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International audience; Background Data regarding characteristics, safety and survival outcomes of patients aged 80 or older treated with immune checkpoint inhibitors (ICI) in routine oncology practice are limited. Materials and methods We retrospectively collected data of patients aged 80 and older with advanced non-small cell lung cancer (NSCLC) or melanoma treated with anti-PD1, anti-PD-L1 or anti-CTLA-4 regardless of the treatment line, in 14 institutions, between January 2014 and June 2017. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan Meier method. Toxicity was assessed according to CTCAE 5.0. Multivariate analyses were performed with the Cox model. Results Eighty-two patients were included (36 with NSCLC, 45 with melanoma). Their median age was 82 years (range 80-93). Nivolumab and pembrolizumab were mainly used. In the NSCLC group, median PFS and OS were 2.3 months (95%CI 1.8-6.1) and 8.8 months (95%CI 5.5-18.1), respectively. In the melanoma group, median PFS and OS were 10.2 months (95%CI 4.5-20.0) and 24.5 months (95%CI 14.1-NR), respectively. The albumin level was found to be independently associated with a better OS in both groups. Grade 3-4 toxicities occurred in 15 patients (18.5%). One patient died from ICI-induced pulmonary toxicity. Conclusion Our study findings suggest that treatment with ICI in elderly patients with NSCLC and melanoma has a risk-benefit ratio that supports its use. However, we report in this cohort that one in five patients has a grade 3-4 IRAEs leading to treatment discontinuation. Geriatric assessment prior to initiation of therapy and during therapy should be routine in patients aged 80 years and older.

Few therapeutic options are approved as second-line treatment after failure of platinum-based chemotherapy for patients with extensive-stage small-cell lung cancer (ES-SCLC). Topotecan widespread use remains challenged by the risk of severe toxicities in a pretreated population. Little is known about the efficacy and safety of epirubicin-paclitaxel doublet in second-line and beyond and especially cerebral outcomes.EpiTax is a retrospective multicenter observational real-life study. We evaluated the efficacy of epirubicin 90 mg/mA total of 29 patients were included. The median of previous systemic therapy lines was 2 (1-4). Eleven patients received the treatment in the second line. Characteristics of patients were a median age of 60 years (45-77), 65.5% of males with 72.4% of PS 0-1. Fifteen patients had a history of brain metastases. Median PFS and OS achieved 11.0 (95% CI, 8.1-16.3) and 23 (95% CI, 14.1-29.6) weeks, respectively. ORR was 34.5% and DCR was 55.2%. ICR was 3/15 (20%). Grade 3-4 adverse events were mainly hematological and concerned 7 patients. No case of febrile neutropenia or toxic death was reported.Epirubicin-paclitaxel association highlighted promising efficacy with PFS and OS of 11 and 23 weeks, respectively, ORR of 34.5%, and a tolerable safety profile. This doublet could represent another valuable therapeutic option for ES-SCLC patients treated in the second line and beyond.

Background A standard of care for pretreated, advanced non–small‐cell lung cancers (NSCLCs), nivolumab has demonstrated long‐term benefit when administered for 2 years. We aimed to better discern an optimized administration duration by retrospectively analyzing real‐life long‐term efficacy in a prospective cohort. Methods All nivolumab‐treated adults with advanced NSCLCs (01/09/2015 to 30/09/2016) from nine French centers were eligible. On 31/12/2018, patients who are alive ≥ 2 years after starting nivolumab were defined as long‐term survivors (LTSs) and were divided into three nivolumab treatment groups: 2 years. Co‐primary endpoints were LTSs’ progression‐free survival (PFS) and overall survival (OS). Results The median follow‐up was 32 months (95% CI, 31.0 to 34.0). The 3‐year OS rate for the 259 cohort patients was 16.6%. Among them, 65 were LTSs: 47 treated 2 years. Their respective characteristics were: median age: 59, 52, and 58 years; smoking history: 92.9, 100, and 100%; adenocarcinomas: 66, 57.1, and 54.5%. LTSs’ median (m)PFS was 28.4 months; mOS was not reached. LTSs’ objective response rate was 61.6%. mOS was 32.7 months for those treated 2‐year group's 3‐year OS was longer. Twenty‐eight LTSs experienced no disease progression; 7 had durable complete responses. However, LTSs had more frequent and more severe adverse events. Conclusion In real‐life, prolonged nivolumab use provided long‐term benefit with 16.6% 3‐year OS and 25% LTSs. Survival tended to be prolonged with nivolumab continued beyond 2 years. Prospective randomized trials with adequate design are needed., Phase III trials didn't provide an optimal duration of immunotherapy for responder or stable patients in advanced non‐small‐cell lung cancer. A 2 years‐fixed duration or long‐term therapy are proposed to clinicians. The results of this observational study of 65 long‐term survivor pretreated patients showed a trends toward improvement of survival outcomes when continuing nivolumab after two years.

PURPOSE Immune checkpoint inhibitors substantially changed advanced non–small-cell lung cancer (aNSCLC) management and can lead to long-term survival. The aims of this study were (1) to use a machine learning method to establish a typology of treatment sequences on patients with aNSCLC who were alive 2 years after initiating a treatment with anti–programmed death-ligand 1 monoclonal antibody nivolumab and (2) to describe the patients' characteristics according to the typology of treatment sequences. MATERIALS AND METHODS This retrospective observational study was based on data from the comprehensive French hospital discharge database for all patients with lung cancer with at least one line of platinum-based chemotherapy, starting nivolumab between January 1, 2015, and December 31, 2016, and alive 2 years after nivolumab treatment initiation. Patients were followed until December 31, 2018. A typology of most common treatment sequences was established using hierarchical clustering with time sequence analysis. RESULTS Two thousand two hundred twelve study patients were, on average, 63.0 years old, 69.9% of them were men, and 61.9% had a nonsquamous cell carcinoma. During the 2 years after nivolumab treatment initiation, clusters of patients with four basic types of treatment sequences were identified: (1) almost continuous nivolumab treatment (44% of patients); (2) nivolumab most of the time followed by a treatment-free interval or a chemotherapy (15% of patients); and a short or medium nivolumab treatment, followed by (3) a long systemic treatment-free interval (17% of patients) or (4) a long chemotherapy (23% of patients). CONCLUSION This machine learning approach enabled the identification of a typology of four representative treatment sequences observed in long-term survival. It was noted that most long-term survivors were treated with nivolumab for well over 1 year.

