Chi-Lu Chiang

Should EGFR mutations be tested in advanced lung squamous cell carcinomas to guide frontline treatment

There is no argument over using epidermal growth factor receptor (EGFR) mutation status to guide the frontline treatment for advanced lung adenocarcinoma (LADC); however, the role of the testing in lung squamous cell carcinoma (LSQC) remains controversial. Currently, the guidelines/consensus statements regarding EGFR mutation testing in LSQC are not consistent among different oncology societies. American Society of Clinical Oncology recommends performing EGFR mutation testing in all patients; European Society for Medical Oncology, College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology, and National Comprehensive Cancer Network suggest for some selected group. EGFR mutation is rarely found in LSQC; however, more importantly, it is not a valid predictive biomarker for EGFR tyrosine kinase inhibitors (EGFR-TKI) in LSQC as it has been shown in LADC. Available data showed that the response rate and progression-free survival in EGFR mutant LSQC patients treated with EGFR-TKI are not better than that observed in patients treated with platinum-doublet chemotherapy in the first-line setting. Therefore, in contrast to advanced LADC, EGFR mutation testing may not be necessarily performed upfront in advanced LSQC because not only the mutation rate is low, but also the predictive value is insufficient. For LSQC patients with known sensitizing-EGFR mutations, both conventional chemotherapy and EGFR-TKI are acceptable frontline treatment options.

Clinical Characteristics and Treatment Outcomes of Lung Adenocarcinomas with Discrepant EGFR Mutation Testing Results Derived from PCR-Direct Sequencing and Real-Time PCR-Based Assays

Introduction: Detection of epidermal growth factor receptor (EGFR) mutation has become the most critical molecular test in managing patients with advanced lung adenocarcinoma. Whether patients with discrepant EGFR mutation results determined by low- and high-sensitivity methods have different clinical outcomes with EGFR tyrosine kinase inhibitor (TKI) treatment needs to be further evaluated. Methods: Genomic DNA from serial lung adenocarcinoma samples that were EGFR wild-type determined by direct sequencing (DS) were reanalyzed using Scorpion/Amplification Refractory Mutation System (ARMS). The outcomes with EGFR-TKI treatment among patients with discrepant EGFR mutation results between DS and Scorpion/ARMS versus patients with EGFR mutations detected by DS were studied. Results: Of the 130 tumors studied, 28 (21.5%) were found to have EGFR mutations by Scorpion/ARMS. Discrepant EGFR mutation testing results were more common in samples from nonsmokers than in samples from smokers (30.7% versus 9.1%; p = 0.003) and in pleural than in nonpleural samples (62.5% versus 18.9%; p = 0.012). There was no significant difference in the abundance of cancer cells in region(s) selected for testing (26.2% in tumor cell percentage ⩽50 versus 16.9% in tumor cell percentage >50; p = 0.201). During EGFR-TKI treatment, the progression-free survival in patients with discrepant EGFR mutation results was similar to those with EGFR mutations detected by DS (median, 13.4 versus 10.9 months; p = 0.225). Conclusions: DS overlooked EGFR mutation in a significant number of lung adenocarcinoma patients. These patients could have obtained the same benefit from EGFR-TKI when a high-sensitivity method such as Scorpion/ARMS was applied.

Radiation recall pneumonitis induced by epidermal growth factor receptor-tyrosine kinase inhibitor in patients with advanced nonsmall-cell lung cancer.

