Helical IMRT-Based Stereotactic Body Radiation Therapy Using an Abdominal Compression Technique and Modified Fractionation Regimen for Small Hepatocellular Carcinoma

Purpose: To assess the efficacy and safety of stereotactic body radiation therapy using an abdominal compression technique and modified fractionation regimen (5-10 fractions) in patients with small-sized hepatocellular carcinoma. Methods: A total of 101 patients with small-sized hepatocellular carcinoma treated with stereotactic body radiation therapy using an abdominal compression technique and modified fractionation regimen were registered between June 2011 and June 2019 in our hospital. A total dose of 48 to 60 Gy was applied over 5 to 14 consecutive days. Liver motion was controlled by abdominal compression, and a helical intensity-modified radiation therapy-based stereotactic body radiation therapy administrated in tomotherapy platform. Results: The median follow-up period was 23.2 months (range: 4.1-99.2 months). Complete response and partial response were observed in 63 (62.4%) patients and in 24 (23.8%) patients, respectively. At the time of our analysis, the 1-, 3-, and 5-year local control rates after stereotactic body radiation therapy were 96.1%, 89.0%, and 89.0%, respectively. However, logistic regression analysis revealed no correlation between the biologically effective dose and 3-year local control rates. The 1-, 3-, and 5-year overall survival rates were 96.9%, 69.0%, and 64.3%, respectively. For patients who were treatment-naive, the 1-, 3-, and 5-year overall survival were 96.3%, 82.0%, and 82.0%, respectively. No patients experienced classic radiation-induced liver disease or nonclassic radiation-induced liver disease after stereotactic body radiation therapy completion. Conclusions: When using an abdominal compression technique and modified fractionation regimen (5-10 fractions) based on helical intensity-modified radiation therapy, stereotactic body radiation therapy led to a lower toxicity and comparative rate of local control and overall survival for patients who with small-sized hepatocellular carcinoma.

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Early stage hepatocellular carcinoma treated with stereotactic body radiation therapy: A pooled analysis from two North American institutions.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.350 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 350-350 ◽

Cited By ~ 1

Author(s):

Ashwathy Susan Mathew ◽

Eshetu G. Atenafu ◽

Dawn Owen ◽

Chris Maurino ◽

Anthony M. Brade ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Radiation Therapy ◽

Local Control ◽

North American ◽

Stereotactic Body Radiation Therapy ◽

Early Stage ◽

Pooled Analysis ◽

Stereotactic Body Radiation ◽

Grade 3

350 Background: To report outcomes of pooled data from patients with early stage hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) at two North American Institutions. Methods: An IRB approved collaborative review of patients with HCC treated with radical intent SBRT was conducted. Inclusion criteria included patients with Stage I-IIIA HCC (UICC/AJCC 7th Ed.) treated with SBRT (≥ 4.5 Gy/ fraction) from June 2003 until Dec 2016. Patients who were treated with SBRT were ineligible for resection, percutaneous ablative or hepatic intravascular therapies. Patients with vascular invasion and those treated with palliative intent (e.g. HCC rupture) were excluded. Overall survival, local control and toxicity of treatment were reviewed retrospectively. Results: Of 310 eligible patients, 23% were Child-Pugh (CP) class B/C (21%/2%), and 40% had failed prior liver directed therapies. The median HCC diameter was 2.4 cm (range 0.5-18.1 cm), and the median prescribed dose was 39 Gray (Gy) in 5 fractions (range: 14 - 60 Gy in 2-6 fractions). Median BED was 78.75 Gy (Range: 23.8-180.0 Gy). 8.4% of patients underwent liver transplant after SBRT. Local control at 1, 3 and 5 years was 91.5%, 82.6% and 82.6%. On multivariable analysis (MVA), the use of breath-hold motion management, but not T stage, size or dose, was significantly associated with local control (p = 0.0098). The 1, 3, and 5 year overall survival (OS) was 77.3%, 37.9% and 23.5%. Factors associated with improved OS on MVA included baseline CP A score (HR = 0.58, p < 0.0045), AFP < 10 µg/L (HR = 0.66, p = 0.0094), and transplant post SBRT (HR = 0.05, p < 0.0001). The median survival of CP A vs. B/C patients was 30.3 and 17.6 months respectively. CTCAE (v4.0) grade 3 or higher luminal gastrointestinal organ toxicity occurred in 2.5% of patients, while a decline in CP score ≥ 2 points was seen in 16.7% of patients at 3 months post SBRT. Grade 3 and above elevated liver enzymes were seen in 12.6% and 8.1% of patients at baseline and at 3 months post SBRT. Conclusions: Similar to Asian series, this North American pooled analysis found high sustained local control and excellent survival in patients with early stage HCC treated with SBRT.