International audience; Systematic molecular profiling and targeted therapy (TKI) have changed the face of Non-Small Cell Lung Cancer (NSCLC) treatment. However, there are no specific recommendations to address the prescription of TKI for older patients. A multidisciplinary task force from the French Society of Geriatric Oncology (SoFOG) and the French Society of Pulmonology/Oncology Group (SPLF/GOLF) conducted a systematic review from May 2010 to May 2021. Protocol registered in Prospero under number CRD42021224103. Three key questions were selected for older patients with NSCLC: (1) to whom TKI can be proposed, (2) for whom monotherapy should be favored, and (3) to whom a combination of TKI can be proposed. Among the 534 references isolated, 52 were included for the guidelines. The expert panel analysis concluded: (1) osimertinib 80 mg/day is recommended as a first-line treatment for older patients with the EGFR mutation; (2) full-dose first generation TKI, such as erlotinib or gefitinib, is feasible; (3) ALK and ROS1 rearrangement studies including older patients were too scarce to conclude on any definitive recommendations; and (4) given the actual data, TKI should be prescribed as monotherapy. Malnutrition, functional decline, and the number of comorbidities should be assessed primarily before TKI initiation.

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International audience; Background With the development of precision oncology, Molecular Tumor Boards (MTB) are developing in many institutions. However, the implementation of MTB in routine clinical practice has still not been thoroughly studied. Material and methods Since the first drugs approved for targeted therapies, patient tumor samples were centralized to genomic testing platforms. In our institution, all tumor samples have been analyzed since 2014 by Next Generation Sequencing (NGS). In 2015, we established a regional MTB to discuss patient cases with 1 or more alterations identified by NGS, in genes different from those related to drug approval. We conducted a retrospective comparative analysis to study whether our MTB increased the prescriptions of Molecular Targeted Therapies (MTT) and the inclusions of patients in clinical trials with MTT, in comparison with patients with available NGS data but no MTB discussion. Results In 2014, 86 patients had UGA, but the results were not available to clinicians and not discussed in MTB. During the years 2015 and 2016, 113 patients with an UGA (unreferenced genomic alteration) were discussed in MTB. No patients with an UGA were included in 2014 in a clinical trial, versus 2 (2%) in 2015-2016. 13 patients with an UGA (12%) were treated in 2015-2016 with a MTT whereas in 2014, no patient (p = 0.001). Conclusions In this retrospective analysis, we showed that the association of large-scale genomic testing and MTB was feasible, and could increase the prescription of MTT. However, in routine clinical practice, the majority of patients with UGA still do not have access to MTT.

Today, patients with lung cancer and their relatives can easily search information on the Internet and express themselves online.Within this web-ethnographic research, we found, based on 246 search terms related to lung cancer, and collected, a sample of 136 online conversations that were published between January 2004 and September 2018, including 1220 messages by 762 authors.The authors of messages, many of them close relatives of patients (35%), share their experience (34%). Seven areas of worrying concern, each of them prominent in 10 to 24% of the corpus, can be grouped under three headings: accepting the disease in order for the patient or their caregiver to fight it ("decide on the prognosis", "managing the treatments", "stopping the progression"), conjuring fate ("naming the guilty ones", "conjuring powerlessness"), asserting resilience ("adopt the right attitude" and "telling one's story in order to survive"). The question of time - disrupted, lost, to be caught up with or controlled - runs through all the issues.The patients' and caregivers' concerns go beyond the pace of medical treatment and beyond death. Their mental representations of the disease influence their adherence to the care pathway. Welcoming them in our care and dialogue goes hand in hand with personalized treatment.

Objectives Pulmonary tularemia is a rare and little-known disease, whose clinical and radiological presentation can be confused with those of much more frequent pathologies, such as lung cancer or B-cell lymphoma (46,000 and 5,000 new cases respectively per year in France). Furthermore, PET/CT is a powerful tool for the diagnosis of malignancies or the exploration of fever of unknown origin. The objective of this study was to describe the characteristics of pulmonary tularemia and to determine whether its PET/CT aspect could help distinguish it from neoplasia. Methods Retrospective observational study collecting all pulmonary tularemia cases for which a PET/CT was performed between 2016 and 2020. Results Twenty-seven cases of pulmonary tularemia were analyzed. The sex ratio was 4.4, and the median age was 60 years. Clinical manifestations were mainly represented by fever (n = 23), arthralgia (n = 7) and cough (n = 6). PET/CT revealed intensely hypermetabolic mediastinal adenopathies in all cases, associated with parenchymal (n = 20) or pleural (n = 6) lesions, suggesting neoplastic pathology in 15 patients. Cytopuncture or lymph node biopsy was performed in 16 patients, revealing non-specific adenitis (n = 8), necrotic epithelio-gigantocellular granuloma (n = 3), or were non-contributory (n = 5). All patients reported significant environmental exposure. The outcome was favorable for all patients, spontaneously for 8 of them and after antibiotic therapy with either doxycycline or ciprofloxacin for the other 19. Conclusions Depending on the epidemiological setting, pulmonary tularemia may be considered an alternative diagnosis to lung cancer, lymphoma, or tuberculosis, in the presence of infectious symptoms and hypermetabolic pulmonary lesions and mediastinal lymphadenopathies on PET/CT.