Background Radiation recall pneumonitis (RRP) is a special form of radiation pneumonitis precipitated by certain pharmacological agents. Epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) is an effective treatment for advanced nonsmall‐cell lung cancer (NSCLC) and has been reported as a potent radiation sensitizer. The incidence and general characteristics of EGFR‐TKI‐related RRP in patients with NSCLC remain unclear. Methods Clinical records and serial chest images of consecutive patients with advanced NSCLC who had received thoracic radiotherapy (TRT) and EGFR‐TKI treatment were retrospectively reviewed. EGFR‐TKI‐related RRP was diagnosed according to history, clinical manifestations, and radiographic characteristics. Potential risk factors were analyzed. Results In total, 160 patients with NSCLC who received EGFR‐TKI after TRT were identified. Of these patients, seven (4.4%) developed EGFR‐TKI‐related RRP. The median time interval between the end of radiotherapy and RRP was 124 days (range, 80–635 days) and that between the initiation of EGFR‐TKI and RRP was 43 days (range, 18–65 days). No risk factor for the development of RRP was identified except that patients in whom EGFR‐TKI was initiated within 90 days after the completion of radiotherapy had significantly higher rates of RRP than those of patients who began receiving EGFR‐TKI treatment after 90 days (21% vs. 2.1%, p = 0.005). Conclusion In patients with NSCLC who have a history of TRT, treatment with EGFR‐TKI may induce not only interstitial lung disease but also RRP. Physicians should be aware of both unexpected adverse events when using EGFR‐TKI.

Effect of postoperative systemic therapy on pulmonary adenocarcinoma with unexpected pleural spread detected during thoracotomy or thoracoscopy

Background Occasionally, malignant pleural disease is only detected unexpectedly during surgery in patients with pulmonary adenocarcinoma. Previous studies mostly focused on the role of main tumor resection on patients outcome, barely addressing the position of postoperative systemic therapy. Methods The medical records of 5321 non-small cell lung cancer patients who underwent thoracic surgery between January 1990 and December 2012 were reviewed. Pulmonary adenocarcinoma patients with unexpected pleural spread noted during surgery were included. The clinical and postoperative treatment variables were assessed for correlation with overall survival. Results In 134 patients identified, main tumor resection was performed in 87 (64.9%) patients, while 89 (66.4%) and 57 (42.5%) patients received postoperative chemotherapy and epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR -TKI) therapy, respectively. Overall, the 5-year survival rate was 30.2% and median survival time was 29.3 months. Multivariate analysis showed main tumor resection and EGFR-TKI therapy were associated with better survival. Mutational status of EGFR was available in 57 patients and 43 (75.4%) had activating mutations. Resection of the main tumor conferred a better outcome in patients without EGFR mutation or with unknown EGFR mutation status and had not been treated with EGFR-TKI therapy (P = 0.003), but not in those with activating EGFR mutation and had been treated with EGFR-TKI (P = 0.857). Conclusions In pulmonary adenocarcinoma patients with unexpected pleural spread detected during surgery, main tumor resection and EGFR-TKI therapy correlated with better survival. Identifying EGFR mutation status before surgery can provide useful information for clinical decision during surgery.

The predictive value of the interferon-γ release assay for chemotherapy responses in patients with advanced non-small-cell lung cancer

OBJECTIVES IFN-γ takes part in immunologic responses to cancer and its interactions with chemotherapy have also been described. Our previous study had showed an association between phytohemagglutinin (PHA)-stimulated IFN-γ (PSIG) response and overall survival in patients with advanced non-small-cell lung cancer (NSCLC). Here, we aimed to evaluate the correlation between PSIG and chemotherapy responses. MATERIALS AND METHODS From January 2011 to August 2012, 340 newly diagnosed patients with lung cancer were enrolled in a prospective latent tuberculosis observational study. Patients with advanced NSCLC who were treated with chemotherapy were included in this analysis. An IFN-γ release assay (IGRA) was used to evaluate pre-treatment PSIG levels. Patients were grouped into low and high PHA response groups according to their PSIG levels. Their demographic characteristics, tumor responses, and survival rates were investigated. RESULTS Eighty-four patients were enrolled. The chemotherapy response rates in the high and low PHA response groups were 45.2% and 35.7% (p=0.190), respectively. The disease control rate in the high PHA response group was 76.2%, versus 52.4% in the low PHA response group (p=0. 023). In multivariate analysis, PHA response was an independent predictor of disease control (odds ratio=3.017, 95% confidence interval=1.115-8.165). The Kaplan-Meier method demonstrated both longer progression-free survival (p=0.008) and overall survival (p=0.003) in the high PHA response group. CONCLUSIONS A higher pre-treatment PSIG response, obtained using the IGRA, was associated with better disease control rate and survival among patients with advanced NSCLC treated with chemotherapy.