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Physician-reported performance status (PS) constitutes the established method for stratifying oncologic patients in therapeutic decision-making. Objective measurements of physical function may further refine prognostication. In this prospective observational study, 103 patients with metastatic cancer who were referred for systemic therapy initiation were evaluated. PS was evaluated using the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and five objective physical function measurements (handgrip strength [HGS], chair stand test [CST], timed up and go [TUG] test, 4-m gait speed [GS] test, and short physical performance battery [SPPB] test). Overall survival and treatment complications were recorded from the medical records. Patients with low PS according to ECOG-PS (hazard ratio [HR]: 3.80, 95% confidence interval [CI]: 1.84, 7.80), HGS (HR: 2.37, 95% CI: 1.24, 4.55), SPPB (HR: 3.43, 95% CI: 1.55, 7.57), GS (HR: 3.03, 95% CI: 1.44, 6.38), and TUG (HR: 5.16, 95% CI: 2.19, 12.14) had shorter overall survival after adjustment for sex, age, symptomatology, comorbidity, percentage of weight loss, and tumor localization. Among the studied objective physical function measurements, HGS, SPPB, GS, and TUG were independent predictors of survival in a sample of patients with metastatic cancer, with TUG showing the highest effect size. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cancer cachexia syndrome (CCS) is a multifactorial metabolic syndrome affecting a significant proportion of patients. CCS is characterized by progressive weight loss, alterations of body composition and a systemic inflammatory status, which exerts a major impact on the host's innate and adaptive immunity. Over the last few years, the development of immune checkpoint inhibitors (ICIs) transformed the treatment landscape for a wide spectrum of malignancies, creating an unprecedented opportunity for long term remissions in a significant subset of patients. Early clinical data indicate that CCS adversely impairs treatment outcomes of patients receiving ICIs. We herein reviewed existing evidence on the potential links between the mechanisms that promote the catabolic state in CCS and those that impair the antitumor immune response. We show that the biological mediators and processes leading to the development of CCS may also participate in the modulation and the sustainment of an immune suppressive tumor microenvironment and impaired anti-tumor immunity. Moreover, we demonstrate that the deregulation of the host's metabolic homeostasis in cancer cachexia is associated with resistance to ICIs. Further research on the interrelation between cancer cachexia and anti-tumor immunity is required for the effective management of resistance to immunotherapy in this specific but large subgroup of ICI treated individuals. [ABSTRACT FROM AUTHOR]

With regard to doctors' interpersonal skills and availability, patients with breast, colorectal and esophageal cancer were less satisfied than patients with lung and head and neck cancer in the multivariate analyses. 0--- ht 1 I N i , number of patients included in the study; I N i invited, number of patients invited per country; Attrition rate, percentage of patients per country who declined to participate. Keywords: cancer; communication; cross-cultural; oncology; psycho-oncology; satisfaction with care EN cancer communication cross-cultural oncology psycho-oncology satisfaction with care 541 547 7 03/11/22 20220301 NES 220301 Key points Patient satisfaction with communication with professionals has been found to be an important endpoint in cancer treatment, especially in studies evaluating routine Patient Reported Outcomes (PRO) monitoring. The greater SC among patients who receive treatment with palliative intention (chemo- and/or radiotherapy) suggests that more attention is given to communication with patients in non-curative treatment. [Extracted from the article]

Background: Cancer‐associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented by the inflammatory biomarker C‐reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate the associations of reduced food intake and CRP with cancer‐associated WL (primary endpoint) and overall survival (OS, secondary endpoint). Methods: The data set included a total of 12,253 patients at risk for cancer‐associated WL. Patient‐reported WL history (% in 6 months) and food intake (normal, moderately, or severely reduced) were measured in all patients; CRP (mg/L) and OS were measured in N = 4960 and N = 9952 patients, respectively. All measures were from a baseline assessment. Clinical variables potentially associated with WL and overall survival (OS) including age, sex, cancer diagnosis, disease stage, and performance status were evaluated using multinomial logistic regression MLR and Cox proportional hazards models, respectively. Results: Patients had a mean weight change of −7.3% (±7.1), which was categorized as: ±2.4% (stable weight; 30.4%), 2.5–5.9% (19.7%), 6.0–10.0% (23.2%), 11.0–14.9% (12.0%), ≥15.0% (14.6%). Normal food intake, moderately, and severely reduced food intake occurred in 37.9%, 42.8%, and 19.4%, respectively. In MLR, severe WL (≥15%) (vs. stable weight) was more likely (P < 0.0001) if food intake was moderately [OR 6.28, 95% confidence interval (CI 5.28–7.47)] or severely reduced [OR 18.98 (95% CI 15.30–23.56)]. In subset analysis, adjusted for food intake, CRP was independently associated (P < 0.0001) with ≥15% WL [CRP 10–100 mg/L: OR 2.00, (95% CI 1.58–2.53)] and [CRP > 100 mg/L: OR 2.30 (95% CI 1.62–3.26)]. Diagnosis, stage, and performance status, but not age or sex, were significantly associated with WL. Median OS was 9.9 months (95% CI 9.5–10.3), with median follow‐up of 39.7 months (95% CI 38.8–40.6). Moderately and severely reduced food intake and CRP independently predicted OS (P < 0.0001). Conclusions: Modelling WL as the dependent variable is an approach that can help to identify clinical features and biomarkers associated with WL. Here, we identify criterion values for food intake impairment and CRP that may improve the diagnosis and classification of cancer‐associated cachexia. [ABSTRACT FROM AUTHOR]

