Safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination in stage IV non-small-cell lung cancer: An open-label phase II trial (VinMetAtezo).

OBJECTIVE: To evaluate the safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination for stage IV non-small-cell lung cancer. METHODS: This was a multicenter, open-label, single-arm Phase II study performed in patients with advanced NSCLC without activating EGFR mutation or ALK rearrangement who progressed after first-line platinum-doublet chemotherapy. Combination treatment was atezolizumab (1200 mg IV day 1, every 3 weeks) and oral vinorelbine (40 mg, 3 times by week). The primary outcome was progression-free survival (PFS) during the 4-month follow-up from the first dose of treatment. Statistical analysis was based on the exact single-stage Phase II design defined by A'Hern. Based on literature data, the Phase III trial threshold was set at 36 successes in 71 patients. RESULTS: 71 patients were analyzed (median age, 64 years; male, 66.2%; ex-smokers/active smokers, 85.9%; ECOG performance status 0-1, 90.2%; non-squamous NSCLC, 83.1%; PD-L1 ≥ 50%, 4.4%). After a median follow-up of 8.1 months from treatment initiation, 4-month PFS rate was 32% (95% CI, 22-44), i.e. 23 successes out 71 patients. OS rate was 73.2% at 4 months and 24.3% at 24 months. Median PFS and OS were 2.2 (95% CI, 1.5-3.0) months and 7.9 (95% CI, 4.8-11.4) months, respectively. Overall response rate and disease control rate at 4 months were 11% (95% CI, 5-21) and 32% (95% CI, 22-44), respectively. No safety signal was evidenced. CONCLUSION: Metronomic oral vinorelbine-atezolizumab in the second-line setting did not achieve the predefined PFS threshold. No new safety signal was reported for vinorelbine-atezolizumab combination.

Performance of an eHealth (NOMHAD) System Comprising Telemonitoring, Telenotification, and Telecoaching for Patients With Multimorbidity: Proof-of-Concept Study.

BACKGROUND: Management of patients with multiple chronic diseases is a growing public health challenge, especially in rural sectors where access to physicians may be limited. Connected medical devices monitoring vital signs, associated with eHealth program and structured telephone support, may improve complex patient management through early detection of disease complications, positive impact on patients' health, and health resources consumption optimization. OBJECTIVE: The aim of this study was to evaluate the technical performance and user experience of the NOMHAD eHealth system in patients with multimorbidity. METHODS: This was a pilot, single-arm, interventional study. Patients with multimorbidity with any combination of chronic heart failure (CHF), chronic obstructive pulmonary disease, and diabetes were followed for 80-100 days using the NOMHAD eHealth system. This system used connected devices telemonitoring symptoms and vital signs (eg, body weight, oxygen saturation, pulse rate, blood pressure, and blood glucose), associated with structured telecoaching and educational support by call center nurses. An overall risk indicator (ORI) was automatically computed after each data teletransmission. The ORI was color coded; green indicated no action required; yellow, orange, and red (low to high priority, respectively) generated telenotifications and indicated to the nurses the need for a telecoaching action. Each ORI was calculated by combining 7 clinical stability system indicators based on symptom questionnaires and vital signs. Technical accuracy of the system was assessed by comparing system-generated ORIs with ORIs recalculated from raw data. Ease of use, usefulness, satisfaction, and acceptability of the system were assessed through patient adherence to self-assessments, and through self-administered questionnaires to patients, call center nurses, and physicians. RESULTS: A total of 23 patients were enrolled in this study and participated between April 2016 and March 2017 at 5 study centers in France. All patients were successfully equipped and evaluable for analysis. Mean age was 68.5 (SD 10.4) years and most patients were men (n=20). The most common multimorbidity was CHF + diabetes (n=15), followed by patients with all 3 diseases (n=5). Mean effective follow-up was 78.7 (SD 24.2) days. The system generated 6263 ORIs, as several ORIs could be generated on a single day for any patient. Overall system sensitivity was 99.2% (95% CI 98.9-99.4) and overall specificity was 91.3% (95% CI 87.7-94.1). Most patients (20/23, 87%) were satisfied with the system and agreed that it helped them to better understand and manage their diseases, and 19/23 (83%) valued the nurse regular contacts. Nurses and physicians were generally satisfied with the system and considered it useful. All users indicated they would agree to long-term use of the system. CONCLUSIONS: This study provides evidence that the NOMHAD eHealth system is accurate, acceptable, informative, and feasible for patients with multimorbidity, supporting further investigation of its clinical benefits. TRIAL REGISTRATION: Agence Nationale de Sécurité du Médicament et des Produits de Santé 2015-A01106-43; https://ictaxercb.ansm.sante.fr/Public/index.php.

