bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of patients (pts) with advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs): Associations with age, race, sex and smoking history.
Authors: Makrakis Dimitrios , Talukder Rafee , Carril Lucia , de Kouchkovsky Ivan , Park Joseph J , Bilen Mehmet Asim , McKay Rana R. , Agarwal Neeraj , Zakharia Yousef , Devitt Michael E. , Pinato David James , Hoimes Christopher J. , Gartrell Benjamin Adam , Tripathi Abhishek , Bamias Aristotelis , Drakaki Alexandra , Murgic Jure , Di Lorenzo Giuseppe , Grivas Petros , Khaki Ali Raza 
Published: June 2021

e16526 Background: ICIs have altered the therapeutic landscape in pts with aUC and new biomarkers are needed to better predict response and outcomes with ICIs. It is unclear whether demographics, such as race, age, sex and history of smoking, are associated with outcomes with ICIs. We hypothesized that specific demographic groups (sex, age, race, smoking history) would be associated with outcomes with ICIs in aUC. Methods: We performed a retrospective cohort study across 25 institutions. Data collected included demographic and clinicopathologic factors, response and outcomes. We calculated observed response rate (ORR), Progression-Free Survival (PFS) and overall survival (OS) for specific demographic groups. We built multivariable models (logistic regression for ORR; Cox regression for PFS and OS) with all demographic groups to assess outcomes. Analysis was done for the overall population and stratified by treatment line (first line [1L]; salvage [2+L]). The stratified analysis was also adjusted for known prognostic risk scores (internally developed for 1L; Bellmunt for 2+L); p-value < 0.05 was significant. Results: We identified 1026 pts; 754, 744 and 780 were included in OS, ORR and PFS analysis. Overall, median age at ICI initiation was 70; 26% female; 75% White, 11% Hispanic, 5% Black, 8% other; 69% had smoking history; 28% with mixed histology; 17% with upper tract UC. In the unstratified analysis, age 65-74 (vs < 65) was significantly associated with higher ORR (32% vs 22%) and median PFS (5 vs 3 mo HR 0.8); otherwise no significant difference was noted among groups for ORR, PFS, OS in both the stratified and unstratified analyses (Table). Conclusions: We did not identify significant associations between age, sex, race or smoking history and ORR, PFS, OS with ICIs in pts with aUC. Limitations include retrospective nature, lack of randomization, possible selection and confounding factors. Further research is required to identify prognostic and predictive biomarkers for ICI therapy in aUC.[Table: see text]
Impact of clinicopathological features on survival in patients treated with immune-based combinations for metastatic urothelial carcinoma: A meta-analysis of randomized clinical trials.
Authors: Mollica Veronica , Rizzo Alessandro , Santoni Matteo , Marchetti Andrea , Rosellini Matteo , Massari Francesco 
Published: June 2021

e16534 Background: Immune checkpoint inhibitors (ICIs) have recently revolutionized the treatment landscape of metastatic urothelial carcinoma (mUC). Nonetheless, little is known regarding the impact of clinicopathological features in this setting. We performed a meta-analysis aiming to evaluate the predictive value of ECOG-PS, age, gender, liver metastases, and histology in randomized controlled trials (RCTs) comparing ICI-based combinations versus chemotherapy in mUC patients. Methods: We retrieved all the relevant RCTs through PubMed/Med, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs comparing ICI-based combinations versus chemotherapy alone in mUC patients. The primary endpoint was overall survival (OS), measured as hazard ratio (HR) with corresponding 95% confidence interval (CI). All statistical analyses were performed using R studio software. Results: Overall, 1032 mUC patients were included in the analysis. Compared with chemotherapy, ICI-based combinations significantly decreased the risk of death in several clinicopathological subgroups, including no liver metastases (HR, 0.84; 95% CI, 0.74-0.95) and ECOG-PS 0 patients (HR, 0.84; 95% CI, 0.72-0.97). Similarly, ICI-based combinations were associated with prolonged OS in mUC patients who were < 65 years old (HR, 0.82; 95% CI, 0.72-0.95), as well as in male (HR, 0.90; 95% CI, 0.82-0.99) and female patients (HR, 0.81; 95% CI, 0.68-0.97). Conversely, a non-statistically significant benefit was observed for chemotherapy alone in mUC patients with liver metastases (HR, 1.06; 95% CI, 0.86-1.31). Conclusions: According to our results, the magnitude of benefit of ICI-based combinations over chemotherapy in mUC was consistent across a number of clinicopathological subgroups, while a proportion of patients could respond to chemotherapy alone.Despite several limitations affect our analysis, we believe these results could guide in everyday treatment decision-making, also assisting in the design and interpretation of future clinical trials on ICIs in mUC.
Cabozantinib versus other TKIs after CPI treatment in the real-world management of patients with mRCC.
Authors: Marteau Florence , Harrow Brooke , McCarthy Christine , Wallace Joel , Monnette Alisha , Wang Yunfei , Doshi Gurjyot K. 
Published: June 2021

