Epidermal growth factor receptor-mutant non-small cell lung Cancer and Choroidal metastases: long-term outcome and response to epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Choroidal metastases are the most common eye metastatic site. The prevalence of choroidal metastases in NSCLC patients has been reported to vary from 0.2 to 7% in historical series. Although previously reported, little is known about choroidal metastasis in Epidermal Growth Factor Receptor (EGFR)-mutant Non-small cell lung cancer (NSCLC). This study sought to describe the prevalence of choroidal metastases among patients with EGFR-mutated NSCLC and their characteristics, and to estimate their impact on prognosis. METHODS: We conducted a single-center retrospective study including all consecutive metastatic EGFR-mutant NSCLC patients, from Sept. 2015 to Oct. 2018. The EGFR-mutant NSCLC patients were identified via the Department of Genetics' files. Patients who exhibited choroidal metastases were compared to patients without choroidal metastases. Kaplan-Meier analysis and log-rank test were conducted to assess median overall survival (OS) from diagnosis for the two groups. The study was approved by the IRB as CEPRO number #2020-010. RESULTS: Prevalence of choroidal metastases in EGFR-mutated NSCLCs was 8.4% (7/83). Five were women, and four current or former smokers. Molecular analysis showed three tumors with exon 19 deletion, three with L858R mutation, and one with complex exon 21 mutation. The choroidal metastases were symptomatic in six/seven patients. Visual disturbances decreased in all but one symptomatic cases upon EGFR TKI, and the choroidal response was maintained over time. Median follow-up was 42.2 mo (95%CI [37.2-47.1]). Median OS in the choroidal metastasis group was 23.4 mo (95%CI [0.1-51.4]) versus 27.9 mo (95%CI [16.9-38.9]) in the non-choroidal metastasis group (p = 0.32). In the choroidal metastasis group, 2-year and 5-year OS were 47.6 and 0%, respectively, versus 55.8 and 26.3% in the non-choroidal metastasis subset. CONCLUSIONS: Choroidal metastases in NSCLC EGFR-mutant patients are rare but should be systematically suspected in case of visual disturbance. TKIs are efficient for treating visual symptoms. Whether choroidal metastases confer a worse prognosis remains unclear owing to the third-generation EGFR TKI osimertinib first-line registration.

Transthoracic lung biopsy for pulmonary nodules ≤20†mm in routine clinical care.

BACKGROUND: Computed tomography (CT) screening has improved lung cancer survival, yet increasingly detects small lung lesions. Thus, the number of transthoracic lung biopsies (TTLB) for small nodules is expected to rise significantly. The aim of the present study was to evaluate the diagnostic accuracy and safety of CT-guided TTLB for nodules ≤20 mm versus nodules >20 mm. STUDY DESIGN AND METHODS: Data for CT-guided TTLBs from 474 consecutive patients were prospectively collected over a 3-year period (198 lesions ≤20 mm and 276 lesions >20 mm) in a teaching hospital and analysed in terms of diagnostic performance and complications. RESULTS: There were more conclusive biopsies in the >20 mm lesion group (n=236, 85.5%) than in ≤20 mm lesion group (n=140, 70.7%; p<0.001). The overall accuracy, sensitivity, specificity and negative predictive value for diagnosing malignant lesions after first TTLB were 88.4%, 84%, 100% and 70.1%, respectively, for ≤20 mm lesions, and 94.2%, 93%, 100% and 74.6%, respectively, for >20 mm lesions. Pneumothorax requiring drainage was significantly more common for ≤20 mm lesions, compared to TTLB of larger lesions (9.6% versus 4.3%; p=0.02). Prolonged hospital stay due to pneumothorax occurred in 27 (17.4%) TTLBs of ≤20 mm lesions and 15 (7%) TTLBs of >20 mm lesions (p=0.002). There were no deaths. The only variable significantly associated with diagnostic failure in the ≤20 mm lesion group was the radiologist's experience. INTERPRETATION: TTLBs for lesions ≤20 mm were associated with slightly lower diagnostic performance, whereas the higher rate of major complications was still inferior to that extrapolated from United States insurance databases.

