scholarly journals Is the Concurrent Use of Sorafenib and External Radiotherapy Feasible for Advanced Hepatocellular Carcinoma? A Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2912
Author(s):  
Chai Hong Rim ◽  
Sunmin Park ◽  
In-Soo Shin ◽  
Won Sup Yoon
Keyword(s):  
Hepatocellular Carcinoma ◽  
Meta Analysis ◽  
External Beam Radiation ◽  
Cochrane Library ◽  
Hematologic Toxicity ◽  
Advanced Hepatocellular Carcinoma ◽  
Beam Radiation ◽  
Concurrent Treatment ◽  
Grade 3 ◽  
Vessel Involvement

We evaluate the feasibility of a concurrent application of sorafenib and external beam radiation therapy (EBRT) for advanced hepatocellular carcinoma (HCC). PubMed, Embase, Medline, and Cochrane Library were searched up to 9 April 2021. The primary endpoint was grade ≥3 complications, and the secondary endpoint was overall survival (OS). Subgroup analyses were performed for studies with the EBRT targets, intrahepatic vs. non-intrahepatic lesions (e.g., extrahepatic metastases or malignant vessel involvement only). Eleven studies involving 512 patients were included in this meta-analysis. Pooled rates of gastrointestinal, hepatologic, hematologic, and dermatologic grade ≥3 toxicities were 8.1% (95% confidence interval (CI): 4.8–13.5, I2 = ~0%), 12.9% (95% CI: 7.1–22.1, I2 = 22.4%), 9.1% (95% CI: 3.8–20.3, I2 = 51.3%), and 6.8% (95% CI: 3.8–11.7, I2 = ~0%), respectively. Pooled grade ≥3 hepatologic and hematologic toxicity rates were lower in studies targeting non-intrahepatic lesions than those targeting intrahepatic lesions (hepatologic: 3.3% vs. 17.1%, p = 0.041; hematologic: 3.3% vs. 16.0%, p = 0.078). Gastrointestinal and dermatologic grade ≥3 complications were not significantly different between the subgroups. Regarding OS, concurrent treatment was more beneficial than non-concurrent treatment (odds ratio: 3.3, 95% CI: 1.3–8.59, p = 0.015). One study reported a case of lethal toxicity due to tumor rupture and gastrointestinal bleeding. Concurrent treatment can be considered and applied to target metastatic lesions or local vessel involvement. Intrahepatic lesions should be treated cautiously by considering the target size and hepatic reserve.

scholarly journals Efficacy of External Beam Radiation-Based Treatment plus Locoregional Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ming-Yang Chen ◽  
Yu-Chao Wang ◽  
Tsung-Han Wu ◽  
Chen-Fang Lee ◽  
Ting-Jung Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Portal Vein ◽  
Surgical Management ◽  
External Beam Radiation ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
External Beam ◽  
Portal Vein Tumor Thrombosis ◽  
Beam Radiation ◽  
Tumor Thrombosis

Background. Portal vein tumor thrombosis (PVTT) is a common event in advanced hepatocellular carcinoma (HCC). The optimal treatment for these patients remains controversial. Methods. A retrospective review of 149 patients who had unresectable HCC associated with PVTT between January 2005 and December 2012 was performed. Outcomes related to external beam radiation-based treatment were measured, and clinicopathological features and parameters affecting prognosis were analyzed as well. Results. The radiotherapeutic response of PVTT was an important element that affected the overall treatment response of HCC. Serum α-fetoprotein < 400 ng/mL, the presence of a radiotherapeutic response on PVTT, and receiving additional locoregional therapy were significant prognostic factors affecting the survival of patients. Patients who had received additional locoregional therapy obtained a better outcome, and six of them were eventually able to undergo surgical management with curative intent. Conclusion. The outcome of HCC associated with PVTT remains pessimistic. In addition to the current recommended treatment using sorafenib, a combination of external beam radiotherapy targeting PVTT and locoregional therapy for intrahepatic HCC might be a promising strategy for patients who had unresectable HCC with PVTT. This approach could perhaps offer patients a favorable outcome as well as a possible cure with following surgical management.

scholarly journals A systematic review and network meta-analysis of second-line therapy in hepatocellular carcinoma

