Safety evaluation of combination treatment of drug-eluting bead transarterial chemoembolization and immune checkpoint inhibitors for hepatocellular carcinoma: An increased risk of liver abscess with treatment interval less than one month.

PURPOSE: To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). METHOD: In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups. RESULTS: The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922). CONCLUSIONS: Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.

Guggulsterone inhibits migration and invasion through proteasomal and lysosomal degradation in human glioblastoma cells.

Glioblastoma multiforme (GBM) is a deadly brain malignancy, and current therapies offer limited survival benefit. The phytosterol guggulsterone (GS) has been shown to exhibit antitumor efficacy. This study aimed to investigate the effects of GS on migration and invasion and its underlying mechanisms in human GBM cell lines. After GS treatment, the survival rate of GBM cells was reduced, and the migration and invasion abilities of GBM cells were significantly decreased. There was also concomitant decreased expression of focal adhesion complex, matrix metalloproteinase-2 (MMP2), MMP9 and cathepsin B. Furthermore, GS induced ERK phosphorylation and autophagy, with increased p62 and LC3B-II expression. Notably, treatment of in GBM cells with the proteasome inhibitor MG132 or the lysosome inhibitor NH4Cl reversed the GS-mediated inhibition of migration and invasion. In an orthotopic xenograft mouse model, immunohistochemical staining of brain tumor tissues demonstrated that MMP2 and cathepsin B expression was reduced in GS-treated mice. GS treatment inhibited GBM cell migration and invasion via proteasomal and lysosomal degradation, suggesting its therapeutic potential in clinical use in the future.

Significant muscle loss after stereotactic body radiotherapy predicts worse survival in patients with hepatocellular carcinoma.

The relationship between sarcopenia and treatment outcomes, especially in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiotherapy (SBRT) has not been well-explored. This study aimed to investigate the effects of sarcopenia on the survival and toxicity after SBRT in patients with HCC. We included 137 patients with HCC treated with SBRT between 2008 and 2018. Sarcopenia was defined as a skeletal muscle index (SMI) of < 49 cm2/m2 for men and < 31 cm2/m2 for women using computed tomography images at the mid-level of the third lumbar vertebra. The SMI change was presented as the change per 90 days. The Kaplan-Meier method was used for survival estimation, and the Cox regression was used to determine prognosticators. Sarcopenia was present in 67 of 137 eligible patients. With the median follow-up of 14.1 months and 32.7 months in the entire cohort and in those alive, respectively, patients with pre-SBRT sarcopenia or SMI loss ≥ 7% after SBRT had worse overall survival than their counterparts. Significant survival predictors on multivariate analysis were SMI loss ≥ 7% after SBRT [hazard ratio (HR): 1.96, p = 0.013], presence of extrahepatic metastasis (HR: 3.47, p < 0.001), neutrophil-to-lymphocyte ratio (HR: 1.79, p = 0.027), and multiple tumors (HR: 2.19, p = 0.003). Separate Cox models according to the absence and presence of pre-SBRT sarcopenia showed that SMI loss ≥ 7% remained a significant survival predictor in patients with sarcopenia (HR: 3.06, p = 0.017) compared with those without sarcopenia. SMI loss ≥ 7% is also a predictor of the Child-Pugh score increase by ≥ 2 points after SBRT. SMI loss ≥ 7% after SBRT is a significant prognostic factor for worse survival and is associated with liver toxicity compared with pre-SBRT sarcopenia.

Developing a novel DNA methylation risk score for survival and identification of prognostic gene mutations in endometrial cancer: a study based on TCGA data.

BACKGROUND: Few studies have focused on DNA methylation in endometrial cancer. The aim of our study is identify its role in endometrial cancer prognosis. METHODS: A publicly available dataset was retrieved from The Cancer Genome Atlas. For validation of expression alteration due to methylation, RNA sequencing data were obtained from other independent cohorts. MethSurv was used to search for candidate CpG probes, which were then filtered by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression analyses to identify final set of CpG probes for overall survival. A methylation-based risk model was developed and receiver operating characteristic analysis with area under curve was used for evaluation. Patients were divided into high- and low-risk groups using an optimal cut-off point. Comprehensive bioinformatic analyses were conducted to identify hub genes, key transcription factors, and enriched cancer-related pathways. Kaplan-Meier curve was used for survival analysis. RESULTS: A 5-CpG signature score was established. Its predictive value for 5-year overall survival was high, with area under curve of 0.828, 0.835 and 0.816 for the training, testing and entire cohorts. cg27487839 and cg12885678 had strong correlation with their gene expression, XKR6 and PTPRN2, and lower PTPRN2 expression was associated with poorer survival in both The Cancer Genome Atlas and the validation datasets. Low-risk group was associated with significantly better survival. Low-risk group harboured more mutations in hub genes and key transcription factors, and mutations in SP1 and MECP2 represented favourable outcome. CONCLUSION: We developed a methylation-based prognostic stratification system for endometrial cancer. Low-risk group was associated with better survival and harboured more mutations in the key regulatory genes.

