bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of cabozantinib in advanced MiT family translocation renal cell carcinomas (TRCC).
Authors: Thouvenin Jonathan , Alhalabi Omar , Hirsch Laure , Hasanov Elshad , Barthelemy Philippe , Martini Dylan J. , Campedel Lucas , Amrane Karim , Borchiellini Delphine , Chahoud Jad , Bakouny Ziad , Ravi Praful , Viswanathan Srinivas Raghavan , Bilen Mehmet Asim , Choueiri Toni K. , Tannir Nizar M. , Malouf Gabriel G. 
Published: March 2021

274 Background: MiT family translocation renal cell carcinomas (TRCC) represent a rare and aggressive subgroup of RCC harboring high expression of c-MET. While response rates of VEGF receptor-tyrosine kinase inhibitor and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a TKI that inhibits VEGFR, MET, and AXL) in this subgroup is unclear. Methods: We performed a multicentre, retrospective, international cohort study of patients with TRCC treated with cabozantinib regardless the line of treatment at 7 centers (3 in France and 4 in the US). The main objectives were to estimate response rate according to RECIST criteria, and to analyze progression-free survival (PFS) and overall survival (OS). Results: Among 31 metastatic patients treated in the participating centers, 24 were evaluable for response and were included in this study (21 with TFE3 and 3 with TFEB translocations). Median age at diagnosis was 43.5 years (range, 22–70). Most frequent metastatic sites at diagnosis were lungs (62.5%), retroperitoneal lymph nodes (45.8%) and bone (37.5%). Patient’s IMDC risk group at diagnosis was favourable (20,8%), intermediate (62,5%) and poor (16,7%). Seven (29%) patients received cabozantinib at first line, 9 (37.5%) at second line and 8 (33%) at third line and beyond. The proportion of patients who achieved an objective response was 16.6%, including 1 complete response and 3 partial responses. For 11 (45.8%) patients, stable disease was the best response. With a median follow-up of 14 months (IQR 5-23), median PFS was 8.4 months (range, 1-34+) and median OS was 17 months (range, 2-43). No PFS difference was detected overall or in any subgroup except in patients with bone metastasis which harbored a median PFS of 3.6 months as compared to 9.1 months for those without (p=0.03). Conclusions: This real-world study provides evidence supporting activity of cabozantinib in TRCC, with more durable responses to therapy than those observed with of VEGF receptor-tyrosine kinase inhibitor and immune checkpoint inhibitors. International collaborations and prospective studies are necessary to identifies efficacious therapies for this rare disease that lacks evidence-based treatment options.
TIVO-3: Tivozanib in patients with advanced renal cell carcinoma (aRCC) who have progressed after treatment with axitinib.
Authors: Rini Brian I. , Pal Sumanta K. , Escudier Bernard , Atkins Michael B. , Hutson Thomas E. , Porta Camillo , Verzoni Elena , Needle Michael N. , McDermott David F. 
Published: March 2021

278 Background: Tivozanib (T) is a potent and highly selective VEGF receptor (R) tyrosine kinase inhibitor in clinical development for RCC. Axitinib is also a potent and selective VEGF-R inhibitor now commonly part of front-line aRCC treatment. The activity of T after axitinib has not been previously defined. The activity of T after prior therapy types including axitinib is of clinical relevance. Methods: The pivotal TIVO-3 study enrolled subjects with mRCC who failed 2 or 3 prior systemic regimens, one of which included a VEGFR TKI, stratified by IMDC risk category and type of prior therapy (two TKIs; TKI plus checkpoint; TKI + other) then randomized in a 1:1 ratio to T or S. The primary objective of the overall trial was to compare progression free survival (PFS) by blinded independent radiological review. Patients with prior axitinib received as monotherapy in the second or third line setting and other predefined subgroups were reviewed for outcome with T. Results: Patients treated with T after prior axitinib had a PFS of 5.5 months and an ORR of 13% compared to 3.7 months and 8% for patients treated with S. Other subgroups are presented in the table below. Clinical trial information: NCT02627963 . Conclusions: Tivozanib improved PFS vs. sorafenib in patients who have progressed after multiple VEGFR-TKIs, including patients with prior second or third line axitinib treatment. These results suggest differential activity from tivozanib and axitinib despite both being potent and selective VEGF-R inhibitors. [Table: see text]
Oral anticancer agent (OAA) adherence and survival in elderly patients with metastatic renal cell carcinoma (mRCC).
Authors: Dinan Michaela Ann , Wilson Lauren E , Greiner Melissa A. , Spees Lisa , Pritchard Jessica , Zhang Tian , Kaye Deborah , George Daniel J. , Scales Charles D. , Wheeler Stephanie B. 
Published: March 2021

