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.

Safe and effective use of nivolumab for treating lung adenocarcinoma associated with sporadic lymphangioleiomyomatosis: a rare case report.

BACKGROUND: Sporadic lymphangioleiomyomatosis (LAM) is a rare form of diffuse parenchymal lung disease. PD-1 blocking antibodies constitute an essential treatment option for advanced non-small-cell lung cancer (NSCLC). The effect of immune checkpoint inhibitors in lymphangioleiomyomatosis patients with non-small cell lung cancer is unknown: concomitant symptomatic interstitial lung disease or the use of immunosuppressors was a key exclusion criterion in the original studies of immune checkpoint inhibitors, especially regarding the risk of interstitial lung disease exacerbation. CASE PRESENTATION: A 48-year-old female, active smoker (36 pack-years), diagnosed with sporadic LAM since 2004 suffered from metastatic adenocarcinoma of the lung. Third-line therapy with nivolumab was started in 2015, with a major partial response. Due to pulmonary function alterations, sirolimus was also reinitiated in 2017 in conjunction with nivolumab, without any undesirable effects and a major partial response continuing up to May 2018. CONCLUSIONS: This case highlights the safe and effective use of nivolumab for managing metastatic lung adenocarcinoma that occurred in a patient with sporadic LAM. In the current case, immunotherapy proved highly successful in managing the NSCLC tumor that occurred upon LAM follow-up, with both a significantly prolonged partial response and acceptable safety profile.

Impact of preexisting interstitial lung disease on outcomes of lung cancer surgery: A monocentric retrospective study.

INTRODUCTION: Interstitial lung disease (ILD) is a known risk factor for lung cancer (LC). However, the surgical risk of LC in patients with ILD remains unclear. Therefore, we conducted a single-center retrospective study to assess clinical features and outcomes of LC population who underwent surgery with or without ILD. METHODS: Patients who underwent surgery for LC between January 2006 and June 2023 in our center were assessed using data extracted from the nationwide EPITHOR thoracic surgery database. Suspicion of ILD was based on patients' records. Confirmation of ILD was then made on the patient's medical and radiological history. Patients were classified according to the pattern of ILD. The study aimed to describe the outcomes after lung cancer resection in patients with confirmed LC-ILD group compared to those without ILD (LC-non-ILD): post-operative complications, disease-free survival (DFS) and overall survival (OS). A subgroup analysis was also performed on patients with idiopathic pulmonary fibrosis and lung cancer (LC-IPF). RESULTS: 4073 patients underwent surgery for LC at Assistance Publique des Hôpitaux de Marseille between January 2006 and June 2023. Of these, 4030 were in the LC-non-ILD group and 30 were LC-ILD patients. In the LC-ILD group, the predominant CT scan pattern was probable UIP (50 %). OS was not significantly lower in the LC-ILD group (45 months versus 84 months, p = 0.068). Dyspnea and tumor size were identified as potential univariate predictors of OS. No significant differences were observed on post-operative complications or their severity. The most common post-operative complications in the LC-ILD group were prolonged air leak, respiratory failure, or pneumonia. 13 patients had cancer recurrence in the LC-ILD group. CONCLUSION: Our study provides a comprehensive analysis of a LC-ILD population features and outcome when undergoing surgery for LC. Patients with LC-ILD appeared to have a reduced OS compared with LC-non-ILD. Further investigations with larger prospective studies could be useful to confirm and develop these preliminary findings.

Measuring Walking Speed Failed to Predict Early Death and Toxicity in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) Selected for Undergoing First-Line Systemic Treatment: An Observational Exploratory Study.

Walking speed (WS) has emerged as a potential predictor of mortality in elderly cancer patients, yet data involving non-small-cell lung cancer (NSCLC) patients are scarce. Our prospective exploratory study sought to determine whether WS would predict early death or toxicity in patients with advanced NSCLC receiving first-line systemic intravenous treatment. Overall, 145 patients of ≥70 years were diagnosed with NSCLC over 19 months, 91 of whom displayed locally-advanced or metastatic cancer. As first-line treatment, 21 (23%) patients received best supportive care, 13 (14%) targeted therapy, and 57 (63%) chemotherapy or immunotherapy. Among the latter, 38 consented to participate in the study (median age: 75 years). Median cumulative illness rating scale for geriatrics (CIRS-G) was 10 (IQR: 8−12), and median WS 1.09 (IQR: 0.9−1.31) m/s. Older age (p = 0.03) and comorbidities (p = 0.02) were associated with Grade 3−4 treatment-related adverse events or death within 6 months of accrual. Overall survival was 14.3 (IQR: 6.1-NR) months for patients with WS < 1 m/s versus 17.3 (IQR: 9.2−26.5) for those with WS ≥ 1 m/s (p = 0.78). This exploratory study revealed WS to be numerically, yet not significantly, associated with early mortality in older metastatic NSCLC patients. Following these hypothesis-generating results, a larger prospective, multicenter study appears to be required to further investigate this outcome.

