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Abstract: Introduction: To compare adequacy of tissue acquisition for EGFR DNA mutation analysis and the resulting complications in CT-guided lung biopsy cases with either 18-gauge or 20-gauge core biopsy needle. Methods: Forty-seven patients with advanced staged non-small cell lung cancers who were failure-treated by conventional chemotherapy were retrospectively reviewed. All had received CT-guided core needle lung biopsy for histology diagnosis and freshly frozen for EGFR mutation analysis before targeted therapy. We compared the complications resulting from these CT-guided lung biopsies and the specimen assessment using 18-gauge (32 patients) or 20-gauge (15 patients) biopsy needle via 17-gauge or 19-gauge coaxial needle. Results: With an overall pneumothorax rate of 12.8%, pneumothorax occurred in 12.5% and 13.3% of patients by 17-gauge and 19-gauge coaxial needles respectively. The overall rate of hemoptysis was 6.4%, with 6.3% by 18-gauge biopsy needle and 6.6% by 20-gauge biopsy needle. Large peritumoral hemorrhage revealed only in 2 cases of those completed with 18-gauge biopsy needles. 18-gauge biopsy needle obtained larger specimens with heavier weight (average 10.15mg vs 9mg) and higher DNA concentration (average 47.13ng/ul vs 35.92ng/ul) than 20-gauge biopsy needle. Otherwise, the range of optical density (1.67–2.09) was more constant in the specimens by 20-gauge biopsy needles. Mutation demonstration was achieved for all samples. Conclusion: CT-guided core needle biopsy is a feasible technique in acquisition of fresh cancer tissues for EGFR gene mutation analysis. The specimen is adequate for gene demonstration either using 18-gauge or 20-gauge tru-cut biopsy needles via 17-gauge or 19-gauge coaxial needles. [Copyright &y& Elsevier]

Summary: To evaluate the association of epidermal growth factor receptor (EGFR) gene copy number with EGFR and k-ras mutation status and tyrosine kinase inhibitor (TKI) sensitivity in non-small cell lung cancer (NSCLC), EGFR gene copy number of 182 NSCLC tumor specimens were analyzed by chromogenic in situ hybridization (CISH). EGFR and k-ras mutation analyses were also performed for, respectively, 176 and 157 of the 182 patients. Additionally, 36 patients in this study had received TKI monotherapy. The tumor was considered to be CISH positive if the gene copy number was ≥5 signals per nucleus in ≥40% of tumor cells. CISH-positive tumors were strongly associated with adenocarcinoma (56.8%) compared with squamous cell carcinoma (15.9%) (p <0.0001). The CISH-positive tumors were also strongly associated with EGFR mutations (78%) compared with wild type (20.2%) (p <0.0001). Only six tumors had k-ras mutations. None had EGFR mutation and only one was CISH positive. In the patients treated with TKI, EGFR mutation was strongly associated with TKI responsiveness (22/25 responders) (p <0.0001), but the CISH-positive tumors were only marginally significant (18/25 responders) (p =0.0665). Patients with EGFR mutations or CISH-positive tumors were all associated with longer median survival, although not statistically significant. Our results suggest Increased EGFR copy number was highly correlated with EGFR mutation in adenocarcinoma. Although it is less correlated with TKI responsiveness when compared with EGFR mutations, it still could be a good alternative molecular predictive marker for TKI responsiveness, since CISH can be done on paraffin section and is much quicker than DNA sequencing. [Copyright &y& Elsevier]

Summary: Purpose: Failure to gefitinib is generally believed to be associated with cross-resistance to other epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Here we report a case whose active EGFR-mutant NSCLC responded to erlotinib treatment. Patient and methods: Lung specimen was obtained during diagnostic procedures from a 41-year-old Taiwanese male smoker with adenocarcinoma. He received cisplatin-based chemotherapy following craniotomy to remove his brain metastasis. Tumor progressed in both lung and left adrenal gland. He underwent second-line docetaxel chemotherapy. Tumor progressed again 7 months later. He was subsequently treated with gefitinib 250mg QD. Complete regression of the lung tumor and partial response of the left adrenal gland mass was achieved. Nine months later, the left lower lobe lung tumor and left adrenal gland tumor progressed. A lung biopsy from the left lower lobe disclosed an adenocarcinoma which harbored an in-frame deletion in exon 19 (heterozygous delE746-A750) of EGFR without a second mutation such as T790M in exon 20. Subsequent erlotinib 150mg QD was administered. He experienced grade 1 skin rash, diarrhea and paronychia following erlotinib. Results: This patient achieved a partial response to erlotinib treatment. He remained on erlotinib for a total of 18 months until the left adrenal gland tumor progressed. Conclusions: This case demonstrated that NSCLC bearing in-frame deletion in exon 19 of EGFR may respond to erlotinib treatment following gefitinib failure. [Copyright &y& Elsevier]