[Management of immunotherapy in patients with non-small cell lung cancer presenting durable oncological response]. / Prescription de l'immunothérapie chez les patients « long-répondeurs ¼.

INTRODUCTION: Concerns about the proper schedule for discontinuing immunotherapy have been raised by many clinicians, as well as the minimal check-up required to assess residual disease before stopping immunotherapy. In fact, there currently exist no recommendations concerning immunotherapy prescription and optimal assessment in the event of persistent oncological response in cases of metastatic non-small cell lung cancer (NSCLC). METHODS: We conducted an online survey among board-certified French Thoracic Oncologists belonging to two professional associations. The survey included multiple-choice questions that either stood alone or were included in case reports. RESULTS: The survey was sent to 490 physicians, of whom 88 responded. For minimal residual disease assessment after 2 years of immunotherapy, PET-scan is prescribed by 92% of respondents and cerebral MRI by 59%. In the event of complete response after 2 years of treatment, 83% of physicians stop prescribing pembrolizumab and 70% discontinue nivolumab. In the event of partial response, 88% of respondents continue immunotherapy. In this case, only 33% use a complementary locoregional treatment such as radiotherapy. CONCLUSION: Our survey highlights a pronounced tendency to stop immunotherapy in the event of complete oncological response. In the event of partial morphologic response, on the other hand, there is a tendency to continue immunotherapy. However, the use of locoregional treatments remains more heterogeneous.

Do systemic treatments delivered after Nivolumab result in better outcomes? A bicentric case-control study.

BACKGROUND: Immune checkpoint inhibitors (ICI) are now widely used at different stages of non-small cell lung cancers (NSCLC). Some clinical studies suggest that chemotherapy and immunotherapy have synergic activities, raising the question of the best therapeutic sequence. We studied the effect of chemotherapy in advanced NSCLC when administered after immunotherapy by nivolumab. METHODS: We performed a bicentric, retrospective, case-control study in two French hospitals. Patients with NSCLC treated with chemotherapy after nivolumab between January 2015 and January 2016 were included. Each case was matched on age and number of previous lines to one lung cancer patient who had not received nivolumab. Each CT-scanner has been reviewed and the objective response to chemotherapy was assessed for each patient according to the RECIST 1.1 criteria. RESULTS: Thirty-one patients with advanced NSCL who had at least received one cycle of chemotherapy after progression under nivolumab in the inclusion period were matched to 31 controls. The median age for cases was 59 yo and the predominant tumoral histology was adenocarcinoma (77%). The progression free survival (PFS) was 2.95 months in the studied group vs 2.69 months (P=0.18) in the control group. At best response, disease control (DC=partial response and stable disease) was better in the case group than in the control group (58% vs 39%, P=0.127). Cases were about five times more likely to get objective response to best evaluation than controls (OR=5.043 [95% CI: 0.975-26.086]; P=0.054). The overall survival (OS) was 7.3 months in the case group and 3.3 months in the control group (P=0.074). Patients who have been treated with targeted therapy instead of chemotherapy and patients with squamous lung cancer had worst PFS and OS. CONCLUSION: In advanced NSCLC, the chemotherapy progression free survival does not seem higher when administered after nivolumab. However, when administered post-nivolumab, traditional chemotherapy has 5 times more chances to achieve objective response and seems to improve overall survival of cases. Pooled analysis with other similar studies might be interesting for a next step.

Proposals for managing patients with thoracic malignancies during COVID-19 pandemic.

The objective of this document is to formalize a degraded mode management for patients with thoracic cancers in the context of the COVID-19 pandemic. The proposals are based on those of the French High Council for Public Health, on published data outside the context of COVID-19, and on a concerted analysis of the risk-benefit ratio for our patients by a panel of experts specialized on thoracic oncology under the aegis of the French-Language Society of Pulmonology (SPLF)/French-language oncology group. These proposals are evolving (10 April 2020) according to the situations encountered, which will enrich it, and are to be adapted to our institutional organisations and to the evolution of resources during the COVID-19 epidemic. Patients with symptoms and/or COVID-19+ are not discussed in this document and are managed within the framework of specific channels.

