Portal vein tumour thrombosis radiotherapy improves the treatment outcomes of immunotherapy plus bevacizumab in hepatocellular carcinoma: a multicentre real-world analysis with propensity score matching.

Background: This study aimed to evaluate the efficacy and safety of sequential immune checkpoint inhibitors (ICIs) plus bevacizumab therapy after radiotherapy for portal vein tumour thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Methods: Retrospective data were collected from 113 patients with HCC with PVTT. Patients in the PVTT radiotherapy (radiotherapy + ICIs + bevacizumab) and control groups (ICIs + bevacizumab) were enrolled according to propensity score matching (PSM) analysis (1:1). The differences in progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and potential factors affecting PFS between the groups were analysed. The adverse events (AEs) were compared between the two groups. Results: There were 47 patients in the two groups after PSM (1:1). The differences in neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), CRP, and CD4, CD8, and CD4-to-CD8 ratio before and after radiotherapy for PVTT (P < 0.05) in the PVTT radiotherapy group were significant. The patients in the PVTT radiotherapy group had a longer PFS (median, 9.6 vs. 5.4 months, P < 0.001), and the PFS rates of 3, 6, 9, and 12 months were 97.87% vs. 94.19%, 80.85% vs. 44.68%, 53.19% vs. 6.38%, and 23.40% vs. 0.00%, respectively (P < 0.001). There were also significant differences in the ORR (48.94% vs. 27.66%, P = 0.0339) and DCR (97.87% vs. 82.98%, P = 0.0141) between the two groups, and no serious AEs were observed. Multivariate Cox analysis showed that AFP expression, gross classification of HCC, PVTT type, extrahepatic metastasis, PVTT radiotherapy, and reduction in PVTT were independent factors influencing PFS (P < 0.05). Conclusions: Sequential ICIs plus bevacizumab therapy after radiotherapy for PVTT in patients with HCC is safe and feasible and may further prolong the PFS of patients.

Role of stereotactic body radiotherapy for inferior vena cava tumour thrombus in hepatocellular carcinoma.

INTRODUCTION: To evaluate the role of stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) patients with inferior vena cava tumour thrombus (IVCTT) who are not suitable for other loco-regional therapies. METHODS: This is an observational retrospective study done between May 2020 and April 2022. The data of 17 patients who underwent SBRT were collected. Patients of Child-Pugh score (CPS) A5-B7 and along with a liver reserve of ≥700 cc were included. Local control (LC), overall survival (OS) and adverse events including hepatic decompensation were carefully recorded. RESULTS: In the cohort, the tumour thrombus was extended to the right atrium in nine (52.9%) patients, and regional nodal and lung were found in 60% and 31.4% of patients respectively. The median gross tumour volume (GTV) was 745 cc (107-1,650 cc). The median SBRT dose prescription was 35 Gy (25-45 Gy) in 5-10 fractions. At 6 months, LC and OS were 80% and 75% respectively. On multivariate analysis, an ALBI score >-2.36 was found to be the predictor for the poor OS. Post-SBRT, a change in CPs by 2 points was observed in one patient (5.9%) which was managed conservatively. Post-radiation, improvement in pain and discomfort was observed in 92.3% and 87% of patients, respectively and bone metastasis related pain was also resolved. CONCLUSION: Stereotactic body radiotherapy is a safe and feasible option for HCC patients with IVC and right atrium tumour thrombosis. It not only improves the quality of life but also results in good LC and OS with acceptable toxicity. SBRT should be considered in a multidisciplinary fashion for patients presenting with tumour thrombosis extending to IVC and the right atrium.

Stereotactic ablative radiotherapy for unresectable inferior vena cava tumor thrombus in a patient with renal cell carcinoma: a case report.

