Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

The Current Evidence of Intensity-Modulated Radiotherapy for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Intensity-modulated radiotherapy (IMRT), an advanced RT technique, is a considerable treatment option for hepatocellular carcinoma (HCC). However, the distinguishing features of IMRT for HCC have not yet been clearly defined. A systematic review was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The PubMed/MedLine, Embase, Cochrane Library, Web of Science, and KoreaMed were used to screen eligible studies focusing on treatment outcomes after IMRT for HCC until 18 April 2023. A total of 1755 HCC patients receiving IMRT among 29 studies from 2009 to 2023 were selected for the meta-analysis. The median proportion of Barcelona Clinic Liver Cancer stage C was 100% (range: 38-100%). Nineteen studies used combined treatment. Pooled rates of response and 1-year local control were 58% (95% confidence interval [CI], 50-65%) and 84% (95% CI, 70-94%), respectively. The median overall survival (OS) was 13 months (range: 5-45 months), and pooled 1- and 3-year OS rates were 59% (95% CI, 52-66%), and 23% (95% CI, 14-33%), respectively. Pooled rates of classic radiation-induced liver disease (RILD), nonclassic RILD, and hepatic toxicity ≥ grade 3 were 2%, 4%, and 4%, respectively. Although most patients had advanced-stage HCC and combined treatment was commonly used, IMRT for HCC showed similar survival to existing RT modalities and relatively low severe toxicity.

Evaluating the Necessity of Adaptive RT and the Role of Deformable Image Registration in Lung Cancer with Different Pathologic Classifications.

BACKGROUND: This study aimed to analyze differential radiotherapy (RT) responses according to the pathological type of lung cancer to see the possibility of applying adaptive radiotherapy (ART). METHODS: ART planning with resampled-computed tomography was conducted for a total of 30 patients (20 non-small-cell lung cancer patients and 10 small-cell lung cancer patients) using a deformable image registration technique to reveal gross tumor volume (GTV) changes according to the duration of RT. RESULTS: The small-cell lung cancer group demonstrated an average GTV reduction of 20.95% after the first week of initial treatment (p = 0.001), whereas the adenocarcinoma and squamous cell carcinoma groups showed an average volume reduction of 20.47% (p = 0.015) and 12.68% in the second week. The application of ART according to the timing of GTV reduction has been shown to affect changes in radiation dose irradiated to normal tissues. This suggests that ART applications may have to be different depending on pathological differences in lung cancer. CONCLUSION: Through these results, the present study proposes the possibility of personalized treatment options for individual patients by individualizing ART based on specific radiation responses by pathologic types of lung cancer.

Stereotactic body radiotherapy using helical tomotherapy for hepatocellular carcinoma: clinical outcome and dosimetric comparison of Hi-ART vs. Radixact.

Background: Helical tomotherapy (HT), a unique rotational dose delivery machine, has been updated from Hi-ART to Radixact. We retrospectively evaluated the treatment outcomes of stereotactic body radiotherapy (SBRT) using HT for hepatocellular carcinoma (HCC) and compared the dosimetric details of Hi-ART and Radixact. Methods: Between April 2014 and November 2020, 28 patients with HCC were treated with SBRT using HT for a cure at Soonchunhyang University College of Medicine, Bucheon. According to the Barcelona Clinic Liver Cancer classification, 9 patients had stage 0 disease, 12 had stage A, 4 had stage B, and 3 had stage C. The tumor size ranged from 1 cm to 8 cm (median, 2 cm). The SBRT dose ranged from 40 to 60 Gy (median, 48 Gy) with 4 fractions. Twenty-three patients were treated with Hi-ART and 5 patients were treated with Radixact. To compare the dosimetric parameters between Hi-ART and Radixact, we created treatment plans with the same constraints, pitch, modulation factor, and field width for the same patient in pairs. Results: The median follow-up time from the date of SBRT administration was 24 months (range, 3-67 months). The local failure-free survival and intrahepatic failure-free survival rates were 96% and 58% at 1 year, 84% and 36% at 2 years, and 76% and 18% at 3 years, respectively. The overall survival rate was 93% at 1 year, 93% at 2 years, and 53% at 3 years, respectively. When the paired treatment plans were reviewed, the beam-on time and intermediate dose-spillage were found to be significantly reduced in Radixact than Hi-ART (P<0.001). With regard to normal organ sparing, the irradiated dose to the total liver, normal liver, heart, and kidney was significantly lower with Radixact (P<0.001). Conclusions: SBRT using HT for HCC showed favorable treatment outcomes. Radixact, the latest version, physically improved treatment efficiency by reducing treatment time and provided better organ sparing than Hi-ART.

