Background: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma, but prognosis is still unsatisfactory. Recently, hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors showed promising results for advanced hepatocellular carcinoma. Considering different anti-malignancy mechanisms, combining these three treatments may improve outcomes. This study aimed to compare the efficacy and safety of lenvatinib, toripalimab, plus HAIC versus lenvatinib for advanced hepatocellular carcinoma. Methods: This was a retrospective study including patients treated with lenvatinib [8 mg (⩽60 kg) or 12 mg (>60 kg) once daily] or lenvatinib, toripalimab plus HAIC [LeToHAIC group, lenvatinib 0–1 week prior to initial HAIC, 240 mg toripalimab 0–1 day prior to every HAIC cycle, and HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 h, every 3 weeks)]. Progression-free survival, overall survival, objective response rate, and treatment-related adverse events were compared. Results: From February 2019 to August 2019, 157 patients were included in this study: 71 in the LeToHAIC group and 86 in the lenvatinib group. The LeToHAIC group showed longer progression-free survival (11.1 versus 5.1 months, p < 0.001), longer overall survival (not reached versus 11 months, p < 0.001), and a higher objective response rate (RECIST: 59.2% versus 9.3%, p < 0.001; modified RECIST: 67.6% versus 16.3%, p < 0.001) than the lenvatinib group. In addition, 14.1% and 21.1% of patients in the LeToHAIC group achieved complete response of all lesions and complete response of the intrahepatic target lesions per modified RECIST criteria, respectively. Grade 3/4 treatment-related adverse events that were more frequent in the LeToHAIC group than in the lenvatinib group included neutropenia (8.5% versus 1.2%), thrombocytopenia (5.6% versus 0), and nausea (5.6% versus 0). Conclusions: Lenvatinib, toripalimab, plus HAIC had acceptable toxic effects and might improve survival compared with lenvatinib alone in advanced hepatocellular carcinoma.

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BackgroundAvascular necrosis of the femoral head (AVNFH) typically constitutes 5 to 15% of all complications of low-energy femoral neck fractures, and due to an increasingly ageing population and a rising prevalence of femoral neck fractures, the number of patients who develop AVNFH is increasing. However, there is no consensus regarding the relationship between blood lipid abnormalities and postoperative AVNFH. The purpose of this retrospective study was to investigate the relationship between blood lipid abnormalities and AVNFH following the femoral neck fracture operation among an elderly population.MethodsA retrospective, comparative study was performed at our institution. Between June 2005 and November 2009, 653 elderly patients (653 hips) with low-energy femoral neck fractures underwent closed reduction and internal fixation with cancellous screws (Smith and Nephew, Memphis, Tennessee). Follow-up occurred at 1, 6, 12, 18, 24, 30, and 36 months after surgery. Logistic multi-factor regression analysis was used to assess the risk factors of AVNFH and to determine the effect of blood lipid levels on AVNFH development. Inclusion and exclusion criteria were predetermined to focus on isolated freshly closed femoral neck fractures in the elderly population. The primary outcome was the blood lipid levels. The secondary outcome was the logistic multi-factor regression analysis.ResultsA total of 325 elderly patients with low-energy femoral neck fractures (AVNFH, n = 160; control, n = 165) were assessed. In the AVNFH group, the average TC, TG, LDL, and Apo-B values were 7.11 ± 3.16 mmol/L, 2.15 ± 0.89 mmol/L, 4.49 ± 1.38 mmol/L, and 79.69 ± 17.29 mg/dL, respectively; all of which were significantly higher than the values in the control group. Logistic multi-factor regression analysis showed that both TC and LDL were the independent factors influencing the postoperative AVNFH within femoral neck fractures.ConclusionsThis evidence indicates that AVNFH was significantly associated with blood lipid abnormalities in elderly patients with low-energy femoral neck fractures. The findings of this pilot trial justify a larger study to determine whether the result is more generally applicable to a broader population.

4083 Background: Combining systemic and locoregional therapies represents a promising treatment strategy for patients with advanced hepatocellular carcinoma (HCC). We investigated the efficacy and safety of combined lenvatinib and toripalimab (recombinant, humanized programmed cell death receptor-1 monoclonal antibody) plus hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment in this patient population. Methods: This single-arm, phase II study included treatment-naive adult (≥18 years) patients with advanced HCC, Eastern Cooperative Oncology Group performance status 0–2, and Child-Pugh Class A liver function (NCT04044313). Patients initiated lenvatinib (8 mg for bodyweight < 60 kg or 12 mg for bodyweight ≥60 kg, orally once daily) 3-7 days prior to initial HAIC to confirm tolerability, and then received 21-day treatment cycles of lenvatinib (day 1 to day 21), toripalimab (240 mg by IV infusion, on day 1), and HAIC (day 1 to day 2) with the FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 24 hours) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) at six months, evaluated using RECIST 1.1. Secondary endpoints were median PFS and overall survival (OS), objective response rate (ORR) per RECIST 1.1 and mRECIST, and safety. Results: Between August 2019 and May 2020, 36 patients (33 men and 3 women; median age, 49 years) were enrolled. The median tumor size was 11.2 cm, 86.1% of patients had portal vein invasion, and 27.8% had extrahepatic metastasis. The primary endpoint showed a 6-month PFS rate of 80.6%. After a median follow up of 11.2 months, the median PFS was 10.5 months (95% CI, 6.21−14.79), and the median OS was not reached. The ORR per RECIST was 63.9% (95% CI, 40.9−73.0), and per mRECIST was 66.7% (95% CI, 43.3−75.1) including five (13.9%) patients who achieved a complete radiological response. The median duration of response was 12.1 months (95% CI, 4.52−19.69). Furthermore, eight patients achieved sufficient downstaging to be converted to resectable disease. Among them, one patient received liver transplantation, and four received curative surgical resection. One of them achieved pathological complete response. Grade 3-4 treatment-related adverse events (AEs) occurred in 72.2% of patients, and the most common were thrombocytopenia (13.9%), elevated aspartate aminotransferase (13.9%), and hypertension (11.1%). All AEs were expected and manageable, and no treatment-related deaths were reported. Conclusions: Combination treatment with lenvatinib and toripalimab plus HAIC showed promising antitumor activity and manageable toxicity in patients with advanced HCC. Further randomized, controlled trials are warranted to validate our findings. Clinical trial information: NCT04044313.