Incidental diagnosis of lung cancer on chest CT scan performed for suspected or documented COVID-19 infection.

CONTEXT: Recent studies have shown a benefit of chest computed tomography (CT scan) in lung cancer screening. The COVID-19 pandemic has led to many chest CT scan performed on a large population. The objective of this study was to describe the incidence and characteristics of lung cancer detected on chest CT scan, outside the framework of a clinical trial, for a suspected or documented COVID-19 infection. METHODS: We conducted a multicenter study, carried out from the analysis of data from the prospective COVID-19 database of the Clinical Data Warehouse of the Greater Paris University Hospitals (AP-HP). We identified the patients who had been diagnosed with a lung cancer, due to a chest CT scan done for a suspected or confirmed COVID-19 infection. The study period was limited to the first two epidemic lockdowns: (03/01/20 - 05/31/20) and (10/10/20 - 11/30/20). RESULTS: Over the study period, 24 390 patients had at least one chest CT scan. Among them, 72 lung cancer diagnoses were made (incidence 0.30 %; median age 67.4 years old, 50.0 % current smokers, 55.6 % adenocarcinoma). Half of the lung cancer patients (n = 36) did not meet the National Lung Screening Trial inclusion criteria. Twenty-six patients (36.1 %) were diagnosed at an early stage, 25 (34.7 %) of whom received radical curative treatment. Twenty-six patients died during the follow-up (36.1 %) but none in early stages. The median overall survival in lung cancer patients was 693 days [532 - NA]. CONCLUSIONS: A large-scale chest CT scan strategy for suspected or documented COVID-19 infection has allowed a significant proportion of early-stage lung cancer diagnosis, all of which have benefited from curative treatment.

Impact of Waiting Response Evaluation to First-Line Systemic Therapy before Considering Local Ablative Therapy in Metastatic Non-Small-Cell Lung Cancer.

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.

[Postoperative radiotherapy in non-small cell lung cancer stage IIIA - N2: Focus and perspectives]. / La radiothérapie postopératoire dans les cancers non à petites cellules de stade IIIA ­ N2 : mise au point et perspectives.

Patients with resectable stage IIIA - N2 lung cancer represent a very heterogeneous population with variable risks of postoperative recurrence depending on the type of N2 involvement (unisite N2, multisite N2, bulky N2, extra-capsular rupture, incomplete resection…). This heterogeneity associated with the difficulty of carrying out prospective randomized studies with sufficient power in stages IIIA - 2, results in the absence of clear and consensual recommendations (except for stages IIIA - N2 resectable R0, since LungART and PORT-C studies). The objective of this article is to make an update on the place of postoperative radiotherapy in the management of stages IIIA - N2 following the publication of two recent randomized trials (PORT-C and LungART) but also compare them fort a better understanding of the current issues raised by these first published results. Indeed, these two trials do not find any benefit in terms of progression free survival and overall survival of postoperative radiotherapy but exploratory analyzes from these two studies seem to show a potential benefit of postoperative in some pN2 populations at high risk of locoregional recurrence (N2 multisite, N2 bulky…). In addition, the advent of immunotherapy (atezolizumab or pembrolizumab) and targeted therapies (osimertinib) in the adjuvant situation are redebating the place of a possible indication for postoperative radiotherapy in stage IIIA - 2.

[Lung cancer screening: Update, news and perspectives]. / Dépistage du cancer du poumon : mise au point, actualités et perspectives.

Lung cancer is the leading cause of cancer death in France and worldwide (20 % of cancer deaths). This mortality is partly linked to an overrepresentation of metastatic stages at diagnosis (approximately 55 % of lung cancers at diagnosis). Low-dose chest CT in a target population to detect early forms accessible to radical treatment has been evaluated through multiple randomized trials (NLST, NELSON, MILD, DANTE…). These trials demonstrated a reduction in lung cancer specific mortality. The current problem is to integrate a CT screening policy CT at a national level, which should be both efficient and cost-effective, while presenting the least harms for the eligible population. Finally, it is necessary to optimize the participation of the eligible population and particularly in the most deprived areas and ensure the proper implementation of smoking cessation measures.

Successful sequential tyrosine kinase inhibitors to overcome a rare compound of EGFR exon 18-18 and EGFR amplification: A case report.