Current usage of stereotactic body radiotherapy for oligometastatic prostate cancer in Korea: patterns of care survey (KROG 19-08).

BACKGROUND: Growing evidence suggests that metastasis-directed therapy and/or prostate-directed therapy may benefit patients with oligometastatic prostate cancer (OMPC). Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastases in various cancers. The purpose of this study was to investigate the current patterns of curative-intent SBRT for OMPC in Korea. METHODS: A 20-item questionnaire was sent to 326 radiation oncologists in 93 institutions in Korea. Only 1 physician per institution was required to complete the survey. Subsequently, the second survey consisting of 3 clinical scenarios was sent to 64 physicians with clinical experience in SBRT: case 1, cT4N0M1 (direct invasion to two pelvic bones); case 2, cT2N0M1 (three bone metastases); and case 3, solitary spine metastasis after radical prostatectomy. RESULTS: Seventy-six physicians from 93 institutions (82%) answered the first survey. The multidisciplinary team approach was practiced in 16 institutions (21%). Most physicians (75%) agreed on the definition of oligometastases as limited lesions and/or organs ≤5: 25% agreed with low-volume disease according to CHAARTED trial. During the last year, 49 physicians (64%) treated OMPC patients with curative intent. Sixty four physicians (84%) had a clinical experience with SBRT: 48 (75%) stated that both dose and fraction number should be considered when defining SBRT, whereas others (25%) stated that only fraction size should be considered. Fifty-five faculties (86%) answered the second survey. Physicians agreed with oligometastases in 89% for case 1, in 80% for case 2, and in 100% for case 3. The rate of SBRT application was the highest in case 3 (70%). CONCLUSIONS: There was diversity in the patterns of SBRT for OMPC in Korea. Additional prospective studies are necessary to strengthen evidence regarding role of SBRT in OMPC.

Treatment outcomes of helical tomotherapy for hepatocellular carcinoma in terms of intermediate-dose spillage.

BACKGROUND: Although helical tomotherapy (HT) tends to increase intermediate-dose spillage by increasing of low-dose region, this has not been fully determined in the clinical setting. Therefore, we investigated treatment outcomes of HT for hepatocellular carcinoma (HCC) with respect to intermediate-dose spillage. METHODS: We retrospectively reviewed 20 HCC patients, who received high-dose radiotherapy (RT) using HT with radical intent between April 2014 and September 2017. In accordance with the Barcelona Clinic Liver Cancer (BCLC) classification, stage was 0 in 7 patients, A in 3 patients, B in 5 patients, and C in 5 patients. Baseline Child-Pugh class was A in 18 patients and B in 2 patients. The median tumor size was 2.5 cm (range, 1-11 cm). Helical intensity-modulated radiotherapy (IMRT) technique was applied in all patients: among these, 13 patients were treated with stereotactic body radiotherapy (SBRT). The median fraction size was 12 Gy (range, 2-15 Gy), and the median total dose was 50 Gy (range, 44-60 Gy). Intermediate-dose spillage was assessed by the Radiation Therapy Oncology Group recommendation from 22 HT planning data, as follows: R50% means the ratio of the 50% prescription isodose volume to the planning target volume (PTV). RESULTS: The median follow-up period after HT was 22 months. The local progression-free survival (LPFS) and progression-free survival (PFS) rates were 89% and 59% at 1 year, and 82% and 30% at 2 years, respectively. The overall survival rate was 100% at 1 year and 85% at 2 years, respectively. In terms of intermediate-dose spillage, minor or major deviations were noted in the R50% of 20 HT plans (91%). However, 1 patient (5%) experienced classic radiation-induced liver disease, and severe toxicity ≥ grade 3 was not reported. CONCLUSIONS: Although HT for HCC tends to increase intermediate-dose spillage, the treatment results were favorable with that reported in other published studies.

A Case of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis Treated by Hepatic Arterial Infusion Chemotherapy and Radiotherapy.

Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Additionally, hepatic arterial infusion chemotherapy has been used as a treatment option for advanced HCC. Here, we report a case of sustained partial response in a patient with advanced HCC with PVT after hepatic arterial infusion chemotherapy and radiation therapy.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.

Treatment Outcome after Fractionated Conformal Radiotherapy for Hepatocellular Carcinoma in Patients with Child-Pugh Classification B in Korea (KROG 16-05).

PURPOSE: There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B. MATERIALS AND METHODS: We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy10 (α/ß = 10 Gy). A total of 184 patients were included in this study. RESULTS: Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy10 (median, 56.0 Gy10). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD. CONCLUSION: Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.

