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PurposeWeight loss is a well-recognized prognostic parameter for survival of lung cancer patients. Computerized-tomography (CT)-based analysis of body composition and blood-based metabolic evaluation are promising prognostic tools. We aimed to assess the correlation between albumin, body mass index (BMI), skeletal muscle mass index (SMI), fat-free mass index (FFMI), fat mass index (FMI) and weight change, as well as their correlation with survival of lung cancer patients on nivolumab treatment.MethodsData were retrospectively collected. Weight was measured at a diagnosis of stage 4 disease and before start of nivolumab. Albumin levels were measured before starting nivolumab. BMI, SMI, FFMI, and FMI were evaluated from CT scans performed at start of nivolumab. Overall survival (OS) was from starting of nivolumab to death or censured at last follow-up. Statistical analysis was done to identify correlation between the various factors and between those factors and survival.ResultsForty-six patients with advanced non-small cell lung cancer (NSCLC) were included. Median follow-up was 22 months. Pathology was Adenocarcinoma/Squamous/non-other specified in 25/15/6 respectively. All patients received nivolumab as an advanced-line treatment for stage IV NSCLC. We observed a significant correlation of weight loss (P=0.01, HR=2.85) and albumin (P=0.043, HR=0.34) with OS in multivariate analysis. A significant correlation was found between BMI to SMI, FFMI, FMI, and weight change.ConclusionWeight loss and low albumin levels are significant negative prognostic factors for NSCLC patients on immunotherapy. CT-based parameters of body composition remain to be proven as more reliable than standard clinical parameters.

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Immune-checkpoint inhibitor (ICI)-related diarrhea is attributed to inflammatory colitis, with no other drug-related differential diagnosis. Here, we investigated the occurrence of pancreatic atrophy (PA) in ICI-treated cancer patients and its correlation to exocrine pancreatic insufficiency (EPI). Metastatic melanoma, non-small cell lung carcinoma, and head and neck squamous cell carcinoma patients (n ¼ 403) treated with anti-PD-1 (n ¼ 356) or anti-CTLA-4 (n ¼ 47) were divided into a case group (radiologic evidence of PA); control group matched by age, gender, and previous lines of treatment; and colitis group (ICI-induced colitis). Quantitative pancreatic volumetry was used for calculation of the decrease in pancreatic volume over time (atrophy rate). Thirty-one patients (7.7%) developed PA compared with 41 matched controls (P ¼ 0.006). Four patients developed EPI, all from the anti-PD-1-treated group, which resolved with oral enzyme supplementation. The atrophy rate did not correlate with EPI (P ¼ 0.87). EPI-related diarrhea presented at a median of 9 months, whereas the diarrhea of anti-PD-1-induced colitis patients (n ¼ 22) was presented at a median of 2 months (P ¼ 0.029). ICI-induced PA is irreversible and can result in EPI. EPI should be suspected in cases of late-onset steroid-resistant diarrhea with features of steatorrhea and treated with oral enzyme supplements.

Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal–epithelial transition ( MET) exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials. Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021. Results: Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed. Median age was 77 years (range, 48–91), 56% were women, 86% had stage IV disease, and 27% had brain metastases. For all patients, the objective response rate (ORR) to capmatinib was 58% (95% CI, 47–69), whereas it was 68% (95% CI, 50–82) in treatment-naïve and 50% (95% CI, 35–65) in pretreated patients. The median progression-free survival was 9.5 months (95% CI, 4.7–14.3), whereas it was 10.6 months (95% CI, 5.5–15.7) in first-line and 9.1 months (95% CI, 3.1–15.1) in pretreated patients. After a median follow-up of 11.0 months, the median overall survival was 18.2 months (95% CI, 13.2–23.1). In patients with measurable brain metastases ( n = 11), the intracranial ORR was 46% (95% CI, 17–77). Capmatinib showed a manageable safety profile. Grade ⩾ 3 treatment-related adverse events included peripheral edema (13%), elevated creatinine (4%), and elevated liver enzymes (3%). Conclusion: In patients with MET exon 14 skipping mutation, capmatinib showed durable systemic and intracranial efficacy and a manageable safety profile. This analysis confirms previously reported phase II data in a real-world setting.

