[ICU admission for cancer patients with respiratory failure: An ethical dilemma]. / Admission aux soins intensifs du patient cancéreux avec une atteinte respiratoire : un dilemme éthique.

In medicine, each decision is the result of a trade-off between medical scientific data, the rights of individuals (protection of persons, information, consent), individual desires, collective values and norms, and the economic constraints that guide our society. Whether or not to admit a cancer patient to an intensive care unit is very often an ethical dilemma. It is necessary to distinguish patients who would benefit from admission to an intensive care unit (ICU) from those for whom it would be futile. In this review, we will discuss the appropriateness of ICU admission and the concept of unreasonable admission, along with the different levels of intensity of ICU care and the alternatives to intensive care. We will then consider how and when to initiate reflection leading to a reasonable decision for the patient.

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.

[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.

[Implication of bronchopulmonary cancer patients in thoracic oncology]. / Implication des patients atteints d'un cancer broncho-pulmonaire en oncologie thoracique.

Changed relationships between patient and health care provider have given patients a greater role in their care. Nowadays, they have the opportunity to be involved in decision-making regarding any diagnostic, therapeutic or monitoring intervention related to their disease. Access to international scientific data through the web, the activity of different patient associations, and the information given by their referring physician can enrich their knowledge about their disease and its possible treatments. In addition to the objective criteria usually assessed, the role currently assumed by patient associations in clinical research helps to identify their expectations. In addition, a number of new tools allow the thoracic oncologist to better understand patients' wishes. Health authorities' use of patient-reported outcomes and patients' use of digital applications contribute to improved survival without any deleterious impact on quality of life. Web applications designed to monitor a patient's toxicities during treatment are now commercially available. To meet our patients' expectations, we are called upon to incorporate these different digital tools into our daily practice.

Quels malades peuvent et doivent aller en réanimation ?: Which patients can and should go to intensive care?

When a lung cancer patient develops an organ failure, the intensity of the care should be decided taking into account patient's wishes and his plan of carekeeping, in mind that the objective of an intensive care unit (ICU) admission is to allow the patient to be discharged from ICU and hospital with an acceptable quality of life. But the physician in charge of the patient at the time of acute disease often does not have these information. It is therefore essential that the referring oncologist had an early discussion with the patient to inform him and collect his opinion. These information have to be noted in the patient's medical chart. The prognostic criteria of lung cancer patients admitted in ICU are related to the patient's characteristics, the cancer's characteristics and the severity of acute disease. In order that a decision of ICU admission is in accordance with the patient's therapeutic project, a close discussion between the oncologist and the intensivist is essential, especially in this period of SARS-CoV2 pandemy.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Management of lung cancer patients' quality of life in clinical practice: a Delphi study.

BACKGROUND: The assessment of health-related quality of life (HRQoL) has seen exponential growth in oncology clinical trials. However, the measurement of HRQoL has yet to be optimised in routine clinical practice. This study aimed at exploring the operationalisation of HRQoL in clinical practice with the goal of reaching a consensus from a panel of physicians. MATERIALS AND METHODS: Physicians involved in the management of lung cancer patients in France were recruited to participate in a Delphi study. The study involved three rounds of iterated queries to gain consensus on management aspects of HRQoL, including timing of discussion on HRQoL, which specific domains of HRQoL should be discussed, and what was the most appropriate method of assessment. The threshold adopted for consensus was at least 70% agreement among physicians. A scientific committee reviewed results following each round of the Delphi study. RESULTS: A representative panel of 60 physicians participated in this study. Consensus was obtained for HRQoL management at all time points in the patient care pathway. Panellists agreed that HRQoL discussions should occur during routine visits and hospitalisation. The involvement of patients' relatives was also recognised as important, except when discussing side-effects and involvement of a multidisciplinary team. There was a lack of consensus on a systematic assessment for all patients at each visit and no consensus on how HRQoL should be measured in clinical practice. CONCLUSIONS: HRQoL discussions are considered an integral part in the management of lung cancer patients, and are deemed key to success in patient-physician interaction. Further research is required to harmonise how best to implement HRQoL assessment.

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.

Impact of systematic advanced care planning in lung cancer patients: A prospective study.

