Role of modern radiotherapy in managing patients with hepatocellular carcinoma.
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ABSTRACT:
SUBMITTER: Chen LC
PROVIDER: S-EPMC8160620 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The incidence of hepatocellular carcinoma (HCC) continues to increase world-wide. Many patients present with advanced disease with extensive local tumor or vascular invasion and are not candidates for traditionally curative therapies such as orthotopic liver transplantation (OLT) or resection. Radiotherapy (RT) was historically limited by its inability to deliver a tumoricidal dose; however, modern RT techniques have prompted renewed interest in the use of liver-directed RT to treat patients with primary hepatic malignancies.The aim of this review was to discuss the use of external beam RT in the treatment of HCC, with particular focus on the use of stereotactic body radiotherapy (SBRT). We review the intricacies of SBRT treatment planning and delivery. Liver-directed RT involves accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. We also summarize the published data on liver-directed RT, and demonstrate that it is associated with excellent local control and survival rates, particularly in patients who are not candidates for OLT or resection.Modern liver-directed RT is safe and effective for the treatment of HCC, particularly in patients who are not candidates for OLT or resection. Liver-directed RT, including SBRT, depends on accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. Further prospective studies are needed to fully delineate the role of liver-directed RT in the treatment of HCC.
| S-EPMC4960357 | biostudies-other
Project description:The aim of this prospective observational trial was to evaluate the efficacy, toxicity and quality of life after stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to assess the results of this treatment in comparison to trans-arterial chemoembolization (TACE). Patients with HCC, treated with TACE or SBRT, over a period of 12 months, enrolled in the study. The primary endpoint was feasibility; secondary endpoints were toxicity, quality of life (QOL), local progression (LP) and overall survival (OS). Between 06/2016 and 06/2017, 19 patients received TACE and 20 SBRT, 2 of whom were excluded due to progression. The median follow-up was 31 months. The QOL remained stable before and after treatment and was comparable in both treatment groups. Five patients developed grade ≥ 3 toxicities in the TACE group and 3 in the SBRT group. The cumulative incidence of LP after 1-, 2- and 3-years was 6, 6, 6% in the SBRT group and 28, 39, and 65% in the TACE group (p = 0.02). The 1- and 2- years OS rates were 84% and 47% in the TACE group and 44% and 39% in the SBRT group (p = 0.20). In conclusion, SBRT is a well-tolerated local treatment with a high local control rates and can be safely delivered, while preserving the QOL of HCC patients.
| S-EPMC8017336 | biostudies-literature
Project description:There is a need to improve the effectiveness of radiotherapy (RT) in hepatocellular carcinoma (HCC). Therefore, the purpose of this study was to explore the efficacy and toxicity of the anti-microtubule agent Vinorelbine as a radiosensitizer in HCC. The radio sensitivity of 16 HCC patient-derived xenograft (PDX) models was determined by quantifying the survival fraction following irradiation in vitro, and Vinorelbine radio sensitization was determined by clonogenic assay. Ectopic HCC xenografts were treated with a single dose of 8 Gy irradiation and twice-weekly 3 mg/kg Vinorelbine. Tumor growth and changes in the proteins involved in DNA repair, angiogenesis, tumor cell proliferation, and survival were assessed, and the 3/16 (18.75%), 7/16 (43.75%), and 6/16 (37.5%) HCC lines were classified as sensitive, moderately sensitive, and resistant, respectively. The combination of RT and Vinorelbine significantly inhibited tumor growth, DNA repair proteins, angiogenesis, and cell proliferation, and promoted more apoptosis compared with RT or Vinorelbine treatment alone. Vinorelbine improved HCC tumor response to standard irradiation with no increase in toxicity. HCC is prevalent in less developed parts of the world and is mostly unresectable on presentation. Vinorelbine and conventional radiotherapy are cost-effective, well-established modalities of cancer treatment that are readily available. Therefore, this strategy can potentially address an unmet clinical need, warranting further investigation in early-phase clinical trials.