Efficacy of Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine in Patients With Thoracic Cancer: A Prospective Study Supporting a Third Dose in Patients With Minimal Serologic Response After Two Vaccine Doses.

INTRODUCTION: Coronavirus disease 2019 resulted in a 30% mortality rate in patients with thoracic cancer. Given that patients with cancer were excluded from serum antisevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine registration trials, it is still unknown whether they would develop a protective antispike antibody response after vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to the SARS-CoV-2 vaccine in patients with thoracic cancer. METHODS: SARS-CoV-2-spike antibodies were measured using the Abbot Architect SARS-CoV-2 immunoglobulin G immunoassay before the first injection of BNT162b2 mRNA vaccine, at week 4, and 2 to 16 weeks after the second vaccine dose administration. The factors associated with antibody response were analyzed. RESULTS: Overall, 306 patients, with a median age of 67.0 years (interquartile range: 58-74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After a 6.7-month median follow-up, eight patients (2.6%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of the 269 serologic results available beyond day 14 after the second vaccine dose administration, 17 patients (6.3%) were still negative (<50 arbitrary units/mL, whereas 34 (11%) were less than 300 arbitrary units/mL (12.5th percentile). In multivariate analysis, only age (p < 0.01) and long-term corticosteroid treatment (p = 0.01) were significantly associated with a lack of immunization. A total of 30 patients received a third vaccine dose, with only three patients showing persistently negative serology thereafter, whereas the others exhibited clear seroconversion. CONCLUSIONS: SARS-CoV2 vaccines were found to be efficient in patients with thoracic cancer, most of them being immunized after two doses. A third shot given to 1% of patients with persistent low antibody titers resulted in an 88% immunization rate.

Grade 3-4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study.

Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3−4 irAEs on overall survival (OS). Methods: This observational study recruited advanced NSCLC patients who received ICIs at Bichat-Claude Bernard University Hospital and in a community hospital, Saint-Joseph Foundation (Paris), between 1 January 2016 and 31 December 2019. Immunotherapy as a single-agent or double-drug combination was applied in the first and later lines. Univariable and multivariable analyses were instrumental in evaluating the prognostic impact of irAEs. Results: Overall, 201 consecutive ICI-treated patients were enrolled. High-grade irAEs (Grades 3−4) occurred in 36 patients (17.9%), including 11 (30.5%) cases of pneumonitis, 8 (22.2%) of colitis, 4 (11.1%) hepatic, 3 (8.3%) dermatological, 2 (5.5%) neurological events, and 2 cases (5.5%) of poly-arthralgia. The median OS was 10.4 ± 1.36 months (95% CI:7.7−13.1), being significantly higher in patients with high-grade irAEs than those without, 27.8 months vs. 8.1 months, respectively (HR = 2.5; p < 0.0001). Multivariable analysis revealed an independent association between high-grade irAEs and longer OS (HR = 0.29, 95% CI: 0.2−0.6, p < 0.0001). Conclusions: Our real-life study confirms that high-grade irAEs predict longer OS in advanced NSCLC.

Poor performance status patient with long-lasting major response to pembrolizumab in advanced non-small-cell lung cancer with coexisting POLE mutation and deficient mismatch repair pathway.

Immunotherapy with immune checkpoint inhibitors (ICIs) represents a major breakthrough in lung cancer treatment. For patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status (PS), the availability of sensitivity markers to immune-checkpoint inhibitors (ICI) would be useful for attending physicians and assist them in their decision-making process. Deficient mismatch repair (dMMR) can lead to high microsatellite instability (MSI-H) and coexist with mutations in polymerase proofreading (DNA polymerase Epsilon POLE and delta 1 POLD1) with a specific mutational signature. This would result in high tumor mutational burden and programmed cell death protein ligand 1 (PD-L1) overexpression. We report herein on a NSCLC case with MSI-H and POLE mutation in a patient with inaugural poor general condition, who exhibited prolonged response to anti-programmed cell death protein (PD-1) therapy. Additionally, there was a marked improvement of the patient's performance status, from PS 3 before ICI administration to PS 1 upon ICI therapy.

Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients.

Anti-PD-1 antibodies prolong survival of performance status (PS) 0-1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3-4 patients is unknown. Conse- cutive PS 3-4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3-4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1-7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41-63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1-3.2). Median OS was 4.4 months (95%CI, 0.5-8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9-14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7-13.8, p = 0.003) predicted worse survival. PS improvement from 3-4 to 0-1 (n = 9) led to a median 43-month (95%CI, 0-102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

[Initial assessment of lung cancer]. / Bilan initial d'un cancer du poumon.

Initial assessment of lung cancer. Lung cancer is frequent with a high mortality rate. Improvement of diagnosis tools provide better staging and tumor characterization enhancing prognosis. We explain in this review the diagnosis procedures emphasizing the most im¬portant techniques and their goals. Clinicians define a target to sample with different means considering general condition and extension of the disease. Staging needs CT-Scan of thorax and abdomen, cerebral imaging, PET-CT, bronchoscopy in order to assess endobronchial invasion especially for localized or locally advanced cancer. New tools are emerging such as EBUS-TBNA or EUS-FNA for mediastinal staging. Transthoracic biopsy and Radial-EBUS or Electromagnetic navigation diagnostic bronchoscopy can be used for small peripheral lung lesions diagnosis. Conse¬quently, patients can benefit from individualized and precise therapeutic approach.

Bilan initial d'un cancer du poumon. Le cancer du poumon est une maladie fréquente, avec une mortalité élevée. Le pronostic est, entre autres, conditionné par l'amélioration des moyens diagnostiques pour une définition précise du stade, et la caractérisation précise histologique et moléculaire de la tumeur. La démarche diagnostique est ici résumée, avec l'importance d'une filière diagnostique rapide, les examens pertinents et les différents objectifs. Le clinicien définit une cible (tumeur primitive, adénopathie, site métastatique) et fait réaliser ou réalise un prélèvement par différentes méthodes. Le choix de la cible est défini par la localisation de la maladie, l'état général du patient et ses comorbidités, et l'extension. Le bilan d'extension associe tomodensitométrie (TDM) thoraco-abdominale injectée , imagerie cérébrale par TDM injectée ou imagerie par résonance magnétique, TDM couplée à la tomographie à émission de positons, fibroscopie bronchique pour évaluer l'extension endobronchique, pour un cancer lo¬calisé ou localement avancé, c'est-à-dire qui pourrait bénéficier d'un traitement local. L'endoscopie bronchique conventionnelle est suppléée par de nouveaux moyens diagnostiques pour l'exploration médiastinale comme l'EBUS-PTBA (endo-bronchial ultrasound - ponction transbronchique à l'aiguille fine) ou l'EUS (échographie transoesophagienne)-PTBA ou le diagnostic des lésions périphériques par ponction sous scanner, l'endoscopie couplée à la mini-sonde et l'apport des techniques de naviga-tion. Cela permet au patient de bénéficier alors d'une stratégie thérapeutique précise et individualisée.

[Epidemiology of lung cancer in France and in the world]. / Épidémiologie des cancers du poumon en France et dans le monde.

Epidemiology of lung cancer in france and in the world. Lung cancer is the leading cause of death from cancer worldwide. In France, lung cancer is the second most common cancer in men (after prostate cancer), and the third in women (after breast and colon cancer). However, it ranks first among the deadliest cancers in men and second among women (after breast cancer). In the United States, mortality from lung cancer in women has exceeded mortality from breast cancer, and it is likely that this will be the case in France in a few years. The main risk factor is smoking. Although the incidence and mortality rates continue to increase in women, they remain twice higher in men compared to women. The development since the 1990s is marked by a clear increase in the incidence of adenocarcinomas in both sexes, probably linked to differences in smoking behavior.

