Radiotherapy For Hepatocellular Carcinoma Research Articles

Use of Contrast-Enhanced Ultrasound with Sonazoid for Evaluating the Radiotherapy Efficacy for Hepatocellular Carcinoma.

Radiotherapy is one of the available curative therapies for hepatocellular carcinoma (HCC). We investigate the use of contrast-enhanced ultrasound using Sonazoid (SCEUS) in evaluating the efficacy of radiotherapy for HCC. We enrolled 59 patients with 59 HCCs in this retrospective study. Tumor size and tumor vascularity were evaluated using SCEUS before and 1, 3, 7, 10, and 13 months after radiotherapy. The median follow-up period was 44.5 months (range: 16–82 months). Of the HCCs, 95% (56/59) had no local recurrence, while 5% (3/59) did. At 13 months after radiotherapy, in cases with no local recurrence, SCEUS showed a reduction in tumor vascularity in all cases, while tumor size reduction (>30% reduction, compared with pre-radiotherapy) was observed in 82.1% (46/56). In all three cases of local recurrence, vascularity and tumor size reduction were not observed during the follow-up period and residual HCCs were demonstrated pathologically. Compared with cases with local recurrence, tumor size reduction and reduction in tumor vascularity (p < 0.001) were significantly greater in cases with no local recurrence at 13 months after radiotherapy. SCEUS may be useful in evaluating radiotherapy efficacy for HCC.

Multi-Institutional Retrospective Study of Radiotherapy for Hepatocellular Carcinoma in the Caudate Lobe.

Background: No studies evaluating the clinical outcomes of radiotherapy (RT) for hepatocellular carcinoma (HCC) in the caudate lobe have been available to date. The purpose of this study was to evaluate the effectiveness and safety of RT for HCC in the caudate lobe.Material and Methods: Seventy patients with HCC in the caudate lobe treated with RT from a multi-institutional database were included in this study. The median equivalent dose in 2 Gy (EQD2) was 80.0 Gy10 (range, 31.3–99.3), and freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were evaluated.Results: The median time of follow-up was 47.9 months (range, 3.4–127), and the 5-year FFLP, PFS, and OS rates were 80.6% [95% confidence interval (CI), 70.8–91.8], 13.8% (95% CI, 7.5–25.4), and 51.3% (95% CI, 39.9–66.1), respectively. In the multivariate analysis, the radiation dose was significantly associated with the FFLP rate [hazard ratio (HR), 0.57 per 10 Gy10 increase, p = 0.001], and the status of FFLP was significantly associated with OS (HR, 2.694, p = 0.014). The overall rate of ≥grade 3 adverse events was 5.7% (4 of 70), and RT-related mortality was not observed.Conclusion: RT for HCC in the caudate lobe showed promising FFLP and OS rates with safe toxicity profiles. These findings suggest that RT may be a promising treatment option for HCC in the caudate lobe.

A preliminary investigation of re-evaluating the irradiation dose in hepatocellular carcinoma radiotherapy applying 4D CT and deformable registration.