CERVOXY CLIN; International audience; Background - Anticancer immune responses are negatively regulated by programmed cell death 1 (PD-1) T-cell membrane protein interaction with its ligand, programmed death ligand 1 (PD-L1), on cancer cells. We sought to assess the prognostic role of PD-L1 expression in tumor samples from patients enrolled onto the IFCT-0701 MAPS randomized phase 3 trial (NCT00651456). Patients and methods - Tumor samples were analyzed by immunohistochemistry for percentages of PD-L1 membrane-stained tumor cells using the E1L3N clone, and data were correlated to survival by multivariate Cox models including stratification variables. Results - PD-L1 staining was assessed in 214 (47.75%) of 448 patients. Epithelioid subtype represented 83.7% (179/214). Absence of PD-L1 staining occurred in 137 (64.1%) of 214 malignant pleural mesothelioma (MPM) samples, while 77 (35.9%) of 214 were PD-L1 positive, with 50 (64.9%) of 77 showing < 50% PD-L1-expressing tumor cells. Sarcomatoid/biphasic subtypes were more commonly PD-L1 positive than epithelioid subtype (P < .001). In patients with 1% or more PD-L1-stained tumor cells, median overall survival (OS) was 12.3 months versus 22.2 months for other patients (hazard ratio [HR] = 1.25; 95% confidence interval [CI], 0.93-1.67; P = .14). OS did not differ according to PD-L1 positivity in multivariate analyses (adjusted HR = 1.10; 95% CI, 0.81-1.49; P = .55). With a 50% cutoff, PD-L1-positive patients displayed a 10.5 months median OS versus 19.3 months for patients with lower PD-L1 expression (HR = 1.93; 95% CI, 1.27-2.93; P = .002). OS did not significantly differ in adjusted Cox models (adjusted HR = 1.20; 95% CI, 0.74-1.94; P = .47). In the 179 epithelioid MPM patients, high PD-L1 staining (≥ 50% of tumor cells) negatively affected OS, although not significantly, showing a 12.3-month median OS (95% CI, 4.3-21.6) versus 23-month (95% CI, 18.5-25.2) for patients with tumor PD-L1 staining in < 50% cells (P = .071). The progression-free survival (PFS) differences were statistically significant, with a longer 9.9-month median PFS in patients with low PD-L1 staining (< 50% cells) compared to 6.7 months of median PFS in patients with high PD-L1 expression (≥ 50% cells) (P = .0047). Conclusion - Although high PD-L1 tumor cell expression was associated with poorer OS in MPM patients from the MAPS trial, its prognostic influence was lost in multivariate analyses in the whole cohort, while PD-L1 expression was strongly associated with the sarcomatoid/biphasic subtypes. In the epithelioid MPM subset of patients, high PD-L1 tumor expression (≥ 50%) negatively affected OS and PFS, with this prognostic influence remaining statistically significant for PFS after adjustment in multivariate Cox model.

The resistance mutation T790M is reported in 50–60% of patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Osimertinib has been approved in these patients, but data in octogenarians remain rare. The objective of this retrospective analysis was to evaluate in real life the efficacy of osimertinib in a population of octogenarian patients. This retrospective multicentric study included pretreated octogenarian patients with EGFR T790M-mutated advanced non-small cell lung cancer (NSCLC) in the setting of the French early access program for osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. In total, 43 patients were included (mean age 84.6 years; women 90.7%: adenocarcinoma 100%; never smokers 90.5%; at osimertinib initiation: performance status ≥ 2, 42.4%; stage 4, 93.0%; brain metastases 16.3%). Patients received a median of two lines of treatment before osimertinib initiation, and all received first- or second-generation EGFR TKIs before osimertinib (first line in 79.1%). Osimertinib was used as a second-line treatment in 41.9% of cases and third line or more in 58.1%. Median PFS was 17.5 (95% confidence interval [CI] 12.2–19.0) months for the entire population: 20.6 (95% CI 18.8–not reached) months in patients with brain metastases and 16.7 (95% CI 10.4–18.9) months in patients without (p = 0.1). There was no significant difference for osimertinib treatment as second or third line or more (17.1 vs. 18.6 months, respectively). OS was 22.8 (95% CI 15.7–not reached) months from osimertinib initiation. The efficacy of osimertinib as second-line treatment or more in octogenarian pretreated patients with EGFR T790M-mutated advanced NSCLC in a real-life setting was similar to that in randomized controlled trials.

Suite aux recommandations vaccinales du Haut Conseil de la sante publique (2012), l’Unite de coordination en oncogeriatrie de Bretagne (UCOG) a etudie leur influence sur le statut vaccinal des sujets âges de 75 ans et plus atteints de cancer grâce aux donnees de l’assurance maladie de Bretagne. La couverture vaccinale contre la grippe etait de 53 % (IC 95 % : [46–60]) entre 2006 et 2012 et de 59 % (IC 95 % : [51–67]) entre 2012 et 2015 (p = 0,2). Pour le pneumocoque et le DTPolio, elle etait respectivement de 18 % (IC 95 % : [11–26]) et 20 % (IC 95 % : [12–28]) avant 2012 vs 22 % (IC 95 % : [14–30]) et 31 % (IC 95 % : [22–40]) apres 2012 (p = 0,57 et p = 0,07). Face au constat du faible impact des recommandations, l’UCOG avec la collaboration de l’Observatoire dedie au cancer a initie une campagne de sensibilisation aupres des professionnels impliques en cancerologie.

