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.
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.
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.
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.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
•Frequent smoking-inducedTP53 mutations in NSCLC lead to genetic instability.•Genetic instability could drive sensitivity to immunotherapy via neo-antigens.•TP53 mutations were found to actually ...drive longer OS upon immunotherapy.
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.
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).
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).
TP53-mutated status correlated with immunotherapy OS benefit in aNSCLC.
•Data about outcome of immunotherapy is scarce in poor Performance Status NSCLC.•Uncommon in NSCLC, dMMR and POLE mutations might predict response to PD1-blockade.•Such predictive biomarkers could ...help for a better selection of poor PS patients.
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.
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