PurposeTo investigate the effect of breathing motion on dose distribution for hepatocellular carcinoma (HCC) patients using four‐dimensional (4D) CT and deformable registration.MethodsFifty HCC patients who were going to receive radiotherapy were enrolled in this study. All patients had been treated with transarterial chemoembolization beforehand. Three‐dimensional (3D) and 4D CT scans in free breathing were acquired sequentially. Volumetric modulated arc therapy (VMAT) was planned on the 3D CT images and maximum intensity projection (MIP) images. Thus, the 3D dose (Dose‐3D) and MIP dose (Dose‐MIP) were obtained, respectively. Then, the Dose‐3D and Dose‐MIP were recalculated on 10 phases of 4D CT images, respectively, in which the end‐inhale and end‐exhale phase doses were defined as Dose‐3D‐EI, Dose‐3D‐EE, Dose‐MIP‐EI, and Dose‐MIP‐EE. The 4D dose (Dose‐4D‐3D and Dose‐4D‐MIP) were obtained by deforming 10 phase doses to the end‐exhale CT to accumulate. The dosimetric difference in Dose‐3D, Dose‐EI3D, Dose‐EE3D, Dose‐4D‐3D, Dose‐MIP, Dose‐EIMIP, Dose‐EEMIP, and Dose‐4D‐MIP were compared to evaluate the motion effect on dose delivery to the planning target volume (PTV) and normal liver.ResultsCompared with Dose‐3D, PTV D99 in Dose‐EI3D, Dose‐EE3D and Dose‐4D‐3D decreased by an average of 6.02%, 1.32%, 2.43%, respectively (P < 0.05); while PTV D95 decreased by an average of 3.34%, 1.51%, 1.93%, respectively (P < 0.05). However, CI and HI of the PTV in Dose‐3D was superior to the other three distributions (P < 0.05). There was no significant differences for the PTV between Dose‐EI and Dose‐EE, and between the two extreme phase doses and Dose‐4D (P> 0.05). Negligible difference was observed for normal liver in all dose distributions (P> 0.05).ConclusionsFour‐dimensional dose calculations potentially ensure target volume coverage when breathing motion may affect the dose distribution. Dose escalation can be considered to improve the local control of HCC on the basis of accurately predicting the probability of radiation‐induced liver disease.

Stereotactic radiotherapy for hepatocellular carcinoma induced by hepatitis C and the relationships of changes in carbohydrate antigen 19-9 with AFP and PIVKA-II

PurposeAssessing the therapeutic effects of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) takes time. Purpose of our study was to explore the relationships of changes in carbohydrate antigen 19-9 (CA 19-9) with those in the existing markers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II). Patients and methodsThe subjects were 16 patients who underwent SBRT for solitary HCC ≤3cm induced by hepatitis C between June 2016 and July 2019. Observation periods ranged from 8–43 (median: 28) months, ages from 59–85 (median: 65) years. ResultsChanges in CA 19-9 levels after SBRT were categorised into three patterns: 1) a transient elevation followed by a decline (75%); 2) a transient decline followed by an elevation (18.8%); and 3) no change (6.3%). Among patients showing a transient CA 19-9 elevation followed by a decline, which was the most frequent pattern, 75% showed these changes in synchronisation with AFP and preceded the changes in PIVKA-II, while in the other 25%, CA 19-9 changes were in synchronisation with PIVKA-II and preceded those in AFP. At the time of recurrence, 62.5% showed a continuous CA 19-9 elevation, either in synchronisation with other markers or by itself. ConclusionsThis is the first investigation of changes in CA 19-9 levels after SBRT for HCC induced by hepatitis C. Characteristic changes in CA 19-9, AFP, and PIVKA-II levels were observed as responses after treatment. As for its correlations with tumour markers, the acute responses of PIVKA-II tended to be slower than those of CA 19-9 and AFP. Although the sample size was small, our findings raise the possibility that measuring these 3 biomarkers after SBRT may be useful for monitoring patients for HCC recurrence.

Survival and morbidity following stereotactic radiotherapy of hepatocellular carcinoma: a ten-year, single institution experience

Background and aim Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option in hepatocellular carcinoma (HCC) in patients ineligible for other local ablative therapies. This study reports on the safety and efficacy of SABR in a Danish cohort of HCC patients. Materials and methods Between January 2009 and December 2018, 28 patients with HCCs were treated with SABR at our institution. The primary endpoint of this retrospective study was local control; secondary endpoints were progression-free survival, overall survival and toxicity. Results In 28 patients, 32 tumors (median size 3.7 cm, range 1.4–6.8 cm) were treated. The median follow-up time was 16 months. Most patients (68%) received previous liver-directed treatments. A dose of 48 Gy in three or six fractions were given to 43% of the patients. Grad 1 or 2 toxicity was reported in 13 patients (46%), whereas 4 patients (14%) needed hospitalization (grade 3). One-year local control and overall survivals were 90% and 71%, respectively. One-year progression-free survival was 32%, and 65% of patients with disease progression received further HCC therapy. In univariate analysis, none of the examined factors predicted recurrence or overall survival. Conclusion SABR provides high local control to inoperable HCC. SABR can be delivered safely even after previous liver-directed therapies and subsequent therapies are feasible after treatment with SABR. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximize disease control.

