Staging of nutrition disorders in non-small-cell lung cancer patients : utility of skeletal muscle mass assessment

Background An international consensus proposed in 2011 a definition and classification system for cachexia (CAX), mainly based on weight loss, sarcopenia [skeletal muscle mass (SMM) loss], inflammation, and anorexia. The aim of this study was to stage CAX in non-small-cell lung cancer (NSCLC) patients by using a classification based on the Fearon criteria and supported by quantifiable parameters. Methods This was a cross-sectional and non-interventional multicentre study. SMM was assessed by analysing L3 computed tomography-scan images. Patients completed the anorexia/CAX subscale of the Functional Assessment of Anorexia/Cachexia Therapy, EORTC QLQ-C30 quality of life (QoL) and International Physical Activity Questionnaire (IPAQ). Results Patients were recruited in 56 sites. The analysis population comprised 531 patients, and SMM was assessed in 312 patients. Male patients were 66.5%, with a mean (SD) age of 65.2 (10.0) years, 79.9% were PS 0-1, and the tumour stage was mainly IIIB-IV (87.3%). Overall, 38.7% of patients had CAX, 33.8% pre-CAX, and 0.9% refractory CAX. Molecular tumour profiles were significantly associated with the presence of CAX: 23.9% in EGFR, ALK, ROS1, BRAF, or HER2+ patients, 41.4% in K-RAS+, and 43.2% in patients with no molecular abnormality (P = 0.003). The more advanced the CAX stage, the poorer the scores of functional items of the QoL (P < 0.001) and International Physical Activity Questionnaire (P < 0.001). Sarcopenia was present in 66.7% of CAX and 68.5% of pre-CAX patients. Overall, 43.8% of pre-CAX patients had only sarcopenia with limited weight loss (<= 2%) and no anorexia. Conclusions This is the first study to show the distribution of CAX in a population of NSCLC patients and an association between molecular abnormality in NSCLC and CAX. The original Fearon classification for CAX stages was supported by the associated functional QoL scores and physical activity levels, resulting in a clinically relevant system for detection of early stages of CAX

FASE-CPHG Study: identification of asthma phenotypes in the French Severe Asthma Study using cluster analysis

BACKGROUND: In France, data regarding epidemiology and management of severe asthma are scarce. The objective of this study was to describe asthma phenotypes using a cluster analysis in severe asthmatics recruited in a real world setting. METHODS: The study design was prospective, observational and multicentric. The patients included were adults with severe asthma (GINA 4-5) followed-up in French Non Academic Hospital between May 2016 and June 2017. One hundred and seven physicians included 1502 patients. Both sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis on a population of 1424 patients. RESULTS: Five clusters were identified: cluster 1 (n = 690, 47%) called early onset allergic asthma (47.5% with asthma before 12 years), cluster 2 (n = 153, 10.5%): obese asthma (63.5% with BMI > 30 kg/m(2)), cluster 3 (n = 299, 20.4%): late-onset asthma with severe obstructive syndrome (89% without atopy), cluster 4 (n = 143, 9.8%): eosinophilic asthma (51.7% had more than 500 eosinophils/mm(3)), and cluster 5 (n = 139, 9.5%): aspirin sensitivity asthma (63% had severe asthma attacks). CONCLUSIONS: In our population of adults with severe asthma followed by pulmonologists, five distinct phenotypes were identified and are quite different from those mentioned in previous studies

Routine molecular profiling of cancer: results of a one-year nationwide program of the French Cooperative Thoracic Intergroup (IFCT) for advanced non-small cell lung cancer (NSCLC) patients.

