Search

Background: Patients with brain oligometastases have better prognosis than those with synchronous extracranial metastases in non‐small cell lung cancer (NSCLC). However, studies focusing on intracranial‐only recurrence after curative surgery remained scarce. This study aimed to explore distinct features of patients with exclusive brain relapse after resection of lung adenocarcinoma. Methods: Records were retrospectively reviewed of 2809 patients who had complete resection and pathologically confirmed stage IB‐IIIA NSCLC in our hospital from October 2012 to September 2019. Patients were enrolled if they were adenocarcinoma and developed intracranial recurrence thereafter. They were divided into two groups depending on whether they had synchronous extracranial metastases. Clinical and pathological features of patients enrolled were collected and compared between groups. Results: Ninety‐seven lung adenocarcinoma patients with intracranial recurrences were enrolled. The median follow‐up time was 40 months. Fifty patients (51.5%) had brain oligometastases and 47 patients had synchronous extracranial metastases (ECM). Multivariate logistic regression suggested EGFR‐sensitive mutation and male sex were positively correlated to brain‐only recurrence (OR = 2.59, 95%CI 1.04–6.84 and OR = 2.58, 95% CI 1.05–6.75), while higher clinical stage was associated with synchronous ECM (stage II (OR = 0.33, 95%CI 0.09–1.14) or stage IIIA (OR = 0.54, 95%CI 0.20–1.38) versus stage I). No other pathological feature (lymphovascular invasion, visceral pleural invasion, low tumor differentiation, etc.) or adjuvant chemotherapy was associated with intracranial‐only relapse after complete resection of primary tumor. Conclusion: Among patients with brain relapse after resection of lung adenocarcinoma, patients with EGFR mutations might have intracranial relapse only without synchronous extracranial metastases. Further prospective studies are warranted to verify this. [ABSTRACT FROM AUTHOR]

Background: Currently, survival benefit of immunotherapy in advanced non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertions (ex20ins) is controversial, though it generally indicates poor response and activity. Compared with standard chemotherapy in combination with bevacizumab, first‐line chemotherapy plus immune checkpoint inhibitor (ICI) in advanced NSCLC with EGFR ex20ins remains elusive and lacks real‐world evidence. Patients and Methods: A retrospective real‐world study was conducted to evaluate clinical outcomes of chemotherapy alone (C), chemotherapy plus ICI (C + I), or chemotherapy plus angiogenesis inhibitors (C + A) as first‐line strategies for advanced NSCLC patients with EGFR ex20ins. Investigator‐assessed response and survival outcomes were compared between subgroups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to reveal concomitant alterations and explore the molecular landscape of ex20ins. Results: A total of 164 patients were screened, identifying 35 kinds of ex20ins, and 122 cases treated with C, C + I, and C + A were finally included in the first‐line analysis. C + A achieved much better objective response rate (ORR, 38.1% vs. 18.2%) and significant progression‐free survival (PFS) benefit compared with C (median, 7.73 vs.5.93 months, HR = 0.60, 95% CI: 0.40–0.90, p = 0.014), and it showed similar ORR (38.1% vs. 40.0%), but higher disease control rate (DCR, 96.8% vs. 80.0%) and numerically longer median PFS (7.73 vs. 6.53 months, HR = 0.83, 95% CI: 0.44–1.56, p = 0.30) than C + I. There was no PFS difference between C + I and C, despite of PD‐L1 expression or tumor mutational burden. KEGG analysis revealed concomitant upregulation of PI3K/AKT signaling might mediate intrinsic resistance to ICI in ex20ins. Conclusion: First‐line chemotherapy plus angiogenesis inhibitors might yield more survival benefits than chemotherapy alone for NSCLC with EGFR ex20ins, whereas, it suggests that chemotherapy in combination with ICI might not obtain a better survival benefit for this subset of patients. Activation of PI3K/AKT signaling might mediate intrinsic immunosuppression in NSCLC with EGFR ex20ins. [ABSTRACT FROM AUTHOR]

Background: ROS1 gene fusion represents a specific subtype of non‐small cell lung cancer (NSCLC). Crizotinib is recommended for ROS1‐positive NSCLC due to its favorable outcome in published clinical trials. However, due to the low incidence of ROS1‐positive NSCLC, there is limited information on real‐world clinical outcomes in patients treated with either crizotinib or platinum‐based doublet chemotherapy. Methods: Outcomes were recorded in 102 patients with stage Ⅲb or Ⅳ NSCLC who were treated at four Chinese hospitals between April, 2010 and June, 2019. Results: Of the 102 patients followed, 71.6% were females, 81.4% were non‐smokers, and 98.0% had adenocarcinoma. First‐line treatment with crizotinib achieved a significantly longer median progression‐free survival (PFS) compared with platinum‐based chemotherapy (14.9 months vs 8.5 months, respectively; P <.001). Next‐generation sequencing (NGS) identified 61 patients who had ROS1 fusion variants, including CD74 (n = 33) and non‐CD74 (n = 28) variants. In patients harboring CD74 fusion variants, the median PFS with first‐line crizotinib treatment was significantly longer than in those harboring non‐CD74 fusion variants (20.1 months vs 12.0 months, respectively; P =.046). However, in patients treated with platinum‐based chemotherapy, there was no significant difference in PFS between the CD74 and non‐CD74 variant groups (8.6 months vs 4.3 months, respectively; P =.115). Overall survival (OS) was not reached. Conclusions: First‐line therapy with crizotinib is more beneficial than platinum‐based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants. Patients harboring CD74 fusion variants appear to respond better to crizotinib. [ABSTRACT FROM AUTHOR]