Objective: To describe long-term outcomes of patients treated with nivolumab for advanced non-small cell lung cancer (aNSCLC) in everyday clinical practice in France, with a focus on patients aged ⩾80 years, patients with renal impairment and patients with brain metastases. Methods: The study included all patients with aNSCLC recorded in the French national hospital database, starting nivolumab in 2015–2016 and followed until December 2018. Patients were stratified by age, the presence of renal impairment and brain metastasis, as documented in the hospital discharge summaries. Information was retrieved on demographics, comorbidities and treatment history at baseline. Time to discontinuation of nivolumab treatment and overall survival were estimated using Kaplan–Meier survival analysis. Results: Overall, 10,452 patients were included, of whom 514 were octogenarians, 479 had renal impairment and 1800 had brain metastases at baseline. Median duration of nivolumab treatment was 2.8 months in the overall population and in both the octogenarian and renally impaired subgroups, and 2.3 months in patients with brain metastases. Median overall survival in these patient groups was 11.7 months (95% confidence interval: 11.3–12.2), 11.7 months (11.3–12.1), 11.7 months (11.3–12.2) and 9.9 months (9.0–10.9) respectively. Three-year overall survival rates were 19.1% (18.1–20.2) in the overall population, 16.5% (11.6–23.4) in octogenarians, 15.9% (11.8–21.4) in patients with renal impairment and 21.7% (19.4–24.2) in those with brain metastases. Conclusion: This large nationwide retrospective real-life cohort provided narrow estimates of long-term overall survival, which reached 19% at 3 years, consistent with data from phase III trials of nivolumab. Survival rates were comparable in the three special populations of interest and the overall population.

Resume En presence d’un cancer bronchique non a petites cellules de stade avance porteur d’une mutation activatrice de l’EGFR, la prescription d’un inhibiteur de tyrosine kinase de l’EGFR de premiere ou seconde generation (ITK-EGFR 1G ou ITK-EGFR 2G) est recommandee des la premiere ligne de traitement. Une progression tumorale survient toutefois inexorablement et est secondaire dans 50 a 60 % des cas a l’existence d’une mutation de resistance T790 M. La prescription de l’osimertinib (ITK-EGFR3G) est autorisee apres echec d’un ITK-EGFR 1G ou 2G en cas de mise en evidence de cette mutation T790 M. Nous rapportons 7 cas cliniques, pour lesquels la mise en evidence de la mutation T790 M a necessite la repetition dans le temps de plusieurs prelevements sur ADN tumoral circulant et/ou biopsies. La positivite n’a ete obtenue parfois que tres a distance de l’objectivation de la progression tumorale sous EGFR-TKI 1G ou 2G. Nous discutons les differentes modalites possibles de cette recherche de mutation T790 M et encourageons a savoir perseverer dans cette recherche en l’absence d’autres mecanismes de resistance mis en evidence.

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Background We aimed to evaluate the toxicity, loco-regional control (LRC) and overall survival (OS) associated with accelerated intensity-modulated radiotherapy (IMRT) for locally advanced lung cancer. Methods Seventy-three patients were consecutively treated with IMRT from November 2011 to August 2016. A total dose of 66 Gy was delivered using two different schedules of radiotherapy: simultaneous modulated accelerated radiotherapy (SMART) (30 × 2.2 Gy, across 6 weeks) with or without chemotherapy, or moderate hypofractionated radiotherapy (HRT) (24 × 2.75 Gy, across 4 weeks) in patients unfit to receive concomitant chemotherapy. Data on esophageal and pulmonary toxicities, LRC and OS were prospectively collected. Results The median follow-up duration was 44 months. Severe pneumonitis and esophagitis (grade 3–4) were observed in 7% and 1% of patients respectively, with only one case of grade 4 (pneumonitis). Overall, the 1-year and 2-year LRCs were 76% [95 confidence interval (CI)%: 66–87%] and 62% [95 CI%: 49–77%] respectively. The 1 and 2-year OS rates were 72% [95% CI: 63–83%] and 54% [95 CI%: 43–68%] respectively. None parameters were correlated with LRC or OS. In particular, no difference was observed between patients treated with SMART and H-RT (p = 0.26 and 0.6 respectively), with a 1-year LRC of 74% [95 CI%: 62–86%] for SMART and 91% [95 CI%: 74–100%] for H-RT. No significant differences were observed in the toxicity rates associated with each of the RT schedules. Conclusions Accelerated IMRT for locally advanced lung cancer is associated with low toxicities and high LRC. Moderate hypofractionated RT, by decreasing the total treatment time, may be promising in improving clinical outcomes.

Objectives The preOVNI study was a randomized, controlled, open-label study that investigated whether preoperative noninvasive ventilation (NIV) could reduce postoperative complications after lung cancer surgery. Methods Adult patients with planned lung cancer resection and with at least 1 cardiac or respiratory comorbidity were included and randomly assigned to preoperative NIV (at least 7 days and 4 h/day) or no NIV. The primary endpoint was the rate of postoperative protocol-defined complications. Results Three hundred patients were included. In the NIV group, the median NIV duration was 8 days. No difference of postoperative complication rates was evidenced: 42.6% in NIV group and 44.8% in no-NIV group (P = .75). The rate of pneumonia was greater in no-NIV group compared with the NIV group, but statistical significance was not achieved (28.0 vs 37.7%, respectively; P = .08). The type of surgery (open or minimally invasive) did not impact these results after multivariable analysis. Conclusions No benefit was evidenced for preoperative NIV before lung cancer surgery. Further studies should determine the optimal perioperative management to decrease the rate of postoperative complications.

