Epidermal Growth Factor Receptor Mutations and Prognosis in Pathologic N1-N2 Pulmonary Adenocarcinoma

Isaka, Tetsuya; Nakayama, Haruhiko; Yokose, Tomoyuki; Ito, Hiroyuki; Miyagi, Yohei; Matsuzaki, Tomohiko; Nagata, Michio; Furumoto, Hideyuki; Nishii, Teppei; Katayama, Kazuhisa; Yamada, Katsushi; Masuda, Munetaka

doi:10.1016/j.athoracsur.2016.06.001

Cited by 14 publications

(18 citation statements)

References 34 publications

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“…We identified four studies that may lead to heterogeneity. 11 , 35 , 36 , 43 No obvious heterogeneity was noted among the studies after excluding four studies ( I 2 =32%, p =0.13). The remaining 13 studies were subject to meta-analysis using fixed-effect model, and the combined HR was 0.77 (95% CI 0.66–0.90, p =0.001; Figure 2B ).…”

Section: Resultsmentioning

confidence: 94%

“…DFS Seventeen studies with 5,261 patients assessed the relationship between EGFR mutations and DFS, 11 , 13 , 22 , 25 , 29 , 31 , 32 , 34 – 38 , 42 – 44 , 46 , 47 and six studies demonstrated that EGFR mutations positively influenced the DFS of resected NSCLC patients. 13 , 25 , 35 , 42 , 43 , 47 Significant heterogeneity was observed between these studies ( I 2 =72%, p <0.00001; Figure S1 ). We used sensitivity analysis to explore the sources of heterogeneity ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 96%

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Prognostic value of EGFR and KRAS in resected non-small cell lung cancer: a systematic review and meta-analysis

Zhang¹,

Zhu²,

Ding³

et al. 2018

CMAR

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BackgroundThe prognostic value of EGFR and KRAS mutations in resected non-small cell lung cancer (NSCLC) has been reported. However, conflicting results were reported in these studies. The effect of mutations in these two genes in resected NSCLC remains controversial.MethodsWe searched Internet databases for studies reporting disease-free survival (DFS) and overall survival (OS) in resected NSCLC patients with EGFR or KRAS mutations. A meta-analysis calculating the pooled hazard ratio (HR) for DFS and OS was used to measure the association of EGFR or KRAS mutations with the prognosis of patients after surgery.ResultsA total of 9,635 patients from 32 studies were included in this analysis. The combined HR for EGFR mutations on DFS was 0.77 (95% CI 0.66–0.90, p=0.001) and on OS was 0.72 (95% CI 0.66–0.80, p<0.00001). In addition, the combined HR for KRAS mutations on DFS was 1.5 (95% CI 1.15–1.96, p=0.002) and on OS was 1.49 (95% CI 1.28–1.73, p<0.00001). Sensitivity analysis, subgroup analysis, and bias analysis proved the stability of the results.ConclusionThe analysis showed that EGFR mutations were significantly associated with DFS and OS. These findings indicated that surgically treated NSCLC patients with EGFR mutations were inclined to exhibit a prolonged DFS and OS. In addition, the results indicated that KRAS mutations predicted worse DFS and OS in patients with resected NSCLC.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 96%

Prognostic value of EGFR and KRAS in resected non-small cell lung cancer: a systematic review and meta-analysis

Zhang¹,

Zhu²,

Ding³

et al. 2018

CMAR

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“…It is important to know the EGFR status of lung cancer because it provides important information on the responsiveness of patients with unresectable advanced lung cancer to tyrosine kinase inhibitors as well as the prognosis of patients with resectable lung cancer following curative resection of the lung. [22][23][24] Moreover, it is often useful in a supplementary diagnosis to distinguish metachronous lung cancer from recurrent lung cancer by comparing the EGFR mutation statuses of the primary and secondary lung cancers. 25,26 Yatabe et al previously reported the homogeneous distribution of EGFR gene mutations in a single lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Detection of tumor spread through airspaces by airway secretion cytology from resected lung cancer specimens

Isaka

Yokose

Miyagi

et al. 2017

Pathology International

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It currently remains unclear whether tumor spread through airspaces (STAS) actually exist in vivo or are an artifact. The morphologies of STAS and tumor cell clusters in airway secretions collected from the segmental or lobar bronchus of resected lung adenocarcinomas and squamous cell carcinomas were compared among 48 patients. The EGFR status of tumor cell clusters in airway secretions was also compared with that of the main tumor in EGFR mutant adenocarcinomas. Tumor cell clusters were observed in the airway secretion cytology of ten patients (20.8%), and eight patients were adenocarcinoma (20.0% of adenocarcinoma). The morphology of STAS closely resembled that of tumor cell clusters detected in airway secretion cytology. The positive rates of airway secretion cytology were 83.3%, 100%, and 50% in papillary adenocarcinoma, micropapillary adenocarcinoma, and invasive mucinous adenocarcinoma, respectively. Among three EGFR mutant adenocarcinomas, the EGFR mutation subtypes of the main tumors in FFPE sections and tumor cell clusters in airway secretions were identical. These indicate that STAS may be detected in the airway secretion cytology. STAS is common in papillary or micropapillary adenocarcinoma and may spread as far as the segmental or lobar bronchus at the time of surgery.

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“…It is to be noted that both EGFR mutation subtypes promoted lung adenocarcinomas with lepidic growth features in transgenic mice (13). Table 1 summarizes ten studies that reported a relationship between EGFR mutation subtypes and prognosis (4,5,11,(14)(15)(16)(17)(18)(19)(20)(21). In focusing on the association between DFS or recurrence and EGFR mutation subtype, Liu et al also reported that patients with Stage I-IIIA lung adenocarcinoma harboring Ex19 had a better DFS rate than those with Ex21 (P=0.056) (14).…”

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confidence: 99%

“…In the study by Isaka et al published in the Annals of Thoracic Surgery, the authors demonstrated that different EGFR mutation subtypes were associated with different prognoses among patients with surgically resected pathologic N1-N2 lung adenocarcinoma (11). This Editorial Comment on prognostic value of epidermal growth factor receptor mutation subtypes in surgically resected non-small cell lung cancer meaningful work showed that patients with Ex19 displayed statistically significant better 5-year disease-free survival (DFS) rate (38.8%) than those with Ex21 (11.8%, P=0.001).…”

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confidence: 99%

Comment on prognostic value of epidermal growth factor receptor mutation subtypes in surgically resected non-small cell lung cancer

et al. 2017

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Epidermal Growth Factor Receptor Mutations and Prognosis in Pathologic N1-N2 Pulmonary Adenocarcinoma

Abstract: For pN1-N2 pulmonary adenocarcinoma, Ex21 mutation was associated with poorer prognosis than Ex19 mutation. Thus, EGFR mutation status should be considered when predicting prognosis.

Cited by 14 publications

References 34 publications

Prognostic value of <em>EGFR</em> and <em>KRAS</em> in resected non-small cell lung cancer: a systematic review and meta-analysis

Prognostic value of <em>EGFR</em> and <em>KRAS</em> in resected non-small cell lung cancer: a systematic review and meta-analysis

Detection of tumor spread through airspaces by airway secretion cytology from resected lung cancer specimens

Comment on prognostic value of epidermal growth factor receptor mutation subtypes in surgically resected non-small cell lung cancer

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