Radiomics-Based Predictive Model of Radiation-Induced Liver Disease in Hepatocellular Carcinoma Patients Receiving Stereo-Tactic Body Radiotherapy.

(1) Background: The application of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) limited the risk of the radiation-induced liver disease (RILD) and we aimed to predict the occurrence of RILD more accurately. (2) Methods: 86 HCC patients were enrolled. We identified key predictive factors from clinical, radiomic, and dose-volumetric parameters using a multivariate analysis, sequential forward selection (SFS), and a K-nearest neighbor (KNN) algorithm. We developed a predictive model for RILD based on these factors, using the random forest or logistic regression algorithms. (3) Results: Five key predictive factors in the training set were identified, including the albumin-bilirubin grade, difference average, strength, V5, and V30. After model training, the F1 score, sensitivity, specificity, and accuracy of the final random forest model were 0.857, 100, 93.3, and 94.4% in the test set, respectively. Meanwhile, the logistic regression model yielded an F1 score, sensitivity, specificity, and accuracy of 0.8, 66.7, 100, and 94.4% in the test set, respectively. (4) Conclusions: Based on clinical, radiomic, and dose-volumetric factors, our models achieved satisfactory performance on the prediction of the occurrence of SBRT-related RILD in HCC patients. Before undergoing SBRT, the proposed models may detect patients at high risk of RILD, allowing to assist in treatment strategies accordingly.

Combination therapy of sorafenib and drug-eluting bead transarterial chemoembolization for advanced hepatocellular carcinoma with and without hepatic arteriovenous shunt.

BACKGROUND: To compare the efficacy and safety of combination therapy with sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in advanced hepatocellular carcinoma (HCC) with or without hepatic arteriovenous shunt (HAVS). METHODS: This retrospective, single-center study enrolled 59 advanced HCC patients treated with combination therapy, of whom 33 (55.9%) patients had HAVS. Tumor response according to the mRECIST criteria was evaluated based on the CT images 1 month after TACE, and changes in the arterial enhancement ratio (AER) of tumors and portal vein tumor thrombosis were also documented. Time-to-progression (TTP), overall survival (OS), and prognostic factors were analyzed. Safety was evaluated with the incidence of TACE-related complications within 6 weeks after TACE. RESULTS: The tumor response between the two groups showed no significant difference in the objective response rate (69.2% in the group without HAVS vs 60.6% in the group with HAVS, p = 0.492) or disease control rate (92.3% vs 87.9%, p = 0.685). The two groups showed comparable TTP (4.23 vs 2.33 months, p = 0.235) and OS (12.77 vs 12.97 months, p = 0.910). A drop in the AER of tumors of more than 20% on post-TACE CT independently predicted better OS. With regard to safety, there was no significant difference between the two groups. CONCLUSION: For advanced HCC, combination therapy had equal efficacy and safety in patients with HAVS compared to those without HAVS, indicating that DEB-TACE is an optional and effective treatment in these patients.

Dynamic Changes in Neutrophil-to-Lymphocyte Ratio are Associated with Survival and Liver Toxicity Following Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

PURPOSE: Immune response to antitumor therapies has been correlated with oncologic outcomes. This study aimed to determine whether dynamic changes in immune parameters could predict survival outcomes and assess their relationship with liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT). METHODS: Data on pre- and post-SBRT (within 3 months) peripheral blood cell counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were retrospectively collected. Kinetic changes in these immune parameters and delta-NLR (dNLR) and delta-PLR (dPLR) in response to SBRT were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared based on baseline NLR/PLR and dNLR/dPLR. Additionally, the association of these dynamic measures with liver toxicity was determined. RESULTS: The study included 93 patients with a median 10.7-month follow-up. Significant increases in NLR (p<0.001) and PLR (p=0.003) were observed after SBRT. In the multivariable analysis, elevated pre-SBRT NLR (p<0.001) and dNLR (p=0.011) were predictive of worse OS. dNLR was not associated with PFS. Neither PLR nor dPLR was predictive of survival outcomes. Patients with Child-Turcotte-Pugh class B had higher dNLR and greater risk of liver toxicity than class A counterparts. Receiver operating characteristic curve analysis found that dNLR ≥1.9 was an optimal cut-off value for determining liver toxicity risk (35.1% vs 7.5%, p=0.002). CONCLUSION: Baseline NLR and dNLR can complementarily predict OS in HCC patients treated with SBRT. Elevated dNLR is associated with worse OS and development of liver toxicity, possibly through their relationship with baseline liver function. Dynamic changes in NLR should be monitored in HCC care.

