Comment on: “Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)”

Abstract

I read with interest the recent article published in Targeted Oncology by Auliac et al. [1]. In addition to clinical trials data, it is always valuable to collect real-life data on the patients’ therapeutic management and follow-up. In this manner, the French retrospective analysis of patients with non-small cell lung cancer (NSCLC) harboring ALK rearrangements, led by Auliac et al., is of particular interest [1]. Nevertheless, besides clinical characteristics, disease management, and outcomes, the diagnostic criteria of the BALK-positivity^ of NSCLC and their potential impact on the patients’ outcomes, especially when treated with the anti-ALK tyrosine kinase inhibitor crizotinib, are not sufficiently taken into account in this study. The 31 participating French centers included 132 patients diagnosed with ALK-positive NSCLC between January 2012 and December 2014 [1]. During this period of inclusion, different diagnostic strategies with varying diagnostic platforms were used in France to test for ALK rearrangement in NSCLC with various combinations of fluorescent in situ hybridization (FISH, being the gold standard in the field of ALK testing), immunohistochemistry (IHC), and sometimes reverse transcription polymerase chain reaction (PCR) [2–5]. Indeed, the French recommendations to perform first line ALK IHC and to further search for the ALK rearrangement using a FISH test only in suspected cases (i.e., scores 1+ or 2+, not 0 or 3+) were just published in May 2017 [6]. In this manner, besides the inclusion criteria mentioned in the study led by Auliac et al. (i.e., BAccording to national recommendations, all advanced NSCLC patients undergo ALK testing using an ALK immunohistochemistry diagnostic assay, and suspected cases are confirmed by fluorescence in situ hybridization^), it is highly likely that at least a subset ofALK positive patients included in their study had been tested and diagnosed as ALK-positive on the basis of a first line FISH test, independently of the IHC result [1]. Discrepancies between ALK FISH and ALK IHC status are well described in the literature, including in French series, and while ALK FISH + IHC+ and ALK FISH-IHC+ cases are often good responders to crizotinib therapy, the response to crizotinib in ALK FISH + IHCpatients is more difficult to predict with about only half of patients responding to this ALKtargeted therapy [2–5, 7–9]. Taking into account the updated guidelines for ALK testing encouraging IHC testing instead of first line FISH testing, ALK FISH + IHCcases, which could represent up to about one case in four ALK-positive NSCLC, are likely to be less and less diagnosed and retrospective studies such as the one led by Auliac et al. present unique opportunities to further investigate the therapeutic relevance of this particular ALK status. In this manner, to retrospectively compare the features of ALK IHC+ and ALK FISH + IHCcases among the 132 BALK-positive^ patients could be highly interesting to provide real-life data for physicians who might have to treat some patients with ALK FISH+ IHCNSCLC.

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