Assessment of Folate Receptor-α and Epidermal Growth Factor Receptor Expression in Pemetrexed-Treated Non–Small-Cell Lung Cancer Patients

IntroductionFolate receptor-α regulates cellular uptake of folates and antifolates (eg, pemetrexed) and is frequently expressed in pulmonary adenocarcinoma. EGFR is an established therapeutic target in NSCLC. Therapies targeting FRA or EGFR are available. The association between FRA and EGFR expression in advanced NSCLC has not been explored. Combining therapeutic FRA antibodies with an EGFR inhibitor might be beneficial, if both of the targets are significantly coexpressed.Patients and MethodsSpecimens from 160 advanced NSCLC patients receiving pemetrexed-based chemotherapy were assessed for membranous FRA and EGFR protein expression using immunohistochemistry and the Hybrid (H)-score. EGFR (exons 18-21) and Kirsten RNA-associated rat sarcoma 2 virus (exon 2) mutations were determined. Results were correlated to patients' clinicopathological data, progression-free survival (PFS), and overall survival (OS).ResultsForty-seven patients (29%) had tumors with strong FRA and EGFR expression, but no statistically significant correlation was seen between protein levels of FRA and EGFR. High membranous FRA expression (H-score ≥ 20) was associated with prolonged PFS (5.5 vs. 3.4 months; hazard ratio [HR], 0.6060; P = .0254) and improved OS (12.1 vs. 6.4 months; HR, 0.5726; P = .0076).ConclusionSurvival times are improved in NSCLC patients whose tumors show strong membranous FRA expression. No statistical correlation between membranous FRA and EGFR expression was demonstrated in advanced NSCLC, but 47 patients (29%) had higher expression of both of the receptors and could be suitable for combined targeted therapies.     

Current Data with Pemetrexed in Non–Small-Cell Lung Cancer

Pemetrexed (Alimta®) is a novel multitargeted antifolate that inhibits 3 enzymes involved in folate metabolism and purine and pyrimidine synthesis. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent has broad antitumor activity in phase II trials in a wide variety of solid tumors. In non–small-cell lung cancer (NSCLC), single-agent activity has been documented in the first- and second-line settings. Promising activity has also been demonstrated when pemetrexed is combined with cisplatin and gemcitabine. A pivotal phase III study in mesothelioma has been presented, indicating the superiority of pemetrexed in combination with cisplatin versus cisplatin alone in this disease. Approval for pemetrexed in combination with cisplatin in advanced mesothelioma is expected within the next 12 months. This review discusses the activity of pemetrexed in NSCLC.     

Importance of Quality of Life in Patients with Non–Small-Cell Lung Cancer

The therapeutic options for patients with advanced non–small-cell lung cancer (NSCLC) are palliative. Therefore, the quality of life in oncology is considered as an endpoint in clinical trials, and several scales have been accepted for its measurement in parallel with other clinical determinations. However, its use in clinical practice is hindered by various obstacles that need to be overcome. In this article we examine the concept of the quality of life in patients with NSCLC, as well as giving an evaluation and interpretation of the results of various clinical trials. We describe the new technological methods used in daily clinical practice to measure the quality of life.     

Expression and Clinicopathologic Significance of Proteolysis-Inducing Factor in Non–Small-Cell Lung Cancer: An Immunohistochemical Analysis

BackgroundProteolysis-inducing factor (PIF) is a 24-kD glycoprotein that has been identified in mice and in humans with cancer cachexia. The PIF is a putative mediator of cancer-associated weight loss, which induces atrophy of skeletal muscle.Materials and MethodsIn this study, we detected the expression of the PIF in 71 patients with non–small-cell lung cancer (NSCLC) and 10 patients with healthy lung tissues as a control group using the immunohistochemical staining method. In addition, weight loss of patients and serum carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) were measured, and an analysis of overall survival was done.ResultsProteolysis-inducing factor was expressed in only 56.3% (40/71) of lung cancers and not in normal tissue. The positive rate of the PIF expression was significantly higher (P < .01) in patients with weight loss than in those without weight loss. There was no significant relationship (P > .05) between the PIF expression and the histology type, degree of differentiation, or tumor clinical stages in lung cancers. The sensitivity of the PIF was better than that of CEA (P < .05), but similar to that of CYFRA 21-1 in NSCLC.ConclusionProteolysis-inducing factor expression was negatively related to the survival of patients with NSCLC in the medium to advanced stages (II-IV). There was a significant correlation between weight loss and survival in the PIF-positive patients.     

Clinical and Imaging Features of Non–Small-Cell Lung Cancer in Young Patients

BackgroundNon–small-cell lung cancer (NSCLC) in young adult patients is rare, with scarce data available in patients aged < 40 years and even less in those aged < 35 years. Our goal was to determine the presenting symptoms, clinicopathologic characteristics, and imaging features of young patients with NSCLC at time of diagnosis and compare them to those of older adults.Patients and MethodsWe retrospectively analyzed the medical records and imaging of young patients (≤ 40 years old) with NSCLC treated at our institution between 1998 and 2018. Patients < 35 years old were compared to those between 35 and 40 years old. Characteristics of patients ≤ 40 years old were compared to older patients (> 40 years) from publicly available data sets.ResultsWe identified 166 young patients with NSCLC (median age, 36.6 years; range, 18-40 years). Most presented with nonspecific respiratory symptoms and were diagnosed with pneumonia (84/136, 62%). Compared to patients < 35 years old, patients 35-40 years old were more likely to have malignancy detected incidentally (15% vs. 5%, P = .04). Patients < 35 years old were more likely to have central tumors (55% vs. 33%, P = .02) and to have bone (38% vs. 19%, P = .007) and lung (39% vs. 24%, P = .03) metastases. Compared to older patients (> 40 years), young patients were more likely to be never smokers (65.0% vs. 14.7%, P < .001) and to have advanced disease (88% vs. 66%, P < .001).ConclusionYoung patients with NSCLC often present with nonspecific symptoms and have advanced disease at diagnosis, often mimicking other pathologies. Awareness of the clinical presentation and imaging features of NSCLC in young patients may help minimize delays in diagnoses.     

Soluble c-Met Levels Correlated With Tissue c-Met Protein Expression in Patients With Advanced Non–Small-Cell Lung Cancer

Background

Immunohistochemistry (IHC) and fluorescent in situ hybridization are reliable methods for identifying c-Met protein expression or c-Met gene amplification. However, each technique requires a high-quality tissue sample, which might not be available. The aim of the present study was to investigate the correlation between the soluble c-Met level and tissue c-Met protein expression and the relationship between these markers and patient prognosis.

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non–Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab

IntroductionData on the risk factors for symptomatic radiation pneumonitis (RP) in non–small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors.Materials and MethodsThis multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP.ResultsIn the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007).ConclusionThe incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.