PURPOSE: Treatment options for renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) are limited and carry substantial risks. Currently, there are no standard treatment options in the setting of recurrent or unresectable RCC with IVC-TT. METHODS: We report our experience of treating an IVC-TT RCC patient with stereotactic body radiation therapy (SBRT). RESULTS: This 62-year-old gentleman presented renal cell carcinoma with IVC-TT and liver metastases. Initial treatment consisted of radical nephrectomy and thrombectomy followed by continuous sunitinib. At 3 months, he developed an unresectable IVC-TT recurrence. A fiducial marker was implanted into the IVC-TT by catheterization. New biopsies were performed at the same time, demonstrating a recurrence of the RCC. SBRT consisted of 5 fractions of 7 Gy to the IVC-TT with excellent initial tolerance. He subsequently received anti-PD1 therapy (nivolumab). At 4 years follow-up, he is doing well with no IVC-TT recurrence and no late toxicity. CONCLUSION: SBRT appears to be a feasible and safe treatment for IVC-TT secondary to RCC in patients who are not candidates for surgery.

Is hepatocellular carcinoma complicated with portal vein tumor thrombosis potentially curable by radiotherapy in the form of stereotactic body radiation therapy?

PURPOSE: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal. Despite best treatment and care, the patients with this malignancy only showed 2.7-4 months of overall survival. It is debatable whether liver transplantation helps PVTT sufferers. The effectiveness of radiation therapy in treating HCC patients with PVTT should not be undervalued. By limiting the high dosage region to a small planning target volume, stereotactic radiation delivery has shifted toward hypofractionation, limiting the radiation exposure to healthy organs and tissues. Stereotactic body radiotherapy (SBRT) has a local control rate of 75-100%, depending on the treatment. The major limitation in SBRT for hepatocellular carcinoma with PVTT is the paucity of prospective evidence for longer periods beyond the first two years after treatment. More prospective studies/randomized clinical trials with a longer follow-up, larger sample size, and adequate statistical power are the dire need of the present situation to ascertain the curative effect of SBRT as primary therapy for advanced HCC with PVTT. CONCLUSION: SBRT can improve survival, particularly for patients receiving multidisciplinary treatment. This review sums up our most current understanding of how radiation therapy, notably SBRT, can be used to treat hepatocellular carcinoma when combined with PVTT. Recent research has led us to believe that irradiation in the form of SBRT may cure hepatocellular carcinoma complicated by PVTT.

Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram.

BACKGROUND: We evaluated the treatment response and predictive factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT), who underwent stereotactic body radiotherapy (SBRT). Additionally, we developed and validated a personalised prediction model for patient survival. METHODS: Clinical information was retrospectively collected for 80 patients with HCC and PVTT, who were treated with SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between December 2015 and June 2019. A multivariate Cox proportional hazard regression model was used to identify the independent predictive factors for survival. Clinical factors were subsequently presented in a nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the accuracy of the model and the net clinical benefit. RESULTS: All patients completed the planned radiotherapy treatment, and the median follow-up duration was 10 months (range, 1-35.3 months). The median survival duration was 11.5 months, with 3-, 6-, and 12-month survival rates of 92.5, 74.5, and 47.5%, respectively. The multivariable Cox regression model indicated that the following were significant independent predictors of OS: clinical T stage (p = 0.001, hazard ratio [HR] = 3.085, 95% confidence interval [CI]: 1.514-6.286), cirrhosis (p = 0.014, HR = 2.988, 95% CI: 1.246-7.168), age (p = 0.005, HR = 1.043, 95% CI: 1.013-1.075), alpha-fetoprotein level (p = 0.022, HR = 1.000, 95% CI: 1.000-1.000), and haemoglobin level (p = 0.008, HR = 0.979, 95% CI: 0.963-0.994). A nomogram based on five independent risk factors and DCA demonstrated a favourable predictive accuracy of patient survival (AUC = 0.74, 95% CI: 0.63-0.85) and the clinical usefulness of the model. CONCLUSIONS: SBRT is an effective treatment for patients with HCC with PVTT. Notably, clinical T stage, presence of cirrhosis, age, alpha-fetoprotein levels, and haemoglobin levels are independent prognostic factors for survival. The presented nomogram can be used to predict the survival of patients with HCC and PVTT, who underwent SBRT.

Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients: A retrospective study.

ABSTRACT: Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45-55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3-26.5 months). The median overall survival was 9.4 months (range, 3.7-26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.

Evaluation of the Efficacy and Toxicity of Radiotherapy for Type III-IV Portal Vein Tumor Thrombi.

BACKGROUND: Type Ⅲ and Ⅳ portal vein tumor thrombi (PVTT) cannot be removed through surgery, and no effective therapeutic procedure is available. Type Ⅲ/Ⅳ PVTT can be downstage to type I/II PVTT by using Radiotherapy, and can further be can be removed surgically. Thus, radiotherapy may be an effective treatment for type Ⅲ/Ⅳ PVTT. This study aims to evaluate the efficacy and toxicity of radiotherapy for type III-IV PVTT. METHODS: This prospective study was conducted from August 1, 2017, to September 30, 2019, for patients with type Ⅲ and Ⅳ PVTT. Patients received radiotherapy with a target dose of 50Gy/25f or 59.5Gy/17 f. Advanced radiological technique such as image fusion technique for CT image and MRI image were utilized to produce more precise lesion localization, and limit the dose to organs at risk in order to get a better downstage rate and less adverse complications. RESULTS: Nine (9) patients with type Ⅲ PVTT and 5 patients with type Ⅳ PVTT were included in this study. 12 patients received a radiotherapy dose of 50Gy/25f, 2 patients received 59.50Gy/17 f. After radiotherapy, 92.9% of patients with PVTT were successfully downstage to type II/I. In patients with primary hepatocellular carcinoma, 8 patients (accounting 88.9%) achieved down-stage. 5 patients with other types of tumors achieved downstage which accounts 100%. In addition, none of the 14 patients observed radiation hepatitis and radiation liver failure. And none of the patients developed gastrointestinal ulcers and thrombocytopenia. CONCLUSION: Radiotherapy is a suitable treatment measure for type Ⅲ and Ⅳ PVTT to get downstage and make the opportunity for surgery. Image fusion technology for precise lesion location such as CT-MRI image fusion, and strict dose limitation of organ at risk, contributed to the improvement of radiotherapy efficiency and the significant decrease in adverse complications.

I125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis.

PURPOSE: A meta-analysis aimed to systematically evaluate the safety and efficiency of I125 irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: The Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software. RESULTS: Totally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I125 irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I125 irradiation stent improved the cumulative stent patency rates in 6months [OR=1.65, 95% CI (1.32-2.05), P<0.001] and 12months [OR=2.55, 95% CI (1.90-3.42), P<0.001] and the survival rates in 6months [OR=1.77, 95% CI (1.41-2.22), P<0.001], 12months [OR=3.14, 95% CI (2.24-4.40), P<0.001] and 24months [OR=7.39, 95% CI (3.55-15.41), P<0.001]. However, there was no difference in the objective response rate of PVTT [OR=1.13, 95% CI (0.87-1.48), P=0.365], main portal venous pressure and the occurrence adverse event [OR=0.88, CI=0.72-1.08, P=0.212] between two groups. CONCLUSION: I125 irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.

INTRABEAM intraoperative radiotherapy combined with portal vein infusion chemotherapy for treating hepatocellular carcinoma with portal vein tumor thrombus.

BACKGROUND: Portal vein tumor thrombus (PVTT) is common in hepatocellular carcinoma (HCC). Recent studies indicate that more aggressive treatments, including surgical resection or locoregional treatment, may benefit selected HCC patients with PVTT. External radiation therapy and infusion chemotherapy were found to achieve good outcomes; however, the use of low-energy x-ray radiation system (INTRABEAM), intraoperative radiation therapy, and portal vein infusion chemotherapy for PVTT has not been reported. We present a case of HCC with PVTT. The patient underwent hemihepatectomy and thrombectomy along with intraoperative radiotherapy (IORT) using a portable INTRABEAM radiation system. Subsequently, to treat PVTT, portal vein infusion chemotherapy with FOLFOX (leucovorin [Folinic acid], fluorouracil, and oxaliplatin) regimen was administered. There were no obvious post-operative complications. After 20 months follow-up period, no obvious tumor recurrence had been observed, and PVTT gradually disappeared completely. CONCLUSIONS: IORT using the INTRABEAM radiation system combined with portal vein infusion chemotherapy is promising for select patients with PVTT.

Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters.

To evaluate the effect and mechanism of radiotherapy (RT)-sorafenib pharmacokinetics (PK) in different regimens with conventional or high dose irradiation. Between February 2012 and December 2018, 43 patients with portal vein tumor thrombosis treated with sorafenib plus conventional RT (58%) or stereotactic body radiation therapy (SBRT, 42%) were retrospectively reviewed. In vivo and in vitro studies of concurrent and sequential RT with sorafenib were designed. SBRT resulted in a 3-fold increase in complete recanalization compared to conventional RT group (28% vs. 8%, p = 0.014). Compared to the control group, the area under the concentration vs. time curve (AUC) of sorafenib was increased in the concurrent RT2Gy and RT9Gy groups and the sequential RT9Gy group by 132% (p = 0.046), 163% (p = 0.038) and 102% (p = 0.018), respectively; and was decreased by 59% in the sequential RT2Gy group (p = 0.036). Sequential RT2Gy and RT9Gy increased CYP3A4 activity by 82% (p = 0.028) and 203% (p = 0.0004), respectively, compared to that with the corresponding concurrent regimen. SBRT produced better recanalization than conventional RT with sorafenib. The AUC of sorafenib was modulated by RT. P-gp expression was not influenced by RT. The sequential RT regimen increased CYP3A4 activity that may increase the RT-sorafenib synergy effect and overall sorafenib activity. The biodistribution of sorafenib was modulated by local RT with the different regimens.

Preoperative Stereotactic Body Radiotherapy to Portal Vein Tumour Thrombus in Hepatocellular Carcinoma: Clinical and Pathological Analysis.

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) is poor. We conducted a prospective study to evaluate the efficacy and safety of tri-modality therapy, including preoperative stereotactic body radiotherapy (SBRT) and surgery, followed by hepatic arterial infusion chemotherapy (HAIC) in HCC patients with PVTT. In this report, we investigated the pathology of the irradiated PVTT specimen in resected cases and SBRT-related acute toxicity. A total of 8 HCC patients with PVTT received preoperative SBRT targeting the PVTT at a dose of 48 Gy in 4 fractions at our institute from 2012 to 2016. Of the eight patients, six underwent surgery, while the remaining two did not because of disease progression. At the pathological examination, all patients' irradiated PVTT specimens showed necrotic tissue, and three of six patients showed complete pathological response. Two patients showed 30% necrosis with high degeneration and one patient, with 30% necrosis without degeneration, was the only recurrent case found during the follow-up period (median: 22.5, range: 5.9-49.6 months). No SBRT-related acute toxicity worse than grade 2 was observed from SBRT to surgery. In conclusion, the preoperative SBRT for HCC was pathologically effective and the acute toxicities were tolerable.

Ablative Transarterial Radioembolization Improves Survival in Patients with HCC and Portal Vein Tumor Thrombus.

