Published papers

PURPOSE: Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non-small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS: Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis-T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS: In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis-4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION: Predictions of SBRT outcomes using NNs were useful for Tis-4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.

The fifth version of the Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence-based medicine and partly to the Grading of Recommendations Assessment, Development and Evaluation system, which was published in October 2021 in Japanese. In addition to surveillance–diagnostic and treatment algorithms, a new algorithm for systemic therapy has been created, as multiple drugs for hepatocellular carcinoma can be currently selected. Here, new or revised algorithms and evidence on which the recommendations are based are described.

Aim: Stereotactic body radiotherapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC) and has shown excellent local control (LC), as has radiofrequency ablation (RFA). As no randomized controlled trial has compared SBRT and RFA for HCC, data from a propensity score matched study (PSMS) are valuable. However, the results varied greatly and depended on composing factors of Barcelona Clinic Liver Cancer staging (BCLC-factors) adjusted. Therefore, we undertook a systematic review and meta-analyses of the studies focusing on BCLC-factors matching. Methods: We systematically searched PubMed, the Cochrane database, EMBASE, and Web of Science to identify studies comparing RFA and SBRT using propensity scores. The hazard ratios (HRs) of overall survival (OS) and LC from BCLC-factor-matched and -unmatched PSMS were pooled. Heterogeneity between the data from these studies was assessed. Results: Three BCLC-factor-matched studies were identified. Stereotactic body radiotherapy led to comparable OS (HR, 0.89; 95% CI, 0.74–1.08; p = 0.24; I2 = 0%; p for heterogeneity, 0.56) and significantly better LC (HR, 0.39; 95% CI, 0.30–0.51; p < 0.001; I2 = 0%; p for heterogeneity, 0.67). We also identified three additional BCLC-factor-unmatched studies (HR of OS, 1.41; 95% CI, 1.21–1.65; p < 0.0001; I2 = 0%; p for heterogeneity, 0.63). However, considerable heterogeneity was observed for HR of OS between BCLC-factor-matched and -unmatched studies (I2 = 92.6%; p for heterogeneity, 0.0002). Conclusions: When BCLC-factors were properly adjusted, the results of the meta-analysis revealed equivalent OS and better LC for SBRT compared with RFA. Stereotactic body radiotherapy could be an alternative treatment option for HCC.

Background: Stereotactic body radiotherapy (SBRT) has been rapidly evolving and increasingly performed in patients with ground-glass opacity (GGO) predominant lung cancer (GGOp-LC). Purpose: To evaluate early-phase CT findings of GGOp-LC after SBRT. Materials and Methods: Patients with GGOp-LC staged as cTis-2bN0M0 treated with SBRT were retrospectively identified. The CT images were analyzed using radiologists’ interpretation and CT-density histograms. Long-term treatment outcomes were also assessed. Results: This study evaluated 126 patients with 133 cases of GGOp-LC, comprising GGOp-LC with pure GGO (pureGGO-LC) (n = 31) and part-solid tumors (partsolid-LC) (n = 102). The median follow-up duration was 64.3 months (range, 10.8-178.9 months). Most GGOp-LC cases were interpreted as stable disease at 1 and 3 months after SBRT (96% [125/130] and 85% [62/73], respectively). However, the solid component was often interpreted as progressive disease (42% [34/82] and 60% [29/48], respectively). The GGO component was interpreted as denser in 47% (61/130) and 86% (63/73) of cases, respectively. For 25 evaluable pureGGO-LC cases at 3 months, the median tumor density values increased over time (P <.001). For 48 evaluable partsolid-LC cases at 3 months, the median areas of CT-density ≥ -160 HU increased over time (P <.001). The 5-year overall survival for GGOp-LC patients was 78.0%. No local or regional recurrence were observed. Conclusion: Clinical outcomes of SBRT for GGOp-LC were excellent, without local or regional recurrence. In the interpretation of early-phase follow-up CT scans of GGOp-LC after SBRT, it should be noted that most GGOp-LC remains stable disease, solid component increases in size, and GGO component is denser.