e16539 Background: Checkpoint inhibitors (CPIs) are a treatment option for patients with metastatic renal cell carcinoma (mRCC), but there is limited clinical data on the efficacy of targeted therapies following CPI treatment. Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets multiple receptor kinases implicated in tumorigenesis. In the US, cabozantinib is approved for use in patients with advanced RCC including after CPI treatment. Methods: This retrospective observational cohort study (NCT04353765) evaluated outcomes associated with cabozantinib or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment. Eligible patients initiated TKI therapy between May 1, 2016 and Sep 31, 2019 and had received a CPI as their last systemic treatment prior to TKI therapy. Patients were identified from the US Oncology Network iKnowMed electronic health record database through structured queries and a targeted chart review. The following real-world outcomes were assessed: 6-month response rate (RR6months; primary); overall response rate (ORR); overall survival (OS); time to treatment discontinuation (TTD); rates of dose reductions, and discontinuation due to adverse events (AEs). The p value for RR6months (χ2 test) was used to test for non-inferiority. Results: Eligible patients ( n = 247) had a mean (SD) age of 65.9 (10.5) years and 74.1% were male; 75.7% ( n = 187) received cabozantinib and 24.3% ( n = 60) received other TKIs. All patients had intermediate or poor MSKCC score; more poor-risk patients received cabozantinib than other TKIs (28.9% vs 20%). Outcomes data are shown in the Table. Compared with other TKIs, cabozantinib was associated with a significantly higher RR6months and ORR, and TTD was twice as long with cabozantinib. Discontinuation due to AEs was more frequent with other TKIs than with cabozantinib, although this was not statistically significant; 21.7% of discontinuations occurred during the first 3 months of treatment. AEs leading to discontinuation were consistent with the known safety profile of the products. Conclusions: In this mRCC population receiving routine care in the US, cabozantinib was used more frequently than other TKIs after CPI treatment. Cabozantinib was an effective and well tolerated option post-CPI, with a high response rate in the real-world setting.abozantinib was associated with a significantly higher response rate and a lower discontinuation rate due to AEs; TTD was double that of other TKIs. Clinical trial information: NCT04353765. [Table: see text]
Does concurrent COX inhibition and immune checkpoint blockade improve clinical outcome in patients with metastatic renal cell carcinoma?
Authors: Zhang Yumeng , Adashek Jacob J. , Kumar Premsai , Skelton William Paul , Li Jiannong , Chahoud Jad , Manley Brandon J , Spiess Philippe E. 
Published: June 2021

e16558 Background: Cyclooxygenase (COX) inhibition is postulated to restore the immune environment and synergizes with immune checkpoint inhibitors (ICI). The concurrent use of COX inhibitors (COXi) and ICI was associated with longer disease control in metastatic melanoma and non-small cell lung cancer. However, its role in mRCC remains unclear. Methods: We retrospectively reviewed 194 patients with mRCC treated with ICI (PD-(L)1 inhibitors +/- CTLA-4 inhibitors or TKIs) at Moffitt Cancer Center between 6/2014-7/2019. Concurrent use of COXi (aspirin [ASA] or NSAIDs) was defined as at least 3 weeks of COXi use during the first ICI course. Clinical characteristics of both arms were compared using Chi-squared or Kruskal-Wallis Rank Sum test. Time to progression (TTP) and Overall survival (OS) were compared using Kaplan Meier’s estimates. Univariate and multivariate Cox proportional hazards model was performed to evaluate the association between clinical factors, TTP, and OS. Results: Of 194 patients, 126 patients (64.9%) took COXi. Median age was 59.7 years and 80.4% were male. COXi arm had fewer patients with < 1 year from diagnosis to systemic treatment (45.9% vs 69.5%, p = 0.006) and more advanced age (median: 66 years vs 60 years, p = 0.01). IDMC risk group, number of prior therapies, neutrophil to lymphocytes ratio were similar between both arms. Median TTP was 8 months (m) for COXi arm and 12m for ICI only (HR 1.38; 95% CI [0.98, 1.94]). Median OS was 27m for COXi arm and 33m for ICI only (HR 1.05, 95% CI [0.69, 1.59]). Early mortality rate (within 3m of ICI treatments) were similar between both arms. Conclusions: In contrast to melanoma and lung cancer, concurrent use of COXi and ICI did not improve TTP and OS in patients with mRCC. The dual blockade showed a trend for shorter TTP. Further validation studies with larger cohorts are needed to confirm this finding.[Table: see text]
Thirty day readmissions and outcomes following radical nephrectomy in renal cell carcinoma: A nationwide analysis.
Authors: Shrivastava Trilok , Salazar Miguel , Prado Victor , Gauto Estefania , Baral Binav , Upadhyay Shristi , Elsebaie Maha A.T. 
Published: June 2021

