RESUMO
Until recently, there have been only modest therapeutic advances in the treatment of hepatobiliary malignancies. However, the introduction of immune checkpoint inhibitors in combination with targeted therapy or chemotherapy has changed the therapeutic landscape of hepatocellular carcinoma and biliary tract cancers. As such, revisions have been made to guidelines reflecting therapeutic advances for patients who can be considered for surgical options including resection and liver transplantation. This article highlights recently published studies that have impacted both the oncological and surgical approach to the treatment of patients with hepatobiliary malignancies.
Assuntos
Neoplasias do Sistema Biliar , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/cirurgiaRESUMO
BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs), trans-arterial chemoembolization (TACE), and radiotherapy to treat hepatocellular carcinoma (HCC) has not been well-defined. We performed a meta-analysis to characterize tumor response and survival associated with multimodal treatment of HCC. METHODS: PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (1990-2022). Random-effect meta-analysis was conducted to compare efficacy of treatment modalities. Odds ratios (OR) and standardized mean difference (SMD) were reported. RESULTS: Thirty studies (4170 patients) met inclusion criteria. Triple therapy regimen (ICI + TKI + TACE) had the highest overall disease control rate (DCR) (87%, 95% CI 83-91), while ICI + radiotherapy had the highest objective response rate (ORR) (72%, 95% CI 54%-89%). Triple therapy had a higher DCR than ICI + TACE (OR 4.49, 95% CI 2.09-9.63), ICI + TKI (OR 3.08, 95% CI 1.63-5.82), and TKI + TACE (OR 2.90, 95% CI 1.61-5.20). Triple therapy demonstrated improved overall survival versus ICI + TKI (SMD 0.72, 95% CI 0.37-1.07) and TKI + TACE (SMD 1.13, 95% CI 0.70-1.48) (both p < 0.05). Triple therapy had a greater incidence of adverse events (AEs) compared with ICI + TKI (OR 0.59, 95% CI 0.29-0.91; p = 0.02), but no difference in AEs versus ICI + TACE or TKI + TACE (both p > 0.05). CONCLUSION: The combination of ICIs, TKIs and TACE demonstrated superior tumor response and survival and should be considered for select patients with advanced HCC.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Terapia Combinada , Resultado do Tratamento , Masculino , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor with poor prognosis and rising incidence globally. Multimodal therapy that includes surgical resection and chemotherapy with or without radiation offers the best chance for optimal outcomes. The development of established criteria for anatomic staging of local primary tumors into potentially resectable (PR), borderline resectable (BR), and locally advanced (LA) has greatly clarified the optimal treatment strategies. While upfront surgical resection was traditionally the recommended approach for localized PDAC, increasingly neoadjuvant therapy (NT) is recommended prior to surgery. Whereas NT can lead to downstaging that facilitates surgical resection for BR/LA cancers, NT also enhances patient selection for surgery, improves margin-negative resection rates, and increases the odds of completing multimodality therapy for all patients with PDAC. Herein, we review the rationale for NT for localized PDAC and summarize existing and ongoing literature.
Assuntos
Carcinoma Ductal Pancreático , Terapia Neoadjuvante , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estadiamento de Neoplasias , Pancreatectomia , Seleção de PacientesRESUMO
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) comprise the two most common primary liver malignancies. Curative treatment options often include hepatectomy or liver transplantation; however, many patients present with advanced disease that is not amenable to surgical management. In turn, many patients are treated with systemic or targeted therapy. The tumor microenvironment (TME) is a complex network of immune cells and somatic cells, which can foster an environment for disease development and progression, as well as susceptibility and resistance to systemic therapeutic agents. In particular, the TME is comprised of both immune and non-immune cells. Immune cells such as T lymphocytes, natural killer (NK) cells, macrophages, and neutrophils reside in the TME and can affect tumorigenesis, disease progression, as well as response to therapy. Given the importance of the immune system, there are many emerging approaches for cancer immunotherapy. We herein provide a review the latest data on immunotherapy for primary HCC and BTC relative to the TME.
Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Neoplasias do Sistema Biliar/terapia , Imunoterapia , Microambiente Tumoral , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-HepáticosRESUMO
Although the incidence of colorectal cancer (CRC) has decreased as a result of increased screening and awareness, it still remains a major cause of cancer-related death. Additionally, early detection of CRC recurrence by conventional means such as CT, endoscopy, and CEA has not translated into an improvement in survival. Liquid biopsies, such as the detection circulating tumor DNA (ctDNA), have been investigated as a biomarker for patients with CRC in terms of prognosis and recurrence, as well as their use to guide therapy. In this manuscript, we provide an overview of ctDNA as well as its utility in providing prognostic information, using it to guide therapy, and monitoring for recurrence in patients with CRC. In addition, we discuss the influence the site of disease may have on the ability to detect ctDNA in patients with metastatic CRC.