Transcatheter Arterial Chemoembolization with Drug-Eluting Beads for the Treatment of Hepatocellular Carcinoma: Recommended Selection for Small-Caliber (<100 µm) Beads.

Drug-eluting beads transarterial chemoembolization (DEB-TACE) is an alternative to conventional lipiodol-based TACE (cTACE) to treat hepatocellular carcinoma (HCC). With the advancement in pharmacology, small-caliber DEB-TACE (<100 µm) has been introduced since 2016. For the treatment of hepatic neoplasms or HCC, there is a tendency to use smaller beads by DEB-TACE to achieve more extensive tumor necrosis and a significant reduction in liver toxicity in comparison with that caused by cTACE. However, the indications and potential complications of small-caliber DEB-TACE remain uncertain and have not been well established, due to lack of randomized phase III clinical trials. Instead of systematic or meta-analysis review, this narrative review article describes the suggested indications and contraindications of DEB-TACE with small DEBs, benefit of super-selective embolization of the feeding arteries and the recommended selection of small-caliber DEB. This review was approved by the institutional review board (File Number: 1-105-05-158).

Gene-associated methylation status of ST14 as a predictor of survival and hormone receptor positivity in breast Cancer.

BACKGROUND: Genomic profiles of specific gene sets have been established to guide personalized treatment and prognosis for patients with breast cancer (BC). However, epigenomic information has not yet been applied in a clinical setting. ST14 encodes matriptase, a proteinase that is widely expressed in BC with reported prognostic value. METHODS: In this present study, we evaluated the effect of ST14 DNA methylation (DNAm) on overall survival (OS) of patients with BC as a representative example to promote the use of the epigenome in clinical decisions. We analyzed publicly available genomic and epigenomic data from 1361 BC patients. Methylation was characterized by the ß-value from CpG probes based on sequencing with the Illumina Human 450 K platform. RESULTS: A high mean DNAm (ß > 0.6779) across 34 CpG probes for ST14, as the gene-associated methylation (GAM) pattern, was associated with a longer OS after adjusting age, stage, histology and molecular features in Cox model (p value < 0.001). A high GAM status was also associated with a higher XBP1 expression level and higher proportion of hormone-positive BC (p value < 0.001). Pathway analysis revealed that altered GAM was related to matrisome-associated pathway. CONCLUSIONS: Here we show the potential role of ST14 DNAm in BC prognosis and warrant further study.

Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy.

In the era of immunotherapy, there lacks of a reliable genomic predictor to identify optimal patient populations in combined radiotherapy and immunotherapy (CRI). The purpose of this study is to investigate whether genomic scores defining radiosensitivity are associated with immune response. Genomic data from Merged Microarray-Acquired dataset (MMD) were established and the Cancer Genome Atlas (TCGA) were obtained. Based on rank-based regression model including 10 genes, radiosensitivity index (RSI) was calculated. A total of 12832 primary tumours across 11 major cancer types were analysed for the association with DNA repair, cellular stemness, macrophage polarisation, and immune subtypes. Additional 585 metastatic tissues were extracted from MET500. RSI was stratified into RSI-Low and RSI-High by a cutpoint of 0.46. Proteomic differential analysis was used to identify significant proteins according to RSI categories. Gene Set Variance Analysis (GSVA) was applied to measure the genomic pathway activity (18 genes for T-cell inflamed activity). Kaplan-Meier analysis was performed for survival analysis. RSI was significantly associated with homologous DNA repair, cancer stemness and immune-related molecular features. Lower RSI was associated with higher fraction of M1 macrophage. Differential proteomic analysis identified significantly higher TAP2 expression in RSI-Low colorectal tumours. In the TCGA cohort, dominant interferon-γ (IFN-γ) response was characterised by low RSI and predicted better response to programmed cell death 1 (PD-1) blockade. In conclusion, in addition to radiation response, our study identified RSI to be associated with various immune-related features and predicted response to PD-1 blockade, thus, highlighting its potential as a candidate biomarker for CRI.