2020 ◽  
Vol 27 (6) ◽  
Author(s):  
S. Delos Santos ◽  
S. Udayakumar ◽  
A. Nguyen ◽  
Y.J. Ko ◽  
S. Berry ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Meta Analysis ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Clinical Benefits ◽  
Baseline Characteristics ◽  
Grade 3

Background In patients with advanced hepatocellular carcinoma (hcc) following sorafenib failure, it is unclear which treatment is most efficacious, as treatments in the second-line setting have not been directly compared and no standard therapy exists. This systematic review and network meta-analysis (nma) aimed to compare the clinical benefits and toxicities of these treatments. Methods A systematic review of randomized controlled trials (rcts) was conducted to identify phase iii rcts in advanced hcc following sorafenib failure. Baseline characteristics and outcomes of placebo were examined for het­erogeneity. Primary outcomes of interest were extracted for results, including overall survival (os), progression-free survival (pfs), objective response rate (orr), grade 3/4 toxicities, and subgroups. An nma was conducted to compare both drugs through the intermediate placebo. Comparisons were expressed as hazard ratios (hrs) for os and pfs, and as risk difference (rd) for orr and toxicities. Subgroup analyses for os and pfs were also performed. Results Two rcts were identified (1280 patients) and compared through an indirect network; celestial (cabozantinib vs. placebo) and resorce (regorafenib vs. placebo). Baseline characteristics of patients in both trials were similar. Both trials also had similar placebo outcomes. Cabozantinib, compared with regorafenib, showed similar os [hazard ratio (hr): 1.21; 95% confidence interval (ci): 0.90 to 1.62], pfs (hr: 1.02; 95% ci: 0.78 to 1.34) and orr (−3.0%; 95% ci: −7.6% to 1.7%). Both treatments showed similar toxicities, but there were marginally higher risks of grade 3/4 hand–foot syndrome (5%; 95% ci: 0.1% to 9.8%), diarrhea (4.8%; 95% ci: 1.1% to 8.5%), and anorexia (4.4%; 95% ci: 0.8% to 8.0%) for cabozantinib. Subgroup results for os and pfs were consistent with overall results. Conclusions Overall, this nma determined that cabozantinib and regorafenib have similar clinical benefits and toxicities for second-line hcc.

Effectiveness and Safety of Combination Therapy of Transarterial Chemoembolization and Apatinib for Unresectable Hepatocellular Carcinoma in the Chinese Population: A Meta-Analysis

Chemotherapy ◽  
2019 ◽  
Vol 64 (2) ◽  
pp. 94-104 ◽  
Author(s):  
Yan Wei ◽  
Jianjun Liu ◽  
Min Yan ◽  
Shuguang Zhao ◽  
Yong Long ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Transarterial Chemoembolization ◽  
Therapy Group ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Combination Therapy Group ◽  
Advanced Hcc

Background: The combination of transarterial chemoembolization (TACE) and apatinib has been used in the treatment of intermediate or advanced hepatocellular carcinoma (HCC). However, its effectiveness and safety are also argued. Methods: Eligible studies were collected from a computer search of literatures published from the database establishment to May 2019 in PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The objective response rate (ORR), the disease control rate (DCR), survival rate (SR), and the incidences of treatment-related adverse effects (AEs) were collected as the relevant outcomes. Data were analyzed through fixed/random effects of meta-analysis models with RevMan 5.3 software. Results: Eight randomized controlled clinical trials comprising 528 patients and 4 cohort studies comprising 226 patients were eventually included. Compared to the control group treated with TACE solely, combination therapy group, in which intermediate or advanced HCC patients were treated with TACE and apatinib, significantly enhanced ORR (relative risk [RR] 2.06, 95% CI 1.63–2.61, p < 0.001), DCR (RR 1.65, 95% CI 1.24–2.20, p < 0.001), and whole SRs of 6-month (RR 1.52, 95% CI 1.08–2.14, p = 0.02), 1-year (RR 1.52, 95% CI 1.25–1.84, p < 0.001), and 2-year (RR 1.84, 95% CI 1.34–2.54, p < 0.001). The incidence of hand foot syndrome, proteinuria, hypertension, and diarrhea was significantly increased in the combination therapy group compared with the control group (p < 0.05), and the incidence of nausea and vomiting, fever, and myelosuppression, respectively, was similar in 2 groups (p > 0.05). Conclusions: The combination therapy of TACE and apatinib can enhance the clinical effectiveness better than TACE solely in patients with intermediate or advanced HCC, while increase in the AEs is usually tolerable.