280 Background: Multiple effective oral anticancer agents (OAAs) are now approved for the treatment of patients with advanced or metastatic renal cell carcinoma (mRCC) based on improvement in overall and progression-free survival in randomized clinical trials. However, real-world adherence and outcomes associated with OAA use in the general mRCC patient population have not been previously investigated. Methods: Retrospective analysis of SEER-Medicare patients with mRCC who received treatment with an OAA between 2007 and 2015. Adherence was assessed as proportion of days covered (PDC) within 3 months of OAA initiation with PDC > 50% categorized as adherent. The impact of initial OAA adherence on overall and disease-specific survival was analyzed landmarked at 3 months after OAA initiation. Results: A total of 905 patients met study criteria, of which 577 (63.8%) were categorized as adherent to initial OAA treatment. Multivariable analysis adjusting for clinical and demographic factors revealed that living within an impoverished neighborhood was associated with a 20% lower likelihood of adherence (OR 0.80, CI 0.68 – 0.93). No association was observed between adherence and race, ethnicity, marital status, or number of comorbidities. In survival analyses OAA adherence was associated with a significant reduction in both overall (HR 0.71, CI 0.58 – 0.87) and RCC-specific mortality (HR 0.68, CI 0.57 – 0.86). Receipt of sunitinib was associated with a significant reduction in overall and disease specific mortality compared with sorafenib. Post-hoc analysis of patients taking pazopanib as their initial OAA (N = 252) demonstrated reduced all-cause mortality if they received the minimum effective dose of 800 mg daily (HR 0.50, CI 0.35 – 0.72) and decreased adherence associated with initial higher out-of-pocket payments (χ2 test, p = 0.003). Conclusions: Socioeconomic factors predict poor adherence to OAA therapy in Medicare beneficiaries with metastatic RCC, which is in turn associated with poor overall and disease-specific survival. Efforts to improve outcomes and mitigate disparities in the general mRCC population should incorporate considerations of OAA adherence and economic factors. Sunitinib and pazopanib appear associated with favorable survival and remain the most commonly used OAAs in this over 65 year old patient population.
Use of 18F-fluciclovine PET/CT (FluPET) for prostate cancer (PC): Initial results from a prospective registry at a tertiary academic center.
Authors: Wong Risa Liang , Cheng Heather H. , Holt Sarah K , Conrad Nathan , Loesch Hannah , Fernandez Sara , Sahoo Rameen , Bauer Zoya , Toulouse Andrea , Grivas Petros , Yezefski Todd , Russell Kenneth J. , Wright Jonathan L. , Schweizer Michael Thomas , Montgomery Robert B. , Lee Jean H , Chen Delphine L. , Zeng Jing , Lin Daniel W. , Yu Evan Y. 
Published: March 2021

29 Background: FluPET, a next-generation imaging modality approved in 2016 for suspected PC recurrence with elevated PSA after prior therapy, is becoming more widely available; however, practice patterns and impact on outcomes is unknown. We hypothesize FluPET is ordered for a variety of reasons, with findings often leading to changes in treatment plan. Methods: In this prospective registry, providers are surveyed before, 1-2 weeks after, and 1 year after FluPET to assess reasons for obtaining FluPET, projected treatment plan, changes in plan due to FluPET findings, and toxicity potentially attributable to change in treatment plan. Baseline patient characteristics, FluPET results, and longitudinal outcomes are collected. We report early descriptive findings with χ2 and student’s t-test used for univariate analyses. Results: 50 patients enrolled 12/2018-08/2020 had baseline characteristics described in Table; 46 underwent FluPET. Rationale for ordering included initial staging prior to definitive local therapy (6.1%), guidance of salvage local therapy for 1st biochemical recurrence (BCR) (46.9%), guidance of additional salvage after ≥2 local therapies and 2nd BCR (36.7%), and confirmation of equivocal metastatic disease (10.2%). When queried on next steps, providers considered observation (67.3%), androgen deprivation therapy (ADT) (26.5%), ADT + docetaxel or novel anti-androgens (AA) (20.4%), and salvage therapy with surgery, radiation, or cryotherapy (26.5%), often selecting ≥1 option. FluPET found ≥1 PC lesion in 73.9% of cases, ≥1 indeterminate lesion in 8.7%, and no lesions in 17.4%. 45.5% of providers reported changing treatment plan based on FluPET results; 6.8% changed to observation, 20.5% to systemic therapy, 13.6% to local salvage therapy, and 4.5% to a combination of local and systemic therapies. Change in therapy was associated with positive FluPET (54.5% vs. 18.2%, p=0.044), and within those cases, with higher SUVMax (mean 7.7 vs. 5.2, p=0.021) but not number of lesions (p=0.804). Conclusions: FluPET is often obtained to guide salvage therapy after BCR but is also used for initial staging or resolving equivocal findings of metastases. Many providers changed intended treatment based on FluPET findings, especially if positive; de-escalation to observation was rare. [Table: see text]
Impact of PSMA PET/CT on SRT planning: Preliminary results from the randomized phase III trial NCT03582774.
Authors: Calais Jeremie , Armstrong Wesley R , Kishan Amar Upadhyaya , Booker Kiara M , Elashoff David , Fendler Wolfgang Peter , Czernin Johannes , Nickols Nicholas George 
Published: March 2021

