Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial.

PURPOSE: In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population. METHODS: In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment. RESULTS: Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75; P < .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 [46%] v 28 [18%]; P < .001) and a longer median progression-free survival (9.6 [95% CI, 7.4 to 11.9] v 5.4 months [95% CI, 3.8 to 7.0], P < .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30% v 19%, P = .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related. CONCLUSION: FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.

Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial.

Importance: Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study. Objective: To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion. Design, Setting, and Participants: This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months. Interventions: Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). Main Outcomes and Measures: The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. Results: For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]). Conclusions and Relevance: Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion. Trial Registration: ClinicalTrials.gov identifier: NCT02774187.

Long-term Outcomes of Thoracoscopic Anatomic Resections and Systematic Lymphadenectomy for Elderly High-risk Patients with Stage IB Non-small-cell Lung Cancer.

BACKGROUND: To evaluate the efficacy and long-term survival outcomes of complete video-assisted thoracoscopic surgery (C-VATS) for the resection of anatomic pulmonary segments and systematic lymphadenectomy in the treatment of elderly and high-risk patients with stage IB for non-small cell lung cancer (NSCLC). METHODS: 242 elderly patients (≥65 years), who were operated on by the same operational team, were divided into high-risk group and conventional risk group from August 2008 to December 2010. All patients were diagnosed in stage IB (pT status: >2 to ≤3) NSCLC by biopsy and examination of PET-CT before operation. The high-risk patients were identified with severe cardiopulmonary and other system dysfunctions as follow-up criteria. They were treated with VATS anatomic pulmonary segments and systematic lymphadenectomy. The conventional risk patients with adequate cardiopulmonary reserve were treated with VATS radical lobectomy and systematic lymphadenectomy. The clinical and pathological data were recorded. The total survival, tumour-free survival, recurrence time and character of patients were followed-up. Appropriate statistical analyses involved the χ(2) test and Kaplan-Meier estimates of total survival and tumour-free survival. RESULTS: A total of 242 patients underwent surgical resection during our study period: Anatomic pulmonary segments in 116 patients and lobectomy in 126. The operative time and blood loss of the VATS anatomic pulmonary segments group (78.0±35.0 min, 95.6±30.4 ml) were significantly less than those of the VATS radical resection group (108.0±25.0 min, 165.6±58.4 ml). Neither group experienced post-operative death. The overall and tumour-free survival rate of the VATS anatomic pulmonary segments group within five years were 62.07% and 29.31%, and those of the VATS radical resection group were 63.49% and 33.33%,%; there was no significant difference (P>0.5). The recurrence rates of the VATS anatomic pulmonary segment group and VATS radical resection group were 13.79% and 12.70%; there was no significant difference (P>0.5). CONCLUSIONS: Thorascopic segmentectomy under anaesthesia and systematic lymphadenectomy is safe and minimally invasive and effective to treat a selected group of patients with stage IB NSCLC.

Roles played by chemolipiodolization and embolization in chemoembolization for hepatocellular carcinoma: single-blind, randomized trial.

BACKGROUND: The aim of our study was to compare the efficacy and safety of: 1) transarterial chemolipiodolization with gelatin sponge embolization vs chemolipiodolization without embolization, and 2) chemolipiodolization with triple chemotherapeutic agents vs epirubicin alone. METHODS: A single-blind, three parallel arm, randomized trial was conducted at three clinical centers with patients with biopsy-confirmed unresectable hepatocellular carcinoma. Arm 1 received triple-drug chemolipiodolization and sponge embolization, whereas Arm 2 received triple-drug chemolipiodolization only. Patients in arm 3 were treated with single-drug chemolipiodolization and sponge embolization. We compared overall survival and time to progression. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS: From July 2007 to November 2009, 365 patients (Arm 1: n = 122; Arm 2: n = 121; Arm 3: n = 122) were recruited. The median tumor size was 10.9cm (range = 7-22cm), and 34.5% had macrovascular invasion. The median survivals and time to progression in Arm 1, Arm 2, and Arm 3 were 10.5 and 3.6 months, 10.1 and 3.1 months, and 5.9 and 3.1 months, respectively. Survival was statistically significantly better in Arm 1 than in Arm 3 (P < .001), whereas there was no statistically significant difference between Arm 1 and Arm 2 (P = .20). Objective response rates were 45.9%, 29.7%, and 18.9% for Arm 1, Arm 2, and Arm 3, respectively. CONCLUSIONS: Chemolipiodolization played an important role in transarterial chemoembolization, and the choice of chemotherapy regimen may largely affect survival outcomes. However, the removal of embolization from chemoembolization might not statistically significantly decrease survival.