Clinical outcome and pathologic correlation of stereotactic body radiation therapy as a bridge to transplantation for advanced hepatocellular carcinoma: a case series.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an emerging modality for hepatocellular carcinoma (HCC). However, there is scant information about its safety and effectiveness in the neoadjuvant setting prior to liver transplantation (LT). We present the clinical outcome and pathologic assessment of SBRT followed by LT for patients with advanced HCC. METHODS: This retrospective study included HCC patients treated with neoadjuvant SBRT prior to LT between 2009 and 2018. Radiographic response and adverse effects, including radiation-induced liver disease (RILD), were evaluated. Pathologic response was assessed by the percentage of tumor necrosis relative to the total tumor volume. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. RESULTS: Fourteen patients underwent SBRT for a total of 25 HCC lesions, followed by LT. The median tumor size was 4.45 cm in diameter, and the median prescribed dose was 45 Gy in 5 fractions. SBRT provided significant AFP reduction, 100% infield control, and a 62.5% response rate. The maximum detected toxicity included grade 3 thrombocytopenia and two grade 3-4 hyperbilirubinemia. One patient developed non-classic RILD. Patients were bridged to LT with a median time of 8.4 months after SBRT, and 23.1% of them achieved a complete pathologic response. The median OS and RFS were 37.8 and 18.3 months from the time of LT, respectively. CONCLUSIONS: SBRT provides favorable tumor control and acceptable adverse effects for patients awaiting LT. Further prospective studies to test SBRT as a bridging therapy for LT are feasible.

Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts Survival and Liver Toxicity in Patients With Hepatocellular Carcinoma Treated With Stereotactic Ablative Radiation Therapy.

PURPOSE: The objective of this study was to determine whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict survival outcomes and liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: In this retrospective study we collected pretreatment NLR of HCC patients treated with SABR between December 2007 and August 2018 and determined its association with overall survival (OS), progression-free survival, and radiation-related liver toxicity defined as an increase in the Child-Turcotte-Pugh score by ≥2 within 3 months after SABR in the absence of disease progression. RESULTS: A total of 153 patients with a median follow-up of 13.3 months were included. Receiver operating characteristic curve analysis found that an NLR ≥2.4 was optimum (area under the curve, 0.762; 95% confidence interval [CI], 0.682-0.841, P < .001) for predicting poor 1-year OS (38.2% vs 83.6%, P < .001). Multivariable analysis demonstrated that NLR was significantly associated with OS, both as a continuous (P = .006) and a binary variable (NLR set at 2.4; P = .003). Multiple tumors (P = .003), macrovascular invasion (P = .024), extrahepatic spread (P = .002), and albumin-bilirubin score (P = .020) were also significant predictors of OS. Elevated NLR independently prognosticated poor progression-free survival (P = .016). Liver toxicity was seen in 22 evaluable patients (15.4%). Receiver operating characteristic curve analysis found NLR ≥4.0 was optimum at predicting liver toxicity (31.4% vs 10.2%, P = .005). A higher NLR (P = .049) and albumin-bilirubin score (P = .002) were independent risk factors for liver toxicity. CONCLUSIONS: NLR is an objective and ubiquitous inflammatory marker that can predict OS and liver toxicity in HCC patients undergoing SABR. NLR could be a useful biomarker for patient risk stratification and therapeutic decision-making.

Development and Validation of a Nomogram for Patients with Nonmetastatic BCLC Stage C Hepatocellular Carcinoma after Stereotactic Body Radiotherapy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for hepatocellular carcinoma (HCC) with promising outcome. However, appropriate survival prediction models are scarce. This study aimed to develop a simple and clinically useful prognostic nomogram for patients with nondistant metastatic Barcelona Clinic Liver Cancer (BCLC) stage C HCC undergoing SBRT. METHODS: The data were based on a prospective multi-institutional registry enrolling 246 patients with nondistant metastatic BCLC stage C HCC treated with SBRT between January 1, 2008 and December 31, 2016. They were randomly divided into two subsets: 164 into the development cohort and 82 into the validation cohort. We identified and included prognostic factors for survival to derive a nomogram in the development cohort. The predictability of the nomogram was evaluated in the validation cohort. The area under the receiver operating characteristic curve (AUROC) and the calibration plot were used to evaluate the performance of the nomogram. RESULTS: The median survival was 13.5 months, with 1- and 2-year overall survival (OS) rates of 55.0 and 32.9%, respectively. Number of tumors, largest tumor size, macrovascular invasion, Child-Turcotte-Pugh class, and biologically effective dose were significantly associated with OS (p < 0.05). These predictors were included to develop a nomogram with an AUROC of 0.77 (0.73-0.87). The prediction model was well calibrated in the validation cohort. The OS for patients who were divided by their risk scores differed significantly (p < 0.001). CONCLUSIONS: The nomogram we generated had discriminatory and satisfactory predictability for OS among nonmetastatic BCLC stage C HCC patients treated with SBRT. It demands further validations with cross-country data to confirm its worldwide usefulness.