Anorexia is a frequent symptom in cancer and we aimed to assess its prevalence among patients at their first cancer diagnosis by different appetite tools and the relationship between each tool with self-reports of food intake. We also tested whether cancer anorexia influences outcomes independently of reduced food intake or body weight loss (BWL) overtime and whether BWL was associated with complications during anticancer-therapy. Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score, self-assessment of appetite, Anorexia Questionnaire (AQ) and Visual Analog Scale (VAS) were administered. Percent of food intake was used as a criterion measure of anorexia. We registered BWL and anticancer-therapy complications over 3-month-follow-up. 438 cancer patients from 7 cancer-centers worldwide were included. The prevalence of anorexia was 39.9% by FAACT score, 40.2% by VAS, 40.6% by the self-assessment of appetite and 65.4% by AQ. Low food intake (≤50%) was reported in 28% of patients. All appetite tools correlated with food intake percent (P < 0.0001). We documented a correlation between self-assessment of appetite, FAACT score, VAS and BWL overtime (P < 0.04). The self-assessment of appetite (P = 0.0152) and the FAACT score (P = 0.043) were associated with BWL independently of anticancer therapies. Among patients with BWL, the risk to develop complications was greater with respect to those who maintained a stable or gained body weight (P = 0.03). In our sample of cancer patients, FAACT score and self-assessment of appetite performed well when low food intake was used as a criterion measure, and revealed an association of anorexia with BWL, which was, in turn, related to the development of anticancer-therapy complications. [ABSTRACT FROM AUTHOR]

Background: Overweight/obese patients' large fat mass can mask the loss of skeletal muscle, which is associated with mortality in the oncology setting. We investigated the prevalence of computed tomography (CT)-defined sarcopenia and myosteatosis across different levels of nutrition risk assessed by the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF). We also evaluated whether the PG-SGA SF, sarcopenia, and myosteatosis were prognostic of overall survival.Methods: This was a prospective, observational study. Consecutive patients with body mass index ≥25.0 kg/m2 with newly diagnosed head and neck cancer (any stage) or lung and gastrointestinal tract cancer (locally recurrent or metastatic) were screened at presentation to oncology clinics. Nutrition risk was assigned based on PG-SGA SF triage recommendations. Based on CT, patients were classified with sarcopenia and/or myosteatosis using published cutoffs. Survival analyses were conducted.Results: Patients (n=1157) were 63.6 ± 11.4 years, 64% male, and 61% had stage IV disease. Sarcopenia and myosteatosis were prevalent across PG-SGA SF nutrition risk categories (scores 0-1 [no risk; 36% sarcopenic; 44% myosteatotic], scores 2-3 [37%; 37%], scores 4-8 [40%; 41%], and scores ≥9 [high risk; 50%; 49%]). In multivariable survival analysis, PG-SGA SF scores ≥9 (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.66-2.60, P<0.001), sarcopenia (HR 1.25, 95% CI 1.06-1.46, P=0.006), and myosteatosis (HR 1.25, 95% CI 1.07-1.46, P<0.001) independently predicted reduced survival.Conclusion: CT-defined sarcopenia and myosteatosis are prevalent across different levels of nutrition risk in overweight/obese patients with cancer. Assessment of skeletal muscle using CT adds prognostic value to the PG-SGA SF. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors." The correction states that an additional affiliation is missing for the second author, Konstantinos Rounis, who is also affiliated with the Laboratory of Translational Oncology, Medical School, University of Crete. The correct affiliations for the authors are provided in the correction notice. The original article was published in PLoS ONE and is available for further reading. [Extracted from the article]

