Clinicopathologic determinants of survival of hepatoid adenocarcinoma of the lungs: Analysis of a pooled database.

Abstract

e20045 Background: Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of thoracic cancer characterized by morphological similarities to hepatocellular carcinoma, including alpha-fetoprotein (AFP) production. Due to its rarity, there is a limited understanding of its clinical behavior and optimal management strategies. This exploratory analysis aims to evaluate an HAL database to identify demographic patterns, therapeutic approaches, and prognostic factors in this rare cancer. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled a pooled database of cases that satisfy the diagnostic criteria for HAL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 104 patients with confirmed HAL were identified. The median age was 63, with a male preponderance (M:F 8). Eighty-seven percent were smokers. The median tumor size was 6cm, and the median AFP level was 5820 ng/ml, with 28% of the cases being non-secretors. The two most commonly involved primary sites were the right upper lobe (38%) and the left upper lobe (23%). Eleven percent presented with stage I, 15% with stage II, 33% with stage III, and 41% with stage IV. CNS metastases were diagnosed in 40%. ALK and EGFR mutations were present in 4% each, dMMR in 7%, KRAS mutations in 11%, and PD-L1>1% in 21%. The median OS and DFS of the cohort were 15 and 12 months, respectively. Ki67 of <50% was associated with better OS (p=0.0006). Early stages (I&II) had a superior median OS to advanced stages (NR vs. 12 months, p=0.0004). In the early stages, surgical resection (S) was associated with superior OS (p=0.02). In stage III, S, radiation (RT), and combined modalities (CM) were superior to chemotherapy (CT) alone (p=0.06). In stage IV, compared to no treatment, S, RT, CT, and CM were statistically superior with a median OS of 0.5, 2, 3, 12, and NR months, respectively (p<0.0001). Incorporating immune checkpoint inhibitors into the treatment of advanced HAL was associated with better median OS at 36 months (p=0.07). While Size>10cm, AFP non-secretors, and CNS metastases had numerically worse OS, they did not reach statistical significance. Age, sex, primary site, and smoking status did not impact OS. Conclusions: This pooled analysis highlights tumor stage, Ki67 index, and treatment modality as key prognostic factors. Surgical resection and combined treatment strategies significantly improve survival in early and advanced disease, respectively, while immune checkpoint inhibitors show promise in advanced stages. These findings underscore the need for tailored therapeutic approaches and further research to optimize outcomes for this rare malignancy.