Epidermal Growth Factor Receptor Mutation-positive Adenocarcinoma Research Articles

Prognostic factors for survival in unresectable stage III EGFR mutation-positive lung adenocarcinoma: impact of pre-CCRT PET-CT

PurposeTo assess the survival impact of pre-concurrent chemoradiotherapy (CCRT) staging with positron emission tomography-CT (PET-CT) in patients with unresectable epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma.MethodsPatients with unresectable stage IIIA–IIIC...

The Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Predicting Treatment Response Before EGFR TKI Treatment in Patients with Advanced Lung Adenocarcinoma.

Objectives:This study makes a retrospective examination of exploring the prognostic value of 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) related metabolic-volumetric variables, nutritional status, and immune and inflammatory markers on progression-free survival (PFS) and overall survival (OS) in advanced adenocarcinoma patients with positive epidermal growth factor receptor (EGFR) mutations undergoing EGFR tyrosine kinase inhibitor (TKI) therapy.Methods:A retrospective examination was made of patients diagnosed with lung adenocarcinoma who underwent 18F-FDG PET/CT imaging for staging maximum four weeks before starting treatment, between January 2015 and July 2020. Included in the study were 68 patients identified histopathologically to have locally advanced/metastatic EGFR mutation-positive adenocarcinoma, and who underwent EGFR TKI therapy. The laboratory data of the patients, obtained 15 days before imaging performed for PET/CT staging, were evaluated.Results:Metabolic tumor volume, modified Glasgow prognostic score and locally advanced disease were identified as independent prognostic parameters for PFS (p=0.004, p=0.029, p=0.016, respectively). A univariate Cox regression analysis revealed albumin/alkaline phosphatase and tumor size to be significant parameters for prognosis (p=0.033, p=0.043, respectively). A multivariate Cox regression analysis revealed that none of the parameters were predictive or OS.Conclusion:The parameters of 18F-FDG PET/CT, especially the volumetric parameters, were found to be strong prognostic factors with statistical significance for predicting PFS. We believe that these parameters are important prognostic markers that should be evaluated together in the management and follow-up of patients with EGFR mutation-positive adenocarcinoma.

Development of Brain Metastases in Patients With Non-Small Cell Lung Cancer and No Brain Metastases at Initial Staging Evaluation: Cumulative Incidence and Risk Factor Analysis.

BACKGROUND. Although established guidelines give indications for performing staging brain MRI at initial diagnosis of non-small cell lung cancer (NSCLC), guidelines are lacking for performing surveillance brain MRI for patients without brain metastases at presentation. OBJECTIVE. The purpose of this study is to estimate the cumulative incidence of and risk factors for brain metastasis development in patients with NSCLC without brain metastases at initial presentation. METHODS. This retrospective study included 1495 patients with NSCLC (mean [± SD] age, 65 ± 10 years; 920 men and 575 women) without brain metastases at initial evaluation that included brain MRI. Follow-up brain MRI was ordered at the discretion of the referring physicians. MRI examinations were reviewed in combination with clinical records for brain metastasis development; patients not undergoing MRI were deemed to have not had metastases develop through last clinical follow-up. The cumulative incidence of brain metastases was determined, with death considered a competing risk, and was stratified by clinical stage group, cell type, and epidermal growth factor receptor (EGFR) gene mutation status. Univariable and multivariable Cox proportional hazards regression analyses were performed. RESULTS. A total of 258 of 1495 patients (17.3%) underwent follow-up brain MRI, and 72 (4.8%) had brain metastases develop at a median of 12.3 months after initial diagnosis of NSCLC. Of the 72 patients who had metastases develop, 44.4% had no neurologic symptoms, and 58.3% had stable primary thoracic disease. The cumulative incidence of brain metastases at 6, 12, 18, and 24 months after initial evaluation was 0.6%, 2.1%, 4.2%, and 6.8%, respectively. Cumulative incidence at 6, 12, 18, and 24 months was higher (p < .001) in patients with clinical stage III-IV disease (1.3%, 3.9%, 7.7%, and 10.9%, respectively) than in those with clinical stage I-II disease (0.0%, 0.8%, 1.2%, and 2.6%, respectively), and it was higher (p < .001) in patients with EGFR mutation-positive adenocarcinoma (0.7%, 2.5%, 6.3%, and 12.3%, respectively) than in those with EGFR mutation-negative adenocarcinoma (0.4%, 1.8%, 2.9%, and 4.4%, respectively). Among 1109 patients with adenocarcinoma, independent risk factors for the development of brain metastasis were clinical stage III-IV (hazard ratio [HR], 9.39; p < .001) and EGFR mutation-positive status (HR, 1.78; p = .04). The incidence of brain metastasis over the study interval was 8.7% among patients with clinical stage III-IV disease and 17.4% among those with EGFR mutation-positive adenocarcinoma. CONCLUSION. Clinical stage III-IV and EGFR mutation-positive adenocarcinoma are independent risk factors for brain metastasis development. CLINICAL IMPACT. For patients with clinical stage III-IV disease or EGFR mutation-positive adenocarcinoma, surveillance brain MRI performed 12 months after initial evaluation may be warranted.