Prognostic Significance of Apparent Diffusion Coefficient in Hepatocellular Carcinoma Patients treated with Stereotactic Ablative Radiotherapy.

The role of diffusion-weighted magnetic resonance imaging (DW MRI) in assessing durable tumor control for patients with hepatocellular carcinoma (HCC) treated with stereotactic ablative radiotherapy (SABR) was not defined. This retrospective study included 34 HCC patients with 45 lesions who had DW MRI data at baseline and within 6 months post-SABR. On the first post-SABR MRI, 13 lesions (28.9%) had a complete response (CR), 12 (26.7%) had a partial response (PR), 17 (37.8%) had stable disease, and 3 (6.7%) had progressive disease by modified Response Evaluation Criteria in Solid Tumors (mRECIST). On subsequent imaging, the response rate improved from 55.6% to 75.6%. The apparent diffusion coefficients (ADCs) (mean ± standard deviation) pre- and post-SABR were 1.43 ± 0.28 and 1.72 ± 0.34 (×10-3 mm2/s), respectively (p < 0.001). An ADC change ≥25% (DW[+]) was identified as a predictor of favorable in-field control (IFC) (1-year IFC, 93.3% vs. 50.0% for DW[-], p = 0.004), but an mRECIST-based positive response (CR and PR) at the first MRI was not (p = 0.130). In conclusion, ADC change on early MRI is closely related to IFC in HCCs treated with SABR. Standardization of the DW MRI protocol, as well as prospective validation studies, are warranted.

Stereotactic ablative radiotherapy versus conventionally fractionated radiotherapy in the treatment of hepatocellular carcinoma with portal vein invasion: a retrospective analysis.

BACKGROUND: This study aimed to compare the clinical outcomes of stereotactic ablative radiotherapy (SABR) and conventionally fractionated radiotherapy (CFRT) in hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). METHODS: HCC patients with PVI treated with radiotherapy from 2007 to 2016 were analysed. CFRT was administered at a median dose of 51.5 Gy (interquartile range, 45-54 Gy) with 1.8-3 Gy per fraction. SABR was administered at a median dose of 45 Gy (interquartile range, 40-48 Gy) with 6-12.5 Gy per fraction. Treatment efficacy, toxicity, and associated predictors were assessed. RESULTS: Among the 104 evaluable patients (45 in the SABR group and 59 in the CFRT group), the overall response rate (ORR, complete and partial response) was significantly higher in the SABR group than the CFRT group (62.2% vs. 33.8%, p = 0.003). The 1-year overall survival (OS) rate (34.9% vs. 15.3%, p = 0.012) and in-field progression-free survival (IFPS) rate (69.6% vs. 32.2%, p = 0.007) were also significantly higher in the SABR vs. CFRT group. All 3 rates remained higher in the SABR group after propensity score matching. Multivariable analysis identified SABR and a biologically effective dose ≥65 Gy as favourable predicators of OS. There was no difference between treatment groups in the incidence of radiation-induced liver disease or increase of Child-Pugh score ≥ 2 within 3 months of radiotherapy. CONCLUSIONS: SABR was superior to CFRT in terms of ORR, OS, and IFPS. We suggest that SABR should be the preferred technique for HCC patients with PVI.

Comparison of Stereotactic Body Radiation Therapy and Transarterial Chemoembolization for Unresectable Medium-Sized Hepatocellular Carcinoma.