A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer: clinical and dosimetric factors analysis.

BACKGROUND AND PURPOSE: Clinical and dosimetric prognostic factors for radiation pneumonitis (RP) have been reported after three-dimensional conformal radiotherapy (3D-CRT) in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-six patients who received 3D-CRT for stage IA to IIIB NSCLC were evaluated prospectively. Surgery was performed before radiation in 51% of the patients (n = 49). RP was diagnosed six-eight weeks after 3D-CRT using the Lent-Soma classification. Factors evaluated included treatment factors such as total mean lung dose (MLD), and dose-volume histogram (DVH) thresholds for several radiation dose steps. These thresholds were originally determined from the median of the irradiated lung volume at each step. RESULTS: Six patients could not be evaluated for RP six weeks after 3D-CRT. Of the 90 remaining patients, 40 (44%) had RP (i.e. grade > or =1) at 6 weeks, including 7 patients (7.8%) with severe RP (grade > or =2). Regarding the whole toxicity (grade > or =1), age (> or =60 years), MLD, V20 and V30 were significantly related to RP. DVH thresholds determined for radiation doses from 20 to 40 Gy were also predictive of RP. Considering only severe RP (grade > or =2), only MLD, V20 and V30 remained associated with increased acute pulmonary toxicity. CONCLUSIONS: In this study, dosimetric factors (MLD, V20, V30) and age (> or =60 years) were predictive of RP regarding the whole pulmonary toxicity (grade > or =1). In addition, thresholds from 20 to 40 Gy, based on a stratification according to the median of the percentage of irradiated lung volume, were also predictive factors. They may, therefore, help discriminate patients at high and low risk for RP. However, only MLD, V20 and V30 remained associated with severe RP (grade > or =2), probably due to the small number of severe events in our series.

Feasibility and clinical impact of re-biopsy in advanced non small-cell lung cancer: a prospective multicenter study in a real-world setting (GFPC study 12-01).

OBJECTIVES: When advanced non-small-cell lung cancer (NSCLC) progresses during first-line treatment, re-biopsy may be indicated to detect a possible new biological profile (comparison to initial status, emergence of resistance biomarkers, or assessment of new biomarkers). The aim of this pragmatic prospective multicenter study was to assess the feasibility and clinical utility of re-biopsy in advanced NSCLC in a real-world setting. METHODS: The main inclusion criteria were advanced NSCLC with an indication for repeat biopsy identified by the patient's clinician. The primary outcome was the percentage of successful procedures. Secondary outcomes were the type of procedure, new biological status, tolerability of the procedure, and clinical utility (treatment modification). RESULTS: From May 2012 to May 2013, 18 centers enrolled 100 patients (males: 44%; median age: 64.8 years; PS 0/1: 88%; adenocarcinoma: 89%; EGFR mutated: 50%; no initial biological profile: 16.4%). Re-biopsy was not possible in 19.5% of cases and provided no or too few tumor cells in 25.6% of cases. Repeat biopsy was useful for guiding treatment in 30.4% (25/82) of cases. Complications were infrequent (2 cases of moderate bleeding and 1 case of pneumothorax). CONCLUSION: Re-biopsy of advanced NSCLC is feasible in the real-world setting, with acceptable adverse events. Guidelines are needed on the indications of re-biopsy, the choice of procedure, the sampling site, and laboratory analysis.