Self-expanding metallic Y-stent compared to silicone Y-stent for malignant lesions of the main carina: A single center retrospective study.

BACKGROUND: Bifurcation stents are often required in patients with malignant airway obstruction or fistulization involving the main carina. The silicone Y stent is the most used but remains challenging to place. The self-expanding metallic Y (SEM) stent appears easy to use. The objective is to report the feasibility, efficacy, and tolerance of SEM Y stent compared to silicone Y stent in patients with malignant tumors involving the main carina. PATIENTS AND METHODS: This retrospective single center study was performed between May 2004 and May 2017. All patients with malignant carina involvement treated with a bronchial Y stent were included. RESULTS: Forty silicone Y stents and 38 SEM Y stents were placed. Seven stenting placements failed in the silicone Y group but none in the SEM Y stent group (P=0.008). The median duration of the procedure was 80min (25-210) in the silicone Y group and.50min (25-110min) in the SEM Y group (P=0.001). There was no significant difference in terms of early or late complications between the 2 groups. Nine silicone Y stents (26.5%) and 7 SEM Y stents (18.4%) were removed (P=0.4). The median survival time following stent insertion was 171 days (Interquartile range (IQR): 53-379) in the silicone Y group and 104 days (IQR: 53-230) in the SEM Y group. CONCLUSION: If silicone Y stent remains the best solution for benign obstruction, SEM Y stent seems to be an easy alternative with no difference in terms of complication or ablation for malignant lesions involving the main carina.

Somatic profile in lung cancers is associated to reproductive factors in never-smokers women: Results from the IFCT-1002 BioCAST study.

BACKGROUND: Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. METHODS: All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. RESULTS: Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age>14 vs. 40% and 41% for 12-14 and ≤12 years, respectively; P=0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P=0.048), and by 9% for each year at age at first birth (P=0.035). ALK alteration frequency was greater in women with high parity (50% in≥5 vs. 12% and 7% for 1-4 and nulliparity, respectively; P=0.021). CONCLUSION: In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

[Predictive factors of complications during CT-guided transthoracic biopsy]. / Facteurs prédictifs de complications des ponctions transpariétales thoraciques.

INTRODUCTION: CT-guided transthoracic core-needle biopsy (TTNB) is frequently used for the diagnosis of lung nodules. The aim of this study is to describe TTNBs' complications and to investigate predictive factors of complications. METHODS: All consecutive TTNBs performed in three centers between 2006 and 2012 were included. Binary logistic regression was used for multivariate analysis. RESULTS: Overall, 970 TTNBs were performed in 929 patients. The complication rate was 34% (life-threatening complication in 6%). The most frequent complications were pneumothorax (29% included 4% which required chest-tube) and hemoptysis (5%). The mortality rate was 0.1% (n=1). In multivariate analysis, predictive factor for a complication was small target size (AOR=0.984; 95% CI [0.976-0.992]; P<0.001). This predictive factor was also found for occurrence of life-threatening complication (AOR=0.982; [0.965-0.999]; P=0.037), of pneumothorax (AOR=0.987; [0.978-0.995]; P=0.002) and of hemoptysis (AOR=0.973; [0.951-0.997]; P=0.024). CONCLUSION: One complication occurred in one-third of TTNBs. The proportion of life-threatening complication was 6%. A small lesion size was predictive of complication occurrence.

[Economic impact of lung cancer screening in France: A modeling study]. / Modélisation de l'impact économique d'un dépistage organisé du cancer du poumon en France.

