Dataset Information

Effects of Stereotactic Body Radiation Therapy Plus PD-1 Inhibitors for Patients With Transarterial Chemoembolization Refractory.

ABSTRACT:

Background and aims

Patients with intermediate-stage hepatocellular carcinoma (HCC) who are refractory to transarterial chemoembolization (TACE) have a poor prognosis. This study aimed to explore whether stereotactic body radiation therapy (SBRT) combined with PD-1 inhibitors could improve the clinical outcomes of such patients.

Methods

This retrospective cohort study included patients with intermediate-stage HCC who were diagnosed with TACE refractoriness between January 2019 and December 2020 in the Eastern Hepatobiliary Surgery Hospital and the First Affiliated Hospital of Wenzhou Medical University. The patients were divided into two groups: (1) those who switched from TACE to receive stereotactic body radiotherapy (SBRT) combined with PD-1 inhibitors; (2) those who continued TACE treatment and added PD-1 inhibitors. Progression-free survival (PFS), overall survival (OS), and tumour response were assessed in both groups after becoming refractory to TACE treatment.

Results

Of the seventy-six patients included in this study, the median PFS was 19.6 months in the SBRT-IO group (n=31) and 10.1 months in the TACE-IO group (n=45, p<0.05). The SBRT-IO group also had a significantly higher OS than the TACE-IO group (p<0.05). The objective response rate (ORR) and disease control rate (DCR) were also better in the SBRT-IO group (ORR, 71.0% vs. 15.6%, OR=8.483, 95% CI 3.319-21.680, P < 0.001; DCR, 80.6% vs. 31.1%, OR=9.226, 95% CI 3.096-27.493, P < 0.001).

Conclusions

SBRT combined with a PD-1 inhibitor improves PFS and OS in TACE-refractory patients with intermediate-stage HCC. Therefore, this therapy is a suitable option in cases of TACE treatment failure.

SUBMITTER: Xiang YJ

PROVIDER: S-EPMC8978966 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Effects of Stereotactic Body Radiation Therapy Plus PD-1 Inhibitors for Patients With Transarterial Chemoembolization Refractory.

Xiang Yan-Jun YJ Wang Kang K Zheng Yi-Tao YT Feng Shuang S Yu Hong-Ming HM Li Xiao-Wei XW Cheng Xi X Cheng Yu-Qiang YQ Feng Jin-Kai JK Zhou Li-Ping LP Meng Yan Y Zhai Jian J Shan Yun-Feng YF Cheng Shu-Qun SQ

Frontiers in oncology 20220321

<h4>Background and aims</h4>Patients with intermediate-stage hepatocellular carcinoma (HCC) who are refractory to transarterial chemoembolization (TACE) have a poor prognosis. This study aimed to explore whether stereotactic body radiation therapy (SBRT) combined with PD-1 inhibitors could improve the clinical outcomes of such patients.<h4>Methods</h4>This retrospective cohort study included patients with intermediate-stage HCC who were diagnosed with TACE refractoriness between January 2019 and ...[more]

PMID: 35387113

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Project description:BackgroundLiver transplantation (LT) presents a curative treatment option in patients with early stage hepatocellular carcinoma (HCC) who are not eligible for resection or ablation therapy. Due to a risk of up 30% for waitlist drop-out upon tumor progression, bridging therapies are used to halt tumor growth. Transarterial chemoembolization (TACE) and less commonly stereotactic body radiation therapy (SBRT) or a combination of TACE and SBRT, are used as bridging therapies in LT. However, it remains unclear if one of those treatment options is superior. The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology.AimTo analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone.MethodsIn this multicenter retrospective study, 27 patients who received liver transplantation for HCC were analyzed. Patients received either TACE or SBRT alone, or a combination of TACE and SBRT as bridging therapy to liver transplantation. Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies. Statistical analysis was performed using Fisher-Freeman-Halton exact test, Kruskal-Wallis and Mann-Whitney-U tests.ResultsFourteen patients received TACE only, four patients SBRT only, and nine patients a combination therapy of TACE and SBRT. There were no significant differences between groups regarding age, sex, etiology of underlying liver disease or number and size of tumor lesions. Strikingly, analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group (8/9, 89%) showed no residual vital tumor tissue by histopathology, whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response (0/14, 0% and 1/4, 25%, respectively, P value < 0.001).ConclusionOur data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation.

