Abstract
BackgroundThe correlation between ALK gene copy number gain (ALK-CNG) and prognosis in the context of advanced non-small-cell lung cancer (NSCLC) remains a controversial issue. This study aimed to evaluate the association among ALK-CNG according to Fluorescent In Situ Hybridization (FISH), clinical characteristics and survival in resectable and advanced NSCLC.MethodsClinical and pathological data of patients with resectable and advanced NSCLC were retrospectively collected. Tumor tissues were analyzed for ALK-CNG by FISH, and patients were divided in 3 groups/patterns on the basis of ALK signals: disomic [Pattern A], 3–7 signals [Pattern B], >7 signals [Pattern C]. The association between clinical and pathological features and ALK-CNG patterns was evaluated. Disease/progression-free and overall survival (DFS/PFS and OS) were estimated using the Kaplan-Meyer method.ResultsA number of 128 (76.6 %) out of the 167 eligible patients were evaluable for ALK-CNG, displaying pattern A, B and C in 71 (42.5 %), 42 (25.1 %) and 15 (9 %) patients, respectively. Gains in ALK-CNG appear to be more frequent in smokers/former smokers than in non-smokers (74.2 % versus 20.4 %, respectively, p = 0.03). Pattern A and C seem more frequently associated with higher T-stage (T3-4), while pattern B appears more represented in lower T-stage (T 1-2) (p = 0.06). No significant differences in survival rate were observed among the above groups.ConclusionsA high ALK-CNG pattern might be associated with smoking status and theoretically it might mirror genomic instability. The implications for prognosis should be prospectively investigated and validated in larger patients’ series.Trial registrationWe confirm that all the study was performed in accordance with relevant guidelines and regulations and that all the protocol (part of a larger project MFAG 2013 N.14282) was approved by the local Ethics Committee of the Azienda Ospedaliera Universitaria Integrata of Verona on November 11st, 2014.
Highlights
The correlation between ALK gene copy number gain (ALK-CNG) and prognosis in the context of advanced non-small-cell lung cancer (NSCLC) remains a controversial issue
In the context of adenocarcinoma, reliable evidence is available suggesting that cancer development and progression might be led by the addiction from aberrant pathways triggered by genetic abnormalities acting as oncogenic drivers
Thirty-eight patients with locally advanced or metastatic NSCLC harboring EGFR activating mutations and ALK rearranged tumors were excluded from the analysis
Summary
The correlation between ALK gene copy number gain (ALK-CNG) and prognosis in the context of advanced non-small-cell lung cancer (NSCLC) remains a controversial issue. In the first-line phase III trial PROFILE 1014, 343 treatment-naive patients with ALK-rearranged NSCLC were randomized to receive either crizotinib or standard platinum-based plus pemetrexed first-line chemotherapy. In this setting, crizotinib met the primary end point, achieving a significantly longer median PFS (10.9 versus 7.0 months; HR 0.45; p < 0.001), and a significantly higher ORR (74 % versus 45 %; p < 0.001). The pre-planned interim analysis of the J-ALEX trial, demonstrated the superiority of alectinib to crizotinib in untreated ALK-rearranged NSCLC patients (median PFS not reached versus 10.2 months; HR 0.34; p < 0.0001) [19]
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