Multi-analyte analysis of cytokines that predict outcomes in patients with hepatocellular carcinoma treated with radiotherapy

AIM To analyze cytokine levels and to identify their association with outcome in patients with hepatocellular carcinoma(HCC) treated with radiotherapy(RT). METHODS Patients with HCC who were treated with RT were eligible for this prospective study. Blood samples were collected before and after RT, and serum cytokine levels including interleukin(IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α were analyzed. RESULTS Between 2008 and 2009, 51 patients were enrolled in this study. Baseline IL-6 level was high in patients with a history of pre-RT treatment. Median survival was 13.9 mo with alpha-fetoprotein(AFP) as a significant factor(P = 0.020). Median failure-free survival(FFS) for infield, outfield-intrahepatic and extrahepatic failures were 23.3, 11.5 and 12.0 mo, respectively. Sex and baseline IL-6 level were associated with infield FFS, and baseline IL-10 level was correlated with outfield-intrahepatic FFS. For extrahepatic FFS, AFP was significant(P =0.034). Patients with a baseline IL-6 level of ≥ 9.7 pg/m L showed worse infield FFS(P = 0.005), and this significance was observed only in treatment-non-na?ve patients(P = 0.022). CONCLUSION In addition to AFP, cytokines seem useful in predicting infield and outfield-intrahepatic failure. Serum cytokines could be useful biomarkers for predicting RT outcome in HCC.

Radiotherapy as an immune checkpoint blockade combination strategy for hepatocellular carcinoma

In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies.Radiotherapy(RT),an attractive modality,can be combined with ICIs,which act as strong modulators of the tumor immune microenvironment.Herein,we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multiinstitutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma(GBC)has remained unclear due to lack of randomized controlled trials;thus,the aim of present study was to evaluate the role of adjuvant treatments,including chemoradiotherapy(CRT)and/or chemotherapy(CTx),in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database.Of 733 patients,372(50.8%)did not receive adjuvant treatment,whereas 215(29.3%)and 146(19.9%)received adjuvant CTx and CRT,respectively.The locoregional recurrence-free survival(LRFS),recurrence-free survival(RFS),and overall survival(OS)of the adjuvant treatment groups were compared according to tumor stage(stage II vs.stage III–IV).Results:In stage II disease(n=381),the 5-year LRFS,RFS,and OS were not significantly different among the no-adjuvant therapy,CTx,and CRT groups,and positive resection margin,presence of perineural invasion,and Nx classification were consistently associated with worse LRFS,RFS,and OS in the multivariate analysis(P<0.05).For stage III–IV(n=352),the CRT group had significantly higher 5-year LRFS,RFS,and OS than the no-adjuvant therapy and CTx groups(67.8%,45.2%,and 56.9%;37.9%,28.8%,and 35.4%;and 45.0%,30.0%,and 45.7%,respectively)(P<0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease.Further study is needed for stage II disease with high-risk features.

Stereotactic body radiation therapy and radiofrequency ablation in patients with hepatocellular carcinoma:not a rival but a partner for the cure

Among various liver-directed local treatments for hepatocellular carcinoma(HCC),stereotactic body radiation therapy(SBRT),which delivers a highly ablative dose to the tumor,has increasingly been adopted in clinical practice and demonstrates favorable outcomes.Given the low priority of SBRT in the current treatment guidelines(1,2),there have been several series comparing SBRT and other local treatments,such as radiofrequency ablation(RFA),transarterial chemoembolization.

The role of postoperative radiotherapy in hepatocellular carcinoma

Surgery is the standard treatment for early-stage hepatocellular carcinoma(HCC).However,the application of surgery is frequently expanded in real-world practice beyond the early stage,involving even advanced HCC associated with vascular invasion(1).Two important issues arise when the scope of surgery in HCC is expanded:achieving R0 resection and preserving sufficient future remnant liver volume.These two issues often contradict each other in HCC with large size or vascular invasion because surgeons try to secure sufficient future remnant liver to avoid post-resection liver failure,thereby leading to narrow-margin hepatectomy.