Objectives Nivolumab is now a reference treatment for patients with advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. Little data are available on treatment approaches following discontinuation of nivolumab and on the interest of a second course of immunotherapy after nivolumab discontinuation. The aims of this study were to describe treatment pathways following nivolumab discontinuation and to describe survival following retreatment with immunotherapy. Materials and methods The analysis includes all patients with NSCLC recorded in a national hospital database, starting nivolumab in 2015-2016. Nivolumab treatment was considered discontinued if ≥3 infusions were missed. Patients starting a second course of PD-1 inhibitor following nivolumab discontinuation were analysed according to the duration of their initial nivolumab treatment course. Results 10,452 patients were included (71 % men; mean age: 63.8 ± 9.6 years; squamous histology: 44 %). Median nivolumab treatment duration was 2.8 months [IQR :1.4–6.9]. Median OS was 11.5 months [95 %CI: 11.1–11.9]; 5118 (53.4 %) patients received post nivolumab therapy lines: 1517 (29.6 %) of these received a second course of PD-1 inhibitor, either after a treatment-free interval (resumption: n = 1127) or after intervening chemotherapy (rechallenge: n = 390). Median OS after nivolumab discontinuation was 15.0 months [13.9–16.7] in the resumption group and 18.4 months [14.8–21.9] in the rechallenge group. Median OS was significantly longer in patients with an initial nivolumab treatment duration ≥3 months. Conclusion In this real-world setting, outcome after retreatment with a PD-1 inhibitor following a first course of nivolumab was significantly better in patients with a longer duration of initial nivolumab treatment.

// Romain Corre 1,12 , Radj Gervais 2 , Florian Guisier 3 , Louis Tassy 4 , Florent Vinas 5 , Regine Lamy 6 , Gislaine Fraboulet 7 , Laurent Greillier 8 , Helene Doubre 9 , Renaud Descourt 10 , Christos Chouaid 5 and Jean-Bernard Auliac 11 1 Department of Pneumology, CHU Pontchaillou, Rennes, France 2 Pneumo-Oncology Department, Centre Francois Baclesse, Caen, France 3 Pneumology Department, CHU Hopitaux de Rouen-Charles Nicolle, Rouen, France 4 Oncology Department, Institut Paoli-Calmette, Marseille, France 5 Pneumology Department, CH Intercommunal de Creteil, Creteil, France 6 Oncology Department, CH Sud-Bretagne, Lorient, France 7 Pneumology Department, Hopital Rene-Dubos, Pontoise, France 8 Pneumo-Oncology Department, Hopital Sainte-Marguerite, Assistance Publique-Hopitaux de Marseille, Marseille, France 9 Pneumology Department, Hopital Foch, Suresnes, France 10 Cancerology Institute, CHU Brest, Brest, France 11 Pneumology Department, CH Francois Quesnay, Mantes La Jolie, France 12 UMR INSERM U1242-COSS, Rennes University, Rennes, France Correspondence to: Romain Corre, email: // Keywords : targeted therapies; tyrosine-kinase inhibitors; non-small cell lung cancer; EGFR; elderly; Gerotarget Received : September 22, 2017 Accepted : November 13, 2017 Published : January 02, 2018 Abstract Objective. To assess efficacy and tolerance of EGFR tyrosine-kinase inhibitors (TKIs) for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in octogenarians. Patients and methods. Patients aged 80 years or older with EGFR-mutated NSCLC treated by EGFR TKI between January 2011 and March 2015 whatever the line of treatment were retrospectively selected. Results. 20 centers retrospectively included 114 patients (women, 77.2%; Caucasians, 98.3%; mean age, 83.9 years). A performance status of 0–1 or 2–3 at diagnosis was reported for 71.6% and 28.4% of patients, respectively. Overall, 95.6% of patients had adenocarcinomas and histological stage at diagnosis was stage IV for 79.8% of patients. EGFR mutations were identified mainly on exon 19 (46.5%) and exon 21 (40.4%). A geriatric assessment was performed in 35.1% of patients. TKI treatment was administered to 97.3% of patients as first or second line of treatment. Overall response rate and disease control rate were 63.3% (69/109) and 78.9% (86/109), respectively. Median progression-free survival was 11.9 months (95% confidence interval [CI], 8.6–14.7) and median overall survival was 20.9 months (95% CI, 14.3–27.1). After progression, 36/95 (37.9%) patients received a new line of chemotherapy. Main toxicities were cutaneous for 66.7% of patients (grade 3–4, 10%), diarrhea for 56.0% (grade 3–4, 15%; grade 5, 2%) and others for 25.7% (grade 3–4, 41%). Conclusions. Octogenarians with EGFR-mutated NSCLC treated by EGFR TKI had clinical outcomes and toxicity profile comparable to younger patients. Geriatric assessment appeared to be underused in this population.

Nocardiosis is an infectious disease with wide range of clinical features, which can eventually lead to death. The agent responsible belongs to the genus Nocardia that includes about fifty different species. Nocardiosis occurs mainly in immunocompromised hosts. We report here three cases of disseminated nocardiosis misdiagnosed initially as cerebral metastatic lung cancer. These patients, including two immunocompetent hosts, presented with both pulmonary and cerebral lesions. In all three patients, the diagnosis was based on magnetic resonance imaging with diffusion sequence, apparent diffusion coefficient reconstruction and neurosurgical cerebral biopsies. Treatment with an appropriate antibiotic regimen was prolonged for several months. Progress was favorable with full resolution of the neurological symptoms and the radiological abnormalities. These three cases emphasize the diagnostic challenge of nocardiosis, especially in disseminated disease.

Resume Le cancer bronchique non a petites cellules (CBNPC) est une maladie majoritairement du sujet âge, son incidence va en augmentant dans les pays occidentaux en raison du vieillissement de la population. L’objet de cet article est de synthetiser les donnees de la litterature disponibles pour la prise en charge des sujets âges atteints d’un CBNPC aux differents stades : precoces, localement avances et metastatiques. Nous developperons dans le cadre du contexte metastatique les apports respectifs de la chimiotherapie, des therapies ciblees et de l’immunotherapie. Des recommandations internationales ont ete emises, leur application est rendue toutefois difficile en raison de l’absence de definition consensuelle des fragilites a prendre en consideration dans les decisions et adaptations de traitement que celles-ci necessitent. Nous aborderons la place de l’oncogeriatrie dans la prise en charge de ces patients. © 2021 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Resume Le cancer bronchique non a petites cellules (CBNPC) est une maladie majoritairement du sujet âge, son incidence va en augmentant dans les pays occidentaux en raison du vieillissement de la population. L’objet de cet article est de synthetiser les donnees de la litterature disponibles pour la prise en charge des sujets âges atteints d’un CBNPC aux different stades : precoces, localement avances et metastatiques. Les donnees publiees sur la prise en charge de ces patients vont croissantes mais demeurent moins abondantes que pour les sujets plus jeunes. Des recommandations internationales ont ete emises, leur application est rendue toutefois difficile en raison de l’absence de definition consensuelle des fragilites a prendre en consideration dans les decisions et adaptations de traitement que celles-ci necessitent. Nous aborderons la place de l’onco-geriatrie dans la prise en charge de ces patients.

