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Global Translational Medicine                               Thromboembolism risk in non-small-cell lung cancer



            3 times in cancer patients . In particular, pneumonectomy   2. Materials and methods
                                [6]
            has been associated with a higher risk of VTE than
            lobectomy for stage I and II lung cancer .         2.1. Study population
                                           [7]
              In comparison to other tumor types, lung cancer has   This retrospective observational study was designed to
            been associated with a moderate risk of VTE, particularly   investigate the relationship between  EGFR and  ALK gene
                                                               mutations and the occurrence of VTE in patients with lung
            during the 1   year following cancer diagnosis. The   adenocarcinoma (LA). The study included patients older than
                       st
            prevalence of VTE in lung cancer patients has been   18 years who had received a histologically confirmed diagnosis
            reported to range between 7% and 15% . Factors such   of either locally advanced or advanced-stage adenocarcinoma
                                             [3]
            as longer life expectancy, advanced age at the time   and followed in our center between January 2014 and
            of cancer diagnosis, and utilization of thrombogenic
            anti-cancer agents have increased the incidence of VTE in   December 2019. Tumor tissue DNA analysis for gene
                                                               mutations was conducted at the time of study entry.
            cancer patients . Although patients diagnosed with lung
                        [4]
            cancer are also predisposed to arterial thromboembolism   The following inclusion criteria were defined as follows:
            (ATE), the effect of lung cancer on ATE development is less   (i) Patients with a confirmed pathological diagnosis of
            pronounced than its effect on VTE development .    adenocarcinoma, (ii) patients who underwent mutation
                                                  [8]
                                                               analysis, and (iii) patients with available data regarding
              Research has indicated that certain laboratory   occurrences of VTE. Exclusions encompassed patients
            parameters can predict an elevated risk of cancer-  with  ROS1 gene mutations, patients with a confirmed
            related thrombosis. However, the identification of a   pathological diagnosis of small-cell lung cancer, patients
            standardized biomarker specific to lung cancer is still   who had undergone surgical intervention, patients receiving
            underway. Therefore, there is a growing need to uncover   anticoagulant therapy, patients with a diagnosis of chronic
            biomarkers that can effectively identify individuals at risk   embolism, and patients in the early stages of the disease.
            for developing thromboembolism and determine suitable
            candidates for thromboprophylaxis.                   The patients were divided into two groups: those with
                                                               gene mutations (mutation [+]) and those without mutation
              Lately, significant advancements have been introduced   (mutation [-]). The mutation (+) group comprised patients
            in the treatment approaches for advanced non-small-cell   with EGFR and ALK gene mutations. This study sought to
            lung carcinoma (NSCLC). Guidelines now recommend the   analyze the incidence of VTE within these groups, discern
            thorough investigation of targetable driver gene mutations   factors affecting the occurrence of VTE, and compare the
            in all patients with advanced NSCLC . At present, lung   OS between the mutation (+) and mutation (-) groups.
                                          [9]
            cancer patients are categorized based on tumor histological
            characteristics and the presence of epidermal growth   2.2. Data collection
            factor receptor (EGFR) mutations or anaplastic lymphoma   The demographic and clinical data of the patients (age, gender,
            kinase (EML4-ALK) translocations such as echinoderm   tumor histopathology, clinical stage, number of metastases, and
            microtubule-associated protein 4 .                 the administration of active cancer therapy within the 4 weeks
                                      [9]
              Studies have indicated a lack of association between   leading up to the diagnosis of VTE), laboratory parameters at
            increased risk of VTE and EGFR mutations in patients with   the time of VTE onset, and the presence of documented VTE
            NSCLC [10,11] . Interestingly, Zer et al. demonstrated that the   were recorded. Clinical staging was determined in accordance
                                                                                   th
                                                                                          [17]
            incidence of VTE was 3 – 5 times greater in cohorts with   with TNM classification (8  edition) .
            anaplastic lymphoma kinase (ALK) gene mutations than in
            the previously reported NSCLC population . Dou et al.’s   2.3. Laboratory methods
                                              [12]
            study, further, corroborated these findings, establishing   All tumor molecular tests were conducted by a pathologist
            a correlation between the increased VTE risk in NSCLC   at regional laboratories.
            patients and the presence of ALK gene mutation . Given   Tumor biopsy specimens were processed as formalin-
                                                   [13]
            the heightened VTE risk in cancer patients, the new   fixed and paraffin-embedded samples for histological
            thromboprophylactic  agents have  garnered  increasing   examination and mutation analysis.  EGRF mutation
            importance [14-16] .                               analysis (covering exons 18, 19, 20, and 21) was performed
              Our study aimed to elucidate the difference in VTE   using real-time PCR.  ALK rearrangement and  ROS1
            occurrence between lung cancer patients with  EGFR   rearrangement were investigated using the FISH method,
            mutations, those with ALK mutations, and patients without   utilizing the BX51 Olympus fluorescence microscope. For
            these  mutations. In  addition,  we evaluated  the effect of   ALK and ROS1 results to be considered positive, a minimum
            VTE on overall survival (OS) within this patient cohort.  of 50 scoreable tumor cells in 4 – 5 μm thick tissue sections


            Volume 2 Issue 3 (2023)                         2                        https://doi.org/10.36922/gtm.1027
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