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1.
JHEP Rep ; 5(1): 100594, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36561128

ABSTRACT

Background & Aims: Radiofrequency ablation (RFA) and ablative external beam radiotherapy (ablative RT) are commonly used to treat small intrahepatic malignancies. We meta-analysed oncologic outcomes and systematically reviewed the clinical consideration of tumour location and size. Methods: PubMed, Medline, Embase, and Cochrane Library databases were searched on February 24, 2022. Studies comparing RFA and ablative RT, providing one of the endpoints (local control or survival), and encompassing ≥5 patients in each arm were included. Results: Twenty-one studies involving 4,638 patients were included. Regarding survival, the odds ratio (OR) was 1.204 (p = 0.194, favouring RFA, not statistically significant) among all studies, 1.253 (p = 0.153) among hepatocellular carcinoma (HCC) studies, and 1.002 (p = 0.996) among colorectal cancer metastasis studies. Regarding local control, the OR was 0.458 (p <0.001, favouring ablative RT) among all studies, 0.452 (p <0.001) among HCC studies, favouring the ablative RT arm, and 0.649 (p = 0.484) among colorectal cancer metastasis studies. Pooled 1- and 2-year survival rates for HCC studies were 91.8% and 77.7% after RFA, and 89.0% and 76.0% after ablative RT, respectively; and for metastasis studies were 88.2% and 66.4% after RFA and 82.7% and 60.6% after RT, respectively. Literature analysis suggests that ablative RT can be more effective than RFA for tumours larger than 2-3 cm or for specific sublocations in the liver (e.g. subphrenic or perivascular sites), with moderate quality of evidence (reference to the grading system of the American Society for Radiation Oncology Primary Liver Cancer Clinical Guidelines). The pooled grade ≥3 complication rates were 2.9% and 2.8% in the RFA and ablative RT arms, respectively (p = 0.952). Conclusions: Our study shows that ablative RT can yield oncologic outcomes similar to RFA, and suggests that it can be more effective for the treatment of tumours in locations where RFA is difficult to perform or for large-sized tumours. Systematic Review Registration: This study was registered with PROSPERO (Protocol No: CRD42022332997). Impact and implications: Radiofrequency ablation (RFA) and ablative radiotherapy (RT) are non-surgical modalities for the treatment of small intrahepatic malignancies. Ablative RT showed oncologic outcomes at least similar to those of RFA, and was more effective at specific locations (e.g. perivascular or subphrenic locations).

2.
Cancers (Basel) ; 14(23)2022 Nov 27.
Article in English | MEDLINE | ID: mdl-36497330

ABSTRACT

We investigated the clinical efficacy of stereotactic ablative radiotherapy (SABR) in patients with oligometastatic hepatocellular carcinoma (HCC). The inclusion criteria were patients receiving definitive treatment for HCC with 1-5 metastatic lesions, <3 metastases in a single organ and receiving radiotherapy with fraction doses ≥6 Gy. A total of 100 patients with 121 metastatic lesions were reviewed. The most common site of metastasis was the bones (40%), followed by the lungs (38%). Systemic therapy was administered to 71% of patients. With a median follow-up of 13 months, the median overall survival (OS) was 16 months. The 2-year OS rate was 40%. The prognostic factors in univariate analysis were performance status, Child-Pugh class, primary HCC status, and time interval of metastasis. Performance status and Child-Pugh class remained in multivariate analysis. OS differed significantly depending on the number of prognostic factors: 46 months in patients with both factors (Group 1), 13 months with one factor (Group 2), and 6 months with no risk factor (Group 3) (p < 0.001). Nine patients experienced grade 1 radiation pneumonitis. Given its efficacy and safety, SABR deserves active consideration in the treatment of oligometastatic HCC.

