Worse disease-free, tumor-specific, and overall survival in surgically-resected lung adenocarcinoma patients with ALK rearrangement

Abstract

IntroductionThis study determined the prevalence of anaplastic lymphoma kinase (ALK) rearrangement, and identified the associations of ALK rearrangement with clinicopathologic characteristics and treatment outcomes in patients with surgically-resected stage I-III lung adenocarcinoma.MethodsA total of 534 surgically-resected lung adenocarcinoma patients were studied. The prevalence of ALK protein over-expression was determined by a fully-automated immunochemistry assay (with mouse monoclonal Ventana D5F3 antibody), and the associations of ALK rearrangement with clinicopathologic characteristics and treatment outcomes were analyzed.ResultsForty-two (7.9%) of the 534 lung adenocarcinoma patients were ALK IHC-positive. ALK rearrangement was significantly associated with younger age (P = 0.011), high T-stage (P = 0.025), high pathologic stage (P = 0.002), solid predominant adenocarcinoma with mucin production (P = 0.006), invasive mucinous adenocarcinoma (P = 0.009), and receipt of adjuvant therapy after surgery (P = 0.036), but no significant associations were found between the ALK rearrangement and sex or smoking status. ALK IHC-positivity was significantly associated with a shorter disease-free survival, tumor-specific survival, and overall survival (P = 0.001, 0.026, and 0.007, respectively). Multivariate analysis showed that ALK IHC-positivity was an adverse prognostic factor for disease-free survival (HR, 1.80; 95% CI 1.18-2.77; P = 0.007), tumor-specific survival (HR, 2.59; 95% CI 1.35-4.97; P = 0.004), and overall survival (HR, 1.92; 95% CI 1.07-3.44; P = 0.030).ConclusionThe clinical characteristics of patients with ALK-positive lung adenocarcinoma were similar to those of EGFR-mutated patients. ALK rearrangement was an adverse prognostic factor in surgically-resected lung adenocarcinoma patients.

Comparison of Clinicopathological Features and Prognosis between ALK Rearrangements and EGFR Mutations in Surgically Resected Early-stage Lung Adenocarcinoma

“…We previously studied only ALK rearrangements in surgically-resected LAC patients; these subjects partially overlapped with those in the present study. In our earlier work 31, we suggested that the clinical characteristics of LAC patients with ALK rearrangements were similar to those of EGFR -mutated patients, and that ALK rearrangements were an adverse prognostic factor. However, we did not determine the EGFR or KRAS status.…”

<p>Clinicopathological and Prognostic Significance of <em>EML4-ALK</em> Rearrangement in Patients with Surgically Resected Lung Adenocarcinoma: A Propensity Score Matching Study</p>

“…6 ALK rearrangement is associated with younger age, never or light smoker, solid nodules, adenocarcinoma and excessive mucin production. [8][9][10] However, the prognosis of patients with ALK-positive surgically resected adenocarcinoma in the absence of TKIs treatment remains controversial. Previous data suggested that ALK positivity was an unfavorable prognostic factor for disease-free survival (DFS).…”

A population‑based study of outcomes in patients with surgically resected non‑small cell lung cancer with anaplastic lymphoma kinase‑rearranged mutations: A matched‑pair study

“…In surgically-resected lung adenocarcinoma patients with A population-based study of outcomes in patients with surgically resected non-small cell lung cancer with anaplastic lymphoma kinase-rearranged mutations: A matched-pair study ALK rearranged mutations, however, controversy persists as to whether the ALK-rearranged mutations is an unfavorable prognostic factor (9-23). Previous reports have variously indicated ALK-rearranged mutations was a favorable prognostic factor (9,10), an unfavorable factor (11)(12)(13)(14)(15)(16)(17)(18), or a factor not associated with prognosis (19)(20)(21)(22)(23). Such different results might be related to the small number of patients with ALK rearranged mutations, and the large difference in the background between patients with and without ALK rearranged mutations.…”

“…Such different results might be related to the small number of patients with ALK rearranged mutations, and the large difference in the background between patients with and without ALK rearranged mutations. That is, the frequency of ALK rearranged mutations was higher among young patients, female patients and non-smokers (6,(13)(14)(15)(24)(25)(26). In addition, it is still unclear whether the presence or absence of the ALK mutations is associated with post-recurrence survival (PRS).…”