Advanced non-Small cell lung cancer patients at the extremes of age in the era of epidermal growth factor receptor tyrosine kinase inhibitors

Chen, Yu‐Mu; Lai, Chia-Yun; Rau, Kun‐Ming; Huang, Cheng-Hua; Chang, Huang‐Chih; Chao, Tung‐Ying; Tseng, Chia‐Cheng; Fang, Wen‐Feng; Chen, Yung‐Che; Chung, Yoon Kyu; Wang, Yi‐Hsi; Su, Mu-Chun; Huang, Kuo‐Tung; Liu, Shih-Feng; Chen, Hung-Chen; Chang, Yu‐Ling; Chang, Yu-Ping; Wang, Chin‐Chou

doi:10.1016/j.lungcan.2016.05.020

Cited by 13 publications

(7 citation statements)

References 33 publications

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“…The results were consistent with a previous study that identified a higher mutation frequency in female patients compared with male patients with squamous cell carcinoma (23). Furthermore, Ueno et al and Chen et al (23,32) concluded that there was no distinct association between EGFR mutation frequency and age; the results of the present study were consistent with this Table VIII. Characteristics and EGFR gene mutation rate of patients with squamous cell carcinoma.…”

Section: Egfr Gene Mutation Type N ---------------------------------supporting

confidence: 93%

Methodological comparison of the allele refractory mutation system and direct sequencing for detecting EGFR mutations in NSCLC, and the association of EGFR mutations with patient characteristics

Pan

et al. 2018

Oncol Lett

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Gefitinib is effective for patients with non-small cell lung cancer (NSCLC) with a mutation in the epidermal growth factor receptor (EGFR) gene, which makes the detection of EGFR mutations a critical step prior to determining a treatment schedule. Therefore, the present study determined the EGFR mutation status in patients with NSCLC using an allele refractory mutation system (ARMS) and analyzed the detection ratio for different specimen types. A total of 1,596 NSCLS samples were collected and EGFR gene mutations were detected on exons 18-21 using ARMS and direct sequencing. The concordance of two methods reached 89.21%, with a total mutation rate of 45.55% (727/1,596), in which the mutation rate in lung adenocarcinoma samples was markedly increased compared with squamous cell carcinoma (51.77 vs. 8.68%). In patients with lung adenocarcinoma, EGFR mutations were more frequent in female patients than male patients (65.53 vs. 39.80%, P<0.01); there was no observable difference depending on age. Similar results were obtained for squamous cell carcinoma. In the present study, certain rare mutations were also identified; these may be subjects for further study. The impact of different sample types on the consistency between the methods was determined to be insignificant. ARMS is a more applicable approach for large-scale clinical detection than direct sequencing, and we hypothesize that ARMS may replace direct sequencing if the drawbacks of ARMS, including its narrow detection range, can be amended.

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Section: Egfr Gene Mutation Type N ---------------------------------supporting

confidence: 93%

Methodological comparison of the allele refractory mutation system and direct sequencing for detecting EGFR mutations in NSCLC, and the association of EGFR mutations with patient characteristics

Pan

et al. 2018

Oncol Lett

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“…However, the authors did not present data regarding other concurrent metastatic sites. Chen et al found that patients younger than 40 years of age were more likely to have brain, bone, liver, and pleural metastasis [21]. Furthermore, NSCLC patients with ALK gene rearrangement and EGFR mutations are more likely to have liver metastasis compared to patients without ALK gene rearrangement, EGFR mutation, and KRAS mutation [22].…”

Section: Discussionmentioning

confidence: 99%

The impact of de novo liver metastasis on clinical outcome in patients with advanced non-small-cell lung cancer

et al. 2017

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Liver metastasis has been found to affect outcome in prostate cancer and colorectal cancer, but its role in lung cancer is unclear. The current study aimed to evaluate the impact of de novo liver metastasis (DLM) on stage IV non-small cell lung cancer (NSCLC) outcomes and to examine whether tyrosine kinase inhibitors (TKI) reverse poor prognosis in patients with DLM and epidermal growth factor receptor (EGFR)-mutant NSCLC. Among 1392 newly diagnosed NSCLC patients, 490 patients with stage IV disease treated between November 2010 and March 2014 at Kaohsiung Chang Gung Memorial Hospital were included. Patients were divided into two groups according to DLM status. There were 75 patients in the DLM group and 415 patients in the non-DLM group. The DLM group included more patients with bone metastasis, fewer patients with a lymphocyte-to-monocyte ratio (LMR) > 3.1, and fewer patients with pleural metastasis. In the DLM group, Eastern Cooperative Oncology Group performance status 3–4 and LMR ≦3.1 were associated with poor outcome. In patients without DLM, overall survival (OS) was longer in patients with EGFR-mutant NSCLC than in those without (20.2 vs. 7.3 months, p < 0.001). Among DLM patients, OS was similar between the EGFR-mutant and wild-type EGFR tumor subgroups (11.9 vs. 7.7 months, p = 0.155). We found that DLM was a significant poor prognostic factor in the EGFR-mutant patients treated with EGFR-TKIs, whereas DLM did not affect the prognosis of EGFR-wild-type patients.

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“…In United States, the incidence rate of lung cancer peaked at the age of 80–84 years in males and 75–79 years in females and then gradually decreased (Dela Cruz, Tanoue, & Matthay, ); in UK, the incidence rate of lung cancer peaked at the age of 85–89 years in males and 80–85 years in females (Data from CRUK); and in China, the incidence of lung cancer peaked at the age group of 60–74 years both in males and females, and then gradually decreased in individuals over 75 years old, and also for the mortality rate (Chen, Zheng, et al, ). Notably, advanced lung cancer associated with a worse prognosis is more frequently reported in younger versus older patients and the underlying mechanism is currently unknown (Bourke et al, ; Chen, Lai, et al, ). Studies using a murine B16 lung melanoma metastasis model demonstrated fewer pulmonary colonies and slower growth in the lungs and longer survival in aged mice (Chen et al, ; Ershler, Stewart, Hacker, Moore, & Tindle, ).…”

Section: Introductionmentioning

confidence: 99%

Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly

et al. 2020

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Cancer is an age-associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung-resident γδT cells was significantly increased with altered gene expression in aged mice (20-24 months) versus young mice (10-16 weeks). Aged lung Vγ4 + and Vγ6 + γδT cells predominantly produced interleukin-17A (IL-17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4 + and Vγ6 + γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103.The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL-17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL-17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the antitumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co-housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age-dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti-tumor immunotherapy.

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Advanced non-Small cell lung cancer patients at the extremes of age in the era of epidermal growth factor receptor tyrosine kinase inhibitors

Cited by 13 publications

References 33 publications

Methodological comparison of the allele refractory mutation system and direct sequencing for detecting EGFR mutations in NSCLC, and the association of EGFR mutations with patient characteristics

Methodological comparison of the allele refractory mutation system and direct sequencing for detecting EGFR mutations in NSCLC, and the association of EGFR mutations with patient characteristics

The impact of de novo liver metastasis on clinical outcome in patients with advanced non-small-cell lung cancer

Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly

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