Assessment of palliative care for advanced non-small-cell lung cancer in France: a prospective observational multicenter study (GFPC 0804 study).

INTRODUCTION: Few studies assessed, in real life, symptoms, specific interventions and factors influencing palliative care (PC) initiation for patients with advanced non-small-cell lung cancer (NSCLC). The objective of this study was to examine, in a prospective cohort of advanced NSCLC patients, PC use and factors associated with early (≤3 months after diagnosis) PC initiation. METHODS: It was an observational multicenter study. Each center included 10 consecutive patients with PC initiation. RESULTS: 514 patients were enrolled by 39 centers (age: 62.3 ± 10.7 years, performance status: 0/1; 68.6% cases). At baseline, the most frequent symptoms concerned pain (43.6%), malnutrition (37%) and psychological disorders (25.3%). Specific interventions were infrequent for pain control and malnutrition, but were more numerous for psychological and social problems and terminal care. Median time between diagnosis and PC initiation was 35 [13-84] days, median PC duration was 4.2 [0.6-9.3] months. Median overall survival was 8.6 [6.6-10.7] months; median survival after PC initiation was 3.6 [3.2-4.5] months. In multivariate analysis, only PS ≥2 was linked to early PC. CONCLUSION: This study showed that early PC initiation is not a standard for patients with advanced NSCLC.

Weekly paclitaxel combined with monthly carboplatin in elderly patients with advanced non-small cell lung cancer: a multicenter phase II study.

INTRODUCTION: We designed this phase II trial to evaluate the efficacy and safety of weekly paclitaxel in combination with monthly carboplatin as first-line treatment in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Main eligibility criteria were histologically or cytologically proven stage IIIB or IV NSCLC, age > or =70 years, Eastern Cooperative Oncology Group performance status 0-2, and measurable disease. The 4-week-based chemotherapy regimen consisted of carboplatin infusion (area under the concentration-time curve 6 mg/ml/min) on day 1 and paclitaxel 90 mg/m as a 1-hour infusion on days 1, 8, and 15. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors criteria, and symptoms were evaluated using the Lung Cancer Symptoms Scale. Analyses were performed on an intention-to-treat basis. RESULTS: From February 2002 to August 2003, 51 patients (median age, 74 years) participated in the study. One complete and 21 partial responses were reported by the independent review committee, leading to an intention-to-treat objective response rate of 43% (95% confidence interval, 30-57%). The median progression-free and overall survivals were 7.5 (95% confidence interval, 6.2-9.4) and 13.6 (95% confidence interval, 7.5-17) months, respectively. Longitudinal evaluation of the Lung Cancer Symptoms Scale demonstrated lack of quality of life modification during the treatment period. Neurotoxicity was mild to moderate, with 6% of patients suffering from a grade 3 or 4 neuropathy. Myelosuppression was the main toxicity; 39% of patients experienced grade 3 or 4 neutropenia, 18% experienced grade 3 anemia, and 8% experienced grade 3 or 4 thrombocytopenia. There was no treatment-related death. CONCLUSIONS: The combination of weekly paclitaxel 90 mg/m administered on days 1, 8, and 15 plus monthly carboplatin area under the curve 6 on day 1 of a 4-week cycle was feasible and active as a first-line treatment for elderly patients with NSCLC with a good safety profile. These results deserve further analysis to compare the standard care for these patients (monotherapies) with this doublet.

Exogenous lipoid pneumonia with unusual CT pattern and FDG positron emission tomography scan findings.

We report a case of an exogenous lipoid pneumonia that appeared as a spiculated calcified mass on CT scan in which a positron emission tomography (PET) scan was performed before histological analysis. The F-18 fluoro-deoxy-D-glucose (FDG) PET showed a pattern highly suggestive of malignancy which, to our knowledge, has not yet been described. Similar to inflammatory and infectious lung diseases, lipoid pneumonia may be a false-positive case of F-18 FDG uptake.