MRI-guided stereotactic radiation therapy for hepatocellular carcinoma: a feasible and safe innovative treatment approach.

Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors. We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment-response assessment. Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5months (1-25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child-Pugh before and after treatment remained unchanged in all but one patient. MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.

CDC20 regulates the cell proliferation and radiosensitivity of P53 mutant HCC cells through the Bcl-2/Bax pathway.

Purpose: The incidence of hepatocellular carcinoma (HCC) is extremely high, and China accounts for approximately 50% of global liver cancer cases. Previous studies reported that CDC20 is involved in the occurrence and progression of a variety of malignant tumors. So, whether CDC20 will affect the development of HCC, we have conducted in-depth research on this.Methods: We selected Hep3B and HepG2 for cell culture, and performed siRNA transfection, lentiviral infection, western blot, MTS determination, cell cycle determination, apoptosis test, immunodeficiency test, clone survival test and subcutaneous parthenogenesis in nude mice.Results: Knockdown of CDC20 greatly enhanced the radiation efficacy on the growth retardation in HepG2, and protein level of CDC20 was decreased for the activation of P53 by radiation. Downregulation of CDC20 combined with radiation can inhibit proliferation, aggravate DNA damage, increase G2/M arrest, and promote apoptosis of HCC cells to a greater extent, and the relative survival fraction of HCC cells was gradually reduced with radiation dose increased in P53 mutated Hep3B cells. After knocking down CDC20 in HCC, Bcl-2 was down-regulated and Bax expression increased. Down-regulation of CDC20 can inhibit further invasion by promoting the radiosensitivity of HCC.Conclusion: In this study, we found that that CDC20 was highly expressed in HCC and participated in radio resistance of HCC cells with P53 mutation Bcl-2/Bax via signaling pathway. This study is the first to present evidence that CDC20 may play a role in improving the efficacy of radiotherapy in HCC.

Stereotactic body radiation therapy for hepatocellular carcinoma with Macrovascular invasion

BackgroundIn patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT). MethodsPatients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed. Results128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT. ConclusionsSBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing.

Dose-Response Relationship in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: A Pooled Analysis of an Asian Liver Radiation Therapy Group Study

Despite the worldwide implementation of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC), there is a lack of consensus guideline on prescription dose. Herein, this multinational study aimed to investigate the effects of the prescribed radiation dose on oncologic outcomes of SBRT for HCC. The multi-institutional retrospective cohort included 510 patients treated with SBRT between 2010 and 2016. All relevant clinical factors and factors related to SBRT were analyzed to evaluate freedom from local progression (FFLP) and overall survival (OS). Based on a biologically effective dose (BED) cutoff value of 100 Gy, 198 tumors were selected from each group in propensity score matching (PSM). Baseline characteristics in the BED <100 Gy group were unfavorable (Child-Pugh class B, 19%; advanced stage, 72%; median tumor size was 4 cm) compared with the BED ≥100 Gy group. With a median follow-up of 22 (interquartile range, 9.8-37.6) months, the 2-year FFLP and OS rates were 77% and 73%, respectively. Patients treated with a BED ≥100 Gy showed better rates of 2-year FFLP and OS than patients treated with a BED <100 Gy (FFLP, 89% vs 69%; OS, 80% vs 67%; P < .001). In the multivariable analysis before and after PSM, BED ≥100 Gy was identified as the main prognostic factor for both FFLP and OS (P < .01). Additionally, a dose-response relationship was observed between FFLP and BED (odds ratio, 0.92 per 5 Gy, P = .048). A BED ≥100 Gy was significantly associated with outcomes, and a dose-response relationship was observed between local tumor progression and BED. Given that SBRT is being increasingly used in HCC, detailed consensus guidelines regarding SBRT dose prescription should be established.

