lenvatinib and Venous-Thrombosis

Portal vein tumour thrombosis is common among patients with advanced hepatocellular carcinoma. Tremendous differences exist in the management of hepatocellular carcinoma with portal vein tumour thrombosis between the east and the west, which derive from heterogeneities in its epidemiology, causes, pathology, comorbidities, prognosis, and other demographics. These divergences between the east and the west are not only caused by hepatocellular carcinoma itself, but are also affected by many variables including social factors, physician preferences, accessibility to costly or novel treatments, and reimbursement schemes. In this Review, we compare and contrast the management of hepatocellular carcinoma with portal vein tumour thrombosis in the east and in the west in terms of systemic and surgical treatments, radiotherapy, transcatheter arterial therapies, and portal vein revascularisation. We conclude that a personalised, data-driven approach to care with active management from a multidisciplinary team, as well as increased communication and collaboration between clinicians and researchers based in east and the west, could help to reduce the differences in management and optimise treatment strategies.

Topics: Anilides; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Endovascular Procedures; Hepatectomy; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Liver Transplantation; Nivolumab; Patient Care Team; Phenylurea Compounds; Portal Vein; Pyridines; Quinolines; Radiotherapy, Adjuvant; Ramucirumab; Sorafenib; Stents; Venous Thrombosis

Hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX), lenvatinib and programmed death receptor-1 signaling inhibitors (PD1s) all alone have been proven effective in treating advanced hepatocellular carcinoma (HCC), yet the efficacy and safety of the tri-combination therapy in treating HCC patients with portal vein tumor thrombosis (PVTT) remains unknown.. In this retrospective study, HCC patients with PVTT received either induction therapy of HAIC and lenvatinib plus PD1s in the initial period of treatment and then dual maintenance therapy of lenvatinib and PD1s (HAIC-Len-PD1) or continuous lenvatinib combined with PD1s (Len-PD1).. In total, 53 and 89 patients were enrolled into the Len-PD1 group and HAIC-Len-PD1 group, respectively. The median overall survival times were 13.8 months in the Len-PD1 group and 26.3 months in the HAIC-Len-PD1 group (hazard ratio (HR) = 0.43, P < 0.001). The median progression-free survival (PFS) time was significantly longer in the HAIC-Len-PD1 group than in the Len-PD1 group (11.5 months versus 5.5 months, HR = 0.43, P < 0.001). Induction therapy showed an objective response rate (ORR) 3 times higher than lenvatinib combined with PD1s therapy (61.8% versus 20.8%, P < 0.001), and exhibited inspiring intra- and extra-hepatic tumor control ability. Induction therapy led to more adverse events than lenvatinib combined with PD1s therapy, most of which were tolerable and controllable.. The induction therapy of FOLFOX-HAIC and lenvatinib plus PD1s is an effective and safe treatment for HCC patients with PVTT. The concept of induction therapy could be applied to other local-regional treatments and drugs combinations in HCC management.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Fluorouracil; Humans; Induction Chemotherapy; Infusions, Intra-Arterial; Liver Neoplasms; Portal Vein; Retrospective Studies; Treatment Outcome; Venous Thrombosis

Advanced hepatocellular carcinoma (HCC) shows poor prognosis. Combined hepatic artery infusion chemotherapy (HAIC) and lenvatinib and PD-1 antibody therapy show promising effects in treating advanced HCC, and salvage hepatectomy further promotes the overall survival in patients who were successfully converted after combined therapy. However, salvage major hepatectomy is not always amenable due to insufficient future liver remnant volume (FLV).. We report the case of a 59-year-old man with a huge HCC as well as multiple intrahepatic foci and portal vein tumor thrombosis at his right hemi-liver. Genomic and pathologic analyses of HCC tissue revealed a TMB-high, TPS, and CPS-high cancer, with mutated DNA damage repair gene FANCC. These results suggested that this patient may benefit from chemotherapy and immunotherapy. Thus, he received combined HAIC, lenvatinib, and PD-1 antibody treatment and showed a quick and durable response. After successful downstaging, this patient was evaluated as not suitable for salvage hepatectomy due to the low FLV. He then received simultaneous transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE). The FLV increased to meet the criteria of salvage hepatectomy. Finally, this patient underwent right hemi-hepatectomy without any severe perioperative complications. In addition, no tumor recurrence occurred during the 9-month follow-up period after surgery.. Combined HAIC, lenvatinib, and PD-1 antibody therapy, followed by simultaneous TACE and PVE, is a safe and effective conversion therapy that promotes tumor necrosis and increase FLV in patients with advanced HCC.