International audienceBackground: The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. Methods This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. Findings 18 679 molecular analyses of 17 664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18–98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7–16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17 706 analyses for which data were available, HER2 mutations in 98 (1%) of 11 723, KRAS mutations in 4894 (29%) of 17 001, BRAF mutations in 262 (2%) of 13 906, and PIK3CA mutations in 252 (2%) of 10 678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8–25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7–38·2] for presence of a genetic alteration vs 33% [29·5–35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0–18·8] vs 9% [6·7–11·9]; p&lt;0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2–10·7] vs 7·1 months [6·1–7·9]; p&lt;0·0001) and overall survival (16·5 months [15·0–18·3] vs 11·8 months [10·1–13·5]; p&lt;0·0001) compared with absence of a genetic alteration. Interpretation Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit

The Importance of Apneic Events in Obstructive Sleep Apnea Associated with Acute Coronary Syndrome

Background. Obstructive sleep apnea (OSA) is a potential cardiovascular risk factor. However, there is currently no prominent screening strategy for its diagnosis in patients with acute coronary syndrome (ACS). The aim of this study was to establish the impact of apneic events in case of OSA associated with ACS. Methods. Between January 1st and June 30th, fifty-three subjects with ACS (first acute myocardial infarction) were prospectively evaluated for OSA. Each patient was evaluated by polysomnography (PSG) two months after the ACS. Results. Mean age of 59±9,6 years, 81,1% males, BMI at 28,5±4,2 kg/m2, neck circumference of 42,5±12,6 cm, and waist circumference os 102,5±16,5 cm. The majority of patients (73,6%) had moderate to severe OSA (apnea-hypopnea index (AHI) ≥ 15/h and arousal index ≥ 10/h). We defined the apneic coefficient (AC) as the ratio between apnea index (AI) and AHI. We chose as cut-off the median value of apnea coefficient in our population which was at 37%. The patients with a higher AC (AC ≥ 37% versus AC < 37%) had higher levels of Troponin-I (63,4±63,2 versus 29,7±36,1 ng/mL, p=0,016), higher levels of NT-proBNP (1879,8±2141,8 versus 480±621,3 pg/mL, p=0,001), higher SYNTAX score (15,8±11,5 versus 10,2±5,9, p=0,049), and lower left ventricle ejection fraction (LVEF 53,3±11,4 versus 59,4±6,4%, p=0,023) and were more likely to have a STEMI (21 patients (77,7%) vesus 14 patients (53,8%), p=0,031). Conclusion. An apneic coefficient (AI/AHI) ≥ 37% is correlated with more severe cardiac impairment, as well as higher hypoxemia and arousal index

Treatment patterns and clinical outcomes of extensive stage small cell lung cancer (SCLC) in the real-world evidence ESME cohort before the era of immunotherapy

International audienceBackground: Small cell lung cancer (SCLC) is a highly aggressive entity of lung cancer with tendency toward early recurrence after first-line treatment. As per recently updated European Society for Medical Oncology recommendations, first-line treatment with up to 4 cycles of platinum-etoposide combined with immune checkpoint inhibitor (ICIs)-targeting PD-L1, is now the standard of care. The purpose of the current analysis is to identify current patient profiles and treatment strategies in real life clinical practice, and report outcomes in Extensive Stage (ES)-SCLC. Methods: Non-interventional, retrospective, multicentre, comparative study was carried out to describe the outcome of ES-SCLC patients included in the Epidémiologie Stratégie Médico–Economique (ESME) data platform for advanced and metastatic lung cancer. Patients were selected from 34 health care facilities between January 2015 and December 2017, before the era of immunotherapy. Results: 1315 patients were identified, including 64% male and 78% under 70 year-old; 24% had at least 3 metastatic sites, mainly liver metastases (43%), bone metastases (36%), brain metastases (32%). 49% received only one line of systemic treatment; 30% and 21% received 2 and 3 lines or more, respectively. Carboplatin was more frequently used than cisplatin (71% and 29%, respectively). Prophylactic cranial irradiation was infrequent (4% of patients), but 16% of patients received thoracic radiation therapy, mainly after the completion of first-line chemotherapy (72% of patients); such strategies were more frequently applied in cisplatin/etoposide than carboplatin/etoposide patients (p = 0.006 and p = 0.015, respectively). After a median follow-up time of 21.8 (95% CI: 20.9–23.3) months, median real-world Progression-Free Survival (rw-PFS) was 6.2 (95% CI: 5.7; 6.9) and 6.1 (95% CI: 5.8; 6.3) months for cisplatin/etoposide and carboplatin/etoposide doublet regimens, respectively; 24-month rwPFS and Overall Survival were 3.2% (95% CI: 2.3; 4;2) and 22.2% (95% CI: 19.4; 25.1) in the whole population, respectively. Conclusion: Our data provide with landmark reference findings on ES-SCLC before the immunotherapy era, and cover many aspects of the treatment strategy, while highlighting on the role of radiotherapy, subsequent lines of therapy, and the outcomes of patients. Generation of real-world data focusing on patients who received platinum-based chemotherapy combined with immune checkpoint inhibitors is under way