Advanced cancer often results in reduced dietary intake; however, data on actual intake at the time of diagnosis are limited. In the present study, a detailed dietary intake assessment was performed in patients with metastatic lung and upper gastrointestinal cancer, before initiation of systemic therapy. Basic demographics and performance status (PS) were recorded. Nutritional status was evaluated through anthropometry, Mini Nutritional Assessment (MNA), and 3 nonconsecutive 24-hour dietary recalls. Of the 84 patients enrolled, 61.4% were protein, energy, or protein–energy undernourished, regardless of body mass index (BMI) or MNA category. No differences in energy, macronutrients, and micronutrients intakes across BMI categories were recorded. Very low consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), irrespective of energy intake, tumor site, BMI category, or PS was found. Suboptimal micronutrients intakes were recorded even in well-nourished and overweight/obese patients. Patients with adequate PS and better MNA score reported significantly higher intake of certain macro- and micronutrients (allP< 0.05). Most patients exhibited reduced dietary intake in terms of energy, macronutrient, and micronutrient. Very low EPA and DHA intake was recorded for the whole sample, whereas micronutrient suboptimal intakes were also prevalent in well-nourished or overweight patients. All the above should be taken into account during patients' nutritional care. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Lung cancer is the most common cause of cancer death. A cumulative prognostic score based on C-reactive protein and albumin, termed the Glasgow Prognostic Score (GPS), indicates the presence of systemic inflammatory response. GPS has been proposed as a powerful prognostic tool for patients with various types of malignant tumors, including lung cancer. The aim of this study was to assess the predictive value of baseline GPS in terms of toxicity and response in lung cancer patients treated with platinum-based chemotherapy. Patients and methods: Patients referred to our institution for consideration of first-line platinum-based treatment were eligible. Demographics and disease-related characteristics were recorded. Toxicity was graded according to NCI CTCAE version 3.0 throughout first-line therapy. GPS was calculated before the onset of treatment and was related to the development of toxicity. Response to first-line therapy and survival data were also collected. Results: Totally, 96 lung cancer patients were accrued. GPS was associated with increased mucositis p =0.004), neurotoxicity (p =0.038), neutropenia (p =0.02), dose reductions or/ and need for granulocyte colony-stimulating factor (G-CSF) support (p =0.005), toxicity-related termination of treatment (p =0.001) and chemotherapy-related toxic deaths (p =0.013). GPS was associated with overall survival (p =0.016) and progression-free survival (p =0.016) as well as response to treatment (p =0.05). Conclusions: Our data demonstrate that GPS assessment is predictive of the most important aspects of platinum-related toxicity and this may partly explain its associations with poor clinical outcome in patients with metastatic lung cancer. [Copyright &y& Elsevier]

Interleukin (IL)-8 promotes cellular proliferation and angiogenesis in patients with non-small-cell lung cancer (NSCLC) and may be related to cachexia. Our aim was to investigate the relationship of IL-8 levels with nutritional status, and clinical outcome of patients with NSCLC. Patients with metastatic NSCLC referred for first-line therapy were eligible. Baseline IL-8 levels were measured in plasma. The Mini Nutritional Assessment (MNA) was used for the evaluation of the nutritional status, and patients were classified into 3 groups: A (score 24–30) “well nourished,” B (score 17–23.5) “risk of malnutrition,” and C (0–16.5) “malnourishment.” Response to first-line chemotherapy, time-to-tumor progression (TTP), and overall survival (OS) were also recorded. In total, 114 patients (101 males, 88.5%; mean age = 67.5 yr) were evaluated. Performance status was 0–1 in 62% of the patients. According to the MNA, the majority of patients (71%) was either at nutritional risk or malnourished. IL-8 levels were significantly different between MNA groups (P = 0.023) and correlated with TTP (P = 0.013) and OS (P = 0.001) in univariate analysis. Baseline IL-8 levels correlate with the nutritional status of patients with metastatic NSCLC, suggesting that this cytokine may be related with cachexia. [ABSTRACT FROM PUBLISHER]