Is transcatheter arterial chemoembolization plus sorafenib better than chemoembolization plus placebo in the treatment of hepatocellular carcinoma?

2020 ◽  
pp. 030089162094502
Author(s):  
Yong Xie ◽  
Huan Tian ◽  
Hua Xiang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcatheter Arterial Chemoembolization ◽  
Meta Analysis ◽  
Survival Rates ◽  
Complete Response ◽  
Cochrane Library ◽  
Control Group ◽  
Significant Difference ◽  
Grade 3 ◽  
Arterial Chemoembolization

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus sorafenib compared with TACE plus placebo for hepatocellular carcinoma (HCC) using meta-analytical techniques. Methods: A search of PubMed, EMBASE, and Cochrane Library databases were done from inception to December 27, 2019. Published trials including a treatment group receiving TACE + sorafenib and a control group receiving TACE + placebo with data for at least 1-year survival or tumor response or time to progression were included. Results: Our study suggested that there was no evidence that TACE plus sorafenib was associated with a lower risk of disease progression compared with TACE plus placebo for treatment of HCC (hazard ratio 0.94 [95% confidence interval (CI), 0.84–1.05]), and no significant difference for treatment of HCC compared with TACE plus placebo in terms of 0.5-, 1-, 1.5-, and 2-year survival rates (risk ratio [RR] 1.01 [95% CI, 0.97–1.05]; RR 1.00 [95% CI, 0.92–1.08], RR 1.04 [95% CI, 0.89–1.23], RR 0.98 [95% CI, 0.72–1.34], respectively). The meta-analysis also showed that TACE + sorafenib seemed to have no significant difference for treatment of HCC compared with TACE + placebo in terms of complete response, partial response, stable disease, progressive disease, overall response rate, and disease control rate. There was an increased incidence of fatigue of grade 3/4 and elevation of aspartate aminotransferase and alanine aminotransferase of grade 3/4 in patients receiving TACE plus sorafenib compared with those receiving TACE plus placebo. Conclusions: There is no additive benefit of TACE plus sorafenib compared to TACE plus placebo for HCC.

Toxicity of chemotherapy dosing using actual body weight in obese versus normal-weight patients: A systematic review and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6013-6013
Author(s):  
Kathryn Cunningham Hourdequin ◽  
William Lewis Schpero ◽  
Breanne Lee Piazik ◽  
Dorothy R McKenna ◽  
Robin Joyce Larson
Keyword(s):  
Systematic Review ◽  
Body Weight ◽  
Actual Body ◽  
Meta Analysis ◽  
Normal Weight ◽  
Cochrane Library ◽  
Hematologic Toxicity ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Grade 3

6013 Background: Because weight-based chemotherapy calculations can be very large in obese patients, oncologists often empirically reduce doses due to fear of excess toxicity. The resulting underdosing may negatively impact survival. We performed a systematic review and meta-analysis to determine whether, among adults receiving chemotherapy dosed by actual body weight (ABW), obese patients experience differing toxicity or survival compared to normal-weight patients. Methods: We searched MEDLINE, Cochrane Library, Web of Science, and ClinicalTrials.gov through October 2011 and reviewed reference lists. We included studies that compared outcomes of obese versus normal-weight adults receiving chemotherapy dosed according to ABW (+/- 5% variability). Studies followed subjects for at least one cycle of chemotherapy and reported at least one pre-specified outcome. Two authors independently abstracted data from eligible studies. We used random effects models to pool odds ratios (OR) for hematologic and non-hematologic toxicities. We summarized survival qualitatively. Results: Of 3,921 studies, five met inclusion criteria, for a total of 6,877 subjects. Based on three studies, Grade 3/4 hematologic toxicity occurred less often in obese patients than normal-weight patients (OR 0.68, 95% CI 0.51-0.89, I2=29%). A fourth study comparing leukocyte nadirs had variable results depending on the regimen, dosing, and patient co-morbidities. Based on two studies, Grade 3/4 non-hematologic toxicity occurred less often in obese patients than normal-weight patients (OR 0.74, 95% CI 0.63-0.87, I2=0%). A third study found rates of infection did not significantly differ. Three of four studies reported reduced overall survival in obese patients (statistical significance not reported). Conclusions: Contrary to common belief, obese patients receiving chemotherapy based on ABW appear to have lower rates of both hematologic and non-hematologic toxicities compared to normal-weight patients. These results do not support the practice of empiric dose reduction in obese patients. Further research should explore etiologies for the reduced survival in this group.