Intensity-modulated radiotherapy for hepatocellular carcinoma: dosimetric and clinical results.

Since the introduction of 3-dimensional conformal radiotherapy (3DCRT), new radiotherapy techniques have expanded the indication of radiotherapy for the treatment of hepatocellular carcinoma (HCC), from the hitherto palliative to a now curative-intent purpose. Intensity-modulated radiotherapy (IMRT), currently the most advanced radiotherapy technique, is considered an attractive option for the treatment of HCC, and is more widely applied because it can deliver a higher dose to the tumor than 3DCRT while sparing surrounding normal organs. However, the advantages and potential disadvantages of IMRT for treating HCC have not been fully established. This article deals with three different IMRT techniques, including static IMRT and volumetric modulated arc therapy using conventional multileaf collimator (MLC) mounted linear accelerators, and helical IMRT using binary MLC mounted helical tomotherapy machine. We review dosimetric and clinical studies for these IMRT techniques for the treatment of HCC.

Quality assurance for a multicenter Phase II study of stereotactic ablative radiotherapy for hepatocellular carcinoma ≤5 cm: a planning dummy run.

OBJECTIVE: The Korean Radiation Oncology Group (12-02) investigated the outcome of stereotactic ablative radiotherapy for hepatocellular carcinoma ≤5 cm using 60 Gy in three fractions. To evaluate dosimetric differences and compliance in a multicenter trial, a planning dummy run procedure was performed. METHODS: All six participating institutions were provided the contours of two dummy run cases. Plans were performed following the study protocol to cover the planning target volume with a minimum of 90% of the prescription dose and to satisfy the constraints for organs at risk. We assessed the institutional variations in plans using dose-volume histograms. RESULTS: Different planning techniques were applied: static intensity-modulated radiotherapy in two institutions, CyberKnife in two institutions and RapidArc in two institutions. The conformity index of all 12 plans was ≤1.2. In terms of the planning target volume coverage, all participants followed our study protocol. For the second dummy run case, located in Segment 8 near the heart, the minimum dose of the planning target volume (D99%: dose covering 99% of the planning target volume) was variable because there was no mention of constraints of D99% of the planning target volume in the study protocol. As an important organ at risk, the normal liver volumes receiving <17 Gy in all 12 plans were >700 ml. CONCLUSIONS: Dosimetric parameters showed acceptable compliance with the study protocol. However, we found the possibility of underdose to the planning target volume if the hepatocellular carcinoma lesion was located near organs at risk such as the heart. Based on this dummy run, we will conduct individual case reviews to minimize the effects of study protocol deviation.

Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma: dosimetric comparison and risk assessment of solid secondary cancer.

PURPOSE: To determine the optimal radiotherapy technique for gastric mucosa-associated lymphoid tissue lymphoma (MALToma), we compared the dosimetric parameters and the risk of solid secondary cancer from scattered doses among anterior-posterior/posterior-anterior parallel-opposed fields (AP/PA), anterior, posterior, right, and left lateral fields (4_field), 3-dimensional conformal radiotherapy (3D-CRT) using noncoplanar beams, and intensity-modulated radiotherapy composed of 7 coplanar beams (IMRT_co) and 7 coplanar and noncoplanar beams (IMRT_non). MATERIALS AND METHODS: We retrospectively generated 5 planning techniques for 5 patients with gastric MALToma. Homogeneity index (HI), conformity index (CI), and mean doses of the kidney and liver were calculated from the dose-volume histograms. Applied the Biological Effects of Ionizing Radiation VII report to scattered doses, the lifetime attributable risk (LAR) was calculated to estimate the risk of solid secondary cancer. RESULTS: The best value of CI was obtained with IMRT, although the HI varied among patients. The mean kidney dose was the highest with AP/PA, followed by 4_field, 3D-CRT, IMRT_co, and IMRT_non. On the other hand, the mean liver dose was the highest with 4_field and the lowest with AP/PA. Compared with 4_field, the LAR for 3D-CRT decreased except the lungs, and the LAR for IMRT_co and IMRT_non increased except the lungs. However, the absolute differences were much lower than <1%. CONCLUSION: Tailored RT techniques seem to be beneficial because it could achieve adjacent organ sparing with very small and clinically irrelevant increase of secondary solid cancer risk compared to the conventional techniques.

Practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea: a survey of the Korean Stereotactic Radiosurgery Group.