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Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Prognostic Factors of Local Control, Overall Survival, and Toxicity

PLoS ONE ◽

10.1371/journal.pone.0077472 ◽

2013 ◽

Vol 8 (10) ◽

pp. e77472 ◽

Cited By ~ 68

Author(s):

Jean-Emmanuel Bibault ◽

Sylvain Dewas ◽

Claire Vautravers-Dewas ◽

Antoine Hollebecque ◽

Hajer Jarraya ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Radiation Therapy ◽

Prognostic Factors ◽

Local Control ◽

Stereotactic Body Radiation Therapy ◽

Stereotactic Body Radiation

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Excessive Toxicity When Treating Central Tumors in a Phase II Study of Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.5937 ◽

2006 ◽

Vol 24 (30) ◽

pp. 4833-4839 ◽

Cited By ~ 940

Author(s):

Robert Timmerman ◽

Ronald McGarry ◽

Constantin Yiannoutsos ◽

Lech Papiez ◽

Kathy Tudor ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Phase Ii ◽

Local Control ◽

Stereotactic Body Radiation Therapy ◽

Early Stage ◽

Stage I ◽

Severe Toxicity ◽

Stereotactic Body Radiation

PurposeSurgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population.Patients and MethodsEligible patients included clinically staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks.ResultsAll 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors.ConclusionHigh rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.

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Repeated CyberKnife stereotactic body radiation therapy in hepatocellular carcinoma

Radiation Oncology ◽

10.1186/s13014-020-1457-z ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 1

Author(s):

Jing Sun ◽

Can Ouyang ◽

Xiaoyun Chang ◽

Aimin Zhang ◽

Quan Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Medical Center ◽

Survival Rates ◽

Progression Free Survival ◽

Interval Time ◽

Stereotactic Body Radiation ◽

Kaplan Meier ◽

Radiation Induced

Abstract Background To explore the survival and side effects of repeated CyberKnife stereotactic body radiation therapy (CK-SBRT) on hepatocellular carcinoma patients. Methods 24 HCC patients were collected at The Fifth Medical Center of PLA General Hospital from November 2011 to July 2016. They received second-course CK-SBRT with a prescribed dose of 50(48–55) Gy/5-8fx, and a single dose of 10 (7–11) Gy/fx. Cumulative overall survival rates (OS), progression-free survival rates (PFS) and local control rates (LC) were calculated by Kaplan-Meier method. Results All patients finished their radiotherapy plans. The 1-,2- and 3-year cumulative OS rate were 95.8,81.1 and 60.8%. The 1-,2- and 3-year LC rate were 95.5,90.7 and 90.7%, respectively. The 1-, 2- and 3-year PFS were 74.8, 49.2 and 39.4%, respectively. 16 patients complained of fatigue during second-course therapy, 2 patients showed Grade 2 gastrointestinal reaction, 1 patient was diagnosed radiation-induced liver disease and none died. PFS was significantly higher in the interval time < 12 months group than in the interval time ≥ 12 months group (p = 0.030). Conclusions It is preliminarily believed that re-CK-SBRT is an effective and safe treatment for HCC patients, but the treatment criteria should be strictly controlled.

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Mean Liver Dose Evaluation by Lyman NTCP Modeling With Stereotactic Body Radiation therapy to Minimize Radiation-Induced Liver Disease for Inoperable Hepatocellular Carcinoma

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2013.06.835 ◽

2013 ◽

Vol 87 (2) ◽

pp. S318 ◽

Cited By ~ 1

Author(s):

M. Camborde ◽

E. Vollans ◽

C. Crumley ◽

R. Ma ◽

R. Kosztyla ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiation Therapy ◽

Liver Disease ◽

Stereotactic Body Radiation Therapy ◽

Dose Evaluation ◽

Stereotactic Body Radiation ◽

Radiation Induced

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Stereotactic body radiation therapy to generate comparable survival to surgery in treating hepatocellular carcinoma (HCC): Results of 756 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4080 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4080-4080

Author(s):