30 Background: The purpose of this trial is to evaluate the success rate of salvage radiation therapy (SRT) for recurrence of prostate cancer (PCa) after radical prostatectomy with and without planning based on prostate specific membrane antigen (PSMA) positron emission tomography (PET). Methods: This is a multicenter, prospective, randomized, controlled, open-label, Phase 3 clinical imaging trial powered for clinical outcome at 5 years. UCLA is the leading central site in which PSMA PET, clinical follow-up and data management are being done. UCSF was a participating site in which PSMA PET imaging can be done. SRT can be performed anywhere, patients are followed remotely by the UCLA investigators. Patients scheduled for SRT for recurrence after primary prostatectomy and with PSA ≥ 0.1ng/ml at time of enrollment were eligible. Patients were randomized to proceed with standard SRT allowing for any conventional imaging aside from PSMA PET/CT (control arm) or undergo a 68Ga-PSMA-11 PET/CT scan prior to SRT planning (investigational arm). The primary endpoint is the success rate of SRT at 5 years in patients who undergo SRT. We report here the preliminary results of a secondary endpoint: the impact of PSMA PET on SRT planning by comparing the pre-randomization RT plans prospectively obtained on surveys before randomization to the actually delivered RT plans obtained after follow-up. Results: Enrollment of the trial was complete. 193 patients were enrolled from 09.06.2018 to 08.17.2020. 7/90 patients (9%) in the control arm dropped-out the study because they underwent a PSMA PET at another institution, while 1/103 (1%) patients of the intervention arm dropped-out due to COVID-19 related complications. After a median follow-up of 13.3 months (last follow-up date 09/01/2020), delivered RT plans were obtained in 60/83 (72%) and 70/102 (69%) of patients of the control and the PSMA arms, respectively. Median PSA at enrollment was 0.32 ng/ml (IQR 0.17-1.35) and 0.22 ng/ml (IQR 0.14-0.50) in the control and PSMA arms, respectively. There was a change between the intended pre-randomization RT plan and the actually delivered RT plan in 17/60 (28%) and 40/70 (57%) of the patients in the control and PSMA arms, respectively (p = 0.002). SRT was aborted in favor of systemic therapy and/or metastasis directed RT for extra-pelvic M1 disease in 2/60 (3%) and 12/70 (17%) of the control and PSMA arms, respectively (p = 0.17). Dose prescription and/or target volume delineation was changed in 2/60 (3%) and 1/70 (26%) in the control and PSMA arms, respectively (p = 0.001). Conclusions: In this prospective randomized phase 3 study, PSMA PET had an impact on the SRT plan in more than half of the patients. Long-term follow-up will show if the impact of PSMA PET on SRT planning translates into improved outcome or not. Clinical trial information: NCT03582774.
Phase II trial of stereotactic ablative radiation (SAbR) for oligometastatic kidney cancer.
Authors: Hannan Raquibul , Christensen Michael , Robles Liliana , Christie Alana , Garant Aurelie , Desai Neil Bipinchandra , Hammers Hans J. , Arafat Waddah , Bowman Isaac Alexander , Cole Suzanne , Courtney Kevin Dale , Woldu Solomon L. , Bagrodia Aditya , Margulis Vitaly , Cadeddu Jeffrey A , Choy Hak , Sher David , Brugarolas James 
Published: March 2021