4.
J Hepatocell Carcinoma ; 9: 707-715, 2022.
Article in English | MEDLINE | ID: mdl-35966184

ABSTRACT

Background/Purpose: The Asian Liver Radiation Therapy Study Group has formed a large and detailed multinational database of outcomes following stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). Here, we explored the potential impact of HCC etiology on SBRT efficacy. Tumor control probability (TCP) models were established to estimate the likelihood of local control (LC). Methods: Data from 415 patients who were treated with SBRT for HCC were reviewed. Cox proportional hazards models were used to identify key predictors of LC. TCP models accounting for biologic effective dose (BED) and tumor diameter were generated to quantify associations between etiology and LC. Results: Cox models demonstrated that hepatitis C virus (HCV) infection was associated with favorable LC following SBRT (HR=0.52, 95% CI 0.04-0.96, p=0.036). The 2-year LC rate for patients with HCV etiology was 88%, compared to 78% for other patients. Small tumor and high BED were also associated with favorable LC. TCP models demonstrated a 10-20% absolute increase in predicted LC across the range of SBRT doses and tumor sizes. Conclusion: We found a novel association between HCV status and LC after SBRT for HCC that warrants further exploration. If validated in other datasets, our findings could help clinicians tailor SBRT schedules.

5.
Liver Cancer ; 11(3): 247-255, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35949293

ABSTRACT

Introduction: In the era of biomarker-driven cancer therapy, robust biomarkers for hepatocellular carcinoma (HCC) have not been well-defined. In this hypothesis-generating study, we investigated biomarkers that can be incorporated to predict treatment outcomes in patients with locally advanced HCC who are administered liver-directed combined radiotherapy (LDCRT). Methods: Ninety-nine patients with HCC who were treated with conventional fractionation LDCRT between July 2016 and October 2018 were enrolled in this prospective single-arm study. Clinical outcomes and possible serum biomarkers, including soluble programmed cell death ligand-1 (sPD-L1), interleukin (IL)-10, IL-6, cell-free DNA (cfDNA), inter-alpha inhibitor H4, and interferon-gamma, were analyzed. The primary endpoint was disease progression, and additional endpoints were local failure-free rate, intrahepatic failure-free rate, and lung metastasis-free rate. Results: The median follow-up period was 18.7 months. The 1-year progression-free rate was 38.2%. Increasing baseline sPD-L1 per pg/mL, previous treatment history, protein induced by vitamin K absence-II >1,629 mAU/mL, and multiple tumors were the adverse factors for progression based on multivariate analysis. Survival tree analysis revealed three prognostic groups for progression, in which patients with multiple lesions and baseline sPD-L1 ≥41.07 pg/mL showed the worst outcomes. For dynamic changes in biomarker levels, sPD-L1 fold change and cfDNA fold-change values were unfavorable factors for progression. Conclusion: Baseline sPD-L1, sPD-L1 fold change, and cfDNA fold-change values showed the highest potential as biomarkers for predicting post-treatment progression after LDCRT in HCC patients. By incorporating clinical factors, these biomarkers may be useful for devising a biomarker-driven treatment paradigm in locally advanced HCC.

6.
Cancers (Basel) ; 14(10)2022 May 12.
Article in English | MEDLINE | ID: mdl-35626001

ABSTRACT

This study aimed to investigate the efficacy of liver-directed concurrent chemoradiotherapy (LD-CCRT) compared with sorafenib in patients with liver-confined locally advanced hepatocellular carcinoma (HCC) presenting portal vein tumor thrombosis (PVTT). This single institute retrospective cohort study included patients treated with sorafenib or LD-CCRT between 2005 and 2016. Patients with extrahepatic disease and those without PVTT were excluded, leaving 28 and 448 patients in the sorafenib and LD-CCRT groups, respectively. Propensity score matching was performed to balance the differences in clinical features between the two groups. At baseline, the sorafenib group presented higher incidences of unfavorable clinical features, including type III-IV PVTT (53.6% vs. 30.6%, p = 0.048) and bilateral disease extent (64.3% vs. 31.5%, p = 0.001), than the LD-CCRT group. A total of 27 patients from the sorafenib group and 52 patients from the LD-CCRT group were matched. At a median follow-up of 73 months, the median overall survival (OS) was 4.3 and 9.8 months in the sorafenib and LD-CCRT groups, respectively (p = 0.002). Patients with PVTT type II and higher benefited more from LD-CCRT in terms of OS. The Cox proportional hazard model showed that LD-CCRT was a significant prognostic factor for OS. One patient from the sorafenib group and seven patients from the LD-CCRT group underwent curative surgical treatment. Patients who underwent surgical treatment had significantly longer OS. In conclusion, LD-CCRT showed superior survival outcomes to sorafenib in HCC patients with PVTT. LD-CCRT needs further consideration for its substantial local tumor control that can enable curative surgical treatment in selected patients.

