Clinical characteristic and survival outcomes of patients with advanced NSCLC according to KRAS mutational status in the French real-life ESME cohort.

PURPOSE: The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. PATIENTS AND METHODS: We conducted a retrospective analysis of the French Epidemiological Strategy and Medical Economics database for advanced or metastatic lung cancer from 2011 to 2021. Patient demographics, histology, KRASm status, treatment strategies, and outcomes were assessed. RESULTS: Of 10 177 assessable patients for KRAS status, 17.6% had KRAS p.G12C mutation, 22.6% had KRAS non-p.G12C mutation, and 59.8% were KRASwt. KRASm patients were more often smokers (96.3%) compared with KRASwt (85.8%). A higher proportion of programmed death-ligand 1 ≥50% was found for KRASm patients: 43.5% versus 38.0% (P < 0.01). KRASm correlated with poorer outcomes. First-line median progression-free survival was shorter in the KRASm than the KRASwt cohort: 4.0 months [95% confidence interval (CI) 3.7-4.3 months] versus 5.1 months (95% CI 4.8-5.3 months), P < 0.001. First-line overall survival was shorter for KRASm than KRASwt patients: 12.6 months (95% CI 11.6-13.6 months) versus 15.4 months (95% CI 14.6-16.2 months), P = 0.012. First-line chemoimmunotherapy offered better overall survival in KRAS p.G12C (48.8 months) compared with KRAS non-p.G12C (24.0 months) and KRASwt (22.5 months) patients. Second-line overall survival with immunotherapy was superior in the KRAS p.G12C subgroup: 12.6 months (95% CI 8.1-18.6 months) compared with 9.4 months (95% CI 8.0-11.4 months) for KRAS non-p.G12C and 9.6 months (8.4-11.0 months) for KRASwt patients. CONCLUSION: We highlighted distinct clinical profiles and survival outcomes according to KRASm subtypes. Notably KRAS p.G12C mutations may provide increased sensitivity to immunotherapy, suggesting potential therapeutic implications for sequencing or combination of therapies. Further research on the impact of emerging KRAS specific inhibitors are warranted in real-world cohorts.

Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. PATIENTS AND METHODS: This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. RESULTS: Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58). CONCLUSION: Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

[Smoking habits, attitudes and knowledges of medical students of Medicine, Pharmacy and Odonto-Stomatology's Faculty of Dakar, Senegal]. / Habitudes de fumer, attitudes et connaissances des étudiants en médecine de la Faculté de Médecine, de Pharmacie et d'Odonto-Stomatologie de Dakar, Sénégal.

INTRODUCTION: Smoking is a public health problem that does not spare the medical profession. We set out to determine the prevalence of smoking in medical students in Dakar and to assess their attitudes and knowledge in the face of this problem. METHODS: A cross sectional study was conducted by means of an auto-questionnaire among 1547 medical students between 3 and 31 May 2001. There were 1061 males (68.6%) and 486 females (31.4%). RESULTS: The overall prevalence of regular or occasional smoking was 34.6%, with 42.8% in the first cycle, 38% in the second and 19% in the third. It was significantly higher among males at 76.4%. The average age of starting smoking ranged from 10 to 22 years and average duration from 5 to 26 years. The influence of fashion was the most frequent initiating factor at 37.4% and 96.6% smoked commercial cigarettes. Nicotine dependence, assessed by the Fagerstrom score, was average in 59.3%, strong in 14% and very strong in 4.7%. 58.8% smoked in public places and 78.2% thought they could give up smoking within the next 5 years. 8.4% were unaware of the effects of tobacco on health and 20.5% of the relationship between tobacco and the diseases quoted. 37.7% of future doctors would not systematically avoid smoking in the presence of patients but 79% wished to ban advertising and 70.4% to ban the use of tobacco in hospitals. 94.4% of students wanted health care workers to be educated about the effects of smoking. CONCLUSIONS: Tobacco smoking among medical students has increased between 1989 (28.7%) and 2001 (35.6%). This observation should stimulate the establishment of a course on the pathology of tobacco smoking and the integration of education and prevention within the medical curriculum, increase the awareness of smokers and above all help them stop.

[Neuron-specific enolase (NSE) in the surveillance of small cell cancers. An evaluation of the prognostic information using Markov's model]. / L'énolase neurone-spécifique (NSE) et la surveillance des cancers bronchiques à petites cellules. Une évaluation de l'information pronostique par le modèle de Markov.

RATIONALE: An elevated serum NSE concentration is generally a bad prognostic sign when a diagnosis of small cell lung cancer is made. However, the marker may vary from time to time crossing the discriminant threshold (12.5 ng/ml) in one direction or the other. These variations are presumed to reflect the progress of the disease but it has not been shown that the risk of death from the disease is changed by alterations in the serum concentration of NSE. To resolve this question we have used Markov's mathematical model (homogeneous over time and in three states). METHOD: A prospective study has included 52 patients suffering from small cell cancer and treated with chemotherapy based on cisplatin. The NSE was measured following each treatment and three monthly in subsequent follow up. Markov's model was studying the intensities of transition and the risks of death between the two following transient states: living with an NSE concentration of < or = to 12.5 ng/ml, living with an NSE concentration of > 12.5 ng/ml, and an absorbing state: death. RESULTS: When a level of > 12.5 ng/ml was noted the mean time of maintaining in this state was short (123 days). During this time when a transfer was effected in 44 per cent of cases there is turn towards the opposite state (living with a concentration < 12.5 ng/ml) showing the real reversibility between the two transient states. When a patient had an elevated concentration of serum NSE the risk of death was 2.23 times greater than in the opposite state (living with a low NSE; P < 0.01). CONCLUSION: The observation of an elevated NSE concentration at any time in the follow up of patients suffering from small cell cancer was strongly associated with an elevated risk of death but a return from this state towards a state of less risk (living with a low NSE level) remains possible. This works suggests that the NSE levels may be useful in the follow up of small cell lung cancer.