| S-EPMC7226273 | biostudies-literature
Project description:PurposeTo stratify patients and aid clinical decision making, we developed machine learning models to predict treatment failure and radiation-induced toxicities after radiotherapy (RT) in patients with hepatocellular carcinoma across institutions.Materials and methodsThe models were developed using linear and nonlinear algorithms, predicting survival, nonlocal failure, radiation-induced liver disease, and lymphopenia from baseline patient and treatment parameters. The models were trained on 207 patients from Massachusetts General Hospital. Performance was quantified using Harrell's c-index, area under the curve (AUC), and accuracy in high-risk populations. Models' structures were optimized in a nested cross-validation approach to prevent overfitting. A study analysis plan was registered before external validation using 143 patients from MD Anderson Cancer Center. Clinical utility was assessed using net-benefit analysis.ResultsThe survival model stratified high-risk versus low-risk patients well in the external validation cohort (c-index = 0.75), better than existing risk scores. Predictions of 1-year survival and nonlocal failure were excellent (external AUC = 0.74 and 0.80, respectively), especially in the high-risk group (accuracy > 90%). Cause-of-death analysis showed differential modes of treatment failure in these cohorts and indicated that these models could be used to stratify RT patients for liver-sparing treatment regimen or combination approaches with systemic agents. Predictions of liver disease and lymphopenia were good but less robust (external AUC = 0.68 and 0.7, respectively), suggesting the need for more comprehensive consideration of dosimetry and better predictive biomarkers. The liver disease model showed excellent accuracy in the high-risk group (92%) and revealed possible interactions of platelet count with initial liver function.ConclusionMachine learning approaches can provide reliable outcome predictions in patients with hepatocellular carcinoma after RT in diverse cohorts across institutions. The excellent performance, particularly in high-risk patients, suggests novel strategies for patient stratification and treatment selection.
| S-EPMC8863122 | biostudies-literature
Project description:Primary liver cancer is one of the most common malignant tumours worldwide; it caused approximately 830,000 deaths in 2020. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for over 80% of all cases. Various methods, including surgery, chemotherapy, radiotherapy, and radiofrequency ablation, have been widely used in the treatment of HCC. With the advancement of technology, radiotherapy has become increasingly important in the comprehensive treatment of HCC. However, due to the insufficient sensitivity of tumour cells to radiation, there are still multiple limitation in clinical application of radiotherapy. In recent years, the role of immunotherapy in cancer has been increasingly revealed, and more researchers have turned their attention to the combined application of immunotherapy and radiotherapy in the hope of achieving better treatment outcomes. This article reviews the progress on radiation therapy in HCC and the current status of its combined application with immunotherapy, and discusses the prospects and value of radioimmunotherapy in HCC.
| S-EPMC10401766 | biostudies-literature
Project description:Background: Sarcopenia is gaining attention as a poor prognostic factor for various types of malignancies. This study evaluated the prevalence and prognostic significance of sarcopenia and its association with survival in hepatocellular carcinoma (HCC) patients who underwent radiotherapy (RT) to the primary site. Materials and Methods: Between January 2009 and November 2016, 156 patients with HCC that underwent RT to the liver were retrospectively studied. Sarcopenia was defined as an L3 skeletal muscle index of <49 cm2/m2 for men and <41 cm2/m2 for women as proposed by Korean-specific cut-off value. Sarcopenia was identified pre- and post-RT (within 3 months from the end of RT). Results: Pre-RT sarcopenia occurred in 99 (63.5%) patients and was significantly associated with higher levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II), lower percentage of overweight/obesity (body-mass index), higher percentage of previous systemic chemotherapy, and lower total RT dose. At a median follow-up of 9.3 months, median overall survival (OS) was significantly lower in patients with pre-RT sarcopenia than in those without (7.1 vs. 15.3 months, p < 0.001). In multivariate analysis [reporting hazard ratio (HR): 95% confidence interval (CI)], albumin-bilirubin score (2.35: 1.33-4.17; p = 0.003), total dose (0.44: 0.27-0.71; p = 0.001), and pre-RT sarcopenia (2.38: 1.53-3.70; p < 0.001) were independent OS prognostic factors. Among patients without pre-RT sarcopenia, 20 newly developed sarcopenia after RT and showed significantly lower OS compared to those without sarcopenia after RT (n = 35) (median 14.1 vs. 17.5 months, p = 0.018). Multivariate logistic regression analysis [reporting odds ratio (OR)] demonstrated older age (310.190; p = 0.007), Child-Pugh classification B or C (15.239; p = 0.047), higher alpha-fetoprotein (128.486; p = 0.008), higher PIVKA-II (118.536; p = 0.027), and larger planning target volume (51.310; p = 0.026) as significant factors for newly developed post-RT sarcopenia. Conclusion: Newly developed sarcopenia after RT, as well as pre-RT sarcopenia, were associated with poor survival for HCC patients who underwent RT to the liver. This result suggests the possibility that early intervention such as nutritional support and exercise therapies before and during RT could prevent muscle wasting and may be effective in improving the prognosis of HCC patients.
