Non–Small Cell Lung Cancer with Resistance to EGFR-TKI Therapy: CT Characteristics of T790M Mutation–positive Cancer

Abstract

Purpose To evaluate the clinical and CT characteristics of T790M mutation-positive non-small cell lung cancer (NSCLC) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy failure. Materials and Methods A retrospective study of 304 patients with NSCLC who underwent rebiopsy after first-line EGFR-TKI therapy was conducted. Rebiopsy methods included CT- or fluoroscopy-guided lung biopsies (n = 105), endobronchial US- or bronchofibroscopy-guided biopsies (n = 66), pleural fluid analysis (n = 47), other solid organ biopsies (n = 43), US-guided axillary or supraclavicular lymph node biopsies (n = 31), and cerebrospinal fluid analysis (n = 12). CT findings at the initial diagnosis and rebiopsy were analyzed. Progression-free survival, the duration from the start of TKI therapy to rebiopsy, and survival were calculated. Results At rebiopsy, 144 (47.4%) patients were T790M mutation positive. The percentages of T790M mutation-positive NSCLCs were similar in 106 patients with rebiopsy of the lungs (53 [50%] of 106) and in 77 patients with rebiopsy of the primary lung lesions (36 [47%] of 77). T790M mutation positivity was associated with peripheral tumors (odds ratio [OR], 2.6; P = .01), pleural tag (OR, 5.0; P < .001), and air bronchogram (OR, 4.0; P = .006) at CT after TKI failure. The duration from the start of TKI therapy to rebiopsy was longer in T790M mutation-positive than in T790M mutation-negative patients (20.5 vs 13.6 months; P < .001). Cumulative survival from the time of rebiopsy to the last follow-up was significantly longer in patients with T790M mutation-positive lung cancers (P = .014). However, median survival time after rebiopsy was not statistically different between patients with and those without T790M mutation. Conclusion Peripheral tumor location with vascular convergence, the presence of a pleural tag, and air bronchogram of lung lesions at CT at the time of rebiopsy were significantly associated with T790M mutation in patients with non-small cell lung cancer after first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy failure. © RSNA, 2018 Online supplemental material is available for this article.

Clinical Features and Progression Pattern of Acquired T790M-positive Compared With T790M-negative EGFR Mutant Non–small-cell Lung Cancer: Catching Tumor and Clinical Heterogeneity Over Time Through Liquid Biopsy

“…We showed, for the first time in a Caucasian population, that age younger than 65 and exon 19 deletion as baseline sensitizing mutation were significantly correlated with acquired T790M mutation at the time of disease progression. Several studies previously investigated age as a clinical factor potentially correlated with T790M mutation, without significant findings in most cases 33,41 ; on the contrary, a Japanese case series showed a positive correlation in patients older than 75 years, but the median age in this patient population was older than our series. 37 Our results are in line with other case series that previously confirmed a correlation between exon 19 deletion and acquisition of T790M mutation probably because of a longer selective pressure of EGFR TKIs in more sensitive mutations.…”

“…Evidence about clinical features of patients with EGFR mutations potentially predicting the acquisition of T790M mutation is currently limited and mostly available on Asian patients. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] This clinical scenario would hopefully help to select the right strategy for every patient, considering the availability of a thirdgeneration TKI both as a firstand second-line treatment option.…”

“…To date, mostly retrospective [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] and 2 prospective 46,47 Asian case series investigated clinical-pathologic characteristics of T790M mutant lung cancer. Only a few data are available in Caucasian patients, and none of these studies investigated clinical progression patterns related to T790M in detail.…”

Nondiagnostic Percutaneous Transthoracic Needle Biopsy of Lung Lesions: A Multicenter Study of Malignancy Risk

“…In this era of targeted therapy, it would be critical to obtain adequate tissue samples not only for a pathologic diagnosis but also for genetic analysis for the management of patients with lung cancer (21). Although several studies (22)(23)(24)(25)(26) reported that the diagnostic yield of PTNB for mutational analysis was 78.8%-96.7%, the yield of adequate tissue for mutational analysis according to different needle types, sizes, and number of tissue samplings remains unclear and needs to be elucidated in future studies.…”

A leopard can’t change its spots: can a T790M mutation-positive cancer change its spots after epidermal growth factor receptor-tyrosine kinase inhibitor therapy?

“…Koo et al retrospectively studied 304 patients with NSCLC who underwent re-biopsy after administration of first-line EGFR-TKI therapy (13). They analyzed computed tomography (CT) findings at the initial diagnosis and those at re-biopsy and attempted to reveal the radiological features of lesions with T790M mutation.…”