PURPOSE: Patients with hepatocellular carcinoma and portal vein tumor thrombus have a poor prognosis and limited therapeutic options. We sought to compare survival, tolerability, and safety in such patients treated with conventional yttrium-90 transarterial radioembolization dosimetric techniques or ablative transarterial radioembolization. MATERIALS AND METHODS: This retrospective, single-center cohort study included patients with hepatocellular carcinoma and right, left, and/or main portal vein tumor thrombus, preserved liver function (Child-Pugh class ≤ B7), and good performance status (Eastern Cooperative Oncology Group score ≤ 1) treated with yttrium-90 microspheres from 2011 to 2018 with ablative intent transarterial radioembolization (A-TARE), or conventional technique (cTARE). Statistical models were used to compare overall survival, post-treatment survival, toxicities, and prognosticators of response. RESULTS: Fifty-seven patients were included (21 [36.8%] ablative and 36 [63.2%] conventional intent). Median overall survival was 15.7 months. Compared to conventional treatment, ablative radioembolization was associated with longer median overall survival (45.3 vs 18.2 months; P = 0.003), longer post-treatment survival (19.1 vs 4.9 months; P = 0.005), a 70% lower risk of death (hazard ratio 0.30; 95% confidence interval, 0.13-0.70; P = 0.005), and improved 4-year survival (53.9% vs 11.2%). Overall survival did not differ significantly between treatment with resin and glass microspheres (27.5 vs 22.2 months; P = 0.62). Acceptable hepatic toxicities were observed after yttrium-90 administration, without statistical differences between the groups. CONCLUSION: In patients with advanced hepatocellular carcinoma and portal vein tumor thrombus, A-TARE is associated with longer survival than cTARE. Neither modality is associated with deleterious effects on liver function.

Radiotherapy for inferior vena cava tumor thrombus in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) involvement is a rare disease with poor prognosis. This study aimed to evaluate the outcome of HCC patients receiving radiotherapy (RT) to IVC tumor thrombus. METHODS: A total of 42 consecutive HCC patients treated with RT to IVC tumor thrombus between September 2007 and October 2018 were enrolled. Overall survival (OS), the response of IVC thrombus, prognostic factors and failure pattern were assessed. RESULTS: The median follow-up time was 4.4 months. The median RT equivalent dose in 2-Gy fractions was 48.75 Gy (range, 3.25-67.10). The objective response rate of IVC thrombus was 47.6% (95% confidence interval [CI], 33.3-64.3%). The OS rate at 1 year was 30.0%, with a median OS of 6.6 months (95% CI, 3.7-9.5) from the start of RT. On multivariate analysis, Child-Pugh class, lymph node metastasis, lung metastasis and objective response of IVC thrombus were independent predictors for OS. Lung was the most common site of first progression in 14 (33.3%) patients. For 32 patients without lung metastasis before RT, use of systemic treatment concurrent with and/or after RT was associated with a significantly longer lung metastasis-free survival (5.9 vs. 1.5 months, p = 0.0033). CONCLUSIONS: RT is effective for IVC tumor thrombus of HCC with acceptable adverse effects. RT might be a treatment option incorporated into combination therapy for HCC involving IVC.

Therapeutic Evaluation of Radiotherapy with Contrast-Enhanced Ultrasound in Non-Resectable Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis.

BACKGROUND Therapeutic evaluation of 3-dimensional conformal radiotherapy (3DCRT) is rarely reported for non-resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). The aim of this study was to determine the value of contrast-enhanced ultrasound (CEUS) in evaluating the therapeutic response of HCC with PVTT treated with 3DCRT. MATERIAL AND METHODS PVTT reduction rate in the study was determined after 3DCRT using time intensity curve (TIC) analysis software before and after radiotherapy. Seventy-nine HCC patients with PVTT treated with 3DCRT were studied. HCC and PVTT were performed by CEUS, before and after 3DCRT, over time. The parameters of blood flow, including arrival time (AT), time to peak (TTP), peak intensity (PI), washout time (WT), and area under the curve (AUC), were quantified and evaluated on still images by CEUS. RESULTS After 3DCRT, typing and staging of PVTT in 38 patients was decreased, the reduction rate was 48.1%. HCC was effective in 45 patients, the effective rate was 57%; No differences were found between the PVTT reduction rate and the HCC effective rate (χ2=2.96, P>0.05). In the effective group, the PI and AUC of HCCs and PVTTs after 3DCRT were significantly lower than before 3DCRT, while the other parameters of TIC were not significantly different before and after 3DCRT. CONCLUSIONS CEUS might be a useful monitoring option for the evaluation of HCC with PVTT treated with 3DCRT. CEUS might be useful as an important choice for monitoring and evaluation HCC with PVTT after 3DCRT. TIC parameters might provide quantitative data for efficacy evaluation, which helps to modify treatment strategies timely and accurately.