311 Background: Stereotactic ablative radiotherapy (SAbR) is a promising treatment option for selected oligometastatic renal cell carcinoma (RCC) patients that can provide longitudinal disease control while preserving quality of life. Retrospective data have shown a local control (LC) rate greater than 90% and longitudinal disease control of over a year without systemic therapy. However, prospective validation of SAbR for oligometastatic RCC is lacking. In this prospective phase II single arm trial, we evaluated the impact of SAbR on freedom from systemic therapy (FFST). Methods: Treatment naïve patients with RCC confirmed by pathology and radiographic evidence of three or fewer extracranial metastases received SAbR with curative intent to all measurable sites of disease. Follow-up included radiographic imaging at three-month intervals to assess disease control. The primary endpoint was FFST defined as time from SAbR to the initiation of systemic therapy. Secondary endpoints included LC, modified progression-free survival (mPFS) (time from first SAbR to progression not amenable to further SAbR), PFS on subsequent systemic therapy, cancer-specific survival (CSS), overall survival (OS), toxicity and health-related quality of life (QOL) indices as measured with EQ-5D-5L and FACT-G. A Wilcoxon signed-rank test was used to evaluate the QOL indices. Results: The trial completed accrual with the enrollment of 23 patients who received SAbR to a total of 38 sites. At a median follow-up of 12 months (interquartile range 1.8-16), 1-year FFST was 87% (95% CI: 56%-96%). The 1-year mPFS was 79% (95% CI:49%-93%), while the median mPFS has not yet been reached. Three patients had disease progression at individual time points of 3.5, 4.0, and 12 months. One of these patients developed brain metastases that were controlled with gamma knife radiosurgery without initiating systemic therapy. The LC, CSS, and OS were 100% (38/38), 100% (23/23), and 95% (22/23), respectively. When compared to baseline, no significant decline in QOL was detected. Three patients experienced treatment-related grade 1 toxicity; no ≥grade 2 toxicities were reported. One patient died of an unrelated cause. Conclusions: SAbR is a safe and effective treatment for oligometastatic RCC that can provide longitudinal disease control and preserve quality of life. These data support further evaluation of SAbR for oligometastatic RCC in a randomized study. Clinical trial information: NCT02956798 .
Association of statins and nivolumab activity in patients with metastatic renal cell carcinoma (mRCC): Results from the phase II nivoren—GETUG AFU 26 trial.
Authors: Colomba Emeline , Flippot Ronan , Dalban Cécile , Negrier Sylvie , Chevreau Christine , Gravis Gwenaelle , Oudard Stephane , Laguerre Brigitte , Barthelemy Philippe , Gross Goupil Marine , Geoffrois Lionnel , Rolland Frederic , Thiery-Vuillemin Antoine , Joly Florence , Ladoire Sylvain , Tantot Florence , Escudier Bernard , Albiges Laurence 
Published: March 2021

359 Background: Statins are HMG-CoA inhibitors that regulate several mechanisms involved in tumor growth, including mitochondrial metabolism, activation of oncogenic signaling pathways, and immune modulation. Population-based studies showed that statin intake may be negatively associated with RCC onset. The impact of statins on response to immunotherapy in mRCC is unknown. Herein we study the association between statin administration and outcomes in patients with mRCC treated with nivolumab in the NIVOREN-GETUG AFU 26 phase II trial (NCT03013335). Methods: Patients with mRCC who failed previous VEGFR inhibitors were included. We assessed nivolumab activity, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to statin intake at baseline. Toxicity was assessed using CTCAE v4.0. Results: Overall,133 patients were treated with statins at baseline among 702 evaluable for concomitant therapies (19%). Among them, median age was 68 (49-90), 84% were male, 85% had a performance status ≥ 80%, 42% were overweight and 20% obese. Patients treated with statins had mostly good (23%) or intermediate (58%) IMDC risk, 64% had grade 3 or 4 tumors, and nivolumab was given in a third line setting or more in 55%. Median follow-up was 23.9 months (95%CI 23.0-24.5) in the overall cohort. The ORR was 26% in patients treated with statins, PFS 5.0 months (CI95% 3.0 – 5.5), OS 27.9 months (CI95% 19.4-30.3). Outcomes of patients with or without statins did not differ significantly. Similar rates of grade 3-5 TRAE were reported in patients with (20%) or without (18%) statin intake. Conclusions: This is the first study to evaluate statin intake and outcomes with nivolumab in patients with mRCC. Despite numerically higher ORR, statins were not significantly associated with improved outcomes. These data require other analyzes considering other factors such as BMI and other comorbidities. Further studies may help better understand the interplay between immunity and metabolic reprogramming in RCC.
Renal sarcomas: Epidemiology, treatment and outcomes.
Authors: Uhlig Johannes , Uhlig Annemarie , Deshpande Hari Anant , Hurwitz Michael E. , Humphrey Peter , Kim Kevin 
Published: March 2021