PURPOSE: This study compared the local control and overall survival (OS) between stereotactic body radiation therapy (SBRT) and transarterial chemoembolization (TACE) in medium-sized (3-8 cm) hepatocellular carcinoma (HCC). METHODS AND MATERIALS: From January 2008 to October 2017, 188 patients with medium-sized HCC underwent either TACE (n = 142) or SBRT (n = 46). We adjusted for imbalances in treatment assignment using propensity score matching. Infield control (IFC) and OS were analyzed retrospectively. RESULTS: The median follow-up time was 17.1 months for all patients and 26.6 months for surviving patients. The 3-year IFC was 63.0% for the TACE group and 73.3% for the SBRT group. Multivariable analysis identified the independent predictors for IFC as treatment modality (SBRT vs TACE), sex (female vs male), and recurrence status (recurrence vs new diagnosis). The 3-year OS was 22.9% for the TACE group and 47.4% for the SBRT group. Multivariable analysis identified the independent predictors of OS as number of tumors, treatment modality (SBRT vs TACE), albumin-bilirubin grade, tumor volume, Eastern Cooperative Oncology Group status, and recurrence status. Propensity score matching analysis revealed that the SBRT group had better IFC (3-year IFC of 77.5% vs 55.6%; P = .007) and OS (3-year OS of 55.0% vs 13.0%; P < .001) than the TACE group. For recurrent HCC, the SBRT group exhibited superior IFC (3-year IFC of 75% vs 57.5%; P = .022) and OS (3-year OS of 58.3% vs 5.9%; P < .001) compared with the TACE group. However, there was no difference in IFC or OS between TACE and SBRT for patients with newly diagnosed HCC. CONCLUSIONS: SBRT has better IFC and OS rates than TACE in patients with medium-sized HCC, particularly for recurrent cases, which warrants prospective randomized controlled trials of TACE and SBRT.

Dose escalation via brachytherapy boost for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy and combined chemotherapy.

To investigate if dose escalation using intracavitary brachytherapy (ICBT) improves local control for nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT) and concurrent chemoradiation treatment (CCRT). We retrospectively analyzed 232 patients with Stage T1-3 N0-3 M0 NPC who underwent definitive IMRT with or without additional ICBT boost between 2002 and 2013. For most of the 124 patients who had ICBT boost, the additional brachytherapy was given as 6 Gy in 2 fractions completed within 1 week after IMRT of 70 Gy. CCRT with or without adjuvant chemotherapy was used for 176 patients, including 88 with and 88 without ICBT boost, respectively. The mean follow-up time was 63.1 months. The 5-year overall survival and local control rates were 81.5% and 91.5%, respectively. ICBT was not associated with local control prediction (P = 0.228). However, in a subgroup analysis, 75 T1 patients with ICBT boost had significantly better local control than the other 71 T1 patients without ICBT boost (98.1% vs 85.9%, P = 0.020), despite having fewer patients who had undergone chemotherapy (60.0% vs 76.1%, P = 0.038). Multivariate analysis showed that both ICBT (P = 0.029) and chemotherapy (P = 0.047) influenced local control for T1 patients. Our study demonstrated that dose escalation with ICBT can improve local control of the primary tumor for NPC patients with T1 disease treated with IMRT, even without chemotherapy.

Comparison Between Child-Turcotte-Pugh and Albumin-Bilirubin Scores in Assessing the Prognosis of Hepatocellular Carcinoma After Stereotactic Ablative Radiation Therapy.

PURPOSE: To evaluate the prognostic performance of the Child-Turcotte-Pugh (CTP) score and the albumin-bilirubin (ALBI) score in hepatocellular carcinoma (HCC) patients treated using stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: This retrospective study evaluated the data of patients with HCC who underwent SABR between December 2007 and June 2015. We collected pretreatment CTP and ALBI scores and analyzed their correlation with survival and liver toxicity. RESULTS: This study included 152 HCC patients: 78.3% of CTP class A and 21.7% of CTP class B. The median ALBI score was -2.49 (range, -3.67 to -0.84) with 39.5% of grade 1, 56.6% of grade 2, and 3.9% of grade 3. The CTP classification and ALBI grade were significantly associated with overall survival (P<.001). Albumin-bilirubin grade (1 vs 2) had a trend to stratify CTP class A patients into 2 risk groups of mortality (P=.061). Combined CTP class and ALBI score could predict development of radiation-induced liver disease (2.4% in CTP A-ALBI < -2.76, 15.1% in CTP A-ALBI ≥ -2.76, and 25.8% in CTP B). CONCLUSION: Albumin-bilirubin score is a potential predictor for both survival and liver toxicity. Complementary use of CTP and ALBI score could predict the risk of post-SABR liver toxicity. Further prospective studies are necessary before use of the ALBI score can become part of daily practice.