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  • On the other hand there was no difference in effectiveness

    2024-04-01

    On the other hand, there was no difference in effectiveness performing ALK by FISH with regard to the sample site. When it was extracted from the primary tumor, we obtained 27.4% of not-evaluable specimens. Similar percentages were found for node (26.7%) and aa2414 synthesis (31.3%) samples (p = 0.903).
    Discussion ALK assessment has become a routine test in patients with advanced NSCLC. The prevalence of NSCLCs with ALK fusion varies from 3% to 7% in the literature but most studies have been conducted in Asian countries or in the United States of America [2,7]. There are few and small cohort studies about the prevalence and clinical characteristics of ALK lung cancer in Latin America [[13], [14], [15], [16]]. To the best of our knowledge, this is the first multi-institutional prospective study evaluating the frequency and clinical characteristics of ALK lung tumors in Argentina. Taking into account that <30% of NSCLCs are resectable at the time of presentation [17] and that availability of minimally invasive tissue collection is currently rising, this can lead to insufficient tissue for some molecular testing. Usually, after pathological and IHC diagnosis, the remaining tissues of the specimens are used for biomarkers testing, so the biopsy sample needs to be sufficient. With the purpose of not wasting material for subsequent molecular testing, the 2015 WHO Classification of Tumours of the Lung [11] and the 2011 IASLC/ATS/ERS International association for the study of lung cancer [18], suggest that IHC may be employed only if histology or cytomorphology are insufficient to differentiate squamous cell carcinoma from adenocarcinoma. In current clinical practice, we use at least four predictive markers (EGFR, ALK, ROS1, PD-L1), so usually the tissue is not enough. Even though liquid biopsy has emerged to help with this problem (mainly in EGFR testing), today we still need adequate tumor tissues for ALK testing.
    Funding This study was supported by Pfizer Oncology and the Argentine Association of Clinical Oncology (AAOC).
    Acknowledgements
    Introduction Lung cancers driven by oncogenic rearrangements involving the anaplastic lymphoma kinase (ALK) gene represent a rare but clinically relevant subset of non-small cell lung cancer (NSCLC) [1]. Sequential use of an ever-expanding repertoire of highly effective ALK inhibitors has significantly improved outcomes for patients with metastatic ALK-positive NSCLC [2]. However, the widespread use of ALK inhibitors has also affected our ability to study the prognostic relevance of this predictive biomarker. Despite being an established therapeutic target in the metastatic setting, the rarity of ALK rearrangements in non-metastatic disease poses a challenge to clinical studies of ALK inhibitors in the resectable or locally advanced setting. Theoretically, determining the prognostic impact of ALK status should be more straightforward in the early-stage setting given the absence of approved targeted therapies. Yet, the few published studies of resectable ALK-positive NSCLC have had conflicting results, likely due to inclusion of molecularly heterogeneous comparator groups [[3], [4], [5], [6]]. Given the limitations of the current literature, we undertook this pooled retrospective analysis to better understand the prognostic implications of ALK rearrangement. Outcomes of patients with resected ALK-positive tumors were compared to two other clinically relevant cohorts: patients with resected tumors harboring activating mutations in the epidermal growth factor receptor gene (EGFR) and Kirsten rat sarcoma virus gene (KRAS).
    Materials and methods
    Results
    Discussion The diagnosis and treatment of patients with metastatic NSCLC has been revolutionized by the detection of driver alterations and development of personalized therapies targeting these alterations [9]. Although widespread implementation of molecular testing for NSCLC has been critical to characterizing these molecular subsets, the speed of drug development has confounded our ability to discern the prognostic implications of these molecular drivers. The same is not true in early-stage disease where studies of targeted therapies lag years behind approvals in advanced disease [10]. The current lack of approved adjuvant/neo-adjuvant targeted therapies offers a unique opportunity to determine whether specific molecular alterations influence the natural aa2414 synthesis history of resected NSCLC. Arguably, establishing prognostic relevance may be most valuable in early- stage disease where rational design of perioperative clinical trials may lead to cures.