Topics: Antibodies; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Portal Vein; Programmed Cell Death 1 Receptor; Venous Thrombosis

The aim of this study was to clarify the adaptation of lenvatinib treatment in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT).. Fifty-three patients with HCC were treated with lenvatinib. Before and after treatment blood sampling, patients were examined by computed tomography and ultrasonography. In patients with portal trunk invasion (Vp4), the analysis focused on the degree of occlusion due to the tumor in the portal trunk. In patients without major PVTT {ie, invasion of the primary branch of the portal vein [Vp3] or Vp4}, portal blood flow volume was measured by Doppler analysis; however, Doppler analysis is difficult to perform in patients with major PVTT, so the time from administration of the contrast agent to when it reached the primary branch of the portal vein (portal vein arrival time) was evaluated with the contrast agent Sonazoid.. Patients with Vp4 had a significantly worse prognosis than patients with Vp3 and a significant increase in Child-Pugh score at 2 months. Patients with major PVTT had a poor prognosis if the degree of occlusion of the portal trunk was 70% or more. In patients without major PVTT, portal blood flow was significantly decreased after administration of lenvatinib; and in patients with major PVTT, the hepatic artery and portal vein arrival times were significantly increased.. Lenvatinib treatment should be avoided in patients with Vp4 with a high degree of portal trunk occlusion because of concerns about decreased portal blood flow.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Hepatocellular; Female; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Phenylurea Compounds; Portal Vein; Prognosis; Quinolines; Venous Thrombosis

In this report, we describe a case of highly advanced hepatocellular carcinoma with tumor thrombosis extending into the main portal vein of the pancreas that was successfully treated with adjuvant lenvatinib after right hepatic resection with thrombectomy. A 70-year-old woman was referred from the clinic because of elevated hepatobiliary enzymes. The patient was positive for the hepatitis B virus antigen at our hospital. The tumor markers were highly elevated with alpha-fetoprotein (14.5 U/mL) and protein induced by vitamin K absence (PIVKAII) (1545 ng/mL), suggesting hepatocellular carcinoma. Dynamic abdominal computed tomography showed an early enhanced tumor approximately 6 cm in size and portal vein tumor thrombosis filling the main portal vein, but not extending into the splenic or superior mesenteric vein (SMV). On magnetic resonance imaging 1 week after CT, portal vein tumor thrombosis had extended to the confluence of the splenic vein with the SMV, indicating rapid tumor growth. Thus, we performed emergent right hepatectomy with tumor thrombectomy. Postoperatively, we treated the patient with lenvatinib for a tumor reduction surgery. Fortunately, the patient was alive 2 years postoperatively without recurrence. This case report suggests that a favorable outcome may be achieved with multidisciplinary treatment including resection and postoperative treatment with lenvatinib.

Topics: Aged; Carcinoma, Hepatocellular; Female; Hepatectomy; Humans; Liver Neoplasms; Phenylurea Compounds; Portal Vein; Prognosis; Quinolines; Splenic Vein; Thrombosis; Venous Thrombosis

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Bevacizumab; Carcinoma, Hepatocellular; Drug Substitution; Female; Hepatitis B, Chronic; Humans; Immune Checkpoint Inhibitors; Liver Cirrhosis; Liver Neoplasms; Middle Aged; Phenylurea Compounds; Portal Vein; Programmed Cell Death 1 Receptor; Quinolines; Salvage Therapy; Tomography, X-Ray Computed; Venous Thrombosis

We aimed to compare the outcomes between sorafenib and lenvatinib as first-line therapy for advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (Vp3/4).. This retrospective study enrolled 41 HCC patients with Vp3/4 and Child-Pugh A.. The outcomes in the lenvatinib group (n=13) were significantly better than those in the sorafenib group (n=28) [best objective response rate according to the modified Response Evaluation Criteria in Solid Tumors: 53.8% vs. 14.3%; p=0.0193, best disease control rate: 92.3% vs. 35.7%; p=0.0008, median overall survival (OS): not reached vs. 187 days; p=0.0040, respectively]. Lenvatinib treatment was the only significant predictor of better OS and time to tumor progression. No patient needed to discontinue lenvatinib treatment due to drug-related adverse events.. Compared with sorafenib, lenvatinib treatment for advanced HCC with Vp3/4 may lead to more favorable outcomes.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Phenylurea Compounds; Portal Vein; Quinolines; Retrospective Studies; Sorafenib; Survival Analysis; Treatment Outcome; Venous Thrombosis