bmRCC is limited. In this study, we observed that the prognosis of patients with bmRCC was poor. Despite a small number of patients, we detected that the effect of tyrosine kinase inhibitors and nivolumab was comparable, and receiving brain radiotherapy was a prognostic factor for OS.
Factors associated with palliative care (PC) utilization in advanced and metastatic renal cell carcinoma (RCC).
Authors: Patel Hiren V. , Sterling Joshua , Srivastava Arnav , Kim Sinae , Saraiya Biren , Mayer Tina M. , Jang Thomas L , Singer Eric A. 
Published: March 2021

297 Background: Palliative care (PC) offers various benefits for patient with cancer that include, but are not limited to, decrease in disease-specific symptoms and improvement in functional status. Several oncological guidelines have adopted early integration of PC into oncologic care to improve quality of life among patients with advanced malignancies. However, PC utilization patterns and factors associated with its use in advanced renal cell carcinoma (RCC) remain poorly understood. Methods: Using the National Cancer Database (NCDB), we abstracted patients with stage III and IV RCC from 2004-2014 and evaluated PC utilization amongst this cohort. Socioeconomic and clinical factors were compared for patient receiving and not receiving PC for advanced RCC. Multivariable logistic regression identified factors that were associated with receipt of PC. Results: We identified 20,122 and 42,014 patients with stage III and IV RCC, respectively. Among this cohort, 329 and 9,317 patients received PC for stage III and IV RCC, respectively. From 2004 to 2014, PC utilization has been stable at ~1% for stage III RCC and has significantly increased from 17% to 20% for stage IV RCC. Multivariable analysis demonstrated that Blacks, income >$48,000, regions outside of Northeast, stage III RCC, and patients that received surgery were less likely to receive PC. Patients that were female, with more comorbidities, uninsured or with government insurance, lower educational status, treated at academic or integrated cancer program, with sarcomatoid histology, receiving systemic therapy were more likely to receive PC. Conclusions: While PC utilization has significantly increased for stage IV RCC, there are several demographic, socioeconomic, and clinical factors that predict PC usage among patients with advanced RCC. Taken together, this suggests the need for more equitable and systematic use of PC among patients with advanced RCC.
ASSET: Alternative schedule sunitinib in metastatic renal cell carcinoma (RCC)—Cardiopulmonary exercise testing (CPET).
Authors: Harrison Michael Roger , Bartlett David , Zhang Tian , Armstrong Andrew J. , Coburn Aubrie , Coyne Brian , Anand Monika , Oyekunle Taofik , Wu Yuan , Khouri Michel , George Daniel J. 
Published: March 2021

300 Background: Sunitinib (SUN) is a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for treatment of advanced RCC and high risk RCC after nephrectomy. Evidence suggests that a 2 week (wk) on, 1 wk off schedule (2/1) of SUN administration may be more tolerable than the standard 4 wk on, 2 wk off schedule (4/2). We investigated changes in cardiopulmonary function and related parameters over time in RCC patients treated with both schedules of SUN. Methods: Patients starting SUN for RCC, with KPS ≥80 and normal organ and marrow function, were enrolled and randomized 1:1 to schedule 4/2 or 2/1. Subjects were required to be able to walk and jog on a treadmill and to complete an acceptable CPET at baseline (BL). Primary endpoint was change in peak oxygen uptake (VO2peak) on both schedules at 12 wk from BL. Key secondary endpoints were change from BL to 12 wk in: left ventricular ejection fraction (LVEF), upper and lower body strength (1-RM), functional measures (chair stand, timed up-and-go [TUG], 6-minute walk test [6MWT], quality of life (QOL; FACT-Fatigue, FKSI-19), anxiety and depression (HADS) and exercise behavior (Godin Leisure Score). ANCOVA models controlling for baseline values were used to analyze the primary and secondary endpoints. Results: Between 11/20/2017 and 6/24/2019, 9 out of a planned 30 patients consented to participate at Duke. Two patients declined to participate and 7 patients were enrolled on study: 4 on Arm A and 3 on Arm B. All 7 patients completed the 12 wk study. Median age, BMI, and VO2peak were 65 yrs, 30.5 kg/m2, and 19.2 ml kg−1 min−1. We observed no difference in the primary endpoint of VO2peak between arms (p=0.84). We report BL to 12 wk change scores for all patients starting SUN (Table). In addition, mean change scores (SE) for QOL by FACIT-Fatigue and FKSI-19 were -2.88 (1.5) and 1.2 [9.8]; anxiety and depression by HADS 1.14 (1.3); and physical activity 1.14 (1.7). Conclusions: We observed non-significant declines in most measures of physical fitness and function during the first 12 wk of treatment with SUN. To our knowledge, this is the first reported study of these parameters in patients with RCC. Given that a VEGF TKI, alone and with an immune checkpoint inhibitor, remains a standard of care for metastatic ccRCC, studies should be undertaken to examine whether exercise training can prevent declines in physical fitness and function. Clinical trial information: NCT03109015 . [Table: see text]
Health-related quality-of-life outcomes from a phase II open-label trial of two different starting doses of lenvatinib in combination with everolimus for treatment of renal cell carcinoma following one prior VEGF-targeted treatment.
Authors: Bergerot Cristiane Decat , Rha Sun Young , Pal Sumanta K. , Koralewski Piotr , Stroyakovskiy Daniil , Alekseev Boris , Parnis Francis , Castellano Daniel , Lee Jae-Lyun , Sunela Kaisa , Ciuleanu Tudor , Heng Daniel Yick Chin , Glen Hilary , Wang Jinyi , Bennett Lee , Pan Janice , O'Hara Karen , Puente Javier 
Published: March 2021

