Features of anaplastic lymphoma kinase rearrangement in early-stage lung cancer: Analysis of a nationwide Japanese database.

Anaplastic lymphoma kinase (ALK) rearrangement is a representative driver mutation in lung cancer. However, the biology of early-stage ALK-rearranged lung cancer remains unclear. We aimed to assess the clinicopathological features, prognostic implications, and influence of ALK rearrangement on the postoperative course in surgically resected lung cancer. We retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database. Of the 12 730 patients with lung adenocarcinoma, 794 (6.2%) were tested for ALK rearrangement and were included. ALK rearrangements were detected in 76 patients (10%). The 5-year overall survival (OS) rate was significantly higher in the ALK rearrangement-positive group than in the ALK rearrangement-negative group (p = 0.030). Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved OS (hazard ratio, 0.521; 95% confidence interval, 0.298-0.911; p = 0.022). Regarding the postrecurrence state, there was no difference in the initial recurrence sites between both groups. Administration of ALK-tyrosine kinase inhibitors (TKIs) improved postrecurrence survival in any treatment lines. In one of the largest national surveys, ALK rearrangement was associated with improved long-term outcomes in surgically resected patients. ALK-TKIs may be an important treatment strategy for ALK rearrangement-positive lung adenocarcinoma in the postrecurrence state.

Matsuura Y ，Mun M ，Shintani Y ，Okami J ，Ito H ，Ohtsuka T ，Mori T ，Watanabe SI ，Chida M ，Endo S ，Nakanishi R ，Kadokura M ，Suzuki H ，Miyaoka E ，Yoshino I ，Date H ，Japanese Joint Committee of Lung Cancer Registry ... -  《-》

Prognostic impact and distinctive characteristics of surgically resected anaplastic lymphoma kinase-rearranged lung adenocarcinoma.

Anaplastic lymphoma kinase (ALK) rearrangement is a representative lung cancer with driver mutation because of the efficacy of ALK-tyrosine kinase inhibitors. ALK-tyrosine kinase inhibitors are extensively used for ALK-rearranged lung cancer, whereas the therapeutic benefit of surgery remains unclear. Thus, we aimed to assess the clinical benefit of surgery in ALK-rearranged lung cancer and to elucidate the oncologic characteristics of ALK-rearranged lung cancer through surgically resected cases. We retrospectively evaluated 1925 lung adenocarcinoma cases surgically resected between 1996 and 2017 at our institute. Moreover, 75 ALK-rearranged and 75 non-ALK-rearranged cases were extracted using propensity score matching. The survival rates, prognostic factors, and post-recurrence state were assessed. Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved cancer-specific survival (hazard ratio, 0.2; 95% confidence interval, 0.05-0.88; P = .033). In the matched cohort, the 5-year cancer-specific survival rates after surgery in the ALK-rearranged and non-ALK-rearranged groups were 97% and 77%, respectively. The ALK-rearranged group had a significantly better cancer-specific survival than did the non-ALK-rearranged group (log-rank test; P = .003). With respect to post-recurrence state, oligo-recurrence was highly frequent in the ALK-rearranged group, and post-recurrence survival was significantly improved by administration of either ALK-tyrosine kinase inhibitors (log-rank test; P = .011) or local ablative therapies (log-rank test; P = .035). Surgically resected ALK-rearranged lung adenocarcinoma has excellent long-term outcome. Not only ALK-tyrosine kinase inhibitors but also a combination of local and systemic therapies may be important treatment strategies for ALK-rearranged lung adenocarcinoma even in the post-recurrence state.

Matsuura Y ，Ninomiya H ，Ichinose J ，Nakao M ，Okumura S ，Nishio M ，Mun M ... -  《-》

The prognostic implications of EGFR mutation and ALK rearrangement for the long-term outcomes of patients with resected lung adenocarcinomas.

To investigate the prognostic impact of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement for the overall survival (OS) of patients with surgically treated lung adenocarcinomas. A total of 689 patients with stage I-III lung adenocarcinomas (male:female = 334:355; median age, 64 years) underwent complete surgical resection between 2007 and 2013. The prognostic impact of EGFR mutation and ALK rearrangement on OS was analyzed using Cox regression analysis. Certain clinicopathological prognostic factors (i.e., age, sex, smoking status, nodule type, solid portion size, pathologic stage, adenocarcinoma subtype, and history of adjuvant chemotherapy) were included for adjustments of the hazard ratio (HR). EGFR mutation was observed in 438 patients (64%) and ALK rearrangement was seen in 28 patients (4%). Multivariable-adjusted Cox regression demonstrated that the prognostic effect of EGFR mutation on OS differed by age (HR, exp.[-5.199 + 0.064* age]). The adjusted HR for EGFR mutation was 0.14 (95% CI: 0.05-0.36; P < 0.001) at 50 years, 0.26 (95% CI: 0.15-0.46; P < 0.001) at 60 years, and 0.50 (95% CI: 0.31-0.81; P = 0.005) at 70 years. However, the effect of ALK rearrangement on OS was without statistical significance (P > 0.05). EGFR mutation was independently prognostic of the long-term outcomes of patients with surgically treated lung adenocarcinomas. A more favorable prognostic effect was seen in younger than in older patients. ALK rearrangement was not associated with OS.

Kim H ，Lee HJ ，Hong H ，Kim YJ ，Kim KG ，Jeon YK ，Kim YT ... -  《-》

Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity.

Ko SJ ，Lee YJ ，Park JS ，Cho YJ ，Yoon HI ，Chung JH ，Kim TJ ，Lee KW ，Kim K ，Jheon S ，Kim H ，Lee JH ，Lee CT ... -  《BMC CANCER》

Clinicopathological and prognostic implications of ALK rearrangement in patients with completely surgically resected lung adenocarcinoma.

The prognostic significance of ALK rearrangement is still contradictory. Here, we aimed to investigate the clinical characteristics and outcomes of lung adenocarcinoma patients with ALK rearrangement, and analyze whether these patients benefited from targeted therapy. This was a retrospective cohort study of 80 ALK-rearranged lung adenocarcinoma patients who had undergone radical surgery and another 3031 ALK mutation-negative patients were retrospectively reviewed for inclusion in this case-controlled analyses. Overall survival (OS) was evaluated using the Kaplan--Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) by the Cox proportional hazards regression identified risk factors that predicted OS. Compared to ALK-negative patients, the ALK rearranged patients were younger, with more non-smokers, more females, a larger primary tumor was demonstrated, and were a higher pathological stage. In particular, the risk of lymph node metastasis was higher. For patients with surgically-resected tumors, the prognosis was better for ALK rearranged patients (HR = 0.503; 95% CI: 0.259-0.974, p = 0.041). In addition, for stage II-III patients, targeted therapy was an independent prognostic factor of better OS (HR = 0.159; 95% CI: 0.032-0.801, p = 0.026). ALK rearranged lung adenocarcinoma patients who have undergone radical surgery have distinct clinical features. Patients with ALK rearrangement may have a favorable prognosis, and stage II-III patients may benefit from targeted treatment.

Zhang H ，Shan G ，Cai B ，Bi G ，Chen Z ，Liang J ，Besskaya V ，Zheng Y ，Guo W ，Wang L ，Xu S ，Zhan C ... -  《-》