INTRODUCTION: The National Lung Screening Trial found that, in a selected population with a high risk of lung cancer, an annual low-dose CT-scan decreased lung cancer mortality by 20% and overall mortality by 7% compared to annual chest X-Ray. In France, a work group stated that individual screening should be considered in this setting. However, the economic impact of an organized and generalized (to all eligible individuals) screening in France was never reported. METHODS: This is a modeling study using French population demographic data and published data from randomized screening trials. We used the same selection criteria as NLST: 55-74-year-old smokers for at least 30 pack-years, current smoker or quit less than 15 years. We computed a second model including also 50-54-year-old individuals. Then, we used different participation rates: 65%, 45%, and 32%. RESULTS: According to the considered model, there would be 1,650,588 to 2,283,993 subjects eligible to screening in France. According to the model and participation rate, lung cancer screening would diagnose 3600 to 10,118 stages 1/2 lung cancer each year. There would be 5991 to 16,839 false-positives, of whom 1416 to 3981 would undergo unnecessary surgery. Screening policy would cost 105 to 215 € million per year. However, increasing the price of a cigarette pack by 0.05 to 0.10 € would fully cover the screening costs. CONCLUSION: Participation rate is a key point for screening impact. Screening could be easily funded by a small increase in cigarette prices.

[Lung screening]. / Le dépistage du cancer du poumon.

The NLST study found in more than 53,000 (former-) heavy smokers that annual screening with low-dose CT-scan (LDCT) reduced lung cancer mortality and overall mortality by 20% and 6.7% respectively. However, several potential harms of such screening strategy were underlined: over-diagnosis bias, irradiation risk, and the high rate of false-positive results that could lead to futile invasive (and potentially harmful) exams, to impact quality of life, to increase patient's anxiety and costs. All these concerns were largely debated in several recent publications. Most of them concluded in a risk/benefit ratio favoring screening strategy by LDCT. Conversely, most of American academic societies currently recommend LDCT-based lung cancer screening. In France, a taskforce edited a common statement recommending screening smokers or ex-smokers, from 55 to 75years old who have smoked at least 30packs/year. The taskforce also underlined the need for clinical trials aiming to translate screening strategy to the French setting. However, the French Health Authority recently claimed that lung cancer screening was not relevant in the current setting.

[Long-term results of lung cancer surgery in octogenarians]. / Résultats à long terme de la chirurgie de résection pulmonaire pour cancer chez l'octogénaire.

INTRODUCTION: This retrospective study was undertaken to evaluate late results of lung cancer surgery in octogenerians. METHODS: All patients 80years old or more who underwent a lung resection for cancer from 2000 to 2010 at Lyon University Hospital were included. No patients were treated with video-assisted surgery. Wedge resections were excluded. RESULTS: Sixty-three patients (42 men, 21 women) were operated. The median age was 82years. Operative mortality was 4.7%. The rate of perioperative complications was 49%. The late survival was 34% at 5years. Five-year survival by nodal involvement was N0, 36%; N1, 29%; N2 20%, P<0.05. Patients with a squamous cell carcinoma (24) had a better long-term survival than patients with an adenocarcinoma (30), 33% and 25% respectively at 5years, P<0.05. The rate of recurrence was 33.9%. CONCLUSIONS: Surgical treatment of lung cancer in selected population of octogenerians is associated with satisfactory early and long-term results. Survival is influenced by nodal involvement and by the pathologic type of the cancer.

[Script concordance test for knowledge assessment of lung cancer screening]. / Évaluation des connaissances sur le dépistage du cancer par test de concordance de script.

BACKGROUND: Annual screening for lung cancer using low-dose CT-scans is associated with decreased mortality. A survey conducted in Rhône-Alpes area in France found that clinicians need education and information on this topic. Script concordance tests (SCT) are a tool for assessing clinical reasoning in situations of uncertainty. They have not previously been used in France in the context of continuing medical education. METHOD: We created a questionnaire with 5 multiple-choice questions (MCQ) and two SCT scenarios. The questionnaire was sent to all clinicians and residents who are members of French-Speaking Respiratory Society or the French Young Pulmonologist Association. RESULTS: One hundred and ninety answers were analyzed. Seventy percent stated that decreasing mortality was the best criterion for assessing the effectiveness of a cancer screening policy, and 75% that low-dose CT scan was the best test to achieve this in lung cancer screening. Forty-five percent knew the eligibility criteria of the population, and 62% that low-dose CT scan should be performed annually. Participation in tumor boards and certification in oncology were significantly associated with a better score at MCQ and SCT. SCT and MCQ scores were significantly correlated (Spearman's Rho 0.339; P<0.0001). CONCLUSION: SCT are feasible by electronic survey and seem relevant. Improving knowledge of clinicians on lung cancer screening is still critical.