Oxaliplatin in Combination With Protracted-Infusion Fluorouracil and Radiation: Report of a Clinical Trial for Patients With Esophageal Cancer

2002 ◽  
Vol 20 (12) ◽  
pp. 2844-2850 ◽  
Author(s):  
Nikhil I. Khushalani ◽  
Cynthia Gail Leichman ◽  
Gary Proulx ◽  
Hector Nava ◽  
Lisa Bodnar ◽  
...  
Keyword(s):  
Combined Modality Therapy ◽  
Stage Iv ◽  
External Beam Radiation ◽  
Hematologic Toxicity ◽  
Esophageal Mucosa ◽  
Beam Radiation ◽  
Grade 3 ◽  
Disease Stages ◽  
Dose Limiting Toxicity

PURPOSE: To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC). PATIENTS AND METHODS: Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m2 on days 1, 15, and 29; PI 5-FU 180 mg/m2 for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients. RESULTS: Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses. CONCLUSION: OXP 85 mg/m2 on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.

scholarly journals The effects of several postoperative adjuvant therapies for hepatocellular carcinoma patients with microvascular invasion after curative resection: a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiarui Yang ◽  
Hao Liang ◽  
Kunpeng Hu ◽  
Zhiyong Xiong ◽  
Mingbo Cao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Conservative Treatment ◽  
Curative Resection ◽  
Postoperative Radiotherapy ◽  
Meta Analysis ◽  
Microvascular Invasion ◽  
Cochrane Library ◽  
Conservative Group ◽  
Adjuvant Therapies ◽  
Significant Difference

Abstract Background For patients with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) after curative resection, the effects of various postoperative adjuvant therapies are not summarized in detail, and the comparison between the effects of various adjuvant therapies is still unclear. Thus, we collected existing studies on postoperative adjuvant therapies for patients with HCC with MVI after curative resection and analyzed the effects of various adjuvant therapies. Method We collected all studies on postoperative adjuvant therapy for patients with HCC with MVI after curative resection from PubMed, EMBASE, Cochrane Library and SinoMed ending on May 1, 2019. Overall survival (OS) and disease-free/recurrence-free survival (RFS) between each group were compared in these studies by calculating the pooled hazard ratio (HR) and 95% confidence interval (CI). All statistical analyses were assessed by two authors independently. Result A total of 13 studies were included in this study, including 824 postoperative adjuvant transarterial chemoembolization (pa-TACE) patients, 90 postoperative radiotherapy patients, 57 radiofrequency ablation (RFA)/re-resection patients, 16 sorafenib patients and 886 postoperative conservative treatment patients. The results showed that pa-TACE significantly improved OS and RFS compared with postoperative conservative treatment in patients with HCC with MVI after curative resection (HR: 0.64, 95% CI: 0.55–0.74, p < 0.001; HR: 0.70, 95% CI: 0.62–0.78, p < 0.001, respectively). There was no significant difference in OS between pa-TACE and radiotherapy in patients with HCC with MVI (HR: 1.75, 95% CI: 0.92–3.32, p = 0.087). RFS in patients with HCC with MVI after pa-TACE was worse than that after postoperative adjuvant radiotherapy (HR: 2.29, 95% CI: 1.43–3.65, p < 0.001). The prognosis of pa-TACE and RFA/re-resection in patients with MVI with recurrent HCC had no significant differences (HR: 0.65, 95% CI: 0.09–4.89, p = 0.671). Adjuvant treatments significantly improved the OS and RFS of patients compared with the postoperative conservative group (HR: 0.580, 95% CI: 0.480–0.710, p < 0.001; HR: 0.630, 95% CI: 0.540–0.740, p < 0.001, respectively). Conclusion Compared with postoperative conservative treatment, pa-TACE, postoperative radiotherapy and sorafenib can improve the prognosis of patients with hepatocellular carcinoma with microvascular invasion after curative resection. Postoperative radiotherapy can reduce the recurrence of patients with HCC with MVI after curative resection compared with pa-TACE.

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