Efficacy of First-Line Chemotherapy in Patients with Advanced Lung Sarcomatoid Carcinoma

Background:Sarcomatoid carcinomas (SCs) are rare tumors that may arise in the lung, accounting for 0.4% of non–small-cell lung cancers; the prognosis is poor. Only few retrospective small-size series have studied the efficacy of chemotherapy (CT) for metastatic SC.Methods:Multicenter study of patients with advanced or metastatic SC who received first-line CT. Clinical characteristics at baseline, response to first-line CT (Response Evaluation Criteria in Solid Tumors version 1.1), progression-free survival (PFS), and overall survival (OS) were retrospectively collected.Results:Ninety-seven patients were included. Median age was 62 (54–72) years. The majority of patients were men (70%), white (84%), and smokers (84%). Overall, 73% of patients received first-line platinum-based CT. At first tumor evaluation, 69% of patients experienced progression, 31% had disease control, and 16.5% had partial response. Partial response was observed in 20% of patients receiving platinum-based CT, and in none of those receiving non–platinum-based CT (p = 0.018). Median PFS was 2.0 months (confidence interval [CI] 95%: 1.8–2.3). PFS was not statistically different between patients receiving or not receiving a platinum-based CT. Median OS was 6.3 months (CI 95%: 4.7–7.8). There was a trend toward better OS for patients treated with platinum-based CT (7.0 months [CI 95%: 4.9–9.0] versus 5.3 months [CI 95%: 2.8–7.6]; p = 0.096). In multivariate analysis, disease control at first evaluation (hazard ratio = 0.38 [CI 95%: 0.21–0.59]) and at platinum-based CT (hazard ratio = 0.92 [CI 95%: 0.85–0.99]) was associated with better OS.Conclusion:SC is associated with poor prognosis and high rate of resistance to conventional first-line CT. New therapeutic strategies are needed, based on better knowledge of the carcinogenesis of SC

Imaging of Hereditary Hemorrhagic Telangiectasia

This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients

Phosphatidylinositol 3-Kinase Mediates Bronchioalveolar Stem Cell Expansion in Mouse Models of Oncogenic K-ras-Induced Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in Western countries. Developing more effective NSCLC therapeutics will require the elucidation of the genetic and biochemical bases for this disease. Bronchioalveolar stem cells (BASCs) are a putative cancer stem cell population in mouse models of oncogenic K-ras-induced lung adenocarcinoma, an histologic subtype of NSCLC. The signals activated by oncogenic K-ras that mediate BASC expansion have not been fully defined. Methodology/Principal Findings: We used genetic and pharmacologic approaches to modulate the activity of phosphatidylinositol 3-kinase (PI3K), a key mediator of oncogenic K-ras, in two genetic mouse models of lung adenocarcinoma. Oncogenic K-ras-induced BASC accumulation and tumor growth were blocked by treatment with a small molecule PI3K inhibitor and enhanced by inactivation of phosphatase and tensin homologue deleted from chromosome 10, a negative regulator of PI3K. Conclusions/Significance: We conclude that PI3K is a critical regulator of BASC expansion, supporting treatment strategies to target PI3K in NSCLC patients

Professional Exposure to Goats Increases the Risk of Pneumonic-Type Lung Adenocarcinoma: Results of the IFCT-0504-Epidemio Study

Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32–7.87, p = 0.010), never- smoker status (OR = 3.57, 95% CI: 1.27–10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10–10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05–24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC

Targeted Therapy for Older Patients with Non-Small Cell Lung Cancer: Systematic Review and Guidelines from the French Society of Geriatric Oncology (SoFOG) and the French-Language Society of Pulmonology (SPLF)/ French-Language Oncology Group (GOLF)

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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Efficacité de la chimiothérapie au cours des carcinomes sarcomatoïdes, à propos de 97 cas

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Facteurs prédictifs de progression d' emblée sous inhibiteurs de tyrosine kinase du récepteur de l' épidermal growth factor

Les ITK de l EGFR sont utilisés depuis plus de 10 ans dans le traitement des cancers pulmonaires non à petites cellules. Nous avons cherché des facteurs prédictifs de progression d emblée sous ITK de l EGFR. Nous avons étudié rétrospectivement une cohorte de 269 patients traités par gefitinib ou erlotinib que nous avons classés selon leur statut au 45è jour du traitement : maladie en progression ou maladie contrôlée. Nous avons comparé ces 2 groupes.Le statut maladie en progression ou contrôlée a pu être déterminé pour 240 patients (n=76 et n=164). On trouvait dans le groupe progression d emblée des patients plus jeunes (p=0,006), avec une fréquence accrue de tabagisme non sevré (p=0,001), un performans status de l Eastern Cooperative Oncology Group plus mauvais (p=0,008) et un amaigrissement plus important (p=0,03). Leur diagnostic était plus récent (p<0,0001). Leur cancer était plus souvent d histologie indifférenciée (p=0,001), avec des métastases abdominales (p=0,008) et/ou un plus grand nombre de sites métastatiques (p=0,018). Ces facteurs, sauf le dernier, étaient prédictifs d une progression d emblée en analyse uni-variée. La présence de métastases abdominales était prédictive d une progression d emblée en analyse multi-variée (odds-ratio 0,463 ; p=0,022). Parmi les 38,3% de patients pour qui le statut mutationnel était connu, un gène EGFR sauvage était plus fréquent dans le groupe progression d emblée (p=0,013).La présence de métastases abdominales est prédictive d une progression d emblée sous ITK de l EGFR. Une étude des bio-marqueurs moléculaires sur les patients de cette cohorte est en cours.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Rôle des polynucléaires neutrophiles dans la progression aérogène des adénocarcinomes pulmonaires

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Crizotinib : enfin l’AMM en 1re ligne des cancers bronchiques non à petites cellules de stade avancé ALK+

International audienceLa présence d’un réarrangement de ALK concerne environ 4 % des cancers bronchiques non à petites cellules (CBNPC). Il induit une sensibilité des cellules tumorales aux inhibiteurs de tyrosine kinase (ITK) de ALK, tels que le crizotinib. L’essai de phase I publié en 2010 a testé le crizotinib (250 mg × 2/jour) en 2e ligne et plus chez 82 patients ayant un CBNPC de stade avancé avec un réarrangement de ALK [1]