OBJECTIVE: To investigate practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea. METHODS: In June 2013, the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology conducted a national patterns-of-care survey about stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma, consisting of 19 questions and 2 clinical scenarios. RESULTS: All 208 radiation oncologists (100%), who are regular members of Korean Society for Radiation Oncology, responded to this survey. Among these, 95 radiation oncologists were specialists for hepatology; 64 physicians did not use stereotactic body radiotherapy for hepatocellular carcinoma, and 31 physicians used stereotactic body radiotherapy. Most physicians (52%) performed stereotactic body radiotherapy to hepatocellular carcinoma in ≤5 cases per year. Physicians applied stereotactic body radiotherapy according to tumour size and baseline Child-Pugh class. All physicians agreed the use of stereotactic body radiotherapy to 2.8-cm hepatocellular carcinoma with Child-Pugh class of A, while 23 physicians (74%) selected stereotactic body radiotherapy for Child-Pugh class of B. Nineteen physicians (61%) selected stereotactic body radiotherapy to 5-cm hepatocellular carcinoma with Child-Pugh class of A, and only 14 physicians (45%) selected stereotactic body radiotherapy for Child-Pugh class of B. On the other hand, the preferred dose scheme was same as 60 Gy in three fractions. CONCLUSIONS: Among radiation oncologists in Korea, there was diversity in the practice for stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma. Additional prospective studies are necessary to standardize the practice and establish Korea-specific practice guidelines for hepatocellular carcinoma stereotactic body radiotherapy.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions.

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity≥grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV5Gy-rV35Gy: normal liver volume receiving

A Survey of Stereotactic Body Radiotherapy in Korea.

PURPOSE: The purpose of this study is to investigate the current status of stereotactic body radiotherapy (SBRT) in Korea. A nationwide survey was conducted by the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology (KROG 13-13). MATERIALS AND METHODS: SBRT was defined as radiotherapy with delivery of a high dose of radiation to an extracranial lesion in ≤ 4 fractions. A 16-questionnaire survey was sent by e-mail to the chief of radiation oncology at 85 institutions in June 2013. RESULTS: All institutions (100%) responded to this survey. Of these, 38 institutions (45%) have used SBRT and 47 institutions (55%) have not used SBRT. Regarding the treatment site, the lung (92%) and liver (76%) were the two most common sites. The most common schedules were 60 Gy/4 fractions for non-small cell lung cancer, 48 Gy/4 fractions for lung metastases, 60 Gy/3 fractions for hepatocellular carcinoma, and 45 Gy/3 fractions or 40 Gy/4 fractions for liver metastases. Four-dimensional computed tomography (CT) was the most common method for planning CT (74%). During planning CT, the most common method of immobilization was the use of an alpha cradle/vacuum-lock (42%). CONCLUSION: Based on this survey, conduct of further prospective studies will be needed in order to determine the appropriate prescribed doses and to standardize the practice of SBRT.

Feasibility and response of helical tomotherapy in patients with metastatic colorectal cancer.

PURPOSE: To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10-30 fractions. When the α/ß value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to 119 Gy10 (median, 55 Gy10). Nineteen lesions were treated with concurrent chemotherapy (CCRT). RESULTS: With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, PTV ≤113 mL and BED >48 Gy10 were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. CONCLUSION: The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.

Risk of secondary cancers from scattered radiation during intensity-modulated radiotherapies for hepatocellular carcinoma.

PURPOSE: To evaluate and compare the risks of secondary cancers from therapeutic doses received by patients with hepatocellular carcinoma (HCC) during intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT), and tomotherapy (TOMO). METHODS: Treatments for five patients with hepatocellular carcinoma (HCC) were planned using IMRT, VMAT, and TOMO. Based on the Biological Effects of Ionizing Radiation VII method, the excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) were evaluated from therapeutic doses, which were measured using radiophotoluminescence glass dosimeters (RPLGDs) for each organ inside a humanoid phantom. RESULTS: The average organ equivalent doses (OEDs) of 5 patients were measured as 0.23, 1.18, 0.91, 0.95, 0.97, 0.24, and 0.20 Gy for the thyroid, lung, stomach, liver, small intestine, prostate (or ovary), and rectum, respectively. From the OED measurements, LAR incidence were calculated as 83, 46, 22, 30, 2 and 6 per 10(4) person for the lung, stomach, normal liver, small intestine, prostate (or ovary), and rectum. CONCLUSIONS: We estimated the secondary cancer risks at various organs for patients with HCC who received different treatment modalities. We found that HCC treatment is associated with a high secondary cancer risk in the lung and stomach.

High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma.

BACKGROUND: Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. METHODS: Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0-7.0 cm), and the median dose was 51 Gy (range, 33-60 Gy). RESULTS: LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45-54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. CONCLUSIONS: This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.