Preliminary evaluation of the radiotherapeutic efficacy of 131I-atorvastatin in rats with hepatocellular carcinoma

As one of the most critical types of cancer, hepatocellular carcinoma (HCC) affects many people worldwide. This study demonstrated the prospective use of atorvastatin, a drug that inhibits the mevalonate pathway, causing hypolipidemia, as a carrier to deliver the iodine-131 (131I) isotope to liver tissues for HCC radiotherapy. The atorvastatin radioiodination method was optimized for utilizing the 131I isotope. The radiochemical quality and the in vitro stability of the generated [131I]atorvastatin were investigated. In addition, the biodistribution experiments of [131I]atorvastatin were evaluated in both normal and HCC-induced rat models. [131I]atorvastatin was produced at a maximum radiochemical yield of 86.7 ± 0.49%. The [131I]atorvastatin solution purified via high-performance liquid chromatography showed good in vitro stability for 12 h after tagging. Biodistribution analyses revealed remarkable liver targeting capacity of [131I]atorvastatin and good localization of 131I in liver tissues. Overall, the encouraging biochemical profile and histopathological findings have been reported, and preliminary investigations on the possible use of [131I]atorvastatin as a radiotracer and its impact on HCC radiotherapy in rats show promise.

Respiratory-Gated Magnetic Resonance Image Guided Radiation Therapy for Hepatocellular Carcinoma: A Pilot Study

Hypofractionated RT has shown encouraging results in hepatocellular carcinoma (HCC) patients. However, HCC adjacent to the gastrointestinal (GI) tract should be carefully treated using the high-precision irradiation technique due to risk of radiation damage. We evaluated the feasibility of a respiratory-gated magnetic resonance image guided radiation therapy (RgMRg-RT) for hepatocellular carcinoma (HCC). Thirty-three patients with HCC underwent RgMRg-RT in our hospital from 2015 to February 2019, including patients with Child-Pugh A/B7 cirrhosis and unresectable tumors near the gastrointestinal tract. The median radiation dose was 50 Gy (range, 25–60) and median fraction number was 5 (range, 4–15). Gating was performed based on real-time magnetic resonance image without an external surrogate. The median follow-up period was 11.7 months (range, 3.6–37.9 months). The rates of local control of the target tumor at 6 months and 1 year were 90.2 and 86.9%, respectively. The overall survival rates at 6 months, 1, and 2 years were 84.3, 76.3, and 61%, respectively. The median distances from gross tumor to the esophagus, stomach, duodenum and colon were 6.1 (range, 1.9-14.3), 6.4 (0-13.4), 3.8 (0-13.5) and 4 cm (0.3-13), respectively. A total of 15 tumors (45.5%) were located within 2 cm of the gastrointestinal tract and 9 tumors (27.3%) within 1 cm. Grades 3 treatment-related bleeding was observed in one patient and one patient had radiation-induced liver disease. Hypofractionated RgMRg-RT was a safe and potentially ablative therapy for HCC. RgMRg-RT is a good alternative treatment for patients with HCCs that are unsuitable for surgical resection or local ablative therapy.

Association of Nadir ALC as a Continuous Variable with Overall Survival in Patients Receiving Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Association of Nadir ALC as a Continuous Variable with Overall Survival in Patients Receiving Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Mid-Ventilation (Mid-V) Approach Combined with 4D Cone Beam CT (CBCT) Guidance in Stereotactic Body Radiotherapy of Hepatocellular Carcinoma (HCC): A Clinical Evaluation