Deep learning has demonstrated high efficacy for automatic segmentation in contour delineation, which is crucial in radiation therapy planning. However, the collection, labeling, and management of medical imaging data can be challenging. This study aims to elucidate the effects of sample size and data augmentation on the automatic segmentation of computed tomography images using U-Net, a deep learning method. For the chest and pelvic regions, 232 and 556 cases are evaluated, respectively. We investigate multiple conditions by changing the sum of the training and validation datasets across a broad range of values: 10–200 and 10–500 cases for the chest and pelvic regions, respectively. A U-Net is constructed, and horizontal-flip data augmentation, which produces left and right inverse images resulting in twice the number of images, is compared with no augmentation for each training session. All lung cases and more than 100 prostate, bladder, and rectum cases indicate that adding horizontal-flip data augmentation is almost as effective as doubling the number of cases. The slope of the Dice similarity coefficient (DSC) in all organs decreases rapidly until approximately 100 cases, stabilizes after 200 cases, and shows minimal changes as the number of cases is increased further. The DSCs stabilize at a smaller sample size with the incorporation of data augmentation in all organs except the heart. This finding is applicable to the automation of radiation therapy for rare cancers, where large datasets may be difficult to obtain.

Background: The feasibility of marker-less stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has not yet been established, and, thus, was examined in the present study. Material and methods: We retrospectively investigated patients who received marker-less SBRT for locally untreated HCC tumors between July 2005 and December 2018. Radiotherapy planning CT was performed under fixation with vacuum cushions and abdominal compression. The clinical target volume (CTV) was equivalent to the gross tumor volume (GTV). The internal target volume (ITV) margin to CTV was determined from calculations based on the motion of the diaphragm. The planning target volume (PTV) margin to ITV was 5–6 mm. In the set-up, radiotherapy planning CT and linac-integrated cone-beam CT performed in the same imaging and fixation settings were merged by referring to the anatomical components surrounding target tumors. The primary endpoint was the 3-year cumulative local tumor progression rate. The upper limit of the 95% confidence interval for the 3-year cumulative local tumor progression rate was less than 7.0%, which was interpreted as favorable local control and feasible for marker-less SBRT. Local tumor progression was assessed by mRECIST. Results: We reviewed 180 patients treated with 35–40 Gy/5 fractions. The median follow-up time for the local tumor progression of censored tumors was 32.3 months (range, 0.3–104). The 3-year cumulative local tumor progression rate was 3.0% (95% CI, 1.1–6.5%). The 3-year overall survival rate was 71.6% (95% CI, 63.5–78.2%). Regarding acute hematologic toxicities, grade 3 hypoalbuminemia and thrombocytopenia were detected in 1 (0.6%) and 5 (2.9%) patients, respectively. Treatment-related death from SBRT was not observed. SBRT was initiated within 7 days after radiotherapy planning CT for 84% (152/180) of patients. Conclusions: Marker-less SBRT for HCC achieved favorable local control that fulfilled the threshold. This result suggests that marker-less SBRT with appropriate settings is a feasible treatment strategy.

Aim: Decisions regarding therapeutic plans for inoperable patients with hepatocellular carcinoma (HCC) adjacent to the gastrointestinal (GI) tract are challenging because radiofrequency ablation has the potential risk of thermal injury. Moreover, the response rate of transcatheter arterial chemoembolization is relatively low and stereotactic body radiotherapy (SBRT) is believed to be too toxic. We have applied hypofractionated radiotherapy (HFRT) for such lesions. This study investigated the outcomes and toxicities of this treatment. Methods: Among consecutive HCC patients treated with radiotherapy with curative intent at our institution between 2015 and 2019, we retrospectively extracted those outside of the indication for SBRT due to exceeding the constraint of the GI tract and who were treated using HFRT with a prescription dose of 42 Gy in 14 fractions and prophylactic proton pump inhibitor administration for 6 months. The oncological outcomes and toxicities were investigated. Results: A total of 66 patients with 73 lesions were eligible. The median follow-up period was 24.0 months. The local recurrence, intrahepatic recurrence, liver-related death, and overall survival rates at 2 years were 11.3%, 50.6%, 15.9%, and 60.4%, respectively. Six (9.1%) patients experienced Child–Pugh score deterioration ≥2 within 6 months following treatment. Two and one patient developed grades 2 and 3 gastroduodenal bleeding, respectively. Conclusions: HFRT can achieve good local control in patients with HCC adjacent to the GI tract, with low GI toxicity incidence. Our study demonstrated that HFRT can be a potentially curative treatment option for lesions.