[Prophylaxis and clinical treatment for surgical margin recurrence of small primary hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Along with the advance of medical technology and instruments, many patients with small primary hepatocellular carcinoma (HCC) had been found, who are mainly treated with surgical resection with high postoperative recurrence rate of over 60%. This study was to explore prophylaxis and clinical treatment for these patients to reduce postoperative recurrence rate. METHODS: Clinicopathologic data of 283 patients with small HCC, treated in Central Hospital of Kaiping and Cancer Center of Sun Yat-sen University from 1991 through May 2003, were analyzed. Over 85% patients suffered cirrhosis with liver reserve dysfunction, and were mainly treated with irregular hepatectomy. Of the 283 patients, 140 received application of anhydrous alcohol injection or alcohol-soaked gelatin sponge on surgical margin (test group), 143 received no application of alcohol on surgical margin (control group). The 2 groups were comparable in age, gender, tumor location, clinical stage, and Child-Pugh stage. RESULTS: The 1-year surgical margin recurrence rate was significantly higher in test group than in control group (21.4% vs. 4.4%, P0.05). Intrahepatic metastasis or recurrence rate, 5-year overall survival rate, and tumor-free survival rate were not different between the 2 groups. Both groups had no severe complications. CONCLUSIONS: Application of anhydrous alcohol on surgical margin or anhydrous alcohol injection in remnant liver after irregular hepatectomy may benefit to reduce postoperative recurrence in surgical margin for small PLC, but has no impact on intrahepatic metastases and recurrence in remnant liver.

[The clinical analysis of lung cancer with paraneoplastic syndrome as initial symptom].

BACKGROUND: To investigate the clinical characteristics and diagnosis of lung cancer with paraneoplastic syndrome as initial symptom. METHODS: The clinical data of 168 cases of lung cancer with paraneoplastic syndrome as initial symptom were analysed from Jan. 1990, to Nov. 2002, in the hospital. RESULTS: (1) Among the patients with lung cancer in the hospital, 11.8% (168/1 426) had paraneoplastic syndrome as initial symptom. The ratio of male to female was 4.25:1. There were 138 cases aged above 45 (82.1%) and 116 with smoking history (69.0%). (2)There were 62 cases of small cell lung cancer (36.9%) and 102 non small cell lung cancer (60.7%) and 4 carcinoid (2.4%). Thirty-three cases (37.5%) were central type and 82 (48.8%) peripheral type and 23 (13.7%) diffuse type. (3) The patients with paraneoplastic syndrome included: 48 cases of osteoarthopathy (28.6%), 27 cachexia (16.1%), 23 cancerous fever (13.7%), 14 myasthenia (8.3%), 12 vegetative nerve hyperfunction (7.1%), 11 cerebellar cortex degeneration (6.5%), 9 acanthosis nigricans (5.4%), 8 cutaneous pigmentation (4.8%), 7 dermatomyositis (4.2%), 5 encephalopathy (3.0%), and 4 gynecomastia (2.4%). (4)The misdiagnosis rate of the first consultation was 44.6% (75/168). (5)Initial chest X-ray positive rate was 61.9% (104/168); initial CT positive rate was 78.6% (132/168). (6)One hundred and thirty-two cases accepted the treatment of lung cancer: 32 cases accepted pure operation, 8 cases accepted pure chemotherapy, 35 cases accepted operation and chemotherapy, 39 cases accepted chemotherapy and radiotherapy, 18 cases accepted operation and chemotherapy and radiotherapy. Totally 8 cases were dead and 17 cases had abandoned treatment. One hundred and seven cases had improvement after complex treatment of lung cancer, including 83 cases with improvement or disappearance of paraneoplastic syndrome, 18 cases with no change, and 6 cases exacerbated. CONCLUSIONS: The lung cancer with paraneoplastic syndrome as initial symptom is difficult to diagnose because of its latent onset. The knowledge of paraneoplastic syndrome should be improved, chst X-ray or CT examination should be done for the high risk group of lung cancer with paraneoplastic syndrome, and these strategies could decrease misdiagnosis rate and increase diagnosis rate of lung cancer in early stage.