Tumor motion typically leads to large treatment volumes with internal-target-volume (ITV) based approach among abdominal tumors. Mid-ventilation (Mid-V) based planning target volume (PTV) margins often lead to smaller treatment volumes, yet clinical experience is limited in hepatocellular carcinoma (HCC). This study aimed at evaluating the Mid-V approach on clinical outcome of stereotactic body radiotherapy (SBRT) among HCC patients. 149 patients with 158 tumors treated during 2011-2016 were analyzed from a prospectively collected database. Each patient was planned on the Mid-V scan from the 4D-CT using volumetric modulated arc radiotherapy (VMAT). Tumor amplitudes were determined separately in left–right (LR), cranio–caudal (CC) and anterior–posterior (AP) directions, to derive the individualized PTV margins by means of the van herk formula. On-line 4D-CBCT was performed to verify the treatment position by lipiodol retention if present and liver or diaphragm otherwise. Primary end point was local control (LC). Secondary end points were overall survival (OS) and objective response rate (ORR) by RECIST 1.1 criteria. The median tumor size was 8.4 cm (range: 1.1 – 20.5 cm) and GTV volume was 322.9 mL (range: 2.9–3990.7 mL). The median total equivalent dose in 2Gy/fr (EQD2, a/b = 10) was 37.5 Gy (range: 28–85.5 Gy). The median LR, CC and AP tumor amplitudes were 1 mm (0.1–5.7 mm), 6.1 mm (0.3–17.5 mm) and 1.7 mm (0.1–15 mm), respectively, yielding a median CTV-to-PTV margin of 11.5 mm (8.4—20.0 mm). While an ITV + 5 mm based PTV margin would have been bigger in 44.3% of the patients, the LC and OS differences of our mid-V generated PTV margins of <10mm and ≥10mm were insignificant (p = 0.587, p = 0.622 respectively). It has yielded overall 1-year and 2-year LC rates of 88.9% (95% CI 86.3—91.5%) and 82.1% (95% CI 78.4—85.8%) respectively, of which tumors <5cm achieved an excellent 1-year LC rate of 96.9% with a trend towards better LC as compared to those ≥5cm (p = 0.062). The overall 1-year and 2-year OS rates of 57.4% (95% CI 53.5—61.3%) and 35.9% (95% CI 32.1—39.7%) respectively. ORR was 57% while clinical benefit rate was up to 94% (complete response: 6.0%, partial response: 51.0%, stable disease: 37.0%, progressive disease: 6.0%). This first report of SBRT with Mid-V planning, 4D CBCT and individualized PTV margin generation by Van herk formula among HCC patients has achieved promising local control results. It supports that such image-guidance strategy is a safe approach and warrants further studies. Table 1. Comparison of local control and overall survival rates of different tumor sizes.Abstract 3463; Table1-year LC rate (%)2-year LC rate (%)p value1-year OS rate (%)2-year OS rate (%)p value<5cm (n = 34)96.996.90.06268.040.00.732≥5cm (n = 124)86.778.255.335.0Overall (n = 158)88.982.157.435.9 Open table in a new tab

Albumin-bilirubin versus Child-Pugh Grade as a Predictor of Survival after Individualised Hypofractionated Radiotherapy for Hepatocellular Carcinoma

Albumin-bilirubin versus Child-Pugh Grade as a Predictor of Survival after Individualised Hypofractionated Radiotherapy for Hepatocellular Carcinoma

Stereotactic body radiotherapy in hepatocellular carcinoma: patient selection and predictors of outcome and toxicity.

Stereotactic Body Radiotherapy (SBRT) emerged as a valuable option in early to advanced-stage Hepatocellular Carcinoma (HCC) as defined by Barcelona Clinic Liver Cancer (BCLC) system. The aim of our study is to evaluate SBRT in HCC patients and to identify predictors of outcome and toxicity. A retrospective review of HCC patients treated at our Institution between November 2011 and December 2018 was carried out. SBRT was delivered in 3-10 fractions to a median Biologically Effective Dose (BED10) of 103Gy10. SBRT was performed in 128 patients to 217 HCC localizations, accounting for 142 treatment courses. BCLC stage was A, B, C in, respectively, 40 (31%), 72 (56%) and 16 (13%) patients. Local Control (LC), Progression Free Survival (PFS) and Overall Survival (OS) at 2years were, respectively: 78%, 15% and 58%. LC was influenced by BED10 > 120Gy10 (Hazard Ratio, HR: 0.08, 95% CI 0.01-0.59; p = 0.013) and size ≥ 3cm (HR: 2.71, 95% CI 1.10-6.66; p = 0.03). BCLC stage was correlated to PFS (median 14 vs 12 vs 5months, p = 0.012). In BCLC stage A-B disease (n = 112), LC was associated with improved survival (median 30months vs not reached, p = 0.036). Acute and late toxicity rate was 26% (n = 37) and 8% (n = 11). Patients with BCLC B-C stage disease showed increased acute toxicity (HR: 2.9, 95% CI 1.10-7.65; p = 0.032). Delivery of ablative doses > 120Gy10 and tumor size are determinants of LC. Prolonged PFS and improved OS can be obtained in BCLC A-B patients. Grade 3 liver dysfunction is infrequent.