Diagnostic Yield of Staging Brain MRI in Patients with Newly Diagnosed Non-Small Cell Lung Cancer.

Background Existing guidelines are inconsistent regarding the indications for staging brain MRI in patients with newly diagnosed, early-stage non-small cell lung cancer (NSCLC). Purpose To evaluate the diagnostic yield of staging brain MRI in the initial evaluation of lung cancer. Materials and Methods This retrospective, observational, single-institution study included patients with newly diagnosed NSCLC who underwent staging chest CT and staging brain MRI from November 2017 to October 2018. Diagnostic yield was defined as the proportion of patients with brain metastases among all patients. Yield was stratified into clinical stage groups per the eighth edition of the American Joint Committee on Cancer staging guidelines, based on staging chest CT and in adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) gene rearrangement. Subgroup analyses were performed on the basis of cell types and molecular markers. The χ2 test was performed to compare the diagnostic yields, and Bonferroni correction was used to account for multiple testing between stage groups. Results A total of 1712 patients (mean age, 64 years ± 10 [standard deviation]; 1035 men) were included. The diagnostic yield of staging brain MRI in newly diagnosed NSCLC was 11.9% (203 of 1712; 95% confidence interval [CI]: 10.4%, 13.5%). In clinical stage IA, IB, and II disease, the diagnostic yields were 0.3% (two of 615; 95% CI: 0.0%, 1.2%), 3.8% (seven of 186; 95% CI: 1.5%, 7.6%), and 4.7% (eight of 171; 95% CI: 2.0%, 9.0%), respectively. The diagnostic yield was higher in patients with adenocarcinoma (13.6%; 176 of 1297; 95% CI: 11.8%, 15.6%) than squamous cell carcinoma (5.9%; 21 of 354; 95% CI: 3.7%, 8.9%) and in patients with EGFR mutation-positive adenocarcinoma (17.5%; 85 of 487; 95% CI: 14.2%, 21.1%) than with EGFR mutation-negative adenocarcinoma (10.6%; 68 of 639; 95% CI: 8.4%, 13.3%) (P < .001 for both). Conclusion The diagnostic yield of staging brain MRI in clinical stage IA non-small cell lung cancer was low, but staging brain MRI had a higher diagnostic yield in clinical stage IB and epidermal growth factor receptor mutation-positive adenocarcinoma. © RSNA, 2020 Online supplemental material is available for this article.

Retreatment with erlotinib of a patient with metastatic NSCLC harboring EGFR mutation: a case report.

Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used for the treatment of advanced stage non-small cell lung cancer (NSCLC). Clinical trials have shown high efficacy of erlotinib, particularly in patients harboring activating mutations in the EGFR gene. Here we describe the case of a 42-year-old female light smoker diagnosed with EGFR mutation-positive adenocarcinoma of the left lung with pleural metastases, pleural effusion and metastases to the thoracic vertebrae (stage IV, T4NXM1). Although the patient developed resistance to erlotinib in the first line, she achieved disease stabilization lasting for 13 months as a response to erlotinib retreatment after 6 cycles of second-line chemotherapy. In conclusion, retreatment with erlotinib in our patient was effective. Therefore it should be considered as a good treatment option for patients with NSCLC harboring EGFR mutation.

How sensitive are epidermal growth factor receptor tyrosine kinase inhibitors for squamous cell carcinoma of the lung harboring epidermal growth factor receptor gene–sensitive mutations?

7609 Background: The efficacy of epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs; gefitinib and erlotinib) has been demonstrated in patients with non-small cell lung cancers (NSCLC) harboring EGFR sensitive mutations. EGFR mutations are found in 30-40% of adenocarcinoma, but rarely in other histologic subtypes. EGFR mutations are occasionally found in squamous cell carcinoma (SCC) in our clinical practice. However, there is little data demonstrating the efficacy of EGFR-TKIs in SCC harboring EGFR mutations. Methods: We investigated the frequency of EGFR mutation positive SCC of the lung between April 2006 and October 2010. The efficacy of EGFR-TKIs in lung cancer patients with SCC harboring EGFR mutations was retrospectively evaluated. Results: Thirty of 249 patients with SCC (13.3%) had EGFR mutations. The types of EGFR mutation were exon 19 deletion (19/33, 58%), L858R point mutation in exon 21 (12/33, 36%), and G719S point mutation in exon 18 (2/33, 6%). Twenty of these 33 patients were treated with EGFR-TKIs (gefitinib 18; erlotinib 2). Five of 20 EGFR mutation positive patients responded to EGFR-TKIs with the response rate of 25.0% (95% confidence interval [CI], 8.7 to 49.1%). Median progression-free survival (PFS) and median overall survival were 1.4 months (95% CI, 0.7 to 5.8 months), and 14.6 months (95% CI, 2.9 months to undeterminable), respectively. Approximately one third of EGFR mutation positive SCC patients obtained PFS greater than six months. Conclusions: Although EGFR-TKIs seem to be less effective in EGFR mutation positive SCC than EGFR mutation positive adenocarcinoma, some EGFR mutation positive patients with SCC can obtain clinical benefit from EGFR-TKIs. EGFR mutational analysis is recommended even in patients with SCC to select and treat patients properly.