e16560 Background: Nephrectomy is one of the primary treatments of Stage I-III renal cell carcinoma (RCC), which is usually associated with low rates of serious morbidity and mortality. However, a fraction of patients gets readmitted after the surgery for numerous reasons which can impact their overall prognosis. Methods: We conducted a retrospective cohort study using the 2017 National Readmission Database of adult patients with RCC readmitted within 30 days after an index admission for nephrectomy. We aimed to identify the 30-day readmission rate, mortality, resource utilization, and independent predictors of readmission. Results: A total of 25,307 patients with RCC underwent nephrectomy. The 30-day readmission rate was 8.7%. The top five causes for readmission were sepsis, AKI, STEMI, surgical infections & metastatic disease. Patients requiring readmission were less likely to be discharged home (56.5 vs 81.8%), have private insurance (27.2 vs 34.7), obesity (14.7 vs 20.6%), hypertension (30.9 vs 47.1%), and be admitted to a teaching hospital (75.8 vs 79.2%). They were more likely to be insured with Medicare (58.3 vs 53.3%), have lower income (28.7 vs 26.3%), type 2 diabetes (32.4 vs 26.7%), CKD (44.1 vs 20.7%), malnutrition (9.2 vs 2.1%), undergo chemotherapy (5.2 vs 1.9%). Readmission was associated with higher in-hospital mortality (1.5 vs. 0.1%), CVA (0.6 vs 0.3%), AKI (29.6 vs 16.9%) and pleural effusion (7.8 vs 1.8%). They were also more likely to require mechanical ventilation (3.5 vs 1.8%), parenteral nutrition (1.2 vs 0.4%) and hemodialysis (11.9 vs 4.5%). The in-hospital economic burden of readmission was $128 million in total charges and $31.8 million in total costs. Independent predictors of readmission were disposition to a short-term hospital or skilled nursing facility, length of stay, need for mechanical ventilation and transfusion of blood products, having type 1 diabetes, malnutrition, pleural effusion, and CKD. Younger age and private insurance were associated with preventing readmission. Conclusions: Readmissions after nephrectomy in patients with RCC are associated with increased in-hospital mortality rate and pose a high health care economic burden. We identified few risk factors and patient characteristics associated with post-surgical readmissions; however, further in-depth studies are needed to find preventable risk factors.[Table: see text]
Sunitinib in metastatic clear cell renal cancer (CCRC): A real life Chilean single institution experience.
Authors: Orlandi Luis J. , Galaz Pedro Pablo , Holloway Robert Melo , Linares Belkys Melina , Garcia Vicente Larrain 
Published: June 2021

e16562 Background: The introduction of biologic and immunologic therapy has produced a profound change in the management of metastatic CCRC but there is no definitive indication on drug selection and therapeutic sequences based on efficacy, toxicity, costs and access. Methods: We report 50 consecutive stage IV CCRC patients treated at our Institution from 12/2007 to 11/2020 with sunitinib at recommended dosage. Median age at stage IV diagnoses was 62.5 months (39 to 79). Sex distribution was 5 women (10%) and 45 (90%) men. Under MSKCC criteria 35 patients were medium + high risk (70%) and 15 (30%) low risk. Results: On an intent to treat basis the complete + partial response rate was 56% (28/50) for the entire group , 45.7% (16/35) for the high-risk group and 80% (12/15) for the low-risk group. Actuarial 5 year survival was 24% for the entire group, 11.4% for the high-risk group and 53.3% for the low -risk group. We explored the effect of metastases-free time on survival. We found that 15 patients were metastatic at the moment of initial diagnoses versus 26 patients who developed metastatic disease at 12+ months after primary tumor diagnoses. Mean survival was 32.7 months (1 - 97) for the first group and 49.5 months (6 - 156) for the second group (p<0.5). Subsequent therapies consisted of pazopanib (25 patients), axitinib (17 patients), everolimus (9 patients), nivolumab (6 patients) and cabozantinib (1 patient). Secondary reactions consisted of emesis (20%), diarrhea (16%), asthenia (14%), skin dispigmentation (12%), mucositis (10%), disgeusia (10%), dermatitis (10%), neutropenia (8%), hand and foot syndrome (4%). Conclusions: Sunitinib is a good choice in low-risk metastatic CCRC and we adopted this regimen as standard therapy in this group of patients at our Institution.
FDG-PET avidity as a prognostic biomarker for overall survival in renal cell carcinoma.
Authors: Ferdinandus Justin , Maríc Ines , Darr Christopher , Kesch Claudia , Hilser Thomas , Fendler Wolfgang Peter , Herrmann Ken , Hadaschik Boris A. , Grünwald Viktor 
Published: June 2021

