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Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer.

ABSTRACT: BACKGROUNDObesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association among BMI, body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI.METHODSWe analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by BMI, fat-mass distribution, and molecular subtypes. Incidence of immune-related adverse events (irAEs) after ICI was also assessed based on BMI status.RESULTS524 EC patients were included in the study. Overweight and obese patients exhibited a significantly prolonged PFS and OS compared with normal BMI patients after treatment with ICI. Multivariable Cox's regression analysis confirmed the independent association of overweight and obesity with improved PFS and OS. Elevated visceral adipose tissue (VAT) was identified as a strong independent predictor for improved PFS to ICI. Associations between obesity and OS/PFS were particularly significant in the copy number-high/TP53abnormal (CN-H/TP53abn) EC molecular subtype. Finally, obese patients demonstrated a higher irAE rate compared with normal BMI individuals.CONCLUSIONObesity is associated with improved outcomes to ICI in EC patients and a higher rate of irAEs. This association is more pronounced in the CN-H/TP53abn EC molecular subtype.FUNDINGNIH/NCI Cancer Center; MSK Gerstner Physician Scholars Program; National Center for Advancing Translational Sciences (NCATS); Cycle for Survival; Breast Cancer Research Foundation.

SUBMITTER: Gomez-Banoy N

PROVIDER: S-EPMC11364395 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer.

Gómez-Banoy Nicolás N Ortiz Eduardo J EJ Jiang Caroline S CS Dagher Christian C Sevilla Carlo C Girshman Jeffrey J Pagano Andrew M AM Plodkowski Andrew J AJ Zammarrelli William A WA Mueller Jennifer J JJ Aghajanian Carol C Weigelt Britta B Makker Vicky V Cohen Paul P Osorio Juan C JC

The Journal of clinical investigation 20240620 17

BACKGROUNDObesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association among BMI, body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI.METHODSWe analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by B ...[more]

PMID: 38900575

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Project description:Despite major improvements in combatting metastatic melanoma since the advent of immunotherapy, the overall survival for patients with advanced disease remains low. Recently, there is a growing number of reports supporting an "obesity paradox," in which patients who are overweight or mildly obese may exhibit a survival benefit in patients who received immune checkpoint inhibitors. We studied the relationship between body mass index and progression-free survival and overall survival in a cohort of 423 metastatic melanoma patients receiving immunotherapy, enrolled and prospectively followed up in the NYU Interdisciplinary Melanoma Cooperative Group database. We analyzed this association stratified by first vs. second or greater-line of treatment and treatment type adjusting for age, gender, stage, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, number of metastatic sites, and body mass index classification changes. In our cohort, the patients who were overweight or obese did not have different progression-free survival than patients with normal body mass index. Stratifying this cohort by first vs. non-first line immunotherapy revealed a moderate but insignificant association between being overweight or obese and better progression-free survival in patients who received first line. Conversely, an association with worse progression-free survival was observed in patients who received non-first line immune checkpoint inhibitors. Specifically, overweight and obese patients receiving combination immunotherapy had a statistically significant survival benefit, whereas patients receiving the other treatment types showed heterogeneous trends. We caution the scientific community to consider several important points prior to drawing conclusions that could potentially influence patient care, including preclinical data associating obesity with aggressive tumor biology, the lack of congruence amongst several investigations, and the limited reproduced comprehensiveness of these studies.

Project description:ObjectiveThe worldwide prevalence of obesity mandates a widely accessible tool to categorize adiposity that can best predict associated health risks. The body adiposity index (BAI) was designed as a single equation to predict body adiposity in pooled analysis of both genders. We compared body adiposity index (BAI), body mass index (BMI), and other anthropometric measures, including percent body fat (PBF), in their correlations with cardiometabolic risk factors. We also compared BAI with BMI to determine which index is a better predictor of PBF.MethodsThe cohort consisted of 698 Mexican Americans. We calculated correlations of BAI, BMI, and other anthropometric measurements (PBF measured by dual energy X-ray absorptiometry, waist and hip circumference, height, weight) with glucose homeostasis indices (including insulin sensitivity and insulin clearance from euglycemic clamp), lipid parameters, cardiovascular traits (including carotid intima-media thickness), and biomarkers (C-reactive protein, plasminogen activator inhibitor-1 and adiponectin). Correlations between each anthropometric measure and cardiometabolic trait were compared in both sex-pooled and sex-stratified groups.ResultsBMI was associated with all but two measured traits (carotid intima-media thickness and fasting glucose in men), while BAI lacked association with several variables. BAI did not outperform BMI in its associations with any cardiometabolic trait. BAI was correlated more strongly than BMI with PBF in sex-pooled analyses (r?=?0.78 versus r?=?0.51), but not in sex-stratified analyses (men, r?=?0.63 versus r?=?0.79; women, r?=?0.69 versus r?=?0.77). Additionally, PBF showed fewer correlations with cardiometabolic risk factors than BMI. Weight was more strongly correlated than hip with many of the cardiometabolic risk factors examined.ConclusionsBAI is inferior to the widely used BMI as a correlate of the cardiometabolic risk factors studied. Additionally, BMI's relationship with total adiposity may not be the sole determinate of its association with cardiometabolic risk.

Project description:BackgroundRecent studies have reported that the combination of immune checkpoint inhibitors (ICIs) and antiangiogenic agents could be a promising therapeutic strategy for advanced non-small cell lung cancer (NSCLC). However, both ICIs and antiangiogenic agents are associated with endocrine dysfunctions, mainly hypothyroidism. The risk of hypothyroidism is potentially increased with the combination of ICIs and antiangiogenic agents. This study aimed to investigate the incidence and risk factors of hypothyroidism in patients receiving combination therapy.MethodsWe performed a retrospective cohort study of advanced NSCLC patients treated with ICIs and antiangiogenic agents at Tianjin Medical University Cancer Institute & Hospital from July 1, 2019, to December 31, 2021. Patients with normal thyroid function at baseline were enrolled, and information on the patients' characteristics before receiving combination therapy, including body mass index (BMI) and laboratory data, was obtained.ResultsAmong the 137 enrolled patients, 39 (28.5%) developed new-onset hypothyroidism, and 20 (14.6%) developed overt hypothyroidism. The incidence of hypothyroidism was significantly higher in obese patients than in patients with a low to normal BMI (P<0.001). Obese patients also had a higher incidence of overt hypothyroidism (P=0.016). Univariate logistic regression showed that BMI as a continuous variable was a significant risk factor for hypothyroidism [odds ratio (OR) 1.24, 95% confidence interval (CI): 1.10-1.42, P<0.001] and overt hypothyroidism (OR 1.17, 95% CI: 1.01-1.38, P=0.039). Multivariate logistic regression revealed that only BMI (OR 1.36, 95% CI: 1.16-1.61, P<0.001) and age (OR 1.08, 95% CI: 1.02-1.14, P=0.006) were significant risk factors for treatment-related hypothyroidism.ConclusionsThe risk of hypothyroidism in patients receiving a combination of ICIs and antiangiogenic therapy is manageable, and a higher BMI is associated with a significantly increased risk of hypothyroidism. Therefore, clinicians should be aware of the development of hypothyroidism in obese advanced NSCLC patients during the administration of ICIs combined with antiangiogenic agents.

Dataset Information

Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer.

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Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer.

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