Feng Ming Kong ◽

Yong Zang ◽

Wenhu Pi ◽

David Long ◽

Susannah Ellsworth ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

External Beam Radiation ◽

Survival Outcomes ◽

Front Line ◽

Stereotactic Body Radiation ◽

Significant Difference ◽

Better Than

4080 Background: Stereotactic Body Radiation Therapy (SBRT) has emerged as a viable treatment option in patients with hepatocellular carcinoma (HCC). This study aimed to compare survival outcomes after SBRT with other front line local treatments for HCC. Methods: This is a retrospective analysis of patients identified through our cancer registry from 2000 to 2016. Patients treated with any local therapy alone were eligible: SBRT, surgery, conventional external beam radiation (CEBRT), and other local therapies including brachytherapy. Patients treated with combined therapies such as SBRT plus liver transplant were excluded. The primary endpoint was overall survival which was estimated from the time of diagnosis. Differences between the groups were compared using log-rank test. The data are presented as median (95%CI). Results: A total of 756 patients with a median follow-up of 45 months (mo) met the selection criteria: 116, 380, 43, and 217 patients received SBRT, surgery, CEBRT, and other local treatment, respectively. Median age was 61, 60, 61 and 60 years, respectively. The median overall survival/3 year overall survival rate were 49 (32-66) mo /53% (44-65%) for patients treated with SBRT, which were not significantly different from 75 (57-94) mo /63% (58-69%) of surgery (p = 0.27), non-significantly better than 22 (13-31) mo /41% (27-60%) of CEBRT (p = 0.13), significantly better than 15 (13-20) mo /26% (20-34%) of other local treatments (p = 3×10-7). After adjusting for significant prognostic factors including age, race, status of tobacco abuse, history of alcohol use, tumor size, histology grade and stage, the survival outcomes of SBRT remained to be insignificantly different from surgery (HR = 0.8, p = 0.2), have a trend of significant difference from CEBRT (HR = 1.4, p = 0.1) and remarkably superior to that of other local treatments (HR = 1.8, p = 2×10-4). Conclusions: This study suggests that SBRT is an excellent front line option for HCC, potentially comparable to surgical resection and associated with longer survival than other front line local treatments. Randomized studies are needed to validate these findings.

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Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0038 ◽

2020 ◽

Vol 26 (4) ◽

pp. 506-515 ◽

Cited By ~ 1

Author(s):

Sang Min Yoon ◽

So Yeon Kim ◽

Young-Suk Lim ◽

Kang Mo Kim ◽

Ju Hyun Shim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Radiation Therapy ◽

Phase Ii ◽

Local Control ◽

Stereotactic Body Radiation Therapy ◽

Tertiary Care ◽

Stereotactic Body Radiation ◽

Small Hccs ◽

Modified Recist

Background/Aims: Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs.Methods: A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria.Results: Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events.Conclusions: SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.

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Dose-survival relationship in patients with hepatocellular carcinoma undergoing stereotactic body radiation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15592 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15592-e15592

Author(s):

Ting-Shi Su ◽

Shi-Xiong Liang ◽

Lequn Li

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Liver Volume ◽

Rank Test ◽

Stereotactic Ablative Radiotherapy ◽

Term Survival ◽

Stereotactic Body Radiation ◽

Dosing Regimens

e15592 Background: Stereotactic body radiation therapy (SBRT) has become a treatment for hepatocellular carcinoma (HCC) from palliative to radical treatment. But there is no clear evidence of a dose-survival relationship among commonly-utilized radiation therapy schedules. We aimed to determine the comparative effectiveness of different SBRT dosing regimens for HCC. Methods: The dataset collected from Guangxi Zhuang Autonomous Region in China was used. In this large single-centered retrospective study, 604 patients treated with SBRT were included from 2011 to 2017. Biologically effective dose (BED10) and equivalent dose in 2 Gy fractions (EQD2) were assumed at an α/β ratio of 10. Overall survival (OS) was the primary endpoint. OS rates were estimated using Kaplan–Meier curves with a log-rank test. Results: The median tumor size was 5.2 cm (interquartile range [IQR], 1.1–21.0 cm). Median follow-up was 21 months in surviving patients (IQR, 3–82 months). The 1-, 3-, and 5-year OSs were 87.1%, 64.7%, and 60.9% in Barcelona Clinic Liver Cancer (BCLC)-A group; 72.9%, 37.2%, and 30.7% in BCLC-B group; and 44.3%, 18.6%, and 12.8% in BCLC-C group; respectively. Increasing the RT dose was associated with improved overall survival. Stereotactic ablative radiotherapy (SART) with BED10≥100 Gy, SBRT with EQD2≥74 Gy and BED10 < 100 Gy, and stereotactic conservative radiotherapy (SCRT) with EQD2< 74 Gy have 3 separate curves for long-term survival post-SBRT. On multivariate analysis, Clinical factors associated with improved OS were BED, alanine aminotransferase (ALT) , and BCLC stage. On the subgroup analysis, BED10 ≥100 Gy was still beneficial against HCCs of BCLC stage A, B, and C. Conclusions: Individualized dose for SBRT are recommended for the treatment of HCC due to different degrees of cirrhosis and liver volume. The RT dose was classified into three levels. If tolerated by normal tissue, SART with BED10 ≥100 Gy as a first-line ablative dose or SBRT with EQD2 ≥74 Gy as a second-line radical dose is recommended. Otherwise, SCRT with EQD2< 74 Gy is recommended as palliative irradiation.

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