314 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer, constituting 80% to 85% of primary renal neoplasms. Preserving health-related quality of life (HRQOL) is an important goal during RCC treatment, but HRQOL analyses in prospective clinical trials in RCC are limited. We report changes in HRQOL, a secondary endpoint of this phase II trial. Methods: HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of two different starting doses of lenvatinib (18 mg vs. 14 mg daily [QD]) in combination with everolimus (5 mg QD), following one prior vascular endothelial growth factor–targeted treatment (NCT03173560). HRQOL was measured using three different instruments, including the FKSI-DRS, EORTC QLQ-C30, and EQ-5D-3L. Change from baseline HRQOL was assessed using linear mixed-effects models. Deterioration events for time to deterioration (TTD) analyses were defined using established thresholds for minimally important differences in the change from baseline for each scale (i.e., 10 points for EORTC, 3 points for FKSI-DRS, 0.08 points for EQ-5D index, and 10 points for EQ-VAS). The distribution of TTD and median TTD for each treatment arm were estimated using the Kaplan-Meier method. Results: Baseline characteristics, including baseline scores of the 343 participants randomly assigned to 14 mg QD lenvatinib (n = 172) and 18 mg QD lenvatinib (n = 171), were well balanced. The average scores for the 18 mg QD group were generally higher, with lower symptom severity than the 14 mg QD group. The least squares mean estimates for change from baseline were favorable for the 18 mg QD group over the 14 mg QD group for the FKSI-DRS and most EORTC QLQ-C30 scales; however, the differences between treatments did not exceed the minimally important difference for clinical significance. Both study arms showed an increase diarrhea severity. Median TTD was longer among participants in the 18 mg QD group than those in the 14 mg QD group for most scales. Conclusions: In most scales, participants who received an 18 mg QD lenvatinib starting dose had better HRQOL and longer time to deterioration than those who received a 14 mg QD starting dose. These findings suggest that the approved treatment regimen of an 18 mg starting dose of lenvatinib in combination with everolimus remains favorable for RCC treatment, following one prior vascular endothelial growth factor–targeted treatment. Clinical trial information: NCT03173560 .
A prospective phase II/III study of PSMA-targeted 18F-DCFPyL-PET/CT in patients (pts) with prostate cancer (PCa) (OSPREY): A subanalysis of disease staging changes in PCa pts with recurrence or metastases on conventional imaging.
Authors: Durack Jeremy C. , Alva Ajjai Shivaram , Preston Mark A. , Pouliot Frederic , Saperstein Lawrence , Carroll Peter R. , Pienta Kenneth J. , Rowe Steven P. , Patnaik Akash , Probst Stephan , Stambler Nancy , Jensen Jessica , Wong Vivien , Siegel Barry A. , Morris Michael J. 
Published: March 2021

32 Background: Conventional imaging and bone scintigraphy are suboptimal modalities for identifying PCa. PSMA-based imaging is highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of PCa. The diagnostic performance, detection rate, and potential impact of 18F-DCFPyL on staging of pts with high- risk PCa have been previously reported. Here we report on the impact of 18F-DCFPyL on staging of pts with PCa recurrence or metastases on conventional imaging. Methods: 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging (CT, MRI) or whole-body bone scintigraphy and in whom at least one lesion was deemed amenable to biopsy. A single dose of 9 mCi (333 MBq) of 18F-DCFPyL was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. Based on TNM staging: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) and other visceral organs/soft tissue (M1c), 18F-DCFPyL-PET/CT detection rates including lesion counts were systematically analyzed. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: In this study, 82 (70%) patients had baseline radiographic M1 stage disease (14 patients with M1a, 50 patients with M1b, 18 patients with M1c) and 33 (28%) patients were M0 stage at baseline by central conventional imaging review; two patients were unevaluable. 18F-DCFPyL-PET/CT up-staged 58% (19/33) of pts from M0 to M1, of whom 91% (10/11) who underwent an extra-pelvic biopsy were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a. Of the patients who were staged M1 at baseline, 18F-DCFPyL-PET/CT upstaged 16% (10/64; M1a to M1b or M1c: n = 4; M1b to M1c: n = 6) of pts to a higher M1 sub-stage and down-staged 22% (18/82) to M0. Conclusions: 18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease. These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging. Clinical trial information: NCT02981368.
Long-term survival of favorable-risk patients with metastatic renal cell carcinoma treated with second-line axitinib in a multicenter phase II study.
Authors: Tsimafeyeu Ilya , Borisov Pavel S. , Semenov Andrey , Leonenkov Roman , Novikova Olga , Gamayunov Sergey , Mikhailova Nadezhda , Bondarenko Anastasia , Abdelgafur Ahmed 
Published: March 2021