Acceptance, efficacy, and safety of COVID-19 vaccination in older patients with cancer.

PURPOSE: The COVID-19 vaccination campaign began in December 2020, in France, and primarily targeted the oldest people. Our study aimed to determine the level of acceptance of vaccination in a population of older patients with cancer. METHODS: From January 2021, we offered vaccination with the BNT162b2 COVID-19 vaccine to all patients 70 years and older referred to our geriatric oncology center in Marseille University Hospital (AP-HM) for geriatric assessment before initiation of an oncological treatment. Objectives were to evaluate acceptance rate of COVID-19 vaccination and to assess vaccine safety, reactogenicity, and efficacy two months after the first dose. RESULTS: Between January 18, 2021 and May 7, 2021, 150 older patients with cancer were offered vaccination after a geriatric assessment. The majority were men (61.3%), with a mean age of 81 years. The two most frequent primary tumors were digestive (29.4%) and thoracic (18%). The vaccine acceptance rate was 82.6% and the complete vaccination rate (2 doses) reached 75.3%. Among the vaccinated patients, 15.9% reported mild side effects after the first dose and 23.4% after the second dose, mostly arm pain and fatigue. COVID-19 cases were observed in 5.1% of vaccinated patients compared with 16.7% in unvaccinated patients. Of the 22 vaccinated patients who agreed to have their serum tested, 15 had antibodies against the spike protein at day 21 after the first dose. CONCLUSION: Our study showed a high acceptance rate of COVID-19 vaccination, with good tolerance in this frail population. These results highlight the benefits of organizing vaccination campaigns at the very beginning of oncological management in older patients. CLINICAL TRIAL REGISTRATION: This study was registered May 23, 2019 in ClinicalTrials.gov (NCT03960593).

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.

A new KIF5B-ERBB4 gene fusion in a lung adenocarcinoma patient.

ERBB4 fusion is a rare, novel oncogenic event involved in the development of lung adenocarcinoma that is not routinely looked for, although ERBB4 fusion is a potential target for existing pan-ErbB tyrosine kinase and must be implemented in the laboratory https://bit.ly/3nYmGQ9.

[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.

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

BACKGROUND: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. MATERIAL AND METHODS: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. RESULTS: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). CONCLUSION: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.

Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer.

INTRODUCTION: Tumor mutational burden (TMB) correlates with response to immune checkpoint inhibitors (ICI) in advanced non-small-cell lung cancer (aNSCLC). We hypothesized that TP53 mutations could reflect TMB and be associated with ICI benefit. METHODS: TP53 mutations were assessed by next-generation sequencing in aNSCLC patients treated with programmed death-1 (PD-1) blockers. Clinical data, tumor programmed death ligand-1 (PD-L1) expression, and KRAS mutational status were collected. The primary endpoint was overall survival (OS). RESULTS: In total, 72 patients (median [interquartile range] age: 61 [33-83] years) were included; 52 (72%) were male; 39 (54%) had performance status 0-1; 53 (74%) had adenocarcinoma; 20 (28%) received first-line ICI, 52 (72%) second line or more. In 65 patients with available data, 36 (55%) expressed PD-L1 in ≥50% of tumor cells, 20 (31%) in 1-49% of cells, and nine (14%) were PD-L1-negative. Non-synonymous TP53 mutations were observed in 41 (57%) and 25 (35%) harbored KRAS-mutated tumors. After a median follow-up of 15.2 months (95% confidence interval [CI] 10.3-17.4 m), the median OS in the TP53-mutated group was 18.1 months (95% CI 6.6-not reached), vs. 8.1 months (95% CI 2.2-14.5, hazard ratio [HR] = 0.48; 95% CI 0.25-0.95, p = 0.04) in the TP53-wild-type group. Median progression-free survival was significantly longer in TP53-mutated patients (4.5 months, 95% CI 2.8-18.1 versus 1.4, 95% CI 1.1-3.5; p = 0.03), although TP53 mutation status failed to significantly influence PFS in the multivariate analysis (p = 0.32). Objective response rate (ORR) was higher in patients with TP53 mutation (51.2% vs. 20.7%; p = 0.01). In multivariate analysis, TP53 mutations independently associated with longer OS (HR = 0.35, 95% CI 0.16-0.77, p = 0.009). CONCLUSIONS: TP53-mutated status correlated with immunotherapy OS benefit in aNSCLC.

Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study.

BACKGROUND: Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy. METHODS: We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively. FINDINGS: Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1. INTERPRETATION: Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.