362 Background: Renal sarcomas are a rare malignancy in adults and have been inadequately evaluated on a US national level regarding epidemiology, treatment, and outcomes. Methods: The 2004-2016 NCDB and SEER databases were queried for adult patients diagnosed with sarcomas of renal origin. Age-adjusted incidence rates were derived from the SEER database. Overall survival (OS) was assessed using multivariable Cox proportional hazards models adjusting for demographics, tumor and treatment variables. Results: 1,279 renal sarcomas comprising 39 subtypes were reported from 2004-2016, contributing 0.3% of all NCDB renal malignancies. As shown in the table below, the most common subtypes were leiomyosarcoma (LMS), angiosarcoma (AS), malignant rhabdoid tumor (MRT), dedifferentiated liposarcoma (DL) and primitive neuroectodermal tumors (PNET). Over the study period, renal sarcoma incidence rates remained constant at 0.5 cases / 1 million citizens. Sex-specific incidence differences were evident with female predominance for LMS, and male predominance for AS. Age at diagnosis and tumor diameter varied according to sarcoma subtypes: for example, median age in LMS was 62y compared to 30y in Ewing sarcoma patients; median tumor diameter was 18cm for solitary fibrous tumors and 7.5cm for synovial sarcoma. Renal sarcoma was staged as T3 in 33.3% and T4 in 14.2%, while distant metastases were evident in 29.1% of cases at diagnosis. Most T1-T3 stage renal sarcomas underwent surgical resection (992/1098, 84%), compared to 71% for T4 renal sarcomas (128/181). Systemic therapy was administered in 32.1% of renal sarcoma cases (23.5% combined with surgical resection). Renal sarcoma 1-,2-, and 5-year OS rates were 48%, 24%, and 13%. OS was worse for T4 vs T1-3 sarcomas (HR=1.6, p<0.001), and cases with distant metastases vs none (HR=3.2, p<0.001). As summarized in the table, OS varied according to sarcoma subtypes with worse OS for AS compared to PNET (HR=1.5, p=0.04). Conclusions: Accounting for 0.3% of renal malignancies in adults, renal sarcomas include 39 different histological subtypes with distinct demographics, tumor parameters and outcomes. Renal sarcomas commonly present with advanced T stage at diagnosis and are treated with surgical resection with or without systemic therapy. [Table: see text]
Time trends of drug specific adverse events among patients on androgen receptor antagonists: Implications for remote monitoring.
Authors: Fleshner Lauren , O'Halloran Sophie , Lajkosz Katherine , Wise Jacob , Kenk Miran , Nguyen Susan , Fleshner Neil Eric 
Published: March 2021

40 Background: In light of the global pandemic, reducing patient exposure via remote monitoring is desirable. Currently, advanced prostate cancer patients prescribed Abiraterone or Enzalutamide are scheduled for an in-person appointment monthly, to screen for adverse events (AEs). We set out to determine time trends of drug specific AEs in order to determine whether reducing in-person visits for patients taking either Abiraterone or Enzalutamide is feasible. Methods: This chart review was conducted on 667 unique advanced prostate cancer patients, being either metastatic hormone sensitive or castration resistant and utilizing Abiraterone or Enzalutamide. Patients who switched courses of treatment and received both drugs were included twice in the data, resulting in 828 “subjects” overall. Data were collected via accessing electronic patient records, to determine the first sign of an AE related to either Abiraterone or Enzalutamide. These AEs include; hypertension, elevated liver enzymes (bilirubin, AST, ALT) or hypokalemia. Survival analysis was used to determine the time to adverse event. All grade AEs are included in this analysis. Results: In this study, 425 and 403 patients received Enzalutamide and Abiraterone, respectively. In total, 36.3% of those who took Enzalutamide experienced an AE, compared to 43.4% of patients on Abiraterone. For patients utilizing Abiraterone, cumulative incidence of AEs at 3,6,9 and 12 months were: 65.0%, 81.2%, 90.9% and 93.9%, respectively. Among Enzalutamide users, cumulative incidence of AEs at 3,6,9 and 12 months were: 46.8%, 67.5%, 81.2% and 88.3%, respectively. The primary first AEs associated with Enzalutamide consumption were hypertension and liver dysfunction (77.48% and 22.52%). In the Abiraterone group, the first associated AEs were liver dysfunction (48.78%), hypertension (46.34%), and hypokalemia (4.88%). Conclusions: These data suggest that the likelihood of attaining AEs associated with Abiraterone or Enzalutamide utilization decreases over time and tend to occur within the first 6 months of therapy. Furthermore, the vast majority of these AEs can be remotely monitored via outside laboratories and remote blood pressure monitoring. In light of the COVID-19 crisis, remote monitoring after 6 months of taking Abiraterone or Enzalutamide would appear appropriate. Efforts to further safely reduce in person visits should be explored.