Introduction Les donnees en vie reelle peuvent completer celles des essais cliniques afin d’optimiser la prise en charge courante du CBNPC. Apres l’arret du nivolumab, peu de donnees existent concernant les pratiques, les options therapeutiques et leurs resultats. Methodes A partir des donnees du PMSI, une cohorte retrospective regroupant tous les patients atteints de CBNOC ayant initie nivolumab en 2015–2016 apres une chimiotherapie a ete suivie jusqu’au 31 decembre 2017 (suivi minimum de 12 mois). Les caracteristiques des patients (donnees demographiques, comorbidites, antecedents de traitement) ont ete recherchees. L’arret du nivolumab etait defini comme l’absence d’au moins 3 perfusions consecutives. Le temps avant arret du traitement (TTD) et la survie globale (SG) ont ete estimes par la methode de Kaplan–Meier. La SG des patients en re-challenge d’immunotherapie a ete analysee en fonction de la duree de leur traitement initial par nivolumab avec les intervalles suivants : Resultats Nous avons identifie 10 452 patients atteints de CBNPC initiant le nivolumab au cours de la periode d’inclusion (homme : 71 % ; âge moyen : 63,8 ± 9,6 ans ; histologie epidermoide : 44 % ; metastases cerebrales : 17,4 % ; anciennete mediane du CBNPC : 12,5 mois ; chirurgie curative anterieure : 15,6 % ; temps median depuis la premiere chimiotherapie : 10,5 mois ; dose moyenne du nivolumab : 213 ± 54 mg). Les medianes de TTD et de SG etaient de 2,8 mois et 11,6 mois. Les taux de SG a 1 an et 2 ans etaient de 48,8 % et 27,4 %. Au total, 5118 (53,4 %) patients ont recu un traitement systemique apres l’arret du nivolumab. Parmi eux, 1517 patients (29,6 %) ont ete traites a nouveau avec un anti-PD1 (nivolumab : 98,8 %) soit apres une pause therapeutique (groupe « reprise » : n = 1127 ; mTTD2 : 4,1 mois ; mSG2 : 14,9 mois a partir de la 2e sequence d’immunotherapie), soit apres une progression traitee par chimiotherapie (« groupe re-challenge » : n = 390 ; mTTD2 : 3,0 mois ; mSG2 : 18,2 mois a partir de la 2e sequence d’immunotherapie). La Fig. 1 presente les courbes de SG2 de l’immunotherapie du « groupe re-challenge » en fonction de la duree du traitement initial par nivolumab. Conclusion Parmi les patients recevant un traitement systemique apres l’arret du nivolumab, environ 30 % ont a nouveau recu une immunotherapie en reprise apres une pause ou en re-challenge apres une chimiotherapie. L’influence de la duree du traitement initial par nivolumab sur la survie en re-challenge doit etre etudiee davantage.

Introduction Les patients et leurs proches partagent sur le web social des questions et des experiences qui ne trouvent pas de reponses immediates aupres des professionnels. Les comprendre est essentiel pour adapter le parcours de soin a la realite des patients. Methodes La web-ethnographie WE-LUNG a cherche a analyser le vecu des patients souffrant de cancer du poumon. Un echantillon representatif des conversations spontanees partagees sur tous types de sites publics a ete collecte grâce a l’outil Net-Conversation®. Deux cent quarante-six termes de recherche ont conduit a 1089 conversations archivees sur le web entre janvier 2004 et septembre 2018. Un echantillon de 164 conversations a ete analyse, soit 1220 messages de 762 auteurs distincts. L’analyse du corpus a ete realisee avec l’algorithme de classification textuelle iRamuteq. Resultats Sur cette pathologie, beaucoup de proches s’expriment (35 %) mais peu de patients (16 %). Trente-deux pour cent de personnes non identifiees et quelques professionnels interviennent. L’analyse identifie 7 classes semantiques, representant autant d’enjeux pour le patient. Leur poids dans le corpus s’echelonne de 24 % a 10 %. Le poids de la culpabilite dans la difficulte des patients a communiquer avec leurs proches et leur medecin ressort. La representation de la maladie (tabagisme et inhalation de toxiques comme cause principale, diagnostic tardif et mauvais pronostic) favorise un sentiment d’impuissance (12 %), de regret et de suspicion (16 %) a l’egard des industriels et des pouvoirs publics. Les patients cherchent a estimer leurs chances de survie, etre impliques dans les choix therapeutiques (10 %) et trouver des alternatives. La lobectomie a une place claire dans l’imaginaire mais l’immunotherapie est tres mal comprise (principe, eligibilite). Des facteurs favorisant la resilience des patients emergent : la prise en compte de leur parole lors de premiers symptomes (11 %) ; la capacite a se projeter dans un avenir proche (12 %) ; l’activite artistique ou spirituelle comme chemin d’acceptation ; les echanges avec des patients en remission ou des proches de patients decedes (24 %). Conclusion L’etude WE-LUNG a permis d’analyser des recits d’experience tres detailles et peu exprimes en consultation. Elle met au jour le role critique des proches et degage 2 leviers susceptibles d’ameliorer la qualite de vie des patients : favoriser (et deculpabiliser) la parole du patient, et produire des representations de la maladie et des traitements qui augmentent sa capacite de comprendre et de participer aux choix.

