Background: Sarcopenia is strongly linked to impaired metabolic health. However, sarcopenia might be omitted in patients (pts) with metabolic syndrome which is commonly predominated by obesity. We ...seek to identify associates of low muscle mass in regard metabolic health and obesity.
Methods: Consecutive pts who presented to internal medicine outpatient clinics of a tertiary hospital for regular follow-up were included in this study. Those with comorbidities that are known to cause secondary sarcopenia such as chronic liver and kidney disease, inflammatory diseases and cancers were excluded. SMI was measured by bioelectrical impedance analysis (TANITA MC780) Pts with at least two components of metabolic syndrome were considered metabolically unhealthy. SMI values of metabolic healthy (MH) and unhealthy (MUH) patient groups were compared across obese and non-obese adults. Multivariate regression analysis was performed to identify factors related to low muscle mass.
Results: Amongst 200 pts (M:F 97:103) included in this study, median age was 49,9 ± 8. Mean SMI was 8.9±0.6 (F:M 8.3:9.5) The MUH phenotype was more frequent in pts with low muscle mass compared to those with normal muscle mass (p=0.048) Obesity was not associated with low muscle mass regardless of MH (p=0.345) Mean SMI was lower in MUH pts regardless of presence of obesity. After controlling the mentioned variables, multivariate analysis didn’t demonstrate an independent effect of MUH phenotype on low SMI but a trend towards effect was observed (Odds ratioOR:1.09 Confidence IntervalCI 95% 0.95-9.51 p=0.062). High waist to hip ratio was the factor independently associated with low SMI (OR: 8.328, CI 95% 8.23-20.43 p=0.009).
Conclusion: Our results identify an association between impaired metabolical health and low muscle mass regardless of the presence of obesity. Most interestingly we observed an interplay between central obesity and impaired muscle mass that warrants further exploration in larger samples.
Disclosure
Y. Onal-Tastan: None. N. Dizman: None. E. Ertur: None. B. Cakir-Guney: None. M. Sargin: None. A. Oguz: None.
Abstract
Introduction
Women and underrepresented groups in medicine hold few academic leadership positions in the field of hematology/oncology. In this study, we assessed gender and race/ethnicity ...representation in editorial board positions in hematology/oncology journals.
Materials and Methods
Editorial leadership board members from 60 major journals in hematology and oncology were reviewed; 54 journals were included in the final analysis. Gender and race/ethnicity were determined based on publicly available data for Editor-in-Chief (EiC) and Second-in-Command (SiC) (including deputy, senior, or associate editors). Descriptive statistics and chi-squared were estimated. In the second phase of the study, editors were emailed a 4-item survey to self-identify their demographics.
Results
Out of 793 editorial board members, 72.6% were men and 27.4% were women. Editorial leadership were non-Hispanic white (71.1%) with Asian editorial board members representing the second largest majority at 22.5%. Women comprised only 15.9% of the EiC positions (90% White and 10% Asian). Women were about half as likely to be in the EiC position compared with men pOR 0.47 (95% CI, 0.23-0.95, P = .03). Women represented 28.3% of SiC editorial positions. Surgical oncology had the lowest female representation at 2.3%.
Conclusion
Women and minorities are significantly underrepresented in leadership roles on Editorial Boards in hematology/oncology journals. Importantly, the representation of minority women physicians in EiC positions is at an inexorable zero.
Assessing gender and race representation in leadership editorial board positions in major journals is critical in furthering equity. This article examines the gender and race/ethnicity representation in editorial board positions at leading hematology and oncology journals.
Combination immune checkpoint inhibitors (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-R-TKI), including pembrolizumab/axitinib, are approved for first-line ...treatment of metastatic renal cell carcinoma (mRCC). Pembrolizumab/axitinib is associated with superior progression free survival (PFS), objective response rate (ORR), and overall survival over sunitinib. However, to date, the activity and safety of pembrolizumab/axitinib in later lines of therapy has not been reported.
Clinical data of consecutive patients receiving pembrolizumab/axitinib in the second-line or beyond for mRCC at Yale-New Haven Hospital were retrospectively collected. Best objective response was assessed using RECIST 1.1 criteria. Kaplan-Meier function was used to analyze survival.
Thirty-eight patients were included. Median age was 64, 92.1% had clear cell mRCC, 18.4% had sarcomatoid dedifferentiation; 94.7% had prior ICI and 39.5% had prior VEGF-R-TKI. Pembrolizumab/axitinib was administered as second-line therapy in 21 (55.5%) patients, third-line in 5 (13.2%) and beyond in 12 (30.2%). Adverse events (AEs) occurred in 86.8% of patients. Grade 3-4 AEs attributed to pembrolizumab and axitinib were seen in 18.4% and 6.4% of patients, respectively. No grade 5 AEs occurred. At a median follow up of 17.1 months, median PFS was 9.7 months (95% CI, 4.1-15.3). Amongst 36 response evaluable patients, the ORR was 25.0% (all partial) and disease control rate (including stable disease for at least 6 months) was 66.6%. The most frequent treatment sequence was first-line nivolumab/ipilimumab followed by second-line pembrolizumab/axitinib (n = 17, 44.7%); among this cohort, median PFS with pembrolizumab/axitinib was 11.1 (95% CI, 8.4-13.7) months, with an ORR of 31.4%.