| S-EPMC6803501 | biostudies-literature
Project description:To assess the role of radiotherapy in metastatic malignant melanoma (MM) patients in modern era.This is a retrospective study of MM patients treated with radiotherapy at Mayo Clinic from 1999 to 2014. Patients with pre- and post-treatment imaging studies (CT, MRI, and/or PET/CT) were assessed for metastasis failure (MF), regional/distant failure, and overall survival (OS).In 75 MM patients, 56 and 68 lesions were treated with conventional/hypofractionated radiotherapy (CHRT) and stereotactic body radiotherapy (SBRT), respectively. The median doses for CHRT and SBRT were 30 Gy and 50 Gy, respectively. 1-year MF was 17% (SBRT 6% vs CHRT 31%, p < 0.01). 1-year regional (5% vs 29%, p < 0.01) and distant progression (75% vs 89%, p < 0.01) were improved with SBRT. Median OS was 15.6 months (CHRT 7.0 vs SBRT 22.9, p < 0.01). Prognostic factors for OS included age ?55 years (RR 0.25), oligometastatic disease (RR 0.34), SBRT (RR 0.38) and treating all lesions (RR 0.28, all p < 0.01).SBRT for extracranial MM exhibited improved MF compared with CHRT, consistent with intracranial radiosurgery data. Though these data are retrospective and subject to selection bias, our findings support the prudent use of SBRT in a select group of favorable, oligometastatic MM patients, and should be discussed as an alternative to surgery and ablation.
| S-EPMC5862645 | biostudies-literature
Project description:Radiation therapy (RT) has improved patient outcomes, but treatment-related complication rates remain high. In the conventional 2-dimensional and 3-dimensional conformal RT (3D-CRT) era, there was little room for toxicity reduction because of the need to balance the estimated toxicity to organs at risk (OARs), derived from dose-volume histogram data for organs including the lung, heart, spinal cord, and liver, with the planning target volume (PTV) dose. Intensity-modulated RT (IMRT) is an advanced form of conformal RT that utilizes computer-controlled linear accelerators to deliver precise radiation doses to the PTV. The dosimetric advantages of IMRT enable better sparing of normal tissues and OARs than is possible with 3D-CRT. A major breakthrough in the treatment of esophageal cancer (EC), whether early or locally advanced, is the use of proton beam therapy (PBT). Protons deposit their highest dose of radiation at the tumor, while leaving none behind; the resulting effective dose reduction to healthy tissues and OARs considerably reduces acute and delayed RT-related toxicity. In recent studies, PBT has been found to alleviate severe lymphopenia resulting from combined chemo-radiation, opening up the possibility of reducing immune suppression, which might be associated with a poor prognosis in cases of locally advanced EC.
| S-EPMC7409878 | biostudies-literature
Project description:This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.
| S-EPMC6985173 | biostudies-literature
Project description:PurposeCarbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for hepatocellular carcinoma (HCC). However, evidence of using the pencil beam scanning (PBS) technique to treat moving liver tumors remains lacking. The present study investigated the efficacy and toxicity of PBS CIRT in patients with HCC.MethodsBetween January 2016 and October 2021, 90 consecutive HCC patients treated with definitive CIRT in our center were retrospectively analyzed. Fifty-eight patients received relative biological effectiveness-weighted doses of 50-70 Gy in 10 fractions, and 32 received 60-67.5 Gy in 15 fractions, which were determined by the tumor location and normal tissue constraints. Active motion-management techniques and necessary strategies were adopted to mitigate interplay effects efficiently. Oncologic outcomes and toxicities were evaluated.ResultsThe median follow-up time was 28.6 months (range 5.7-74.6 months). The objective response rate was 75.0% for all 90 patients with 100 treated lesions. The overall survival rates at 1-, 2- and 3-years were 97.8%, 83.3% and 75.4%, respectively. The local control rates at 1-, 2- and 3-years were 96.4%, 96.4% and 93.1%, respectively. Radiation-induced liver disease was not documented, and 4 patients (4.4%) had their Child-Pugh score elevated by 1 point after CIRT. No grade 3 or higher acute non-hematological toxicities were observed. Six patients (6.7%) experienced grade 3 or higher late toxicities.ConclusionThe active scanning technique was clinically feasible to treat HCC by applying necessary mitigation measures for interplay effects. The desirable oncologic outcomes as well as favorable toxicity profiles presented in this study will be a valuable reference for other carbon-ion centers using the PBS technique and local effect model-based system, and add to a growing body of evidence about the role of CIRT in the management of HCC.
| S-EPMC10759913 | biostudies-literature