e16564 Background: Positron emission tomography with (18F)-fluorodeoxyglucose (FDG-PET) is not considered a standard of care (SOC) in renal cell carcinoma (RCC) because of its variability in metabolic activity. We investigated the rate of PET-positivity in our institutional cohort and tested whether PET-positivity had prognostic value in metastatic (m)RCC. Methods: Patients with FDG-PET imaging at any time during the course of disease were identified from medical records. PET-positivity was defined according to PERCIST criteria and a five-point rating scale analogue to Deauville Scoring was used to stratify PET-avidity. Tracer uptake of the hottest lesion was measured as SUVmax. Clinical parameters and PET-positivitywere correlated with overall survival (OS). Kaplan-Meier plots, log-rank analyses, kendall rank correlation, univariate and multivariable cox regression models were employed, where appropriate. Results: A totalof 90 patients was analyzed. The median age was 64.0 (34.0-83.0) and 56 (62.2%) patients had clear cell RCC. Metastatic disease was present in 64 (71.1%) and 22 (24.4%) patients received ongoing medical treatment. 72 (80.0%) patients had prior nephrectomy. PET-positivity occurred in 57 (63.3%) patients, with similar rates among metastatic (41/64; 64%) and non-metastatic patients (16/26; 62%). PET-positive patients had shorter median OS compared to PET-negative patients (38.5 months (CI95:24.5-NR) vs. not reached (CI95: 69.6-NR), P= 0.0013). A weak correlation was found between PET-Uptake and histologic grade (Kendall’s tau 0.22; P= 0.03). Prior nephrectomy, presence of primary lesions, presence of distant metastases, histologic grade and PET-positivity were significant predictors of OS in univariate regression. In multivariable analysis, only PET-positivity remained significant (HR 4.1 (CI95: 1.1-15.4), P= 0.04). Conclusions: RCC is a metabolically active cancer, which in the majority of patients is suitable for FDG-PET diagnostic procedures. PET-positivity was an independent prognostic factor for OS in RCC, indicating its putative clinical use. Further studies to define the role of FDG-PET imaging in RCC are ongoing.
Bone-targeted therapy in patients with renal cell carcinoma bone metastases undergoing palliative surgery.
Authors: Garmezy Benjamin , Brozovich Ava , Feng Lei , Deveza Lorenzo , Satcher Robert L. 
Published: June 2021