Background: New mutational detection techniques like next-generation sequencing have resulted in an increased number of cases with uncommon mutation and compound mutations [3%-14% of all epidermal growth factor receptor (EGFR) mutations]. In rare exon 18 mutations (3%-6%), G719X and E709X represent the majority, but CMut associating these exon 18 points mutations are even rarer, making the understanding of the impact of epidermal growth factor receptor tyrosine kinase inhibitors still limited. Three generations of EGFR tyrosine kinase inhibitors (TKIs) are available to target EGFR mutations, but according to the types of mutations, the sensitivity to TKI is different. Afatinib, osimertinib, and neratinib have showed some effectiveness in single exon 18, but no report has precisely described their efficiency and acquired mechanism of resistance in a CMut of exon 18-18 (G719A and E709A). Case presentation: We report a case of a 26-year-old woman with bilateral advanced adenocarcinoma of the lung harboring a compound mutation associating G719A and E709A in exon 18, who developed an EGFR amplification as resistance mechanism to osimertinib. She presented a significant clinical and morphological response under sequential TKIs treatment (afatinib, osimertinib, and then neratinib). Conclusion: A non-small cell lung cancer (NSCLC) with rare compound mutation exon 18-exon 18 (G719A and E709A) and EGFR amplification can be overcome with adapted sequential second- and third-generation TKIs. This report has potential implications in guiding decisions for the treatment of these rare EGFR mutations.

Paclitaxel-bevacizumab combination in advanced non-squamous non-small-cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study.

Introduction: Compared with docetaxel, the phase-III trial, ULTIMATE, showed a significant improvement of progression-free survival (PFS) with paclitaxel-bevacizumab combination (PB) as second- or third-line treatment in advanced non-small cell lung cancer (NSCLC). With the increase of immunotherapy treatment in first-line settings, the optimal treatment after first-line failure must be redefined. Methods: This multicentric retrospective study identified all advanced NSCLC patients treated with PB as second-line therapy and beyond. The main efficacy outcomes assessed were objective response rate (ORR), disease control rate (DCR), PFS, and overall survival (OS). The adverse events were reported according to Common Terminology Criteria for Adverse Events (CTCAE). Results: From January 2010 to February 2020, 314 patients in 16 centers received the PB combination. Most patients were male (55%), with a median age of 60 years (19-82), 95% had adenocarcinoma, 27% had a performance status ⩾2, 45% had brain metastases at the time of inclusion. They mostly received the PB combination either in second (20%) or in third-line (39%), and 28% were treated just after ICI failure. ORR and DCR were 40% and 77%, respectively; median PFS and OS were 5.7 [interquartile range (IQR): 3.2-9.6] and 10.8 [IQR: 5.3-19.6] months, respectively. All grade adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued monotherapy (mostly with bevacizumab) alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compared with those not previously treated with ICI (ICI-): 7.0 [IQR: 4.2-11.0] versus 5.2 [IQR: 2.9-8.8] months, p = 0.01, without statistically significant difference for OS between these two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment and performance status of 0-1. Only a performance status of 0-1 was associated with superior OS. Conclusion: PB combination as second-line treatment or beyond for advanced non-squamous NSCLC had acceptable toxicity and a clinically relevant efficacy and is an option as salvage treatment for these patients, more particularly after ICI progression.

Updated Prognostic Factors in Localized NSCLC.

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.

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.

Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study.

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.

Liver function test abnormalities are associated with a poorer prognosis in Covid-19 patients: Results of a French cohort.

AIM: To assess the impact of liver function test (LFT) abnormalities on the prognosis of patients with coronavirus disease 2019 (COVID-19) in a French cohort of hospitalized patients. PATIENTS AND METHOD: From March 13 to April 22, 2020, we collected on a computerized and anonymized database, medical records, laboratory data and clinical outcomes of patients hospitalized for confirmed cases of COVID-19 infection (RT-PCR and/or CT-scan). Patients were followed up until April 22, 2020 or until death or discharge. We have considered for statistical analysis, LFT abnormalities with levels greater than two times the upper limit of normal. Composite endpoint included admission to ICU, mechanical ventilation, severe radiologic injury and death to define disease severity. RESULTS: Among 281 patients (median age 60 years) with COVID-19, 102 (36.3%) had abnormal LFT. Hypertension (45.6%) and diabetes (29.5%) were the main comorbidities. 20.2% were taken liver-toxic drugs at the admission and 27.4% were given drugs known to induce hepatic cytolysis during hospitalization. Patients with elevated levels of ALT or AST were significantly more severe with a higher rate of admission to ICU (40.0% vs 6.0%, p< 0.0001), and global mortality (26.7% vs 12.1%, p= 0.03). In multivariate analysis, obesity and cytolytic profil were associated with the composite endpoint (respectively 2.37 [1.21; 4.64], p= 0.01 and OR 6.20, 95% confidence interval [1.84, 20.95], p-value 0.003) CONCLUSION: Most of liver injuries are mild and transient during COVID-19. LFT abnormalities are associated with a poorer prognosis and could be a relevant biomarker for early detection of severe infection.