Correction: Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

[This corrects the article DOI: 10.1371/journal.pone.0277708.].

Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

Obesity and sarcopenia have been reported to affect outcomes in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We analyzed prospective data from 52 patients with non-oncogene driven metastatic NSCLC treated with ICIs. Body tissue composition was calculated by measuring the fat and muscle densities at the level of 3rd lumbar vertebra in each patient computed tomography scan before ICI initiation using sliceOmatic tomovision. We converted the densities to indices [Intramuscular Fat Index (IMFI), Visceral Fat Index (VFI), Subcutaneous Fat Index (SFI), Lumbar Skeletal Muscle Index (LSMI)] by dividing them by height in meters squared. Patients were dichotomized based on their baseline IMFI, VFI and SFI according to their gender-specific median value. The cut-offs that were set for LMSI values were 55 cm2/m2 for males and 39 cm2/m2 for females. SFI distribution was significantly higher (p = 0.040) in responders compared to non-responders. None of the other variables affected response rates. Low LSMI HR: 2.90 (95% CI: 1.261-6.667, p = 0.012) and low SFI: 2.20 (95% CI: 1.114-4.333, p = 0.023) values predicted for inferior OS. VFI and IMFI values did not affect survival. Subcutaneous adipose and skeletal muscle tissue composition significantly affected immunotherapy outcomes in our cohort.

Cancer cachexia syndrome and clinical outcome in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors: results from a prospective, observational study.

BACKGROUND: Cancer cachexia syndrome (CCS) is an adverse prognostic factor in cancer patients undergoing chemotherapy or surgical procedures. We performed a prospective study to investigate the effect of CCS on treatment outcomes in patients with non-oncogene driven metastatic non-small cell lung cancer (NSCLC) undergoing therapy with programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. METHODS: Patients were categorized as having cancer cachexia if they had weight loss >5% in the last 6 months prior to immunotherapy (I-O) initiation or any degree of weight loss >2% and body mass index (BMI) <20 kg/m2 or skeletal muscle index at the level of third lumbar vertebra (LSMI) <55 cm2/m2 for males and <39 cm2/m2 for females. LSMI was calculated using computed tomography (CT) scans of the abdomen at the beginning of I-O and every 3 months thereafter. RESULTS: Eighty-three patients were included in the analysis and the prevalence of cancer cachexia at the beginning of I-O was 51.8%. The presence of CCS was associated with inferior response rates to ICIs (P≤0.001) and consisted an independent predictor of increased probability for developing disease progression as best response to treatment, OR =8.11 (95% CI: 2.95-22.40, P≤0.001). In the multivariate analysis, the presence of baseline cancer cachexia consisted an independent predictor for inferior survival, HR =2.52 (95% CI: 1.40-2.55, P=0.002). Reduction of LSMI >5% during treatment did not affect overall survival (OS; P=0.40). CONCLUSIONS: CCS is associated with reduced PD-1/PD-L1 inhibitor efficacy in NSCLC patients and should constitute an additional stratification factor in future I-O clinical trials. Further research at a translational and molecular level is required to decipher the mechanisms of interrelation of metabolic deregulation and suppression of antitumor immunity.

Evaluation of a high nutritional quality snack based on oat flakes and inulin: effects on postprandial glucose, insulin and ghrelin responses of healthy subjects.

The consumption of high nutritional value snacks may favorably affect the diet quality. Biscuits manufactured with oat flakes and maltitol were assessed for glycemic, insulinemic and ghrelin responses. Enrichment with inulin, a fructooligosachararide (FOS) which acts as soluble fiber, was performed in an attempt to further increase the dietary fiber content and examine potential additional postprandial benefits. Eleven healthy subjects participated in the study and consumed either 80 g oat biscuits (OB) or 81 g oat biscuits with 4% inulin (OBIN) or a solution containing 50 g of glucose (reference food), each yielding 50 g of available carbohydrates. Venous blood samples were collected before consumption and at 15, 30, 45, 60, 90, 120 and 180 min postprandially. The developed products were also evaluated for physicochemical properties, including porosity, density, texture, color, sensory attributes and microstructure (by scanning electron microscopy). Both biscuits demonstrated a low glycemic index (GI), which was found to be 32.82 ± 8.07 for OB and 45.68 ± 9.64 for OBIN. Compared to OB, OBIN demonstrated higher insulin response at 45 and 60 min and higher ghrelin suppression at 60 and 120 min postprandially (P < 0.05). Furthermore, OBIN demonstrated increased hardness and color values, lower porosity, and higher rate of starch granule gelatinization, without significantly altering the sensory attributes. Biscuits formulated with oat flakes and maltitol with or without 4% inulin can be classified as low GI foods. Inulin addition significantly lowered the ghrelin response to OBIN, suggesting an advantage of OBIN in the modulation of satiety; however, no further benefits regarding glucose and insulin responses were observed.