Circulating receptor activator of nuclear factor kappa-B ligand (RANKL) levels predict response to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC).

BACKGROUND: Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment and immune cell responses. This study aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy. METHODS: Plasma RANKL levels were measured in 100 patients with advanced NSCLC without bone metastases undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. To establish the optimal cut-off value, we used the Cutoff Finder package in R. Survival curves for four distinct patient groups, according to their RANKL and PDL1 levels (high or low), were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS). RESULTS: The optimal RANKL cut-off was established at 280.4 pg/mL, categorizing patients into groups with high or low RANKL levels. A significant association was observed between increased RANKL concentrations and decreased survival rates at 24 months, only within the subgroup expressing high levels of PDL1 (p=0.002). Additionally, low RANKL levels in conjunction with elevated PDL1 expression correlated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, p=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, p=0.003), indicating RANKL's potential as an indicator of adverse prognosis in these patients. Multivariate analysis identified RANKL as an independent negative prognostic factor for both PFS and OS, regardless of other clinicopathological features. CONCLUSION: These results highlight the prognostic and predictive value of RANKL specifically in patients with high PDL1 expression.

Sarcopenia in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: We estimated the prevalence and clinical outcomes of sarcopenia among breast cancer patients. (2) Methods: A systematic literature search was carried out for the period between July 2023 and October 2023. Studies with breast cancer patients evaluated for sarcopenia in relation to overall survival (OS), progression-free survival (PFS), relapse of disease (DFS), pathological complete response (pCR), or toxicity to chemotherapy were included. (3) Results: Out of 359 screened studies, 16 were eligible for meta-analysis, including 6130 patients, of whom 5284 with non-MBC. Sarcopenia was evaluated with the computed tomography (CT) scan skeletal muscle index and, in two studies, with the dual-energy x-ray absorptiometry (DEXA) appendicular lean mass index. Using different classifications and cut-off points, overall, there were 2007 sarcopenic patients (33%), of whom 1901 (95%) presented with non-MBC. Sarcopenia was associated with a 33% and 29% higher risk of mortality and progression/relapse of disease, respectively. Sarcopenic patients were more likely to develop grade 3-4 toxicity (OR 3.58, 95% CI 2.11-6.06, p < 0.0001). In the neoadjuvant setting, a higher rate of pCR was observed among sarcopenic patients (49%) (OR 2.74, 95% CI 0.92-8.22). (4) Conclusions: Our meta-analysis confirms the correlation between sarcopenia and negative outcomes, especially in terms of higher toxicity.

Standardization of Body Composition Status in Patients with Advanced Urothelial Tumors: The Role of a CT-Based AI-Powered Software for the Assessment of Sarcopenia and Patient Outcome Correlation.

BACKGROUND: Sarcopenia is a well know prognostic factor in oncology, influencing patients' quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. METHODS: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. RESULTS: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10-20% up to ~45-55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. CONCLUSIONS: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes.

Third Cranial Nerve Palsy after Monoclonal Antibody Therapy for Lung Cancer: A Case Report.

Immune checkpoint inhibitors (ICIs) have shown promise in treating cancer patients, and pembrolizumab is a monoclonal IgG4 antibody that targets a human cell surface protein (receptor) called PD-1. Among the side effects, a rare cranial nerve palsy unrelated to the surgical treatment may occur. We report a case of a woman, which after neurosurgical treatment for cerebellar metastasis presented painless third cranial nerve palsy. The benefits of ICIs have been ascertained, but side effects also take place. Neurological symptoms should be recognized early to avoid substantial morbidity, and if necessary, the oncologic treatment should be changed.