BACKGROUND: End-of-life (EOL) communication is crucial, particularly for cancer patients. While advanced care planning is still uncommon, we sought to investigate its impact on care intensity in case of organ failure in lung cancer patients. METHODS: We prospectively included consecutive lung cancer patients hospitalised at the Grenoble University Hospital, France, between January 1, 2014 and March 31, 2016. Patients could be admitted several times and benefited from advanced care planning based on three care intensities: intensive care, maximal medical care, and exclusive palliative care. Patients' wishes were addressed. RESULTS: Data of 739 hospitalisations concerning 482 patients were studied. During the three first admissions, 173 (25%) patients developed organ failure, with intensive care proposed to 56 (32%), maximal medical care to 104 (60%), and exclusive palliative care to 13 (8%). Median time to organ failure was 9 days [IQR 25%-75%: 3-13]. All patients benefited from care intensity that was either equal to or lower than the care proposed. Specific wishes were recorded for 158 (91%) patients, with a discussion about EOL conditions held in 116 (73%). CONCLUSIONS: In case of organ failure, advanced care planning helps provide reasonable care intensity. The role of the patient's wishes as to the proposed care must be further investigated. CLINICAL TRIAL REGISTRATION: The study was registered at www.ClinicalTrials.gov with the identifier NCT02852629.

Current opinions in immune checkpoint inhibitors rechallenge in solid cancers.

Immune checkpoint inhibitors (ICI) completely upset the therapeutic algorithm of several type of solid cancer conferring in some patients a long clinical benefit with an acceptable toxicity. ICI rechallenge is an attractive option being a palliative chemotherapy the only alternative treatment in most of cases. Despite this strategy recently entered into the clinical practice, no widely recognized recommendation is currently available to select the good candidates. Anti-Cytotoxic T Lymphocyte Antigen 4 (Anti-CTLA4) rechallenge and a sequential administration of anti-CTLA4 and anti-Programmed cell Death protein 1 (anti-PD1) or Anti-Programmed Death Ligand 1 (anti-PDL1) agents have been explored in melanoma patients in several clinical trials while the anti-PD1/anti-PDL1 rechallenge has been little investigated. Here we performed a literature revision about efficacy and tolerability of ICI rechallenge across solid tumors also focusing on inclusion criteria used into clinical trials.

[Concomitant use of nivolumab and immunosuppressants in a renal transplant patient]. / Utilisation concomitante du nivolumab et d'immunosuppresseurs chez un patient greffé rénal.

INTRODUCTION: Immune-checkpoint inhibitors have been approved for first and second line treatments of metastatic non-small cell lung cancer based on the results of several phase III trials. Patients with organ transplantation were excluded from these studies because checkpoint inhibitors could activate allo-reactive T cells leading to acute graft rejection. CASE REPORT: A 71-year-old Caucasian-male was diagnosed with stage IV pulmonary adenocarcinoma with multiple metastases, without molecular alteration and negative PD-L1 status. He had a left kidney transplant, and his immunosuppressive regimen consisted of sirolimus and mycophenolate mofetil. After failure of two therapeutic lines (carboplatin-paclitaxel and erlotinib) a multidisciplinary oncology meeting with the nephrologist started third line treatment with nivolumab 3mg/kg every 15 days, with no modification of the immunosuppressive treatment. The patient received a total of 14 injections of nivolumab with stable disease but treatment was discontinued due to acute rejection of the transplanted kidney 6 months later, without need for dialysis. The patient died of a chylothorax related to progression of the tumour 12 months after initiation of nivolumab. CONCLUSION: Immune checkpoint inhibitors are a potential treatment for solid organ transplant patients despite the risk of graft rejection.

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

[Emergency room management of patients with lung cancer and organ failure]. / Prise en charge aux urgences de patients avec cancer thoracique et défaillance d'organe.

BACKGROUND: When patients with lung cancer present to the emergency department with organ failure the question of admission to intensive care has to be considered. Our aim is to describe the process leading to the proposed management. METHODS: Retrospectively, all patients admitted to the emergency room between December 2010 and January 2015 with a diagnosis of ICD-10 C34.9 (lung cancer) were reviewed. Those with at least one organ failure were included. RESULTS: The records of 561 patients were reviewed, 79 (14%) had at least one organ failure. The majority of these patients received maximal medical care (59%), 25% exclusive palliative care, and 15% intensive care. Performance status, metastatic status and efficacy of anti-tumor treatment were recorded in the emergency medical record in 20%, 66% and 74% of cases, respectively. An opinion was obtained from the oncologist in 44% of cases and from the intensivist in 41% of cases. No external advice was provided in 27% of cases. CONCLUSION: In the majority of cases, the decision on the intensity of care to be provided to patients with lung cancer and organ failure was made in a collective manner.

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs).

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.

CT-texture analysis of subsolid nodules for differentiating invasive from in-situ and minimally invasive lung adenocarcinoma subtypes.