Background: Loss of normal cell cycle control is an early event in the evolution of cancer. The expression of cyclin-dependent kinase (CDK) inhibitors p16 and p27 has been previously associated with progression of prostate cancer (PC). 70 patients diagnosed with early stage PCwere treated with radical prostatectomy (RP) at our institution and their tumor specimens were immunohistochemically evaluated for expression of p16 and p27. Available clinical data of time to PSA recurrence were correlated with the examined parameters and combined with pre-operative PSA level, Gleason score and pathological TNM (pT) stage assessment. Results: Nuclear overexpression of p16 was not associated with time to biochemical failure (BF) (p = 0.572). Same was the case for nuclear p27 overexpression (p = 1.000). Also, no significant correlations were found between either p16 or p27, and pre-operative PSA level, pT stage and Gleason grade. pT stage emerged as the only independent prognostic factor for biochemical recurrence (p = 0.01). Conclusions: These data question previously reported data supporting the prognostic relevance of both p16 and p27 proteins in early PC. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Lung cancer patients frequently present with weight loss in the context of the cachexia syndrome. Despite its high clinical significance, definite diagnostic criteria of cachexia are lacking. Nutritional screening questionnaires, like the Mini Nutritional Assessment (MNA), have been proposed for the timely diagnosis of the syndrome. The aim of this study was to evaluate the correlation of MNA with laboratory markers of inflammation/cachexia in patients with metastatic lung cancer. The prognostic value of the measured parameters was also examined. Patients and methods: Patients with metastatic lung cancer referred for systemic therapy were eligible. Baseline clinical characteristics were recorded and nutritional status was assessed using MNA. Blood samples were also collected and the following parameters were measured: hemoglobin (Hb), albumin (Alb), C-reactive protein (CRP), ghrelin, adiponectin, leptin and insulin growth factor I (IGF-I). Results: Totally, 115 patients (101 males) [median age 66 years (range 32–86)] were evaluated. According to MNA score, 27 (23.5%) patients were well nourished, 59 (51.3%) were at nutritional risk and 29 (25.2%) were already malnourished at diagnosis. MNA correlated with the following parameters: Hb (p =0.001), albumin (p <0.001), CRP (p =0.002), adiponectin (p =0.037) and leptin (p =0.008). After a median follow up of 38.2 months, multivariate analysis revealed that age (p =0.008), number of metastatic sites (p <0.001), MNA (p =0.044) and leptin (p =0.004) independently correlated with overall survival. Conclusions: Based on the MNA, the majority of patients were either malnourished or at nutritional risk. MNA correlated with laboratory parameters related to inflammation/cachexia and was independently associated with survival. [Copyright &y& Elsevier]