e16572 Background: RCC bone metastases (RCCBM) are found in 20-39% of patients and are becoming more prevalent. RCCBM cause significant morbidity and often require surgical intervention. Current bone-targeted therapies include bisphosphonates and denosumab. Previous literature has suggested that bisphosphonates do not improve survival or reduce skeletal related events and little has been published about the effect of denosumab. Here we present experience describing outcomes and therapeutic effect in patients with RCCBM following palliative surgery for bone metastasis. Methods: We performed a retrospective analysis of 226 patients with RCCBM who underwent orthopedic surgery at MD Anderson Cancer Center between 11/2005 – 8/2019. The Kaplan-Meier method and log-rank test were used to estimate and evaluate survival differences. Results: Patient characteristics included: median age 58.2, male 66.4%, clear cell histology 93.5%, metastatic at presentation 57.9%, nephrectomy 79.8% (63.9% prior to orthopedic intervention), received radiation to the surgical site (pre-op: 13.0%, post-op: 41.4%). First orthopedic intervention: resection arthroplasty 37.2%, curettage and intramedullary nailing (IMN) 18.6%, IMN 16.4%, open reduction internal fixation 15.0%, amputation 2.7%, 10.2% other. Pre-op therapy: bisphosphonate 12.4%, denosumab 5.8%, both 2.7%, none 79.2%. Post-op therapy: bisphosphonate 18.1%, denosumab 13.7%, both 0.9%, none 67.2%. With a median follow up of 3.1 years after first orthopedic intervention, median overall survival (OS) was 2.7 yr (95% CI 2.1 – 3.6). Progression free survival (PFS) was calculated from time of first surgery to either first progression or death; median PFS was 5.2 months (95% CI 4.6 – 7.5). Pre-op or post-op bone-targeted therapy was not significantly associated with PFS (yes vs no: Pre-op: median 3.4 vs 6.3 mth, p=0.42; Post-op: median 4.3 vs 5.8 mth, p=0.61) or OS (Pre-op: 2.1 vs 2.9 yr, p=0.45; Post-op: 2.4 vs 3.2 yr, p=0.18). Post-op denosumab compared to bisphosphonate was associated with increased PFS (9.6 vs 3.8 mth, p=0.03) and OS (3.3 vs 1.6 yr, p=0.02). However, post-op denosumab vs no bone-targeted therapy was not significantly associated with increased PFS (9.6 vs 5.8 mth, p=0.42) or OS (3.3 vs 3.2 yr, p=0.85). Of note, post-op bisphosphonate vs no bone-targeted therapy was associated with reduced PFS (3.8 vs 5.8 mth, p=0.04) and OS (1.6 vs 3.2 yr, p=0.01). Conclusion: Addition of bone-targeted therapy did not significantly improve PFS or OS in patients with RCCBM undergoing orthopedic intervention. Post-op denosumab was associated with better PFS and OS compared to bisphosphonates and bisphosphonates were associated with worse PFS and OS compared to no bone-targeted therapy. Patient selection for therapy may be an important source of bias. Prospective research is needed to clarify the role and selection of bone-targeted therapy in RCCBM patients.
Inpatient outcomes of pathological fractures in metastatic prostate cancer.
Authors: Ahuja Kriti , Lingamaneni Prasanth , laswi hisham , Kumi Dennis Danso , Chhabra Navika , Darweesh Omnia , Batra Kunnal 
Published: June 2021

e17007 Background: Bone is a frequent site of metastasis in prostate cancer and is involved in 88% of patients with metastatic prostate cancer. Metastasis to bone increases the risk of pathological fractures, which are associated with increased morbidity and mortality. We performed a retrospective analysis on inpatient outcomes of pathological fractures in prostate cancer metastatic to bone in comparison to men with osteoporotic fractures. We also examined the disposition of these patients. Methods: We queried the Nationwide Inpatient Sample between 2016 and 2018 to retrospectively identify adult males with osteoporotic fractures and those with pathological fractures secondary to metastatic prostate cancer. We used T-test and chi-square test to compare means of continuous variables and compare proportions of categorical variables respectively. Multivariate analysis of predictors of mortality, length of stay, hospitalization costs and disposition in this group were performed. Results: A total of 22,800 fractures, combining osteoporotic fractures and pathological fractures due to metastatic prostate cancer were identified, of which the latter accounted for 13.6%. Patients with pathological fractures secondary to metastatic prostate cancer were younger (mean age 73.5 vs 77.5 years, p < 0.0001) and more likely to be black (16.4% vs 4.6%, p < 0.0001) or Hispanic (8.4% vs 5.1%, p < 0.0001). Adjusting for demographic variables and comorbidity burden, pathological fractures in patients with prostate cancer metastasis to the bone were not associated with a significant increase in mortality (aOR 1.46, 95% CI 0.82-2.60, p = 0.20) or length of hospital stay. However, they did have higher hospitalization costs by $2,610 per admission (p = 0.01). Patients with pathological fractures secondary to prostate cancer are less likely to be discharged to a nursing facility (aOR 0.50, 95% CI 0.40-0.62, p < 0.001) and are more likely to be transitioned to home health care (aOR 1.49, 95% CI 1.20-1.84, p < 0.001). Conclusions: Pathological fractures secondary to prostate cancer are less frequent than osteoporotic fractures in men and are not independent predictors of mortality or length of stay. This is in keeping with the relatively indolent course of prostate cancer. However, there is an increased cost of hospital stay associated with pathological fractures in metastatic prostate cancer. Interestingly, these patients are more likely to be discharged with home health care and are less likely to go to a nursing facility, making disposition a crucial aspect in the care of these patients.