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  • Accumulating evidence suggest that patients with advanced po

    2024-06-22

    Accumulating evidence suggest that patients with advanced -positive NSCLC are at increased risk of VTE or coagulation disorders during the course of their disease, indicating that cancer genotype might play a role in the occurrence of cancer-related thromboembolism . Here we report the case of a patient who presented with fatal acute DIC as onset of advanced -positive NSCLC. A 68-year old former smoker man was incidentally diagnosed with left lung opacity in January 2017 during the pre-operative evaluation for a radical prostatectomy. Upon documentation of a upper left lobe opacity at routine pre-operative chest radiography, the patient was promptly admitted to our department and underwent total body contrast enhanced CT scan that revealed a 41×35mm consolidation of the upper left lobe with bilateral multiple nodules, and synchronous pulmonary embolism involving the lobar inferior artery and a segmental branch of the posterior basal artery (A–B). The patient began taking apixaban and underwent a subsequent CT-guided transthoracic biopsy. Unfortunately the clinical course was suddenly complicated by acute onset of monocular loss of vision and confusion. A roxadustat MRI was performed and showed multiple areas of restricted diffusion due to multiple ischemic and synchronic sub-acute ischemic lesions (C–D) and multiple parenchymal metastases. Electrocardiogram analysis at symptom onset showed ST elevation in DII-DIII-aVF and V4-V5 derivations with T waves inversion, which were consistent with acute myocardial infarction. Laboratory investigation confirmed increased troponin (2.14ng/ml) and signs suggesting acute DIC, namely increase of LDH (2372 UI/L), D-Dimer (5718ng/ml) and INR (2.40), hypofibrinogemia (34mg/dl) and thrombocytopenia (platelet count: 7.000 mmc). Peripheral blood smear showed the presence of schistocytes. With no other causes assumed to have induced the DIC, a paraneoplastic genesis was considered. Unfortunately the clinical conditions rapidly worsened and the patient died few days later despite intensive life support measures were adopted. The results of lung biopsy turned out to be consistent with primary lung adenocarcinoma. The immunohistochemical profile was as follows: CK7+, TTF1 1+, PASD+ (focal), p40 -, PSA -, PSAP – (E–H). The determination of the gene rearrangement by immunochemistry was positive in the 90% of the neoplastic cells with a moderate intensity (IHC score 2+) (Fig. 2D). Molecular profiling excluded additional genetic alterations. Lung cancer has been considered for decades as a single disease. Nevertheless, recent advancement in the understanding of the molecular mechanism underling the development of this deadly disease has led to the discovery of distinct disease genotypes, which exhibit exquisite responses to targeted therapies. Patients harboring rearrangements have excellent sensitivity to the administration of ALK inhibitors, which translates in meaningful clinical benefit and unprecedented survival. In this unexpected scenario oncologists and intensive care unit (ICU) operators have had to face with a changed perception on admission criteria to ICU for patients with oncogene addicted NSCLC. Although data are limited to case reports and small case series, administration of ALK TKIs in critically ill -positive NSCLC patients has been associated with a dramatic improvement of short-term prognosis, resulting occasionally in the so-called Lazarus effect. In our case, the patient developed an acute and fatal DIC with both venous and arterial thrombotic involvement, including pulmonary embolism, ischemic stroke and acute ST segment elevation myocardial infarction (STEMI). However, the clinical conditions worsened so rapidly that we were not able to start any first-line treatment, as histological diagnosis and molecular profiling came back too late. Nonetheless, our case raises the question of how critically ill patients with oncogene addicted NSCLC should be managed, in light of the expected efficacy of targeted therapies. In this regard, Ahn and colleagues reported three cases of -rearranged NSCLC, in which all patients were completely weaned from mechanical ventilation after treatment with crizotinib in ICU . Furthermore, Yoshida et al. reported about a 29-years old ALK-positive patient with poor performance status (PS) and respiratory failure because of disseminated intravascular coagulation who experienced a rapid and dramatic response to alectinib . Together, these data suggest that acute ill patients with advanced NSCLC and actionable genetic alteration might be considered candidate for ICU admission.