Project description:Background and Objective: It is unclear if stereotactic body radiation therapy (SBRT) or transarterial chemoembolization (TACE) is better for the treatment of inoperable early-stage hepatocellular carcinoma (HCC). This study aimed to retrospectively compare the efficacy of SBRT to TACE in patients with inoperable Barcelona Clinic Liver Cancer (BCLC)-A stage HCC. Materials and Methods: In this multi-institutional retrospective study, a total of 326 patients with inoperable BCLC-A stage HCC were enrolled. Totally, 167 patients initially received SBRT and 159 initially received TACE. Overall survival (OS), local control (LC), intrahepatic control (IC), and progression-free survival (PFS) were evaluated in univariable and propensity-score matched analyses. Results: There was a smaller median tumor size in the SBRT group than in the TACE group (3.4 cm vs. 7.2 cm, P < 0.001). After propensity score matching in the selection of 95 patient pairs, SBRT had better LC, IC, and PFS than TACE but showed comparable OS. The accumulative 1-, 3-, and 5-year OS rates were 85.7, 65.1, and 62.8% in the SBRT group and 83.6, 61.0, and 50.4% in the TACE group, respectively (P = 0.29). The accumulative 1-, 3-, and 5-year PFS were 63.4, 35.9, and 27.5% in the SBRT group and 53.5, 27.4, and 14.2% in the TACE group, respectively (P = 0.049). The accumulative 1-, 3-, and 5-year LC were 86.8, 62.5, and 56.9% in the SBRT group and 69.3, 53.3, and 36.6% in the TACE group, respectively (P = 0.0047). The accumulative 1-, 3-, and 5-year IC were 77.3, 45.9, and 42.4% in the SBRT group and 57.3, 34.1, and 17.7% in the TACE group, respectively (P = 0.003). On multivariate analysis, treatment (SBRT vs. TACE) was a significant covariate associated with local and intrahepatic control (HR = 1.59; 95% CI: 1.03-2.47; P = 0.04; HR = 1.61; 95% CI: 1.13-2.29; P = 0.009). Conclusions: SBRT was an alternative to TACE for inoperable BCLC-A stage HCC with better local and intrahepatic control. Controlled clinical trials are recommended to evaluate the actual effects of this novel regimen adequately.

Project description:Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

Project description:IntroductionPrior studies suggest lymphopenia following radiation therapy may impact toxicity and cancer control. Chronic radiation-related lymphopenia (RRL) has been noted in prostate cancer patients treated with conventionally fractionated pelvic radiation therapy. The impact of utilizing hypofractionated high integral dose therapies such as stereotactic body radiation therapy (SBRT) on RRL is less well characterized. This prospective study sought to evaluate the impact of prostate SBRT plus or minus supplemental pelvic nodal radiation (PNI) on RRL.MethodsBetween 2012 and 2023, serial serum absolute lymphocyte counts (ALCs) were measured in 226 men treated at MedStar Georgetown with robotic SBRT using the CyberKnife® (CK) (36.25 Gy in 5 fractions) alone or CK (19.5 Gy in 3 fractions) followed by supplemental PNI using VMAT (37.5-45.0 Gy in 15-25 fractions) per an institutional protocol (IRB#: 2012-1175). Baseline ALC (k/μL) was measured 1-2 hours prior to robotic SBRT and at each follow-up appointment (1, 3, 6, 9, 12, 18, and 24 months post-treatment). Lymphopenia was graded using the CTCAEv.4: Grade 1 (0.8-1.0 k/μL), Grade 2 (0.5-0.8 k/μL), Grade 3 (0.2-0.5 k/μL) and Grade 4 (<0.2 k/μL). To compare two different treatment groups, the Wilcoxon signed-rank test was used. A p-value of < 0.05 determined statistical significance.ResultsOf 226 patients (SBRT alone: n = 169, SBRT + PNI: n = 57), the median age was 72 years and 45% of patients were non-white. Baseline lymphopenia was uncommon and of low grade. In the SBRT alone group, the baseline ALC of 1.7 k/μl decreased by 21% to 1.4 k/μL at 3 months and then stabilized. 38% of these men experienced lymphopenia in the two years following SBRT, however, no patient presented with Grade 3 lymphopenia. Patients who received SBRT + PNI had a lower baseline ALC (1.5 k/μl), and a significantly greater decrease in ALC relative to individual baseline value throughout the 2-year follow-up period, decreasing by 57% to 0.6 k/μL at 3 months and recovering to a 36% decrease from baseline (1.0 k/μL) at 24 months. Notably, 12% of the men treated with SBRT + PNI experienced Grade 3 lymphopenia. No patient in either cohort experienced Grade 4 lymphopenia.DiscussionThe low incidence of high-grade lymphopenia within this elderly patient population further supports the safety of prostate SBRT plus or minus PNI for the treatment of prostate cancer. However, RRL was more severe when PNI was utilized. The effect of SBRT and PNI on lymphocytes in prostate cancer patients could act as a model for other cancers, specifically those involving treatment with immunomodulatory agents. Future studies should focus on the clinical implications of RRL and the effects of specifically irradiating lymphoid tissues on lymphocyte biology.

Dataset Information

Effects of Stereotactic Body Radiation Therapy Plus PD-1 Inhibitors for Patients With Transarterial Chemoembolization Refractory.

Background and aims

Methods

Results

Conclusions

Publications

Effects of Stereotactic Body Radiation Therapy Plus PD-1 Inhibitors for Patients With Transarterial Chemoembolization Refractory.

Similar Datasets

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