Staging of nutrition disorders in non‐small‐cell lung cancer patients: utility of skeletal muscle mass assessment

Background An international consensus proposed in 2011 a definition and classification system for cachexia (CAX), mainly based on weight loss, sarcopenia [skeletal muscle mass (SMM) loss], inflammation, and anorexia. The aim of this study was to stage CAX in non-small-cell lung cancer (NSCLC) patients by using a classification based on the Fearon criteria and supported by quantifiable parameters. Methods This was a cross-sectional and non-interventional multicentre study. SMM was assessed by analysing L3 computed tomography-scan images. Patients completed the anorexia/CAX subscale of the Functional Assessment of Anorexia/Cachexia Therapy, EORTC QLQ-C30 quality of life (QoL) and International Physical Activity Questionnaire (IPAQ). Results Patients were recruited in 56 sites. The analysis population comprised 531 patients, and SMM was assessed in 312 patients. Male patients were 66.5%, with a mean (SD) age of 65.2 (10.0) years, 79.9% were PS 0-1, and the tumour stage was mainly IIIB-IV (87.3%). Overall, 38.7% of patients had CAX, 33.8% pre-CAX, and 0.9% refractory CAX. Molecular tumour profiles were significantly associated with the presence of CAX: 23.9% in EGFR, ALK, ROS1, BRAF, or HER2+ patients, 41.4% in K-RAS+, and 43.2% in patients with no molecular abnormality (P = 0.003). The more advanced the CAX stage, the poorer the scores of functional items of the QoL (P < 0.001) and International Physical Activity Questionnaire (P < 0.001). Sarcopenia was present in 66.7% of CAX and 68.5% of pre-CAX patients. Overall, 43.8% of pre-CAX patients had only sarcopenia with limited weight loss (<= 2%) and no anorexia. Conclusions This is the first study to show the distribution of CAX in a population of NSCLC patients and an association between molecular abnormality in NSCLC and CAX. The original Fearon classification for CAX stages was supported by the associated functional QoL scores and physical activity levels, resulting in a clinically relevant system for detection of early stages of CAX

Rurality and survival differences in lung cancer: a large population-based multivariate analysis.

International audienceSeveral studies have suggested rural health disadvantages. In France, studies on rural-urban patterns of lung cancer survival have yielded conflicting results. The aim of this analysis was to determine whether rural residence was associated with poor survival in three French counties. The database consisted of all primary lung cancer cases diagnosed in 2000 and 2001 collected through the Doubs cancer registry. A degree of rurality, obtained from socio-demographic and farming parameters of the 1999 French census treated with factor analysis, was attributed to each patient according to his/her place of residence. Among the 802 patients, 21% resided in rural areas, 11% were semi-urban inhabitants and 68% were urban residents. Survival differed significantly between these three rurality categories (p=0.04), with 2-year survival rates of 18, 29 and 24%, respectively. Using a Cox model, rural areas were significantly correlated with poor survival as compared with semi-urban areas (OR=1.42; 95% confidence interval=1.06-1.90; p=0.02). There was no survival difference between semi-urban and urban patients (OR=1.18; 95% confidence interval=0.91-1.53; p=0.21). Patient and tumour characteristics, especially stage and staging procedures, as well as first line treatment, did not vary with the degree of rurality. In conclusion, rurality has to be considered as a strong prognostic factor. Several intricate factors might be hypothesized such as increasing time to diagnosis leading to heavier tumour burden, worse treatment compliance and socioeconomic status. Before practical interventions can be proposed, prospective studies are warranted with further definition of rural risk factors for decreased survival in rural lung cancer patients