Objectives: Crizotinib has demonstrated good efficacy in patients with anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Continuing crizotinib therapy beyond progressive disease (CBPD) can achieve ongoing survival benefit in real‐world clinical practice. In terms of survival, progression‐free survival (PFS), the most commonly used endpoint in efficacy evaluations, may not provide accurate information on the impact of this intervention when crizotinib is administered in sequential therapy. Materials and Methods: A single‐center, retrospective study of 201 ALK‐positive advanced NSCLC patients was conducted to analyze the PFS, overall survival (OS), and treatment duration (TD) of crizotinib. The correlations between the TD of crizotinib and OS in CBPD and non‐CBPD groups of patients were compared. Results: All patients were treated with crizotinib, 150 of whom eventually developed progressive disease (PD). The median PFS1 and PFS2 were 13.2 months and 10.5 months, respectively. The OS of the whole population was 50.5 months. The median TD was 20.7 months, which is shorter than direct PFS1 + PFS2. The TD of crizotinib in CBPD group was significantly longer than that in non‐CBPD group (median 39.7 vs 15.0 months, P < .001). TD correlated better with OS (R = .79) than PFS (R = .64) in the CBPD group. Conclusions: Crizotinib showed good efficacy in patients with ALK‐positive advanced NSCLC. Instead of PFS, treatment duration might be a more reasonable surrogate clinical endpoint in patients who received crizotinib in sequential therapy. [ABSTRACT FROM AUTHOR]

There is inconsistent evidence of associations between socioeconomic status ( SES) and lung cancer stage in non-Chinese populations up to now. We set out to determine how SES affects stage at diagnosis at both individual and area levels, from a hospital-based multicenter 10-year (2005-2014) retrospective clinical epidemiological study of 7184 primary lung cancer patients in mainland China. Individual-level SES data were measured based on two indicators from case report forms of the study: an individual's education and occupation. Seven census indicator variables were used as surrogates for the area-level SES with principal component analysis ( PCA). Multivariate analysis was undertaken using binary logistic regressions and multinomial logit model to describe the association and explore the effect across tertiles on stage after adjusting for demographic variables. There was a significant stepwise gradient of effect across different stages in the highest tertile of area-level SES, comparing with the lowest tertile of area-level SES ( ORs, 0.77, 0.67, and 0.29 for stage II, III, and IV). Patients with higher education were less likely to have stage IV lung cancer, comparing with the illiterate group ( ORs, 0.52, 0.63, 0.71, 0.64 for primary school, middle school, high school, college degree or above subgroup, respectively). Findings suggest that the most socioeconomically deprived areas may be associated with a higher risk of advanced-stage lung cancer, and increasing educational level may be correlated with a lower risk to be diagnosed at advanced stage in both men and women. [ABSTRACT FROM AUTHOR]

Poor prognosis of advanced non-small-cell lung cancer ( NSCLC) patients and the promising therapeutic effect of platinum urge the oncologists to evaluate the role of platinum doublet as second-line chemotherapy and establish the definition of platinum sensitivity in NSCLC. We retrospectively analyzed 364 advanced NSCLC patients who received platinum-doublet regimens as second-line chemotherapy after platinum-based first-line treatment. Patients were divided into four groups by their time-to-progression ( TTP) after first-line chemotherapy: 0-3, 4-6, 7-12, and >12-month group, respectively. Treatment efficacy of patients' overall survival ( OS), progression-free survival ( PFS), and response rate ( RR), as well as treatment-related toxicity, were compared among the four groups. A prognosis score system and a nomogram were established by Cox proportional hazard model, and validated by concordance index (c-index). Median OS was 14.0, 16.0, 20.0, 25.0 months for patients in the 0-3, 4-6, 7-12, >12-month group, respectively. Age ≤60 years ( P = 0.002), female ( P = 0.019), and TTP>12 months ( P = 0.003) were independent prognostic factors. Prognostic score was calculated by adding 1 point each for any of the above three indicators, with a c-index of 0.590 (95% confidential interval [ CI], 0.552-0.627). Median OS were equal to 25.0, 16.0, and 11.0 months for best (2-3 points), intermediate (1 point) and worst (0 point) category, respectively ( P < 0.0001). A nomogram that integrated patient's age, gender, and TTP for OS has a c-index of 0.623 (95% CI, 0.603-0.643). Female, younger than 60 years, and TTP greater than 12 months may indicate prolonged survival after platinum-doublet second-line chemotherapy in advanced NSCLCpatients. [ABSTRACT FROM AUTHOR]