7.
Hepatol Int ; 16(3): 712-727, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35532861

ABSTRACT

BACKGROUND AND PURPOSE: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies. METHODS: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm). RESULTS: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted. CONCLUSION: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment. PROTOCOL REGISTRATION: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).


Subject(s)
Gallbladder Neoplasms , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/radiotherapy , Humans , Neoplasm Recurrence, Local , Radiotherapy, Adjuvant/methods
8.
J Hepatocell Carcinoma ; 9: 357-366, 2022.
Article in English | MEDLINE | ID: mdl-35520947

ABSTRACT

Purpose: Skull base metastasis (SBM) from hepatocellular carcinoma (HCC) presents detrimental survival outcomes with cranial nerve symptoms; however, they have received little attention. This study aimed to investigate the clinical presentation and efficacy of radiation therapy (RT) in patients with SBM from HCC. Patients and Methods: We identified patients with SBM from HCC in Yonsei Cancer Center from 2005 to 2019. Image evaluations and SBM-related symptoms were reviewed. Overall survival was calculated using the Kaplan-Meier method and compared through the Log rank test. The oligometastasis group included patients with less than five foci of tumors, while the extensive metastasis group presented five or more sites. Results: The incidence of SBM from HCC was 1.5% (58/3793 patients), commonly found in the middle cranial fossa. SBM associated symptoms presented in 51 patients, and the most common were head and neck area pain, and orbital symptoms, The palliation rate after RT was 65% (24/39 patients) for overall symptoms and 83.3% (20/24 patients) for cranial nerve symptoms. In whole cohort, overall survival was analyzed, and the median overall survival of patients with oligometastasis was better than extensive metastasis (23.7 months vs 1.8 months, p < 0.001). In subgroup who received RT (39 patients), the median overall survival was 23.7 and 2.7 months for patients with oligo and extensive metastasis, respectively (p < 0.001). Conclusion: This study confirmed clinical features of SBM from HCC. Overall survival was generally poor, but patients presenting oligometastasis seemed to have possibility of relative long-term survival. Although radiation was effective in SBM-induced symptom relief, dose-response relationship in local control rate and overall survival needs further studies with larger number of patients.

9.
Jpn J Clin Oncol ; 52(6): 616-622, 2022 May 31.
Article in English | MEDLINE | ID: mdl-35311896

ABSTRACT

OBJECTIVE: Hypofractionated radiotherapy has recently been applied to treat pulmonary metastases of hepatocellular carcinoma. However, there is no definite evidence on its safety and efficacy. We evaluate the clinical outcomes of hypofractionated radiotherapy for oligo pulmonary metastases of hepatocellular carcinoma in the multicenter and retrospective study. METHODS: From March 2011 to February 2018, 58 patients with fewer than five pulmonary metastases of hepatocellular carcinoma who underwent hypofractionated radiotherapy in nine tertiary university hospitals were analyzed retrospectively. The primary endpoint was the local control rate. The secondary endpoints were overall survival, progression-free survival, prognostic factors affecting the treatment outcomes and treatment-related side effects. RESULTS: The local tumor response rate including complete and partial response was 77.6% at 3 months after hypofractionated radiotherapy. The median survival and progression-free survival times were 20.9 and 5.3 months, respectively. The 1-year overall survival and progression-free survival rates were 65.5 and 22.4%, respectively. The good treatment response after hypofractionated radiotherapy (P = 0.001), the absence of intrahepatic tumor (P = 0.004) and Child-Pugh class A (P = 0.010) were revealed as significant prognostic factors for overall survival in the multivariate analysis. A progression-free interval of <6 months (P = 0.009) was a negative prognostic factor for overall survival in the multivariate analysis. Of 58 patients, five (8.6%) had grade 2 or higher radiation pneumonitis after hypofractionated radiotherapy. CONCLUSIONS: The favorable local control rate and acceptable toxicity indicate the clinical usefulness of hypofractionated radiotherapy for hepatocellular carcinoma patients who have less than five pulmonary metastases.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Lung Neoplasms , Radiosurgery , Carcinoma, Hepatocellular/radiotherapy , Humans , Liver Neoplasms/radiotherapy , Lung Neoplasms/pathology , Radiosurgery/adverse effects , Retrospective Studies , Treatment Outcome
10.
Hepatobiliary Surg Nutr ; 11(1): 123-125, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35284525
11.
Eur J Cancer ; 157: 31-39, 2021 11.
Article in English | MEDLINE | ID: mdl-34474218