Stereotactic body radiotherapy based treatment for hepatocellular carcinoma with extensive portal vein tumor thrombosis.

BACKGROUND: There is currently no worldwide consensus for the management of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). We evaluated the efficacy of stereotactic body radiotherapy (SBRT) as the initial treatment for HCC with extensive PVTT based on a relatively large number of patients. METHODS: In our multidisciplinary approach for patients with hepatobiliary tumors, SBRT is recommended for unresectable HCC with PVTT or those with contraindication for transarterial chemoembolization (TACE). The aim is to shrink the tumor thrombus and preserve adequate portal venous flow, thus facilitating subsequent treatments such as TACE and tumor resection. In the present study, 70 continuous cases of HCC patients with extensive PVTT initially treated with SBRT were studied. The median follow-up period was 9.5 months (range, 1.0-21.0 months). The dynamic changes of tumor thrombosis with time after SBRT were also analyzed. RESULTS: The median survival time for the whole group was 10.0 months (95% CI, 7.7-12.3 months), with a 6- and 12-month overall survival (OS) rate of 67.3%, and 40.0% respectively. Patients who received combined SBRT and TACE showed significantly longer OS than those without indication for TACE after SBRT (12.0 ± 1.6 vs. 3.0 ± 1.0 months). Patients with good response to radiation usually had better survival. SBRT was well tolerated in our patient series. CONCLUSIONS: In conclusion, SBRT used as the initial treatment for HCC patients with extensive PVTT originally unsuitable for resection or TACE can achieve adequate thrombus shrinkage and portal vein flow restoration in the majority of cases. It could thus offer the patients an opportunity to undergo further treatment such as resection or TACE procedure. Such therapeutic strategy may result in survival advantage, especially for those who do receive combined modality with SBRT.

Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization.

BACKGROUND: To determine the effect of Yttrium-90 (Y90) radioembolization on health-related quality of life (HRQOL) and its effect on overall survival advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with concurrent portal vein thrombosis (PVT). METHODS: Consecutive patients with unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36) questionnaire was used to assess HRQOL for consecutive patients treated with glass-based Y90 based on a prospective phase II trial. MR imaging was used to determine tumor progression every 3 months post-treatment. Overall survival (OS) from treatment and time to progression (TTP) was analyzed using Kaplan-Meier estimation and log-rank test. RESULTS: Thirty patients were treated and followed for 17.4 months; physical and mental component summary scores (PCS & MCS) remained unchanged at one, three, and six months. While no difference was observed in baseline SF-36 scores for patients with prolonged TTP (≥4 months) and OS (≥ 6 months), corresponding 1-month PCS were significantly higher than those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations (SD) of US normalized baseline scores had a significantly prolonged median OS (15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared those with physical component scores greater than 2SD below normalized US population values. CONCLUSION: Y90 radioembolization for HCC demonstrated long-term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer OS. Early (1 month post-treatment) significant decreases in PCS were independent predictors of poorer OS and TTP. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01556282 , registered March 16, 2012.

Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area.

