Burden of comorbidities: Osteoporotic vertebral fracture during non-small cell lung cancer - the BONE study.

INTRODUCTION: Immunotherapy and targeted therapy have extended life expectancy in non-small cell lung cancer (NSCLC) patients, shifting it into a chronic condition with comorbidities, including osteoporosis. This study aims to evaluate the prevalence and incidence of osteoporotic vertebral fracture (OPVF) during NSCLC follow-up, identify risk factors of OPVF, and determine the impact on overall survival (OS). METHODS: We performed a longitudinal single-center retrospective cohort study involving patients with histologically proven NSCLC of any stage. Chest-abdomen-pelvis computed tomography (CAP CT) at diagnosis and during follow-up were double-blind reviewed to determine OPVF site, count, type, time to incident OPVF, and trabecular volumetric bone density (TVBD). An institutional expert committee adjudicated discrepancies. Binary logistic regression was used to predict the occurrence of incident OPVF. OS was calculated using the Kaplan-Meier method. RESULTS: We included 289 patients with a median follow-up of 29.7 months. OPVF prevalence was 10.7% at inclusion and 23.2% at the end of follow-up. Cumulative incidence was 12.5%, with an incidence rate of 4 per 100 patient-years. Median time to incident OPVF was 13 months (IQR: 6.7-21.2). Seven of the 36 patients with incident OPVF received denosumab or bisphosphonates. In multivariable analysis, independent risk factors for incident OPVF were BMI < 19 kg/m2 (OR: 5.62, 95%CI 1.84-17.20, p = 0.002), lower TVBD (OR: 0.982 per HU, 95%CI 0.97-0.99, p = 0.001) and corticosteroid use (OR: 4.77, 95%CI: 1.76-12.89, p = 0.001). OPVF was not significantly associated with OS. CONCLUSIONS: Osteoporosis should be screened for in NSCLC patients. Thoracic oncologists must broaden the use of steroid-induced osteoporosis recommendations.

[Non-infectious respiratory emergencies in patients with cancer]. / Urgences respiratoires (non infectieuses) du patient d'onco-hématologie.

Patients with a solid tumor or hematologic malignancy are often addressed to emergency units for an acute respiratory complication associated with the underlying cancer or secondary to treatments. The current article is part of a thematic series: "Intensive care and emergencies in solid tumours and blood cancer patients" and will develop the following points: (1) malignant proximal airway obstruction and, more specifically, the role of therapeutic bronchoscopy; (2) superior vena cava syndrome by tumor compression and/or secondary to thrombosis (diagnosis, local and systemic treatments); (3) cancer-related pulmonary embolism (incidence, indications for low-molecular weight heparins and direct oral anticoagulants). Other respiratory emergencies will be dealt in the other articles of this series.

Patients avec cancers thoraciques et COVID-19 : au cœur de la tempête: Patients with chest cancer and COVID-19: at the heart of the storm.

A meta-analysis of the Chinese studies in April 2020, including 3600 patients with cancer and COVID-19, first reported an increase of the COVID-19 risk and the case-fatality in these patients. Then, North-American and European series confirmed the increased COVID-19 risk for patients with cancer, as the increased risk of severe COVID-19 and death, when compared with general population, adjusting for age. Patients with lung cancer have the highest risk of severe respiratory forms, and the highest risk of SARS-CoV2-induced death (25 to 30%), after patients with hematological cancers. Metastatic patients, with poor PS, and those having received a cytotoxic chemotherapy within the weeks preceding SARSCoV2 infection, are those with the highest risk of death. Conversely, being treated with immune checkpoint inhibitors would not favor the cytokine storm, which makes the severity of COVID-19. SARS-CoV2 pandemic, beyond having needed the generalization of drastic social distancing measures in hospitals, also needed organizational changes, to allow healthcare continuity for cancer patients. Adaptation of therapeutic protocols was needed, with increased intervals between cycles, the choice of less toxic protocols, the systematic use of hematological growth factors, and teleconsultations follow-up. Lastly, mRNA-based SARS-CoV2 vaccines are efficient in patients with thoracic cancer, provided the interval of 21/28 days between the two injections is maintained, since protective immunization seems delayed, especially after cytotoxic chemotherapy. Only 13% of patients with very low protective antibodies titers would need a third booster injection, with a clear rise in protective antibodies titers induced by such a third injection.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Definitions, outcomes, and management of hyperprogression in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: The advent of immune checkpoint inhibitors (ICI) has been a breakthrough in the care of patients with non-small-cell lung cancers (NSCLC). However, physicians are now facing a previously unidentified clinical situation called hyperprogression (HP), which presents as a fast and unexpected increase in tumor burden. HP's existence and specificity to ICIs remains controversial because a widely acknowledged definition is currently lacking. Meanwhile, management remains elusive. METHODS: Medical records from all consecutive NSCLC patients who were treated with ICI from 2015 to 2018 were retrospectively analyzed. The HP incidence rate was calculated according to five definitions (tumor growth rate [TGR]ratio, ΔTGR, tumor growth kinetic [TGK], RECIST, and time to treatment failure [TTF]), and the agreement between such definitions was determined. The HP impact on overall survival (OS) was then assessed. The association between HP (defined using the TGRratio definition) and clinical and biological variables was also assessed. Clinical HP management and its impact on outcomes were described. RESULTS: We identified 169 consecutive ICI-treated patients, with potential HP accounting for 11.3 %, 5.7 %, 17.0 %, 9.6 %, and 31.7 % patients, according to TGRratio, ΔTGR, TGK, RECIST, and TTF definitions. Agreement between the different HP definitions was highly heterogeneous (range 29 %-77 %) and globally poor. HP was associated with shorter OS, compared to standard RECIST progressive disease, but this difference only reached statistical significance when using the TTF definition. TGRratio-based HP was significantly associated with hepatic metastases. In TGRratio-based HP patients, neither resuming chemotherapy nor corticosteroids use was associated with statistically significant impact on overall survival. CONCLUSION: We found fairly heterogeneous HP rates using different definitions. TTF was the only definition leading to significantly worsened OS. Further studies are needed to provide consensus recommendations for the assessment, definition, and management of HP, whose existence is likely real.

