Lung cancer is the most common cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) represents 80% of lung cancer subtypes. Patients with localized non-small cell lung cancer may be considered for upfront surgical treatment. However, the overall 5-year survival rate is 59%. To improve survival, adjuvant chemotherapy (ACT) was largely explored and showed an overall benefit of survival at 5 years < 7%. The evaluation of recurrence risk and subsequent need for ACT is only based on tumor stage (TNM classification); however, more than 25% of patients with stage IA/B tumors will relapse. Recently, adjuvant targeted therapy has been approved for EGFR-mutated resected NSCLC and trials are evaluating other targeted therapies and immunotherapies in adjuvant settings. Costs, treatment duration, emergence of resistant clones and side effects stress the need for a better selection of patients. The identification and validation of prognostic and theranostic markers to better stratify patients who could benefit from adjuvant therapies are needed. In this review, we report current validated clinical, pathological and molecular prognosis biomarkers that influence outcome in resected NSCLC, and we also describe molecular biomarkers under evaluation that could be available in daily practice to drive ACT in resected NSCLC.

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.

Background Hydroxychloroquine combined with azithromycin (HCQ/AZI) has initially been used against coronavirus disease-2019 (COVID-19). In this retrospective study, we assessed the clinical effects of HCQ/AZI, with a 28-days follow-up. Methods In a registry-study which included patients hospitalized for COVID-19 between March 15 and April 2, 2020, we compared patients who received HCQ/AZI to those who did not, regarding a composite outcome of mortality and mechanical ventilation with a 28-days follow-up. QT was monitored for patients treated with HCQ/AZI. Were excluded patients in intensive care units, palliative care and ventilated within 24 hours of admission. Three analyses were performed to adjust for selection bias: propensity score matching, multivariable survival, and inverse probability score weighting (IPSW) analyses. Results Overall, 203 patients were included: 60 patients treated by HCQ/AZI and 143 control patients. During the 28-days follow-up, 32 (16.3%) patients presented the primary outcome and 23 (12.3%) patients died. Propensity-score matching identified 52 unique pairs of patients with similar characteristics. In the matched cohort (n = 104), HCQ/AZI was not associated with the primary composite outcome (log-rank p-value = 0.16). In the overall cohort (n = 203), survival and IPSW analyses also found no benefit from HCQ/AZI. In the HCQ/AZI group, 11 (18.3%) patients prolonged QT interval duration, requiring treatment cessation. Conclusions HCQ/AZI combination therapy was not associated with lower in-hospital mortality and mechanical ventilation rate, with a 28-days follow-up. In the HCQ/AZI group, 18.3% of patients presented a prolonged QT interval requiring treatment cessation, however, control group was not monitored for this adverse event, making comparison impossible.

Stereotactic radiotherapy (SRT) is gaining increasing importance in metastatic non-small-cell lung cancer (mNSCLC) management. The optimal sequence of tumor irradiation relative to systemic treatment remains unclear. If waiting response evaluation to first-line systemic therapy (FLST) before considering local treatment may allow for the exclusion of poorer prognosis progressive tumors that may not benefit from SRT, performing irradiation near immune check point inhibitor (ICI) first administration seems to improve their synergic effect. Herein, we aimed to determine whether delaying SRT after response evaluation to FLST would result in better prognosis. We compared overall survival (OS), progression-free survival (PFS), and time to first subsequent therapy (TFST) for 50 patients locally treated before or within 90 days of initiating FLST (early SRT), with 49 patients treated at least 90 days after initiating FLST (late SRT). Patients treated with conventional chemotherapy alone exhibited significantly poorer median OS, PFS, and TFST in the early SRT arm: (in months) 16.5 [8.33-NR] vs. 58.3 [35.05-NR] (p = 0.0015); 4.69 [3.57–8.98] vs. 8.20 [6.66–12.00] (p = 0.017); and 6.26 [4.82–11.8] vs. 10.0 [7.44–21.8] (p = 0.0074), respectively. Patient receiving ICI showed no difference in OS (NR [25.2-NR] vs. 36.6 [35.1-NR], p = 0.79), PFS (7.54 [6.23-NR] vs. 4.07 [2.52-NR], p = 0.19), and TFST (13.7 [9.48-NR] vs. 10.3 [3.54-NR], p = 0.49). These results suggest that delaying SRT treatment in order to filter a rapidly growing tumor may be less necessary when ICI is administered in mNSCLC.