BACKGROUND & AIMS: This nationwide, multicenter study investigated treatment outcomes as well as the optimal radiotherapeutic strategy in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT). METHODS: We retrospectively reviewed the records of 985 patients who received radiotherapy (RT) for PVTT. The median equivalent RT dose was 48.75 Gy. Combined treatment, defined as liver-directed treatments performed within a month of RT, was administered to 657 patients (66.7%). The PVTT and primary tumour were irradiated in 413 patients (41.9%), and PVTT only was targeted in 572 patients (58.1%). RESULTS: The response rate of the PVTT was 51.8%, and RT responders had a significantly longer survival than non-responders (15.2 vs. 6.9 months). Equivalent RT dose and combined treatment predicted response of PVTT. The median overall survival (OS) was 10.2 months. Multivariate analysis revealed the equivalent RT dose ˃45 Gy and combined treatment as significant positive factors for OS. In the propensity score matching analysis, the combined treatment group had better OS than the no combined treatment group, whereas the OS of the PVTT + primary tumour group did not differ significantly from that of the PVTT only group. CONCLUSION: The equivalent RT dose ˃45 Gy, given in combination with other treatments, provided better PVTT control and OS. The optimal RT volume is suggested for either PVTT + primary or PVTT only. Taken together, multimodal treatment with equivalent RT dose higher than 45 Gy is recommended for patients with HCC and PVTT.

Efficacy of External Beam Radiation-Based Treatment plus Locoregional Therapy for Hepatocellular Carcinoma Associated with Portal Vein 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.

Three-dimensional conformal radiotherapy for locally advanced hepatocellular carcinoma with portal vein tumour thrombosis: evaluating effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification.

OBJECTIVE: The purpose of this study was to retrospectively evaluate the effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification in patients who received three-dimensional conformal radiotherapy (3D CRT) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) by analyzing toxicity and prognostic factors. METHODS: 56 consecutive patients who had locally advanced HCC with PVTT treated by 3D CRT between September 2007 and April 2013 were retrospectively reviewed. RESULTS: The median survival time of all patients was 6.4 months. Receiver-operating characteristic (ROC) analysis identified MELD score = 7.5 [area under the curve (AUC) 0.81] and Child-Pugh score = 6.5 (AUC 0.86) as the best cut-off values for predicting the incidence of complications over Common Terminology Criteria for Adverse Events grade 2. There was no significant difference in the discrimination power between the MELD score and the Child-Pugh score on comparison of the two ROC curves (p = 0.17). On multivariate analysis, age, MELD score and radiotherapy dose were significant prognostic factors for overall survival (p = 0.021, 0.038 and 0.006, respectively). In contrast, the Child-Pugh classification, tumour response, PVTT response and the number of prior interventional radiologic treatments were not significant on multivariate analysis. CONCLUSION: This study showed that the best MELD score cut-off value is 7.5 and that the MELD score is a better prognostic factor than the Child-Pugh classification in 3D CRT for HCC with PVTT. ADVANCES IN KNOWLEDGE: The MELD score is useful for predicting the risk of severe toxicities and the prognosis of patients treated with 3D CRT for PVTT.

Combination treatment of trans-arterial chemo-embolisation, radiotherapy and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumour thrombosis: Interim analysis of prospective phase II trial.

Objectives This study evaluated the objective response to and toxicity of trans-arterial chemo-embolisation (TACE) followed by radiotherapy and hyperthermia (CERT) in hepatocellular carcinoma patients with portal vein tumour thrombosis. Methods The study design was a single-centre prospective phase II trial. Patients were first treated with TACE, with the first hyperthermia session 1 week later. Respiration-gated radiotherapy (RT) was delivered in 10 fractions of 3-5 Gy after another week. Six sessions of hyperthermia were delivered twice a week according to an energy escalation protocol. Response evaluation was planned at 1 month after RT completion using the modified Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was determined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Interim analysis was conducted on patients enrolled from October 2013 to November 2014. During this period, 46 patients (90.2%) who received at least one hyperthermia session were eligible and enrolled. Median follow-up was 6.7 months (range 2.0-15.0 months). Complete response was observed in 10 (21.7%) patients and partial response in 27 (47.8%). Most toxicities were grade I or II. One death was related to severe pneumonia of unknown cause in the left lung and one patient could not complete planned treatment because of continuous elevation of bilirubin after TACE. Late, asymptomatic gastroduodenal toxicities were noticed in 13 (28.3%) patients. Conclusion Preliminary evaluation of CERT showed a promising response rate with acceptable toxicities.