Combination pembrolizumab/axitinib among previously treated mRCC patients has activity, with AE rates comparable to those reported in the first line. Prospective studies evaluating ICI-VEGF-R-TKI combinations beyond first-line are warranted to identify the most beneficial treatment sequencing in mRCC.
Immune checkpoint inhibitor-based combinations have an established role in the first-line treatment of patients with metastatic renal cell carcinoma; however, evidence on the selection of therapies in subsequent lines is limited. Herein, we present a retrospective analysis of patients who received pembrolizumab/axitinib beyond first line. In this heavily pretreated patient population, we observed an objective response in one-fourth of patients, with progression-free survival and response duration outcomes encouraging for further efforts examining this combination in prospective randomized settings.
Background
Infigratinib (BGJ398) is a potent and selective fibroblast grown factor receptor 1 to 3 (FGFR1‐3) inhibitor with significant activity in patients with advanced or metastatic urothelial ...carcinoma bearing FGFR3 alterations. Given the distinct biologic characteristics of upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB), the authors examined whether infigratinib had varying activity in these settings.
Methods
Eligible patients had metastatic urothelial carcinoma with activating FGFR3 mutations and/or fusions. Comprehensive genomic profiling was performed on formalin‐fixed, paraffin‐embedded tissues. Blood was collected for cell‐free DNA analysis using a 600‐gene panel. Patients received infigratinib at a dose of 125 mg orally daily (3 weeks on/1 week off) until disease progression or intolerable toxicity occurred. The overall response rate (ORR; partial response PR plus complete response CR) and disease control rate (DCR; CR plus PR plus stable disease SD) were characterized.
Results
A total of 67 patients were enrolled; the majority (70.1%) had received ≥2 prior antineoplastic therapies. In 8 patients with UTUC, 1 CR and 3 PRs were observed (ORR, 50%); the remaining patients achieved a best response of SD (DCR, 100%). In patients with UCB, 13 PRs were observed (ORR, 22%), and 22 patients had a best response of SD (DCR, 59.3%). Notable differences in genomic alterations between patients with UTUC and those with UCB included higher frequencies of FGFR3‐TACC3 fusions (12.5% vs 6.8%) and FGFR3 R248C mutations (50% vs 11.9%), and a lower frequency of FGFR3 S249C mutations (37.5% vs 59.3%).
Conclusions
Differences in the cumulative genomic profile were observed between patients with UTUC and those with UCB in the current FGFR3‐restricted experience, underscoring the distinct biology of these diseases. These results support a planned phase 3 adjuvant study predominantly performed in this population.
Infigratinib demonstrates activity in patients with metastatic urothelial carcinoma (UC) bearing fibroblast growth factor receptor 3 (FGFR3) mutations and/or fusions, with particular activity noted in patients with upper tract UC (UTUC). Key differences in FGFR3 alterations are noted between UTUC and UC of the bladder in the genomically selected patients in the current study.
Renal cell carcinoma (RCC) is one of the 10 most commonly diagnosed solid tumors. Most RCCs are histologically defined as clear cell, comprising approximately 75% of diagnoses. However, the remaining ...RCC cases are composed of a heterogeneous combination of diverse histopathologic subtypes, each with unique pathogeneses and clinical features. Although the therapeutic approach to both localized and metastatic RCCs has dramatically changed, first with the advent of antiangiogenic targeted therapies and more recently with the approval of immune checkpoint inhibitor (ICI)-based combinations, these advances have primarily benefited the clear cell RCC patient population. As such, there remains critical gaps in the optimization of treatment regimens for patients with non-clear cell, or variant, RCC histologies. Herein, we detail recent advances in understanding the biology of RCC with variant histology and how such findings have guided novel clinical studies investigating precision oncology approaches for these rare subtypes. Among the most common variant histology RCCs are papillary RCC, comprising approximately 15%-20% of all diagnoses. Although a histopathologically diverse subset of tumors, papillary RCC is canonically associated with amplification of the
protooncogene; recently completed and ongoing trials have investigated
directed therapies for this patient population. Finally, we discuss the unique biology of RCC with sarcomatoid dedifferentiation and the recent clinical findings detailing its paradoxical sensitivity to ICIs.
There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic ...renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings.
We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression.
Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts 46% White, 7 pts 7% Asian, and 3 pts 3% Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios HR 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff.
Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC.
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