Both pembrolizumab (P) and combination of pembrolizumab with platinum-based chemotherapy (PCT) represent standard 1 st -line options for advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score (TPS) ≥50%. The two strategies have never been compared in a randomized trial. 256 consecutive patients with EGFR/ALK/ROS1-wild-type PD-L1 TPS ≥50% aNSCLC receiving P (group P, n = 203) or PCT (group PCT, n = 53) as a 1 st -line treatment were identified in the electronic databases of 4 Israeli cancer centers. Time-to-treatment discontinuation (TTD) and overall survival (OS) were assessed. Baseline characteristics were well balanced, except for age and ECOG PS differences in favor of group PCT. Median (m)TTD was 4.9 months (mo) (95% CI, 3.1-7.6) vs 8.0mo (95% CI, 4.7-15.6) (p-0.09), mOS was 12.5mo (95% CI, 9.8-16.4) vs 20.4mo (95% CI, 10.8-NR) (p-0.08), with P and PCT, respectively. In the propensity score matching analysis (n = 106; 53 patients in each group matched for age, sex and ECOG PS), mTTD was 7.9mo (95% CI, 2.8-12.7) vs 8.0mo (95% CI, 4.7-15.6) (p-0.41), and mOS was 13.3mo (95% CI, 6.8-20.3) vs 20.4mo (95% CI, 10.8-NR) (p-0.18), with P and PCT, respectively. Among various subgroups of patients examined, only in females (n = 86) mOS differed significantly between treatments (10.2mo (95% CI, 6.8-17.2) with P vs NR (95% CI, 11.4-NR) with PCT; p-0.02). In the real-world setting, no statistically significant differences in long-term outcomes with P vs PCT were observed; a prospective randomized trial addressing the comparative efficacy of P and PCT in different patient subgroups is highly anticipated. List of abbreviations: AE -adverse events; ALK -anaplastic lymphoma kinase gene; ALT -alanine aminotransferase; (a)NSCLC -(advanced) non-small cell lung cancer; AST -aspartate aminotransferase; BRAF -v-Raf murine sarcoma viral oncogene homolog B; BRCA2 -BReast CAncer gene 2; c-Met -tyrosine-protein kinase Met; CTCAE, v. 4.03 -Common Terminology Criteria for Adverse Events, version 4.03; CTLA-4 -cytotoxic T-lymphocyteassociated protein 4; ECOG PS -Eastern Cooperative Oncology Group performance status; EGFR -epidermal growth factor receptor gene; FISH -fluorescent in situ hybridization; HER2 -human epidermal growth factor receptor 2; IC -tumor-infiltrating immune cells; ICI -immune check-point inhibitors; IHC -immunohistochemistry; IQR -interquartile range; irAE -immune related adverse events; ISCORT -Israeli Society for Clinical Oncology and Radiotherapy; KRAS -Kirsten rat sarcoma viral oncogene homolog; (m)TTD -(median) time-to-treatment discontinuation; mo -months; (m)OS -(median) overall survival; (m)PFS -(median) progression-free survival;muts/Mb -mutations per megabase; NA -not specified/not available; NOS -not otherwise specified; NR -not reported/not reached; ORR -objective response rate; P -pembrolizumab; PCR -polymerase chain reaction; PCTcombination of pembrolizumab with platinum-based chemotherapy; PD -progression of disease; PD-1programmed cell death-1; PD-L1 -programmed cell death ligand...

failure is associated with aortic valve calcification. Using our rat model of uremiainduced reversible aortic valve calcification, we assessed the role of apoptosis and survival pathways in that disease. We also explored the effects of raloxifene, an estrogen receptor modulator, on valvular calcification. Gene array analysis was performed in aortic valves obtained from three groups of rats (n ϭ 7 rats/group): calcified valves obtained from rats fed with uremic diet, valves after calcification resolution following diet cessation, and control. In addition, four groups of rats (n ϭ 10 rats/group) were used to evaluate the effect of raloxifene in aortic valve calcification: three groups as mentioned above and a fourth group fed with the uremic diet that also received daily raloxifene. Evaluation included imaging, histology, and antigen expression analysis. Gene array results showed that the majority of the altered expressed genes were in diet group valves. Most apoptosisrelated genes were changed in a proapoptotic direction in calcified valves. Apoptosis and decreases in several survival pathways were confirmed in calcified valves. Resolution of aortic valve calcification was accompanied by decreased apoptosis and upregulation of survival pathways. Imaging and histology demonstrated that raloxifene significantly decreased aortic valve calcification. In conclusion, downregulation of several survival pathways and apoptosis are involved in the pathogenesis of aortic valve calcification. The beneficial effect of raloxifene in valve calcification is related to apoptosis modulation. This novel observation is important for developing remedies for aortic valve calcification in patients with renal failure.growth arrest-specific 6; uremia CARDIOVASCULAR CALCIFICATION is one of the highest causes of morbidities and mortalities in patients with end-stage renal disease. These patients develop aortic valve calcification (AVC) and coronary calcification at an accelerated rate. Associated with this cardiovascular calcification are increased rates of myocardial infarctions and valvular heart disease. The pathogenesis of AVC in renal failure (RF) is not fully elucidated. It has been suggested that the process involves active osteoblast transformation of valve tissue, which results in increased formation of bone matrix (4, 25). Most of the data regarding the pathogenesis of AVC were obtained from animal models based on various components of the metabolic syndrome, emphasizing the role of atherogenesis in AVC (26, 37). In patients with RF, AVC and aortic stenosis are common and progress especially rapidly (18). The prevalence and extent of AVC in this population is poorly explained by traditional cardiovascular risk factors; abnormalities of mineral metabolism are likely to contribute to its development and progression. Current models of RF and accelerated calcification have demonstrated that calcium phosphate metabolism is critical for disease development (13), and inhibitors of calcification (fetuin A) are important in its prevention...