Detection of secondary causes of spontaneous pneumothorax: Comparison between computed tomography and chest X-ray.

PURPOSE: The aim of this study was to compare the effectiveness of chest X-ray to that of thoracic computed tomography (CT) for the detection of the causes of secondary spontaneous pneumothorax (SP). METHODS: A prospective cohort of patients with SP was studied. All chest X-ray and CT examinations of the patients were reviewed retrospectively by an expert radiologist blinded to clinical data. The concordance between the CT examination and chest X-ray was assessed using the Cohen Kappa coefficient (κ), based on a bootstrap resampling method. RESULTS: A total of 105 patients with SP were included. There were 78 men and 27 women, with a mean age of 34.5 years±14.2 (SD) (range: 16-87 years). Of these, 44/105 (41%) patients had primary SP and 61/105 (59%) had secondary SP due to emphysema (47/61; 77%), tuberculosis (3/61, 5%), lymphangioleiomyomatosis (3/61; 5%), lung cancer (2/61, 3%) or other causes (6/61; 10%). Apart from pneumothorax, CT showed abnormal findings in 85/105 (81%) patients and chest X-ray in 29/105 (28%). Clinically relevant abnormalities were detected on 62/105 (59%) CT examinations. The concordance between chest X-ray and CT was fair for detecting emphysema (κ=0.39; 95% CI: 0.2420-0.55), moderate for a mass or nodule (κ=0.60; 95% CI: 0.28-0.90), fair for alveolar opacities (κ=0.39; 95% CI: -0.02-1.00), and slight for interstitial syndrome (κ=0.20; 95% CI: -0.02-0.85). CONCLUSION: Chest X-ray is not sufficient for detecting the cause of secondary SP. As the detection of the cause of secondary SP may alter the therapeutic approach and long-term follow-up in patients with SP, the usefulness of a systematic CT examination should be assessed in a prospective trial.

Diagnostic of mediastinal lymphadenopathy in extrathoracic cancer: A place for EBUS-TBNA in real life practice?

INTRODUCTION: Mediastinal lymphadenopathy in patients with extrathoracic malignancy is common. To obtain tissue proof of metastatic spread, EBUS-TBNA is an alternative to mediastinoscopy or thoracoscopy, but there are limited data about its diagnostic performance. The aim of this study was to determine the diagnostic accuracy of EBUS-TBNA for the evaluation of mediastinal lymphadenopathy in patients with extrathoracic cancers. METHODS: We performed a multicenter retrospective study based on an online questionnaire to collect data from January 2011 to December 2012 in all patients with proven extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases who underwent EBUS-TBNA for diagnosis. RESULTS: Hundred and eighty-five patients were included. Extrathoracic malignancies observed were urological (43), breast (35), gastrointestinal (33), head and neck (30), melanoma (11), lymphoma (6), and others (27). EBUS-TBNA confirmed malignancy in 93 patients (50.3%): concordant metastases in 67 (36.2%); new lung cancer in 25 (13.5%); and 1 unidentified cancer. The diagnostic accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were respectively 54.6%, 68.4%, 100%, 53.3%, and 100%. CONCLUSION: Mediastinoscopy remain the reference, but EBUS-TBNA may be considered as first line investigation in patients with suspected mediastinal lymph node metastases and extrathoracic malignancy. It prevented a surgical procedure in 50.3% of patients.

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.

Effect of cannabis and tobacco on emphysema in patients with spontaneous pneumothorax.