Introduction En France, environ 10 % des patients diagnostiques avec un cancer bronchique non a petites cellules (CBNPC) sont octogenaires. L’efficacite du nivolumab dans cette population specifique est peu connue et les donnees de vie reelle representent une source d’information pertinente. Le but de cette etude etait de decrire l’utilisation et l’efficacite du nivolumab chez les patients âges de 80 ans et plus. Methodes A partir des donnees hospitalieres du PMSI, une cohorte retrospective, regroupant tous les patients atteints de cancer bronchique (code CIM10 : C34*) et ayant initie nivolumab en 2015–2016 apres une chimiotherapie, a ete suivie jusqu’au 31 decembre 2017 (suivi minimum de 12 mois). Les caracteristiques des patients (donnees demographiques, comorbidites, antecedents de traitement) ont ete recherchees selon deux populations distinctes : ≥ 80 ans et Resultats Parmi les 10 452 patients atteints de CPNPC initiant nivolumab pendant la periode d’inclusion, 514 (4,9 %) etaient âges de 80 ans ou plus. L’âge moyen a l’initiation du groupe octogenaire etait de 82,5 ans (± 2,4) vs 62,8 ans (± 8,8) pour le reste de la cohorte. Les patients octogenaires etaient plus frequemment des hommes (p Tableau 1 . Conclusion Parmi les patients initiant nivolumab au cours de la periode d’etude, seul un faible pourcentage etaient âges de 80 ans ou plus (

Background Anti-PD1 immunotherapy has emerged as a gold-standard treatment in stage IV non-small cell lung cancer (NSCLC). Despite long-term disease control in 5-20% of patients, secondary resistance often occurs. Local ablative treatment (LAT) and treatment beyond progression for oligo-progressive disease may improve long-term outcomes in stage IV non-small cell lung cancer after tumor response to anti-PD1 treatment. Methods In this retrospective multicentric cohort study, stage IV NSCLC patients treated with LAT for oligo-progression after initial tumor response to anti-PD1 were identified using electronic medical records from 3 centers. Here are reported clinical characteristics and outcomes of 27 patients. Quantitative data were summarized as median. Survival was estimated using Kaplan-Meier method. Results Twenty-seven patients received 31 LAT with surgery (n = 3, 10%), stereotactic radiotherapy (n = 18, 58%) or conformational radiotherapy (n = 10, 32%) after nivolumab (n = 19, 70%) or pembrolizumab (n = 8, 30%) treatment. Patients received anti-PD1 treatment in first (n = 3, 11%), second (n = 18, 67%) or third-line (n = 6,22 %) for stage IV NSCLC (adenocarcinoma/ squamous/not-otherwise specified: 18/8/1; PDL1 not evaluated/negative/1-49/>50: 10/8/1/6). Oligo-progression site was: brain (n = 19, 61%), lung (n = 5, 16%), adrenal gland (n = 2, 6%) and bone (n = 4, 13%). Anti-PD1 treatment was continued beyond progression after LAT in 22 (81%) patients. Oligo-progression occurred 6.9 months after anti-PD1 initiation. Progression Free Survival (PFS) after oligo-progression was 13.1 months (IC95: 7.0-not reached). Nine (33%) patients experienced ≥1 grade ≥2 immune adverse event before LAT. One patient had grade 3 toxicity after LAT (cerebral radionecrosis). Overall survival was not mature after a median follow-up of 9.1 months from LAT. Data will be updated before presentation and subgroup analysis will be presented. Conclusions LAT and treatment beyond progression for oligo-progression after initial tumor response to anti-PD1 treatment provide encouraging survival outcomes in selected stage IV NSCLC patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure F. Guisier: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: MSD / Merck US; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (institution): Boehringer Ingelheim. R. Gervais: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. M. Geier: Honoraria (self): BMS; Honoraria (self): MSD / Merck US. R. Corre: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD / Merck US. R. Descourt: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Roche. C. Chouaid: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD / Merck US; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca. All other authors have declared no conflicts of interest.

There is no recommended therapy for malignant pleural mesothelioma that has progressed after first-line pemetrexed and platinum-based chemotherapy. Disease control has been less than 30% in all previous studies of second-line drugs. Preliminary results have suggested that anti-programmed cell death 1 (PD-1) monoclonal antibody could be efficacious in these patients. We thus aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma.This multicentre randomised, non-comparative, open-label, phase 2 trial was done at 21 hospitals in France. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, histologically proven malignant pleural mesothelioma progressing after first-line or second-line pemetrexed and platinum-based treatments, measurable disease by CT, and life expectancy greater than 12 weeks. Patients were randomly allocated (1:1) to receive intravenous nivolumab (3 mg/kg bodyweight) every 2 weeks, or intravenous nivolumab (3 mg/kg every 2 weeks) plus intravenous ipilimumab (1 mg/kg every 6 weeks), given until progression or unacceptable toxicity. Central randomisation was stratified by histology (epithelioid vs non-epithelioid), treatment line (second line vs third line), and chemosensitivity to previous treatment (progression ≥3 months vs3 months after pemetrexed treatment) and used a minimisation method with a 0·8 random factor. The primary outcome was the proportion of patients who achieved 12-week disease control, assessed by masked independent central review; the primary endpoint would be met if disease control was achieved in at least 40% of patients. The primary endpoint was assessed in the first 108 eligible patients. Efficacy analyses were also done in the intention-to-treat population and safety analyses were done in all patients who received at least one dose of their assigned treatment. This trial is registered at ClinicalTrials.gov, number NCT02716272.Between March 24 and August 25, 2016, 125 eligible patients were recruited and assigned to either nivolumab (n=63) or nivolumab plus ipilimumab (n=62). In the first 108 eligible patients, 12-week disease control was achieved by 24 (44%; 95% CI 31-58) of 54 patients in the nivolumab group and 27 (50%; 37-63) of 54 patients in the nivolumab plus ipilimumab group. In the intention-to-treat population, 12-week disease control was achieved by 25 (40%; 28-52) of 63 patients in the nivolumab group and 32 (52%; 39-64) of 62 patients in the combination group. Nine (14%) of 63 patients in the nivolumab group and 16 (26%) of 61 patients in the combination group had grade 3-4 toxicities. The most frequent grade 3 adverse events were asthenia (one [2%] in the nivolumab group vs three [5%] in the combination group), asymptomatic increase in aspartate aminotransferase or alanine aminotransferase (none vs four [7%] of each), and asymptomatic lipase increase (two [3%] vs one [2%]). No patients had toxicities leading to death in the nivolumab group, whereas three (5%) of 62 in the combination group did (one fulminant hepatitis, one encephalitis, and one acute kidney failure).Anti-PD-1 nivolumab monotherapy or nivolumab plus anti-CTLA-4 ipilimumab combination therapy both showed promising activity in relapsed patients with malignant pleural mesothelioma, without unexpected toxicity. These regimens require confirmation in larger clinical trials.French Cooperative Thoracic Intergroup.