PURPOSE: The purpose of this study was to evaluate the usefulness of computed tomography-texture analysis (CTTA) in differentiating between in-situ and minimally-invasive from invasive adenocarcinomas in subsolid lung nodules (SSLNs). MATERIAL AND METHODS: Two radiologists retrospectively reviewed 49 SSLNs in 44 patients. There were 27 men and 17 women with a mean age of 63±7 (SD) years (range: 47-78years). For each SSLN, type (pure ground-glass or part-solid) was assessed by consensus and CTTA was conducted independently by each observer using a filtration-histogram technique. Different filters were used before histogram quantification: no filtration, fine, medium and coarse, followed by histogram quantification using mean intensity, standard deviation (SD), entropy, mean positive pixels (MPP), skewness and kurtosis. RESULTS: We analyzed 13 pure ground-glass and 36 part-solid nodules corresponding to 16 adenocarcinomas in-situ (AIS), 5 minimally invasive adenocarcinomas (MIA) and 28 invasive adenocarcinomas (IVA). At uni- and multivariate analysis CTTA allowed discriminating between IVAs and AIS/MIA (P<0.05 and P=0.025, respectively) with the following histogram parameters: skewness using fine textures and kurtosis using coarse filtration for pure ground-glass nodules, and SD without filtration for part-solid nodules. CONCLUSION: CTTA has the potential to differentiate AIS and MIA from IVA among SSLNs. However, our results require further validation on a larger cohort.

[Limitations of active therapeutic and palliative care in chronic respiratory disease]. / Intensité des soins lors des exacerbations et des complications des pathologies respiratoires chroniques.

The issue of intensive and palliative care in patients with chronic disease frequently arises. This review aims to describe the prognostic factors of chronic respiratory diseases in stable and in acute situations in order to improve the management of these complex situations. The various laws on patients' rights provide a legal framework and define the concept of unreasonable obstinacy. For patients with chronic obstructive pulmonary disease, the most robust decision factors are good knowledge of the respiratory disease, the comorbidities, the history of previous exacerbations and patient preferences. In the case of idiopathic pulmonary fibrosis, it is necessary to know if there is a prospect of transplantation and to assess the reversibility of the respiratory distress. In the case of amyotrophic lateral sclerosis, treatment decisions depend on the presence of advance directives about the use of intubation and tracheostomy. For lung cancer patients, general condition, cancer history and the tumor treatment plan are important factors. A multidisciplinary discussion that takes into account the patient's medical history, wishes and the current state of knowledge permits the taking of a coherent decision.

Personalized chemotherapy of lung cancer: What the radiologist should know.

Lung cancer is the leading cause of deaths due to cancer in France. More than half of lung cancers are discovered at an advanced-stage. New anticancer treatment strategies (i.e., the so-called personalized or targeted therapy) have recently been introduced and validated for non-small-cell lung cancer (NSCLC), in addition to or in association with standard chemotherapy. Personalized therapy includes tyrosine kinase inhibitors (TKIs), antiangiogenic treatments and immunotherapy. Because these treatments may be responsible for atypical thoracic adverse effects and responses as compared to standard chemotherapy, RECIST 1.1 criteria may be inadequate to evaluate the responses to these agents. The goal of this article was to review personalized treatment strategies for NSCLC, to consider the therapy-specific responses and thoracic complications induced by these new therapeutic agents and finally to discuss future directions for the personalized assessment of tumor response.

[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.

[Paclitaxel-bevacizumab is a possible alternative as salvage chemotherapy in advanced non-small cell bronchial carcinoma]. / L'association paclitaxel-bevacizumab est une alternative intéressante dans le traitement des cancers bronchopulmonaires non épidermoïdes avancés en troisième ligne et plus.

INTRODUCTION: Bevacizumab is recommended in first line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). Paclitaxel is a doublet drug also widely used in cisplatin-based regimens. Paclitaxel plus bevacizumab is a standard regimen as first line treatment of metastatic breast cancer. Since there is no guideline for third line treatment of NSCLC, some oncology units use paclitaxel-bevacizumab in some NSCLC patient after relapse of the second line. The aim of this study was to assess retrospectively the feasibility and efficacy of this treatment option in stage IV NSCLC. METHODS: Patients who had received the combination of paclitaxel (80 to 90 mg/m(2) in a weekly schedule) and bevacizumab (7.5 to 15 mg/kg every 21 days) in the thoracic oncology departments of two university hospitals in the Rhone-Alpes Department were retrospectively reviewed. RESULTS: Twelve patients underwent this treatment. Their mean age was 56 years and their performance status was less or equal to 1 in 50 % of the cases. The chemotherapy was given as fifth line in 67 % of the patients and 67 % were antiangiogenic naïve. They received a mean of 6 courses. The overall response rate was 33 % and the disease control rate 66 %. Median progression-free survival was 5.1 months (95 %CI 1.0-9.1). Ten patients (82 %) experienced toxicity, the majority grade 1 to 2 events, and only one a grade 3 event (febrile neutropenia). There were no severe bleeding episodes. CONCLUSION: Combined paclitaxel-bevacizumab chemotherapy seems feasible in patients with NSCLC. The toxicity profile is acceptable. This regimen should be evaluated in further prospective studies.