Background: Non-platinum-containing regimens have been proposed as alternatives to platinum-based doublets in the first-line treatment of patients with non-small cell lung cancer (NSCLC). However, conflicting results about their equivalence have been reported. Methods: We reviewed the records of patients enrolled in randomized controlled first-line trials conducted by the Hellenic Oncology Research Group from February 1997 to September 2006. The outcome of patients treated with first-line non-platinum-based chemotherapy who received platinum-based chemotherapy upon progression (cohort A) or platinum-based first-line chemotherapy followed by non-platinum-containing second-line chemotherapy (cohort B) was retrospectively analyzed. Results: Two-hundred and sixty-seven patients were identified in cohort A, and 123 in cohort B. Median follow-up time was 12.5 and 15.7 months for cohorts A and B. A significantly higher response rate and time to tumor progression (TTP) was recorded for patients treated with platinum-based compared to those receiving non-platinum-based first-line chemotherapy (45.5 vs. 21.3%, p < 0.0001 and 5.8 vs. 3.1 months, p= 0.002, respectively). Platinum-based regimens administered as second-line treatment resulted in a 13.1% response rate. TTP for second-line chemotherapy did not differ significantly between the two cohorts. Median overall survival was 13.3 and 15.7 months for cohorts A and B (p = 0.538). Conclusion: Both sequences resulted in similar efficacy in terms of overall survival. Encouraging median survival was achieved for selected patients with NSCLC who received both first- and second-line chemotherapy. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The oncofetal CRD-BP/IMP1 RNA binding protein regulates posttranscriptionally a handful of RNA transcripts, implicated in cell adhesion and invadopodia formation and was recently identified as a target of the β-catenin/Tcf transcription factor that is constitutively activated in colorectal carcinomas (CRCs). The expression of CRD-BP/IMP1 was studied in normal adult intestines and CRCs. In normal mucosa, CRD-BP/IMP1 immunoreactivity was observed in few scattered cells located predominantly at or near the bottom of the crypts, whereas in CRCs the protein was detectable in tumor cells of 50% of the specimens analyzed. CRD-BP/IMP1 mRNA expression was measured by qRT-PCR in 78 CRCs. Thirty-two (41%) of the specimens were negative or had negligible expression, whereas the remaining forty-six (59%) expressed a wide range of CRD-BP/IMP1 mRNA levels. CRD-BP/IMP1 mRNA expression correlated with that of the putative stem/progenitor cell marker Musashi-1 mRNA ( p = 0. 035). CRD-BP/IMP1 positive tumors metastasized and/or recurred more frequently ( p = 0.001) and its expression defined a group of patients with shorter survival ( p = 0.014). Furthermore, in a multivariate analysis CRD-BP/IMP1 expression was found to be an independent predictor of survival ( p = 0.015). For stage I & II patients, the differences in metastasis/recurrence and survival rates remained significant ( p = 0.001 and 0.033, respectively). These findings indicate that CRD-BP/IMP1 positive tumors exhibit early disease dissemination and unfavorable prognosis. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To determine the dose-limiting toxicities (DLTs) and the maximum-tolerated doses of the paclitaxel, oxaliplatin (LOHP) and capecitabine combination in patients with advanced solid tumors. Patients and Methods: Patients received escalating doses of paclitaxel (starting dose 100 mg/m2) and LOHP (starting dose 40 mg/m2) on days 1 and 15 and capecitabine (starting dose 800 mg/m2/day) on days 1–7 and 15–21 every 28 days. DLTs were evaluated in the first cycle. Results: Sixteen patients were treated at four dose-escalating levels. Eleven (68.7%) patients had received two or more prior chemotherapy regimens. The DLT level was reached at paclitaxel 110 mg/m2, LOHP 50 mg/m2 and capecitabine 1,000 mg/m2/day. DLTs due to grade 2–3 neutropenia resulted in treatment delays. No febrile neutropenia or treatment-related death occurred. Grade 2–3 neutropenia occurred in 3 (19%) patients each, grade 2–4 fatigue affected 6 (37.5%) patients, and grade 2–3 neurotoxicity was observed in 2 (12.5%) and 1 (6%) patients, respectively. Two partial responses and four disease stabilizations were achieved. Conclusion: The recommended doses for phase II studies are paclitaxel 100 mg/m2 and LOHP 50 mg/m2 on days 1 and 15 and capecitabine 1,000 mg/m2/day on days 1–7 and 15–21 every 4 weeks. This regimen is well tolerated and merits further evaluation. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g. chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Materials and methods Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan–Meier and Cox regression methods were used to compare these prognostic factors. Results 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59–73) and patients had stage IV non-small cell ( n = 288) (73.8%) or extensive stage small cell lung cancer ( n = 102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50–2.02) and mGPS (HR 1.67, CI 1.40–2.00) predicted survival ( p < 0.001). Survival at 3 months ranged from 99% (ECOG 0–1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0–1) to 33% (mGPS2, ECOG 3). Conclusion Performance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone. [ABSTRACT FROM AUTHOR]

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/m 2 or skeletal muscle index at the level of third lumbar vertebra (LSMI) <55 cm 2 /m 2 for males and <39 cm 2 /m 2 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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-460). The authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Purpose: To determine the tolerability and efficacy of the combination of gefitinib with gemcitabine plus vinorelbine in metastatic breast cancer (MBC) patients, pretreated with anthracyclines and taxanes., Patients and Methods: Women with measurable MBC pretreated with anthracycline- and taxane-based chemotherapy received oral gefitinib (250 mg/day) continuously combined with intravenous gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 on day 1, every 2 weeks. The first 10 enrolled patients were evaluated for the safety and tolerability of the proposed fixed-dose regimen., Results: The study was discontinued prematurely due to low accrual. Twenty-five (71%) of the originally scheduled 35 patients received a total of 154 chemotherapy cycles. All the patients had previously received taxane- and 72% additionally anthracycline-based chemotherapy and 64% of them had progressive disease as best response to first-line treatment. Three episodes of dose-limiting toxicities (one non-febrile neutropenia grade 4 and two non-neutropenic infections grade 3) were observed in the safety analysis of the first 10 patients. In an intent-to-treat analysis, the overall response rate was 12% (95% CI, 0-24.7%), the median time to tumour progression was 3.5 months (range 1.0-11.5) and the median overall survival was 10.4 months (range 1.0-46.0). The main toxicity was hematological, with grade 3 and 4 neutropenia occurring in 6 (24%) and 4 (16%) patients, respectively. Febrile neutropenia occurred in 2 (8.0%) patients., Conclusion: Although well tolerated, the gefitinib plus gemcitabine and vinorelbine regimen achieved a low response rate in this prematurely terminated trial and therefore cannot be recommended for women with pretreated MBC.