[Endobronchial ultrasound transbronchial needle aspiration initiation into the Lyon Sud hospital center: Experience of the first three years]. / Initiation de la technique d'écho-endoscopie bronchique au centre hospitalier Lyon-Sud : expérience des trois premières années.

INTRODUCTION: Endobronchial ultrasound is a recent technique for the diagnosis and the lymph node staging in lung cancer. It also showed interest in non tumoral mediastinal lymph nodes diagnosis. This work relates the CHLS first three years' experience in terms of EEB practical use as a new diagnostic tool in this field. METHODS: Retrospective study of consecutive cases patients having undergone endobronchial ultrasound from November 2008 till June 2011 in the CHLS. RESULTS: On 65 endobronchial ultrasound, general anesthesia was practiced in 89 % of the cases, with a good tolerance in 81 % of the cases. In 77 % cases, EEB allowed diagnosis and avoided mediastinoscopy in 60.5 % of the cases. The respective sensibility, specificity, positive and negative predictive values were 74 %, 100 %, 100 % and 48 %. CONCLUSION: These data, reflect of a novice team experience, illustrate the results obtained in the current practice in terms of etiologic diagnosis. Endobronchial ultrasound seems destined to a bright future but requires the development of dedicated centers allowing pulmonologists training and specialized pathologists in this field.

[Free circulating DNA as a tool for lung cancer patients management]. / Intérêts de l'ADN circulant pour la prise en charge du cancer broncho-pulmonaire.

Free circulating DNA (cfDNA) has been known for several decades. These small DNA fragments are released into the circulation from nucleated cells through necrosis, apoptosis and/or active secretion. These genomic fragments are mainly constitutional (nucleated blood cell DNA), but in patients with cancer, a fraction comes from tumor cells. Although poorly known in the field of thoracic oncology, quantitative and qualitative analysis of the cDNA is nevertheless of great interest. Total cfDNA concentration appears to be an independent prognostic factor in lung cancer. Although changes in total cfDNA concentration is not informative to assess the effectiveness of chemotherapy, following-up the fraction of mutated genes such as EGFR during therapy with tyrosine kinase inhibitors appears to be particularly promising for the early detection of disease progression. The use of cfDNA as liquid biopsy is also very promising for the non-invasive somatic molecular profile either at baseline either for sampling at follow-up. Thus, cfDNA is a very promising tool in thoracic oncology and its translation into practice should be developed quickly.

[Patient's beliefs about oral targeted therapies and impact on drug adherence in lung cancer: A pilot prospective study]. / Croyances des patients envers les thérapies ciblées orales et leur influence sur l'observance dans le cancer broncho-pulmonaire : une étude pilote prospective.

INTRODUCTION: Oral targeted therapies are a new option for lung cancer treatment. However, patient's belief about these drugs - which may interact with adherence - is poorly known in this setting. METHOD: Our study is a pilot prospective unicentric study. Inclusion criteria were: to have been diagnosed with a lung cancer; and to be prescribed with an oral targeted therapy in second line or more. The main objective was to assess patient's specific (SB) and general beliefs (GB) about these drugs according to the Beliefs about Medicines Questionnaire (BMQ). The declared adherence was assessed with the Morisky's test. All included patients underwent a semi-structured interview with a psychologist. RESULTS: Fifthteen patients were included: 12 underwent erlotinib treatment and 3 a crizotinib treatment. The mean score (±standard deviation) at BMQ was 54/85 (±6) overall; 34/50 (±5) for specific belief and 19/35 (±3) for general belief about drugs. During interview, 47% believed in efficacy of targeted oral therapy; 93% reported concerns about their drug; 80% considered that the information given by the physician about the drug was comprehensive; but 40% still required additional information about it. The mean score at Morisky's test was 3/4 (±2) and 53% reported to have forgotten at least once their antineoplastic drug. No correlation was found between belief and adherence. CONCLUSION: Belief about t anti-cancer targeted oral therapy is relatively fair but adherence is moderate in this pilot study. Interview shows the need for additional information about the prescribed drug.

