Assuntos
Leucemia Linfocítica Crônica de Células B , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Idoso , Pessoa de Meia-Idade , Segunda Neoplasia PrimáriaRESUMO
The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell proliferation and is present in 90% of unresectable or metastatic pancreatic adenocarcinomas. Of these, the G12C variant of K-RAS genes accounts for 1-2% of mutations. A 65-year-old woman initially diagnosed with T3N0M0 pancreatic adenocarcinoma, underwent six cycles of neoadjuvant chemotherapy with mFOLFIRINOX followed by Whipple procedure. Her pathological stage was T4N2. She then received adjuvant mFOLFIRINOX but unfortunately her disease progressed through multiple lines of chemotherapy. Molecular analysis by Next Generation Sequence(NGS) panel revealed KRAS G12C mutation. Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Feminino , Idoso , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Triazóis/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Pirimidinas/uso terapêutico , Mutação , Antineoplásicos/uso terapêutico , Irinotecano/uso terapêutico , Oxaliplatina/uso terapêutico , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Uso Off-Label , Piperazinas , PiridinasRESUMO
Type B lactic acidosis has been described infrequently in hematologic malignancies, but even less often in solid tumors. Since 1978, there have been only 58 cases of solid tumor associated Type B lactic acidosis described in the literature. Lung cancer (neuroendocrine) is the most common tumor; others frequently have a poorly/undifferentiated histology. The prognosis is dismal. Malignancy associated type B lactic acidosis is not associated with hypoxemia. The most highlighted pathogenetic mechanism is the Warburg effect (aerobic glycolysis of tumor cells causing excess lactate). We describe a patient with metastatic GI neuroendocrine carcinoma with profound lactic acidosis, who died within 24 hours. When extremely ill cancer patients present with lactic acidosis, sepsis is usually a primary concern. This case highlights the need for providers to consider malignancy associated lactic acidosis (MA-LA) in the differential diagnosis, particularly in patients with advanced malignancies, of lung origin, of neuroendocrine or poorly/undifferentiated histologic subtypes. The implications and approach are distinct from Type A/D lactic acidosis, and would involve treatment of the underlying malignancy at the earliest.