ABSTRACT

PURPOSE: To evaluate the role of adjuvant radiotherapy (RT) after curative resection in patients with extrahepatic bile duct (EHBD) cancer. METHODS: Between January 2000 and December 2015, 1475 patients with EHBD cancer who underwent curative resection were accrued from 14 institutions in Korea. Among these, 959 patients did not receive any adjuvant therapy (RT(-) group), while 516 underwent postoperative RT with or without chemotherapy (RT(+) group). RESULTS: The median age was 67 years. Nodal involvement was present in 482 patients (32.7%), and resection margin was involved in 293 patients (19.9%). RT(+) group had more patients with proximal tumours, advanced tumours, nodal involvement, perineural invasion, and involved resection margin than RT(-) group (all p < 0.001). With a median follow-up of 36 months, there were 211 locoregional recurrences, 307 distant metastases and 322 combined locoregional and distant failures. On multivariate analysis incorporating age, tumour location, differentiation, pT classification, pN classification, perineural invasion and resection margin, adjuvant RT was associated with improved overall survival (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p < 0.001). When RT(+) group was separated into RT alone, concurrent chemoradiotherapy (CCRT) and CCRT followed by chemotherapy, the greatest benefit was observed in patients treated with CCRT followed by chemotherapy (hazard ratio, 0.52; 95% confidence interval, 0.41-0.68). CONCLUSIONS: Adjuvant RT combined with chemotherapy improved survival outcomes of resected EHBD cancer patients. Considering the greatest benefit observed in patients receiving CCRT followed by chemotherapy, a randomised controlled trial comparing chemotherapy alone and CCRT followed by chemotherapy is urgently needed.


Subject(s)
Bile Duct Neoplasms/therapy , Bile Ducts, Extrahepatic , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Chemoradiotherapy, Adjuvant , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies
12.
Cancer Biol Med ; 19(6)2021 12 20.
Article in English | MEDLINE | ID: mdl-34919359

ABSTRACT

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.


Subject(s)
Chemoradiotherapy, Adjuvant , Gallbladder Neoplasms , Combined Modality Therapy , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/surgery , Humans , Neoplasm Staging
13.
Liver Cancer ; 10(5): 419-432, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34721505

ABSTRACT

INTRODUCTION: The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. METHODS: PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). RESULTS: Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10-21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, p = 0.035; 34.3% versus 44.7%, p = 0.025; 25.6% versus 31.7%, p = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (p = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, p = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, p = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, p = 0.143; 38.5% versus 49.2%, p = 0.026; and 27.8% versus 34.5%, p = 0.11, respectively. CONCLUSIONS: ART was shown to improve OS in all studies and in those selected for their reliable comparability.

14.
Radiat Oncol ; 16(1): 161, 2021 Aug 23.
Article in English | MEDLINE | ID: mdl-34425855

ABSTRACT

BACKGROUND: Gastric bleeding negatively impacts the quality of life of patients with unresectable advanced gastric cancer and is frequently lethal. We investigated the efficacy of RT for palliation of gastric bleeding from gastric cancer and identified an optimal radiotherapy (RT) strategy. METHODS: The study analyzed 57 patients submitted to palliative RT for gastric bleeding associated with gastric cancer between January 2009 and February 2019. Changes in hemoglobin (Hb) levels were analyzed based on measurements taken before and immediately, 1 month, and 2 months after RT. Re-bleeding after RT was identified as either Hb level dropping to < 7.0 g/dL or the administration of a blood transfusion after RT. RESULTS: The median biologically effective dose (α/ß = 10) was 37.5 Gy (range 23.6-58.5). The most common regimen was 25 Gy in five fractions. The mean Hb levels before, immediately after, 1 month, and 2 months after RT (6.6, 9.7, 10.3, and 9.7 g/dL, respectively) were significantly higher than that before RT (all p < 0.001). No significant differences in re-bleeding rates were observed according to total dose, fractional dose, and fraction number. Gastric tumor response evaluated by computed tomography within 2 months after RT showed partial responses were more frequent in patients achieving bleeding control (25.0% vs. 10.8%, p = 0.023) and overall survival was significantly improved for bleeding control within 3 months after RT (median, 15.4 vs. 10.0 weeks, p = 0.048). CONCLUSIONS: RT was an effective modality for gastric bleeding control in gastric cancer, which can be achieved with a short course scheme with five fractions.