PURPOSE: To compare imaging findings on thoracic computed tomography (CT) examination in patients with primary spontaneous pneumothorax (SP), depending on their tobacco and/or cannabis consumption. MATERIALS AND METHODS: A total of 83 patients who had thoracic CT for primary SP were prospectively included. There were 65 men and 18 women with a median age of 33 years (IQR: 27; 44 years). The patients were further categorized into three groups according to their smoking habits. Thirteen patients were non-smokers, 38 were tobacco only smokers and 32 were tobacco and cannabis smokers. CT examinations were retrospectively reviewed for the presence of blebs, centrilobular and paraseptal emphysema and lung nodules in each group for comparison. RESULTS: Emphysema was detected in 43/85 patients (51.8%), including 1/13 patients (7.7%) in the non-smoking group, 19/38 patients (50%) in the tobacco only group and 23/32 patients (71.9%) in the tobacco and cannabis smokers, with no difference between tobacco only and tobacco and cannabis smokers. No differences in type and location of emphysema was found between tobacco only and tobacco and cannabis smokers. Tobacco and cannabis smokers with emphysema were significantly younger than tobacco only smokers with emphysema (35 vs. 46 years, respectively) (P=0.009). CONCLUSION: The prevalence of emphysema visible on CT is not different between tobacco and tobacco/cannabis smokers, however, it occurs at a younger age in tobacco and cannabis smokers. This result suggests that cannabis, when added to tobacco, may lead to emphysema at a younger age.

[Current knowledge on perioperative treatments of non-small cell lung carcinomas]. / Traitements péri-opératoires des carcinomes bronchiques non à petites cellules.

Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%. Conversely perioperative treatments were not validated for stage IA and IB patients. In more advanced stage patients, neo-adjuvant radio-chemotherapy has not been validated either. Adjuvant radiotherapy for N2 patients is currently tested in the large international phase 3 trial Lung-ART/IFCT-0503. The development of video-assisted thoracic surgery (VATS) has helped adjuvant chemotherapies for elderly patients. Perioperative targeted treatments in NSCLC with EGFR or ALK molecular alterations is currently assessed in the U.S. ALCHEMIST prospective trial. Finally, the role of immune check-points inhibitors is currently evaluated in a large international phase 3 trial testing adjuvant anti-PD-L1 monoclonal antibody, the BR31/IFCT-1401 trial, while a proof-of principle neo-adjuvant trial IONESCO/IFCT-1601, has just begun by the end of the 2016 year, with survival results of both trials expected in 5 to 7 years.

[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.

Contribution of magnetic resonance imaging in lung cancer imaging.

Lung cancer is the leading cause of cancer death worldwide. Prognosis and treatment outcomes are known to be related to the disease stage at the time of diagnosis. Therefore, an accurate assessment of the extent of disease is critical to determine the most appropriate therapy. Currently available imaging modalities for diagnosis and follow-up consist of morphological and functional imaging. Morphological investigations are mainly performed with CT-scan and in some cases with MRI. In this review, we describe the contribution of MRI in lung cancer staging focusing on solid pulmonary nodule characterization and TNM staging assessment using chest and whole-body MRI examinations, detailing in each chapter current recommendations and future developments.

Nivolumab-induced organizing pneumonitis in a patient with lung sarcomatoid carcinoma.

Immune checkpoint inhibitors are known to induce 'immune pneumonitis' in 3-6% of patients treated for lung cancer. However, their dramatic efficacy in as much as 20% of patients led to recent registrations in squamous, and then non-squamous lung carcinoma, in second line setting after failure of first-line chemotherapy, while large phase 3 trials are on-going, to assess first-line immunotherapy, either alone or in combination with chemotherapy. Pulmonary Sarcomatoid carcinomas consist of a rare subset of highly aggressive and poorly differentiated non-small-cell lung carcinomas (NSCLC), with poor prognosis and chemo-resistance. Although exhibiting high expression of programmed death ligand-1 (PD-L1), their sensitivity to inhibitors of PD-1/PD-L1 axis is still unknown. Here we report a case of lung sarcomatoid carcinoma with Nivolumab dramatic and long-lasting efficacy, but occurrence of a very specific pattern of lung toxicity, the so-called 'organizing bronchiolitis syndrome'. As more and more NSCLC patients are promised to receive PD-1 inhibitors as part of their treatment, we feel that specific features of such Nivolumab-induced organizing pneumonitis should be known. Although corticosteroid sensitivity is high, recurrence is frequent because of premature steroid tapering, as for all other causes of organizing pneumonias, and probably because of the Nivolumab long tissue half-life.

2014 update on non-small cell lung cancer (excluding diagnosis).

Lung cancer (LC) is a major public health issue because of its frequency, but especially because of the severity of this disease. The epidemiology has changed with an increased incidence in non-smokers and women. The ATS/ERS/IASLC classification of adenocarcinomas was modified in 2011, and they are now the most frequent histological subtype. More than half the cases of LC are diagnosed at the metastatic stage. Biopsies must provide tissue samples that are quantitatively large enough and of a good enough quality for diagnosis and to search for biomarkers. When the cancer seems to be localized, precise staging must be obtained. Treatment is based on the TNM classification. In localized stages, lobectomy associated with lymph node dissection is the standard therapy. Intraoperative chemotherapy improves survival in case of lymph node infiltration. Stereotactic radiation therapy and radiofrequency can be considered as specific cases. In cases with local progression, treatment is more controversial. In the presence of metastases, the goal is not a cure, but improving survival and quality of life. Numerous advances have been made with personalized treatment, (in particular in relation to the histological type and oncogenic addiction in tumors, access to new drugs, and improved management). Clinical research in thoracic cancer is very active. The fight against tobacco should remain a priority.