[Severe complications of systemic treatment in thoracic oncology]. / Complications sévères des traitements systémiques du patient cancéreux thoracique (complications hors infections et urgences respiratoires).

Primary thoracic cancers affect a large number of patients, mainly those with lung cancer and to a lesser extent those with pleural mesothelioma and thymic tumours. Given their frequency and associated comorbidities, in patients whose mean age is high, these diseases are associated with multiple complications. This article, the last of a series dedicated to emergencies in onco-haematological patients, aims to present a clinical picture of the severe complications (side effects, immune-related adverse events) associated with systemic treatments, excluding infections and respiratory emergencies, with which general practitioners and specialists can be confronted. New toxicities are to be expected with the implementation of innovative therapeutic approaches, such as CAR-T cells, along with immunomodulators and antibody-drug conjugates.

[Olimetastatic disease: Current status and perspectives in non-small cell lung cancer]. / Les maladies oligométastatiques : état actuel et perspectives dans les cancers bronchiques non à petites cellules.

The concept of oligometastatic disease was first introduced in the late 1990s to describe an situation more or less midway between locally advanced tumours and multifocal metastatic cancer. Four concepts are currently used: synchronous oligometastatic disease, metachronous oligometastatic disease (or oligo-recurrence), oligo-persistence and oligo-progression. Some phase II studies, randomised or not, have validated this concept in non-small cell lung cancer (NSCLC) and suggest the interest of adding local ablative therapy to systemic treatment. That said, numerous questions remain, and the impact of this therapeutic approach in the framework of immunotherapies and targeted therapies has yet to be assessed. Which of these new treatments offer hope of significantly improved long-term survival in stage IV NSCLC? This article appraises current knowledge and therapeutic regarding oligometastatic NSCLC.

Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial.

BACKGROUND: Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. MATERIALS AND METHODS: NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. RESULTS: From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. CONCLUSIONS: Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab.

Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform.

Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients' molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency.

[Lung cancer screening with low dose computed tomography : a systematic review]. / Dépistage du cancer bronchique par tomodensitométrie à faible dose : une revue systématique des essais contrôlés randomisés.

INTRODUCTION: Bronchial cancer, often diagnosed at a late stage, is the leading cause of cancer death. As early detection could potentially lead to curative treatment, several studies have evaluated low-dose chest CT (LDCT) as a screening method. The main objective of this work is to determine the impact of LDCT screening on overall mortality of a smoking population. METHODS: Systematic review of randomised controlled screening trials comparing LDCT with no screening or chest x-ray. RESULTS: Thirteen randomised controlled trials were identified, seven of which reported mortality results. NSLT showed a significant reduction of 6.7% in overall mortality and 20% in lung cancer mortality after 6.5 years of follow-up. NELSON showed a significant reduction in lung cancer mortality of 24% at 10 years among men. LUSI and MILD showed a reduction in lung cancer mortality of 69% at 8 years among women and 39% at 10 years, respectively. CONCLUSION: Screening for bronchial cancer is a complex issue. Clarification is needed regarding the selection of individuals, the definition of a positive result and the attitude towards a suspicious nodule.

[The role of prophylactic cranial irradiation in small cell lung cancer]. / Quel rôle pour l'irradiation cérébrale prophylactique dans le cancer à petites cellules ? Une étude rétrospective unicentrique.

INTRODUCTION: Prophylactic cranial irradiation (PCI) is considered standard therapeutic management in small cell lung cancer (SCLC). This is based on old randomised trials with methodological limitations, namely the absence of magnetic resonance imaging (MRI) of the brain. The aim of this study is to assess the risk not administering PCI when systematic brain imaging is applied. METHODS: Retrospective study including untreated SCLC, without PCI and receiving brain imaging at the time of diagnosis. Kaplan-Meier and log-rank statistics were used for survival analyses. RESULTS: Among 150 patients, 75 were possibly eligible for PCI. Thirteen patients presented with an isolated brain recurrence as the first site of progression with no other metastatic sites apparent, and in 6 patients, the brain was the only recurrent site during the whole follow-up. In the group of patients eligible for PCI, there was no statistically significant survival difference according to the brain progression status (P=0.11). CONCLUSIONS: The expected impact of PCI seems limited in terms of overall survival and prevention of isolated brain metastases in patients having systematic brain imaging during SCLC work-up.

[Perioperative treatment for resected non-small cell lung cancer: Which option in 2020?] / Les traitements périopératoires des cancers bronchiques non à petites cellules : quelles options en 2020 ?