[Lung function in patients with diabetes mellitus]. / Fonction pulmonaire du patient diabétique.

INTRODUCTION: Diabetes mellitus is a disease affecting a lot of organs. One of the little known diabetes complication is impairment of pulmonary function. The aim of this study was to compare pulmonary function in two groups: diabetic individuals and obese non-diabetic individuals and to investigate predictive factors of alteration of diffusing capacity of lung for carbon monoxide (DLCO). PATIENTS AND METHOD: We retrospectively included all patients hospitalized in department of endocrinology between 1st July 2013 and 31 December 2013 and who underwent pulmonary function tests. All these medical charts of patients were reviewed and patients were classified in two groups: diabetic and obese non-diabetic individuals. RESULTS: Overall, 89 patients were included, 62 diabetic patients and 27 obese non-diabetic patients. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), medium expiratory flow, expiratory residual volume, total lung capacity (TLC) and DLCO were significantly lower in patients with diabetes mellitus compared to obese non-diabetic patients. A low DLCO was significantly associated with diabetic neuropathy, macrovascular complication (carotid atheroma), impairment of renal function, and insulin treatment. CONCLUSION: Respiratory function is impaired in diabetes mellitus, with a significant decrease in FVC, FEV1, TLC and DLCO.

Management of emerging multidrug-resistant tuberculosis in a low-prevalence setting.

Multidrug-resistant (MDR) tuberculosis (TB) is an emerging concern in communities with a low TB prevalence and a high standard of public health. Twenty-three consecutive adult MDR TB patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-TB treatment management, which included surgical procedures and long-term patient follow-up. This report of our experience emphasizes the need for an individualized approach as MDR TB brings mycobacterial disease management to a higher level of expertise, and for a balance to be found between international current guidelines and patient-tailored treatment strategies.

[Assessment of a tool for decision making in case of worsening condition of cancer patients]. / Évaluation d'une fiche d'aide à la décision en cas d'aggravation d'un patient cancéreux.

BACKGROUND: In response to questions regarding the appropriate intensity of care for some patients, "a decision support aid regarding the intensity of care in case of worsening condition of a patient with a chronic disease" has been established at the Grenoble university hospital. According to patient's wishes and the experience of the medical and paramedical team who are responsible for him, a level of intensity of care will be suggested. METHODS: We propose a prospective and multicenter study conducted in the Rhône-Alpes-Auvergne area. All lung cancer patients admitted to a pulmonology unit in 2014 would be included. This document would be used if a decision to withhold life-sustaining treatment exists. We would assess the relationship between the planned intensity of care and those established when the patient develops organ failure. Patient characteristics and factors associated with proposed levels and types of care would be analyzed. Patient and family opinions will be obtained at 3 months. The number of subjects to be included is 468. EXPECTED RESULTS: Therefore, we hope to be able to define the wishes of patients' and to propose an appropriate and adapted aid for decisions if they develop organ failure.

[Impact of lung cancer treatments on renal function]. / Impact des traitements utilisés en oncologie thoracique sur la fonction rénale.

INTRODUCTION: Renal failure in patients with lung cancer may be multifactorial: related to the patients and their comorbidities, direct tumor compression or the toxicity of cancer treatments and other associated medications. This literature review is intended to describe the state of knowledge regarding the nephrotoxicity of treatments used in thoracic oncology. FINDINGS: The majority of chemotherapy treatments are potentially nephrotoxic. Cisplatin and pemetrexed exhibit mainly renal tubular toxicity, while vascular renal impairment is found with gemcitabine and bevacizumab. Cisplatin results in acute renal failure in 30% of patients. Renal protective strategies (compliance with recommendations, limitation of nephrotoxic treatments, hydration, magnesium supplementation) must be employed systematically. Targeted therapies do not require any adjustment of the dosage in case of moderate or severe renal insufficiency but adapting the doses of biphosphonates to renal function is necessary. CONCLUSION: This review highlights the need for monitoring of renal function in patients with lung cancer during treatment with chemotherapy or biphosphonates.