Sci Rep

Treatment of metastatic non-small cell lung cancer (mNSCLC) has been modified due to the development of immunotherapy. We assessed survival outcomes (overall [OS] and progression-free [rwPFS] survivals, time-to-next-treatment [TNT]) in mNSCLC patients after first-line immunotherapy and chemotherapy in real-life settings. Association between rwPFS and TNT, two candidate surrogate endpoints (SE), with OS was assessed. This retrospective multi-center study uses data from patients included in the Epidemio-Strategy Medico-Economic program with mNSCLC over 2015-2019. The impact of treatment on rwPFS/OS was evaluated with Cox models. Individual-level associations between SE and OS were estimated with an iterative multiple imputation approach and joint survival models. The population included 5294 patients (63 years median age). Median OS in immunotherapy group was 16.4 months (95%CI [14.1-NR]) and was higher than in chemotherapy group (11.6 months; 95%CI [11.0-12.2]). Improved OS was observed for the immunotherapy group after 3 months for subjects with performance status 0-1 (HR = 0.59; 95%CI [0.42-0.83], p < 0.01). The associations between rwPFS and TNT with OS were close ([Formula: see text]=0.57). Results emphasized a survival improvement with immunotherapy for patients in good health condition. There was moderate evidence of individual-level association between candidate SE and OS

Phenotyping to Target Obstructive Sleep Apnoea Syndrom (OSAS) in adults patients with severe asthma

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) and severe asthma are frequently associated. This article focuses on the relationship between severe asthma phenotypes and OSAS. METHODS: FASE-CPHG was an observational, cross-sectional, prospective, multicentric study conducted in 104 non-academic hospitals from May-16 to July-17. 1465 patients with severe asthma were analysed and 1424 patients phenotyped. Clusters were compared for OSAS presence; independent factors associated with OSAS were identified by logistic regression. RESULTS: 11% of patients with severe asthma reported OSAS. OSAS incidence differed according to asthma phenotypes. 98% of OSAS patients belonged to the "obese asthma" cluster, and none to the "early onset allergic asthma" cluster. Independent factors associated with OSAS were obesity (OR=5.782 [3.927-8.512]), male gender (OR=3.047 [2.059-4.510]), high blood pressure (OR=2.875 [1.978-4.181]), depression (OR=2.552 [1.607-4.050]), late-onset asthma (OR=1.789 [1.167-2.743]) and atopy (OR=0.622 [0.408-0.948]). Moreover, OSAS patients were more frequently treated with long-term oral corticosteroids (30% vs 15%, p < 0.0001), that may contribute to the high prevalence of obesity in this group of patients. They were more frequently uncontrolled (78% vs 69%, p = 0.03) and they engaged in low level physical activity (vs 80% vs 68% p ≤ 0.001). CONCLUSION: Our study gives an innovative insight into OSAS associated with severe asthma. Most of patients with OSAS belonged to the cluster "obese asthma" and none to the cluster "early onset allergic asthma". In addition to male gender, arterial hypertension and depression, obese asthma, late onset asthma and non-atopic status were identified as specific risk factors. Oral corticosteroids seems to play a deleterious role. Phenotyping asthma can help physicians target severe asthmatic patients with OSAS and may avoid unnecessary examinations