Surgery is the ultimate curative treatment for resectable non-small cell lung cancer (NSCLC). However, the prognosis for operated patients remains disappointing. Multiple randomized studies have shown that administering perioperative chemotherapy improves the prognosis and increases the cure rate by around 3-5%. The purpose of this article is to take stock of the role of perioperative treatments for NSCLC, which can be completely resected. Six questions were evaluated: 1) What is the place of (neo) adjuvant chemotherapy in 2020, among others in the early stages (IB)? 2) Can new chemotherapy agents be combined with a platinum derivative? 3) What is the place of radiochemotherapy for resectable NSCLC? 4) Is there a place for postoperative radiotherapy (PORT)? 5) Is there a place for targeted therapies for resectable NSCLC? 6) What is the place of immunotherapies in the perioperative period?

[Lung cancer: Prognosis in intensive care depends mainly on the acute complication]. / Cancer bronchique : le pronostic en soins intensifs dépendrait surtout de la complication.

INTRODUCTION: It has been demonstrated in unselected populations of cancer patients that prognosis in intensive care is essentially dependent on the extent of the acute physiological disturbance caused by the complication precipitating the admission. By contrast, the prognosis after hospital discharge remains dependent on the characteristics of the underlying neoplasm. The aim of our study was to confirm whether this general finding was the case in a specific population of lung cancer patients, since there are no data on this patient group in the literature. PATIENTS AND METHODS: We conducted a retrospective study including all patients with lung cancer admitted to our ICU between September 1, 2008 and December 31, 2013. RESULTS: During this period, 180 different patients with lung cancer were admitted into ICU. The simplified acute physiology score II (SAPS II) (OR 1.07 ; 95% CI 1.04-1.11), respiratory failure (OR 4.00; 95% CI 1.76-9.07) and the presence of therapeutic limitations were the 3 factors independently affecting hospital mortality in multivariate analysis. Considering only patients discharged alive from the hospital, the presence of metastases (HR 2.30; 95% CI 1.44-3.65) and limitations on therapy (HR 5,89; IC 95% 3,11-11,14) were the two statistically independent prognostic factors for overall survival. CONCLUSION: In this population of lung cancer patients admitted into ICU, independent predictors of hospital mortality are determined by the physiological perturbations induced by the acute presenting complication. After recovery from this, prognosis is again determined by the characteristics of the underlying cancer.

[Impact of routine brain imaging in the initial management of lung cancer]. / Impact de l'imagerie cérébrale systématique dans le bilan initial des cancers du poumon.

INTRODUCTION: Brain metastases are a common complication of bronchial carcinoma (BC). There is no consensus as to the need to undertake a systematic search for these lesions during the initial assessment. The aim of this study was to evaluate the contribution of brain imaging in the initial evaluation of patients with CB. METHODS: We undertook a retrospective analysis of patients treated in the Thoracic Oncology Clinic at the Institute Jules-Bordet between 01/09/2008 and 31/08/2013, who were treatment-naïve and were having a full diagnostic work-up including brain imaging. RESULTS: Four hundred and sixty-three patients consecutively diagnosed with BC were included. Brain magnetic resonance imaging and/or CT-scan showed brain metastases in 101 patients (21.8%), of whom 67 had no symptoms suggestive of brain metastatic disease. The addition of a brain imaging into the work-up procedure resulted in a stage migration for 30 patients (6.5%), mainly otherwise staged IIIA (n=10) or IIIB (n=14) without brain imaging. CONCLUSION: The addition of brain imaging in the initial assessment of bronchial carcinoma allows the identification of brain metastases in one case among 5, of which 2/3 are asymptomatic. This leads to a change in staging, primarily for disease otherwise considered to be stage III.

[Immune checkpoint inhibitors (antibodies to PD1 and PD-L1), a new therapeutic weapon against non-small cell bronchial carcinoma]. / Les inhibiteurs des freins immunitaires (anticorps anti-PD1 et anti-PD-L1), une nouvelle arme thérapeutique dans les cancers bronchiques non à petites cellules.

INTRODUCTION: Classical therapeutic strategy for advanced and metastatic non-small cell lung cancer, without activable oncogenic driver mutation, has been based mainly on cytotoxic chemotherapy with modest benefits in terms of increased survival. BACKGROUND: A better understanding of the mechanisms involved in the regulation of the immune system led to the development of antibodies directed against immune checkpoints such as PD-L1. The first encouraging clinical data from phase I studies assessing anti-PD1 and anti-PD-L1 antibodies have been confirmed in randomised phase III trials. CONCLUSIONS: These new drugs now constitute a standard second-line treatment for metastatic tumours and in the future, at least for pembrolizumab, in the first line. Their adjuvant role after locoregional treatment with curative intent is currently under investigation.