Background: In the phase I I I CheckMate 227 s tudy, fi r s t - l ine nivolumab þ ipilimumab significantly prolonged progression-free survival (co-primary endpoint) versus chemotherapy in patients with advanced nonesmall-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; 10 mutations/megabase). Aim: To evaluate patient-reported outcomes (PROs) in this population. Methods: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ- 5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. Results: In the high TMB population, PRO questionnaire completion rates were w90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab þ ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab þ ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab þ ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4e22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab þ ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. Conclusion: First-line nivolumab þ ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB, This work was supported by Bristol-Myers Squibb and Ono Pharmaceutical

CERVOXY; International audience; Background: The Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS/NCT00651456) phase 3 trial demonstrated the superiority of bevacizumab plus pemetrexed–cisplatin triplet over chemotherapy alone in 448 malignant pleural mesothelioma (MPM) patients. Here, we evaluated the prognostic role of Hippo pathway gene promoter methylation.Methods: Promoter methylations were assayed using methylation-specific polymerase chain reaction in samples from 223 MAPS patients, evaluating their prognostic value for overall survival (OS) and disease-free survival in univariate and multivariate analyses. MST1 inactivation effects on invasion, soft agar growth, apoptosis, proliferation, and YAP/TAZ activation were investigated in human mesothelial cell lines.Results: STK4 (MST1) gene promoter methylation was detected in 19/223 patients tested (8.5%), predicting poorer OS in univariate and multivariate analyses (adjusted HR: 1.78, 95% CI (1.09–2.93), p = 0.022). Internal validation by bootstrap resampling supported this prognostic impact. MST1 inactivation reduced cellular basal apoptotic activity while increasing proliferation, invasion, and soft agar or in suspension growth, resulting in nuclear YAP accumulation, yet TAZ cytoplasmic retention in mesothelial cell lines. YAP silencing decreased invasion of MST1-depleted mesothelial cell lines.Conclusions: MST1/hippo kinase expression loss is predictive of poor prognosis in MPM patients, leading to nuclear YAP accumulation and electing YAP as a putative target for therapeutic intervention in human MPM.

International audience; Les anti-PD-1 s’imposent dernièrement comme un traitement de référence dans de nombreux cancers métastatiques. Ils présentent l’avantage d’une efficacité significative doublée d’un profil de toxicité favorable en monothérapie. Les taux et durées de réponse sont toutefois très variables, ce qui implique, vu leur coût, d’identifier des biomarqueurs prédictifs de réponse. Dans cette revue de la littérature, nous nous intéressons aux biomarqueurs de réponse des immunothérapies anti-PD1 et anti-CTLA-4. L’expression de PD-L1 par les cellules tumorales et du micro-environnement évaluée par immunohistochimie est prédictive de réponse pour certains cancers mais reste une approche mal standardisée avec différents anticorps, différents seuils de positivité et différentes cibles (tumeur ou micro-environnement). Il s’agit aussi d’une expression dynamique au cours du temps et hétérogène donc souvent discordante entre biopsies et pièces opératoires. Les lymphocytes circulants pourraient représenter un biomarqueur prédictif notamment via la mesure du ratio polynucléaires neutrophiles sur lymphocytes (NLR), ratio simple à réaliser en pratique courante. Un taux de néoantigènes élevé serait également associé à une réponse plus importante ce qui expliquerait les taux de réponses particulièrement élevés des tumeurs avec instabilité micro-satellitaire. Des signatures génomiques pourraient également prédire la sensibilité aux anti-PD1. Par ailleurs, la présence de certaines bactéries de la flore intestinale favoriserait la réponse immunitaire antitumorale même si le mécanisme demeure mal compris. Enfin, des signatures d’expression de cytokines, médiatrices de la réponse immune, pourraient constituer des biomarqueurs pertinents. Plusieurs biomarqueurs de réponse potentiels semblent donc intéressants mais aucun n’est encore prospectivement validé à ce jour.

Le cancer bronchique non a petites cellules (CBNPC) est une maladie majoritairement du sujet âge, son incidence devrait augmenter dans les pays occidentaux en raison du vieillissement de la population. Malgre tout, les donnees disponibles sur la prise en charge de ces patients restent relativement limitees comparativement a celles concernant les sujets plus jeunes. Des recommandations internationales ont ete emises, mais leur application est rendue difficile par l’absence de definition consensuelle des fragilites a prendre en consideration dans la decision de traitement et des adaptations de traitement que celles-ci necessitent. L’objet de cet article est de synthetiser les donnees de la litterature disponibles pour la prise en charge des sujets âges atteints d’un CBNPC aux differents stades: precoces, localement avances et metastatiques. Nous aborderons par ailleurs la place de l’oncogeriatrie dans la prise en charge de ces patients.