332 Background: Tyrosine kinase inhibitors remain possible treatment options in favorable risk patients newly diagnosed with metastatic renal cell carcinoma (mRCC). In phase II study (FavorAx), axitinib showed the activity in mRCC patients with a favorable risk and history of prior VEGFR-directed therapy. Here we present the outcomes from expansion study cohort with 4 years follow-up. Methods: Patients were required to have clear-cell mRCC, favorable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. Axitinib was given orally at a starting dose of 5 mg twice daily with possible dose titration. Treatment was continued until disease progression according to RECIST version 1.1, unacceptable toxicity, death, or withdrawal of consent. All patients were assessed for efficacy. Endpoints included progression-free survival (PFS, primary); overall survival (OS), objective response rate (ORR), and safety (secondary). Results: A total of 55 patients were assessed, 58% of whom were male. Median age was 64 years. 29 (53%) patients had 2 and more metastatic sites. 73% and 27% of patients received first-line sunitinib or pazopanib. The median PFS was 19 months (95% CI, 15–23) and the median OS was 29.4 months (95% CI, 21.5–37). The 4-year OS rate was 36%. The objective response rate was 31% and 2 (3.6%) patients achieved a complete response. Disease progression was the single reason for discontinuation of axitinib. After disease progression, 62% of patients received third-line therapy. The toxicity was consistent with previously reported data. The most common adverse events associated with axitinib were hypertension, fatigue, and diarrhea, each occurring in more than 20% of patients. Conclusions: Second-line axitinib continues to show efficacy in favorable risk patients with mRCC. Long-term OS and PFS were observed with axitinib. Clinical trial information: NCT02700568 .
Combination therapy with avelumab (Ave) and cabozantinib (Cabo) in patients (pts) with newly diagnosed metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Li Haoran , Swami Umang , Boucher Kenneth M , Gupta Sumati , Hawks Josiah , Sirohi Deepika , Agarwal Neeraj , Maughan Benjamin Louis 
Published: March 2021

334 Background: Immune therapy combinations are now standard first-line therapy for pts with mccRCC. Cabo modulates key components of the immune system such as decreasing regulatory T-cells and increasing T-effector cell populations and is approved for treatment of mRCC. We hypothesize that Ave + Cabo will be safe and show clinical activity in mccRCC. Methods: Prospective phase I clinical trial using a 3+3 design with three planned dose cohorts: Cabo 20mg/day, 40mg/day and 60mg/day + Ave (10mg/kg q2weeks) in each arm. The primary endpoint was safety and identification of the recommended phase II dose (RP2D). Key secondary endpoints included objective response rate (ORR) and radiographic progression free survival (PFS). No dose modifications were allowed for Ave but dose delays were permitted. Dose reductions were allowed for Cabo. There were an additional 3 patients included in the final dose cohort as a confirmation of the RP2D. RECIST 1.1 was used to determine ORR. Treatment beyond progression was allowed. Results: Twelve patients with newly diagnosed mccRCC were enrolled from 08/2018 through 03/2020. Three patients were enrolled into the 20 and 40mg cohorts each, six patients enrolled in the 60mg cohort. IMDC risk: favorable 4 patients, intermediate 6 patients, poor 2 patients. No dose limiting toxicities were observed in any cohort. Only one SAE related to study treatment was observed, thromboembolism, after the DLT period. Immune related adverse events (irAE) occurred in six patients (50%) and included hypothyroidism, colitis, nephritis, allergic rhinitis and rash. Six patients required dose reductions of cabozantinib after the DLT period: one in the 40mg cohort and five in 60mg cohort, most frequently due to oral mucositis and hand foot syndrome. One patient discontinued Ave due to irAE (nephritis). No patients discontinued Cabo due to toxicity. The ORR was 33% (all PR). The clinical benefit rate (CR+PR+SD) was ~ 92%. One patient experienced PD on the first scan and then continued on the protocol treatment without further progression at the time of this report (follow up to date ~ 7 months). Seven of 12 pts are still on protocol treatment. Conclusions: Ave + Cabo in mccRCC is safe and preliminarily efficacious. Even though the DLT was not met in any of the cohorts, based on dose reduction required in 5 of 6 pts in the Cabo 60 mg cohort after the DLT period, the recommended RP2D dose for the combination is Cabo 40mg/day and Ave 10mg/kg q2 weeks. Safety and efficacy data will be elaborated in the meeting. * NA & BLM: equal contribution Clinical trial information: NCT03200587 .