ABSTRACT
Brain metastases are rare for patients with pancreatic adenocarcinoma. The incidence of brain metastasis may increase as improved systemic treatment regimens improve overall survival. Given the low incidence of brain metastasis, recognition of disease and management remain a challenge. We report three cases of metastatic pancreatic adenocarcinoma with brain metastases, review the literature and discuss its management principles.
Subject(s)
Adenocarcinoma , Brain Neoplasms , Pancreatic Neoplasms , Humans , Adenocarcinoma/pathology , Pancreatic Neoplasms/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/therapy , Brain Neoplasms/secondary , Incidence , Pancreatic NeoplasmsABSTRACT
INTRODUCTION: Biomarkers that predict the risk of immune-mediated adverse events (irAEs) among patients with non-small cell lung cancer (NSCLC) may reduce morbidity and mortality associated with these treatments. METHODS: We carried out high resolution human leucocyte antigen (HLA)-I typing on 179 patients with NSCLC treated with anti-program death (PD)-1/program death ligand (PDL)-1. Toxicity data were collected and graded as per common terminology criteria for adverse event (CTCAE) v5.0. We used 14.8-week for landmark analysis to address lead-time bias to investigate the correlation between HLA-I/II zygosity, supertypes and alleles with irAE. Furthermore, we assessed the association for irAE with clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS). RESULTS: Homozygosity at one or more HLA-I loci, but not HLA-II, was associated with a reduced risk of irAE (relative risk (RR) = 0.61, 95% CI 0.33-0.95, P = 0.035) especially pneumonitis or any grade 3 toxicity. Patients with HLA-A03 supertype had a higher risk of developing irAE (RR = 1.42, 95% CI 1.02-2.01, P = 0.039). The occurrence of any irAE was significantly associated with improved CBR (RR = 1.48, P < 0.0001), PFS (HR = 0.45, P = 0.0003) and OS (HR = 0.34, P < 0.0001). CONCLUSIONS: Homozygosity at one or more HLA-I loci may serve as biomarker to predict patients who are unlikely to experience severe irAEs among patients with NSCLC and treated with anti-PD1/PDL1, but less likely to derive clinical benefit. Patients with HLA-I homozygous might benefit from additional therapy.