Subject(s)
Gastrointestinal Hemorrhage/radiotherapy , Stomach Neoplasms/complications , Adult , Aged , Aged, 80 and over , Blood Transfusion , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Palliative Care , Radiotherapy Dosage , Recurrence
15.
Yonsei Med J ; 62(5): 409-416, 2021 May.
Article in English | MEDLINE | ID: mdl-33908211

ABSTRACT

PURPOSE: The optimal timing for radiotherapy (RT) after incomplete transarterial chemoembolization (TACE) remains unclear. This study investigated the optimal timing to initiate RT after incomplete TACE in patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma. MATERIALS AND METHODS: This study included 116 lesions in 104 patients who were treated with RT after TACE between 2001 and 2016. The time interval between the last TACE session and RT initiation was retrospectively analyzed. The optimal cut-off time interval that maximized the difference in local failure-free rates (LFFRs) was determined using maximally selected rank statistics. RESULTS: The median time interval was 26 days (range: 2-165 days). At a median follow-up of 18 months (range: 3-160 months), the median overall survival was 18 months. The optimal cut-off time interval appeared to be 5 weeks; using this cut-off, 65 and 39 patients were classified into early and late RT groups, respectively. Early RT group had a significantly poorer Child-Pugh class and higher alpha-fetoprotein levels compared to late RT group. Other characteristics, including tumor size (7 cm vs. 6 cm; p=0.144), were not significantly different between the groups. The 1-year LFFR was significantly higher in the early RT group than in the late RT group (94.6% vs. 70.8%; p=0.005). On multivariate analysis, early RT was identified as an independent predictor of favorable local failure-free survival (hazard ratio: 3.30, 95% confidence interval: 1.50-7.29; p=0.003). CONCLUSION: The optimal timing for administering RT after incomplete TACE is within 5 weeks. Early administration of RT is associated with better local control.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
16.
J Cancer Res Clin Oncol ; 147(10): 3123-3133, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33893539

ABSTRACT

BACKGROUND: We compared the clinical efficacies of hepatic arterial infusion chemotherapy (HAIC) vs. sorafenib as sequential maintenance therapy following liver-directed concurrent chemoradiotherapy (LD-CCRT) for locally advanced-stage hepatocellular carcinoma (HCC). METHODS: Patients undergoing HAIC with 5-fluorouracil and cisplatin (HAIC-maintain group, n = 151) or sorafenib (Sorafenib-maintain group, n = 37) after LD-CCRT were consecutively enrolled. The study endpoints were overall survival (OS), progression-free survival (PFS), and treatment response rates. RESULTS: The median OS among HAIC-maintain and Sorafenib-maintain groups were 15.9 and 24.3 months (p = 0.287), whereas the median PFS were 8.1 and 9.1 months (p = 0.651), respectively. During the planned treatments, the radiological objective response rate (54.3% vs. 64.9%; p = 0.246), and conversion rate to surgical resection or liver transplantation after successful down-staging (15.9% vs. 18.9%; p = 0.657) were comparable between the HAIC-maintain and Sorafenib-maintain groups. Similar results were found after the inverse probability of treatment weighting and propensity score-matching analyses. Regarding treatment-related adverse events, the HAIC-maintain group showed worse profiles in terms of leukopenia (all grades [p = 0.001] and grades 3 or 4 [p = 0.041]) and hypoalbuminemia (p = 0.001) than the Sorafenib-maintain group. CONCLUSIONS: The overall clinical efficacies between the sequential treatment of HAIC vs. sorafenib after LD-CCRT were comparable for locally advanced HCC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/pathology , Chemoradiotherapy/mortality , Liver Neoplasms/pathology , Maintenance Chemotherapy/mortality , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/therapy , Cisplatin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Infusions, Intra-Arterial , Liver Neoplasms/drug therapy , Liver Neoplasms/therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Sorafenib/administration & dosage , Survival Rate
17.
World J Gastroenterol ; 27(10): 919-927, 2021 Mar 14.
Article in English | MEDLINE | ID: mdl-33776363

