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• W4387248000 abstract "SESSION TITLE: Lung Cancer Case Report Posters 8 SESSION TYPE: Case Report Posters PRESENTED ON: 10/09/2023 02:10 pm - 02:55 pm INTRODUCTION: Lung cancer is the leading cause of cancer-related deaths but incidence in young adults is 0.3 per 100,000 in US. In a study done on adults aged <35 years with lung cancer, about 70% were noted to be non-smokers and only 1% had positive family history. Non-small cell lung cancers (NSCLC) are associated with genetic mutations, notably KRAS, EGFR and TP53. Fusion of Echinoderm microtubule-associated protein-like 4 (EML4) - Anaplastic lymphoma kinase (ALK) is a subset of NSCLC, accounting for 5% of cases. Prevalence of these mutations is common in Asians and Caucasians however few cases have been reported in black population [1].Younger patients are believed to have better performance status and overall survival compared to older patients with same stage of disease. CASE PRESENTATION: 23-year-old Liberian male with no medical/addiction history was admitted for worsening shortness of breath, cough, hemoptysis, and unintentional weight loss for 5 months. On presentation, he was tachycardic, work-up revealed hypercalcemia 10.3mg/dl, and elevated alkaline phosphatase 114 IU/L. Chest CT showed markedly enlarged mediastinal and right hilar lymphadenopathy, right hilar mass encasing and occluding the right upper and middle lobe pulmonary arteries causing marked narrowing with multiple areas of mass-like consolidations and moderate right-sided pleural effusion (figure1). Tuberculosis test was negative, fluid studies revealed exudative effusion. Immunohistochemistry showed primary lung cancer with TTF-1, CK7 positive tumour cells. Biopsy followed by Next Gene Sequencing Fusion Panel were significant for invasive poorly differentiated adenocarcinoma with high PD-L1 expression and EML4-ALK fusion. Staging scan revealed stage IVb disease. Prior to receiving any treatment, he was readmitted due to facial swelling, neck pain concerning for superior vena cava syndrome. Imaging revealed enlarging mass, multiple hepatic metastases, bilateral renal metastases, enlarged cardiophrenic lymph nodes (figure 2). He received ten cycles of palliative radiation and oral Alectinib however, got readmitted owing to worsening respiratory failure, was intubated and eventually underwent tracheostomy. Due to significant loculation, he was transferred to a tertiary center, underwent bronchoscopy however was a poor candidate for stenting/VATS, received oral salvage chemotherapy with Lorbrena. Hospital course was complicated by deep vein thrombosis, refractory hypoxemia and cause of death was septic shock. DISCUSSION: Although pathophysiology of early-onset lung cancer is unclear, genetic factors play a prominent role. Younger patients mostly present with advanced-stage disease and have an increased frequency of gene mutations, hence, benefit from targeted therapies. Next-generation ALK inhibitors like Alectinib and Brigatinib, have demonstrated clinical improvement and overall survival benefits in ALK-positive tumors when compared to chemotherapy. While treatment with tyrosine kinase inhibitors remains the mainstay of therapy, mutations in EML4-ALK conferring resistance to the drugs have been identified, posing a threat to improved outcomes [2]. CONCLUSIONS: With this case, we emphasise the role of NGS, identification of EML4-ALK fusion in NSCLC and the potential role of tyrosine-kinase inhibitors in personalizing lung cancer therapy. Using combination therapy with ALK-TKIs and anti-PD1/PD-L1 antibodies in ALK positive NSCLC is an option that has not been sufficiently studied however is worth exploring in patients with resistant NSCLC [3]. REFERENCE #1: Lo Russo G, Imbimbo M, Corrao G, Proto C, Signorelli D, Vitali M, Ganzinelli M, Botta L, Zilembo N, de Braud F, Garassino MC. Concomitant EML4-ALK rearrangement and EGFR mutation in non-small cell lung cancer patients: a literature review of 100 cases. Oncotarget. 2017 Apr 26;8(35):59889-59900. doi: 10.18632/oncotarget.17431. PMID: 28938691; PMCID: PMC5601787. REFERENCE #2: Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H; ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010 Oct 28;363(18):1734-9. doi: 10.1056/NEJMoa1007478. PMID: 20979473. REFERENCE #3: Hong S, Chen N, Fang W, Zhan J, Liu Q, Kang S, He X, Liu L, Zhou T, Huang J, Chen Y, Qin T, Zhang Y, Ma Y, Yang Y, Zhao Y, Huang Y, Zhang L. Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients. Oncoimmunology. 2015 Dec 21;5(3):e1094598. doi: 10.1080/2162402X.2015.1094598. PMID: 27141355; PMCID: PMC4839382. DISCLOSURES: No relevant relationships by Krishna Desai No relevant relationships by Sohiel Deshpande No relevant relationships by Sabah Iqbal No relevant relationships by Nithya Ramesh No relevant relationships by Rajesh Thirumaran" @default.
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• W4387248000 date "2023-10-01" @default.
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• W4387248000 title "MALIGNANT HEMOPTYSIS LEADING TO A DEVASTATING DIAGNOSIS OF METASTATIC LUNG CANCER IN A 23 YEAR OLD" @default.
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