Épidémiologie des cancers du poumon en france et dans le monde. Le cancer du poumon est la première cause de décès par cancer dans le monde. En France, le cancer du poumon est le 2e cancer le plus fréquent chez l'homme (après le cancer de la prostate) et le 3e chez la femme (après le cancer du sein et du côlon). Néanmoins, il se situe au premier rang des cancers les plus mortels chez l'homme et au 2e rang chez la femme (après le cancer du sein). Aux États-Unis, la mortalité par cancer du poumon chez la femme a dépassé la mortalité par cancer du sein, et il est probable que ce constat soit fait en France dans quelques années. Le principal facteur de risque est le tabagisme. Bien que les taux d'incidence et de mortalité ne cessent d'augmenter chez la femme, ils demeurent néanmoins deux fois plus élevés chez l'homme. L'évolution depuis les années 1990 est marquée par une augmentation nette de l'incidence des adénocarcinomes dans les deux sexes, probablement liée aux modifications de comportement tabagique.

Development and validation of a prognostic index for survival in non-small cell lung cancer: Results from a Tunisian cohort study.

INTRODUCTION: Despite the continuous efforts made with the TNM system, the issue of heterogeneity of prognosis within the stages of non-small cell lung cancer (NSCLC) could not be resolved. Our aim was to identify prognostic factors and develop an index to predict NSCLC survival with greater accuracy. METHODS: We conducted a survival study over 5 years on patients with NSCLC. Kaplan-Meier analysis followed by Cox regression modelling were used. Prognostic indices were derived, using either an additive or a multiplicative pattern, and were compared by their receiver operating characteristics (ROC) curves. We then proceeded to a risk stratification and validation of the index on the derivation cohort. RESULTS: Two hundred and sixty-two NSCLC patients were included. Two models were constructed, using the following nine variables as prognostic factors: age, performance status, haemoglobin level, leucocyte count, calcium, lactate dehydrogenase, alkaline phosphatase levels, histological type and TNM stage. Four prognostic indices were derived, and the best one was picked and validated on a population of five risk groups. The higher the risk group, the shorter the survival. CONCLUSIONS: This novel and simple prognostic tool could predict survival more accurately in patients with NSCLC.

Second lung malignancy and Richter syndrome in chronic lymphocytic leukemia: case report and literature review.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most frequent lymphoproliferative disease. Transformation into Richter disease and occurrence of second malignancies involving the lungs are rare complications. The hallmarks of any thoracic involvement are still unknown. CASE PRESENTATION: We report a case of a 56-year-old male patient, with history of tobacco smoking, who presented with recurrent hemoptysis, fatigue and weight loss. Physical examination was normal except a slightly enlarged supraclavicular lymph node. Chest x-ray revealed a mediastinal widening due to enlarged paratracheal nodes and a left parahilar infiltrate. Blood tests showed a hyperlymphocytosis and a biological inflammatory syndrome. CT scan showed bilateral mediastinal and axillary lymphadenopathy, as well as left supraclavicular lymphadenopathy, with a left upper lobe alveolar attenuation and a solitary contralateral pulmonary nodule. Examination of Virchow's node and bone marrow biopsies confirmed metastasis of a pulmonary adenocarcinoma, as well as chronic lymphocytic leukemia with Richter's transformation. The clinical course was unfavorable since the first days of therapy as the patient passed away in a matter of a few days. CONCLUSIONS: Steady surveillance of CLL patients and systematic screening for second solid tumors, particularly lung cancer, and Richter's transformation seem to be relevant more than ever. Early diagnosis might help us understand the pathways leading to these complications and adapt therapy.

Spontaneous resolution of a tumor like pulmonary sarcoidosis.

We report a case of thoracic sarcoidosis in a 72-year-old female, snuff taker, who presented with multinodular pulmonary lesions on chest x-ray. Clinical and biological findings were poor. Thoracic imaging showed soft tissue density nodules with irregular borders. The diagnosis of 'cannon ball' metastases was suspected. A thorough investigation strategy could not prove malignancy. A complete radiologic clearing was obtained spontaneously within three months. A rereading of pathology slides performed afterwards showed multinucleated giant cells on hemorrhagic background with a lymphocytic alveolitis. The diagnosis of pseudotumoral sarcoidosis was made. The clinical course was favorable with a 6years follow-up.