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/radiotherapy , Combined Modality Therapy , Humans , Immune Checkpoint Inhibitors , Liver Neoplasms/drug therapy , Liver Neoplasms/radiotherapy , Tumor Microenvironment
18.
J Hepatocell Carcinoma ; 8: 35-44, 2021.
Article in English | MEDLINE | ID: mdl-33604314

ABSTRACT

PURPOSE: With respect to various solid cancers, patients with oligometastasis may benefit from local therapy. However, this approach is not widely accepted for hepatocellular carcinoma. This study investigated the efficacy of local therapy for oligometastatic lesions in patients with hepatocellular carcinoma. PATIENTS AND METHODS: The study included 69 hepatocellular carcinoma patients presenting with oligometastasis to the lung. Characteristics of the patients and treatment options for metastatic lesions were reviewed, and a survival analysis was performed. After propensity score matching, overall survival and progression-free survival were calculated from the time of pulmonary metastasis detection. Factors predicting prognosis were analyzed using a multivariate Cox regression analysis. RESULTS: After propensity score matching, 58 patients with Child-Pugh grade A disease were selected. Among them, 22 patients were treated with systemic therapy alone while 36 patients received local therapy or a combination of local and systemic therapies for metastatic lesions. Survival rates were higher in patients receiving local therapy than in those receiving systemic therapy (2-year overall survival rate, 66.6 vs 31.2%, p<0.001; 2-year progression-free survival rate, 47.0 vs 10.6%, p=0.005). In the multivariate Cox regression analysis, alpha-fetoprotein levels less than 400 ng/mL and the use of local therapy for metastatic lesions were found to be significant favorable prognostic factors. CONCLUSION: Local therapy for metastatic lesions improved the oncologic outcomes of patients with hepatocellular carcinoma with pulmonary oligometastasis.

19.
J Cancer Res Clin Oncol ; 147(9): 2693-2700, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33582874

ABSTRACT

PURPOSE: For bone metastasis from hepatocellular carcinoma (HCC), radiotherapy (RT) has been used a palliative treatment with little impact on survival. Currently, ablative RT is popularly used, and a more than palliative effect is expected. Herein, we investigated the clinical efficacy of ablative RT in patients with bone metastasis from HCC. METHODS: In total, 530 patients with 887 lesions treated in 1992-2019 were reviewed. Oligometastasis was defined as the presence of < 5 lesions. Total doses were normalized to obtain biologically effective doses (BEDs). The cut-off threshold of the BED was determined via receiver operating characteristics curve analysis. The Kaplan-Meier method was used to calculate overall survival (OS); propensity score matching (PSM) was performed to balance the heterogeneity in cases while comparing BEDs of ≥ 60 and < 60 Gy. RESULTS: The most common site of metastasis was the spine (59%); 59 patients (11%) presented with oligometastasis, and 76.2% of patients showed objective pain palliation after RT. Median OS was 5.1 months for all patients; patients with oligometastasis showed longer OS than those without (9.8 vs. 4.7 months). A Cox proportional hazards model showed that performance status, Child-Pugh class, extraosseous metastasis, primary HCC status, α-fetoprotein level, and radiation dose (BED) were significant prognostic factors. Post PSM, BED was the only treatment-related prognostic factor that remained significant; the median OS durations were 8.1 and 4.4 months when the BEDs were ≥ 60 and < 60 Gy, respectively. CONCLUSION: Ablative RT improved OS and pain palliation in patients with bone metastasis from HCC.


Subject(s)
Bone Neoplasms/radiotherapy , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Radiofrequency Ablation/mortality , Adult , Aged , Aged, 80 and over , Bone Neoplasms/secondary , Carcinoma, Hepatocellular/pathology , Female , Follow-Up Studies , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Radiotherapy Dosage , Retrospective Studies , Survival Rate , Young Adult
20.
Cancer Res Treat ; 53(4): 962-972, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33540496

ABSTRACT

PURPOSE: Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia. MATERIALS AND METHODS: A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/µL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively. RESULTS: Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. -0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months. CONCLUSION: IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.


Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Interleukin-7/blood , Liver Neoplasms/radiotherapy , Lymphocytes/pathology , Lymphopenia/pathology , Radiotherapy/adverse effects , Recovery of Function , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Female , Follow-Up Studies , Humans , Liver Neoplasms/pathology , Lymphopenia/blood , Lymphopenia/etiology , Lymphopenia/prevention & control , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate
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