Repeated Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

PurposeIn clinical practice, whether cirrhotic livers in patients with hepatocellular carcinoma (HCC) can withstand repeated stereotactic body radiation therapy (SBRT) remains unclear. This study aimed to evaluate the outcomes and toxicities in these patients. Methods and materialsThis retrospective study included patients with HCC who were treated with SBRT at least twice between January 2012 and June 2019. Local control and overall survival rates were calculated. Liver function before and after irradiation was evaluated using the Child-Pugh score and modified albumin-bilirubin grade. All toxicities were assessed using the Common Terminology Criteria for Adverse Events (version 4.0). ResultsFifty-two patients underwent 136 courses (148 lesions) of SBRT, which was mostly performed for out-of-field tumors but 3 in-field recurrences. The median follow-up duration from the first SBRT was 52.6 months (range, 15.7-89.3 months). The median gross tumor volume was 4.6 cm3 (range, 0.8-55.2 cm3) at the second SBRT. The 3-year local control rate was 94.5% (95% confidence interval, 88.0%-97.5%). The 3-year overall survival rate after the second course was 62.8% (95% confidence interval, 45.1%-76.2%). Although the Child-Pugh score did not deteriorate after the second course, deterioration of the modified albumin-bilirubin grade at 6, 12, and 24 months was statistically significant compared with that before the second course. One patient (1.9%) experienced grade 3 hypoalbuminemia and 2 patients (3.8%) had grade 3 thrombocytopenia 6 months after the second course. Mild fatigue and nausea were reported in 9 (17.3%) and 6 (11.5%) patients, respectively. One instance of grade 5 toxicity was observed. Two patients (1.5%) had grade 2 gastric ulcers. No other grade ≥3 gastrointestinal toxicities occurred. ConclusionsRepeated SBRT is feasible and produces minimal toxicity in patients with HCC and Child-Pugh scores of ≤7 and a low normal liver dose.

RETRACTED ARTICLE: Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3

BackgroundThe signal transducer and activator of transcription-3 (STAT-3) can facilitate cancer progression and metastasis by being constitutively active via various signaling. Abundant evidence has indicated that STAT-3 may be a promising molecular target for cancer treatment.MethodsIn this study, a dual-luciferase assay-based screening of 537 compounds for STAT-3 inhibitors of hepatocellular carcinoma (HCC) cells was conducted, leading to the identification of genipin. Effects of genipin on HCC were assessed in a patient-derived xenograft nude mice model. Western blotting assay, chromatin immunoprecipitation (ChIP) assay, molecular docking study, tube formation assay, three-dimensional top culture assay, histological examination, and immunofluorescence were utilized to evaluate the regulatory signaling pathway.ResultsOur research demonstrated that genipin suppresses STAT-3 phosphorylation and nuclear translocation, which may be attributed to the binding capacity of this compound to the Src homology-2 (SH2) domain of STAT-3. In addition, the therapeutic effects of genipin in a patient-derived HCC xenograft nude mice model were also demonstrated.ConclusionsIn conclusion, genipin showed therapeutic potential for HCC treatment by interacting with the SH2-STAT-3 domain and suppressing the activity of STAT-3. In the future, further research is planned to explore the potential role of genipin in combination with chemotherapy or radiotherapy for HCC.

The utility of 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT/CT for selective internal radiation therapy in hepatocellular carcinoma.

Studies assessing the impact of selective internal radiation therapy (SIRT) on the regional liver function in patients with hepatocellular carcinoma (HCC) are sparse. This study assessed the changes in total and regional liver function using hepatobiliary scintigraphy (HBS) and investigated the utility of HBS to predict post-SIRT liver dysfunction. Patients treated with SIRT for HCC between 2011 and 2019, underwent Tc-mebrofenin HBS with single-photon emission computed tomography/computed tomography (SPECT/CT) before and 6 weeks after SIRT. The corrected mebrofenin uptake rate (cMUR) and corresponding volume was measured in the total liver, and in treated and nontreated liver regions. Patients with and without post-SIRT liver dysfunction were compared. A total of 29 patients, all Child-Pugh-A and mostly intermediate (72%) stage HCC were included in this study. Due to SIRT, the cMURtotal declined from 5.8 to 4.5%/min/m (P < 0.001). Twenty-two patients underwent a lobar SIRT, which induced a decline in cMUR (2.9-1.7%/min/m, P < 0.001) and volume (1228-1101, P = 0.002) of the treated liver region, without a change in cMUR (2.4-2.0%/min/m, P = 0.808) or volume (632-644 mL, P = 0.661) of the contralateral nontreated lobe. There were no significant pre-SIRT differences in total or regional cMUR or volume between patients with and without post-SIRT liver dysfunction. In patients treated with SIRT for HCC, HBS accurately identified changes in total and regional liver function and may have a complementary role to personalize lobar or selective SIRT. In this pilot study, there were no pre-SIRT differences in cMUR or volume to aid in predicting post-SIRT liver dysfunction.

Virologic Impact of Radiotherapy in Hepatitis C Virus-Infected Patients With Hepatocellular Carcinoma.

Hepatitis B virus (HBV) reactivation had been reported following radiotherapy in patients with hepatocellular carcinoma (HCC) along with limited data focused on patients infected with hepatitis C virus (HCV). Herein, we aimed to examine the virologic impact of radiotherapy in HCV-infected patients with HCC. In this case-control study, we identified all patients with unresectable HCC who received radiotherapy directed to the liver at MD Anderson from March 2009 through November 2018. Cases were defined as patients with HCV infection; controls were defined as patients without HCV infection. The case to control ratio was 1:3, and the subjects were matched by age, radiation dose, and fractionation or biologically effective dose of the radiation to the normal liver (α/β=2.5) and tumor (α/β=10). Thirty-two patients were studied, including 8 cases and 24 controls. No HCV reactivation was observed among the cases. Hepatitis flare was observed in 2 (25%) of 8 cases and 2 (8%) of 24 controls (p=0.25). The peak alanine aminotransferase level within 6 months after radiotherapy did not differ significantly between the cases and controls. Radiotherapy completion rates were similar in the two groups. This is the first report analyzing changes in HCV RNA levels after radiation for HCV-associated HCC. Our results suggest that the effects of radiotherapy on the liver function of HCV-infected patients with HCC do not differ from the HCV-uninfected patients. Therefore, it may not be necessary to monitor for HCV replication in HCV-infected patients receiving radiotherapy for HCC or to incorporate a biological variable based on HCV infection status in mathematical models of liver dose-volume constraints that predict radiation-induced liver disease.

Comparison of feature selection in radiomics for the prediction of overall survival after radiotherapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth more frequent cancer worldwide. This type of cancer has a poor overall survival rate mainly due to underlying cirrhosis and risk of recurrence outside the treated lesion. Quantitative imaging within a radiomics workflow may help assessing the probability of survival and potentially may allow tailoring personalized treatments. In radiomics a large amount of features can be extracted, which may be correlated across a population and very often can be surrogates of the same physiopathology. This issues are more pronounced and difficult to tackle with imbalanced data. Feature selection strategies are therefore required to extract the most informative with the increased predictive capabilities. In this paper, we compared different unsupervised and supervised strategies for feature selection in presence of imbalanced data and optimize them within a machine learning framework. Multi-parametric Magnetic Resonance Images from 81 individuals (19 deceased) treated with stereotactic body radiation therapy (SBRT) for inoperable (HCC) were analyzed. Pre-selection of a reduced set of features based on Affinity Propagation clustering (non supervised) achieved a significant improvement in AUC compared to other approaches with and without feature pre-selection. By including the synthetic minority over-sampling technique (SMOTE) for imbalanced data and Random Forest classification this workflow emerges as an appealing feature selection strategy for survival prediction within radiomics studies.