Purpose: The purpose of this study was to assess the impact of local recurrence (LR) on cause-specific death (CSD) in patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). A dynamic prediction model that incorporated LR as a time-dependent covariate was used. Methods and materials: This study included 535 stage I (cT1–T2aN0M0) NSCLC patients treated with SBRT from two institutions. We developed a landmark dynamic prediction model to estimate the probability of a CSD. This model determined the probability of surviving for an additional 3 years at different prediction time points during follow-up, given the history of recurrence status. The baseline covariates included in the model were age, sex, T stage, and histology, while the time-dependent covariates were LR and regional and/or distant recurrence (RDR) status. Results: Overall, 137 patients (25.6%) died of lung cancer within a median follow-up of 4.1 years. Of the 195 patients who developed recurrence, 28, 125, and 42 patients had LR only, RDR only, and both, respectively. The landmark model showed that older age, advanced T stage, LR, and RDR were significantly associated with an increased risk of subsequent CSD. Among these covariates, LR (odds ratio [OR], 8.5; 95% confidence interval [CI], 6.0–12.0; P < .001) and RDR (OR, 11.6; 95% CI, 9.1–14.9; P < .001) demonstrated strong effects on CSD within 3 years after the prediction time points. The dynamic prediction provided information on the probability of future CSD according to individual recurrence status during follow-up. Conclusions: Dynamic prediction using the landmark model showed that LR had a substantial impact on subsequent CSD, which was comparable to that of RDR. This result supports the notion that strategies to improve local control are reasonable.

Purpose: Local control (LC) is an important outcome of local cancer therapy, besides overall survival (OS). We conducted a comprehensive literature search to investigate whether a high LC rate contributes to good OS in radiotherapy for early-stage non-small cell lung cancer (ES-NSCLC). Materials and methods: Studies in patients receiving radiotherapy for peripheral ES-NSCLC, mainly staged as T1-2N0M0 were included for a systematic review. Relevant information was collected including, dose fractionation, T stage, median age, 3-year LC, cancer-specific survival (CSS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and OS. Correlations between outcomes and clinical variables were evaluated. Results: After screening, 101 data points from 87 studies including 13,435 patients were selected for the quantitative synthesis. Univariate meta-regression analysis revealed that the coefficients between the 3-year LC and 3-year DFS, DMFS, CSS, and OS were 0.753 (95% confidence interval (CI): 0.307–1.199; p < 0.001), 0.360 (95% CI: 0.128–0.593; p = 0.002), 0.766 (95% CI: 0.489–1.044; p < 0.001), and 0.574 (95% CI: 0.275–0.822; p < 0.001), respectively. Multivariate analysis revealed that the 3-year LC (coefficient, 0.561; 95% CI: 0.254–0.830; p < 0.001) and T1 proportion (coefficient, 0.207; 95% CI: 0.030–0.385; p = 0.012) were significantly associated with the 3-year OS and CSS (coefficient for 3-year LC, 0.720; 95% CI: 0.468–0.972; p < 0.001 and T1 proportion, 0.002; 95% CI: 0.000–0.003; p = 0.012). Toxicities ≥ grade 3 were low (3.4%). Conclusions: Three-year LC was correlated with three-year OS in patients receiving radiotherapy for ES-NSCLC. A 5% increase in 3-year LC is expected to improve the 3-year CSS and OS rates by 3.8% and 2.8%, respectively.

Aim: To prospectively evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for patients with previously untreated solitary primary hepatocellular carcinoma (HCC). Methods: The main eligibility criteria included the following: (1) primary solitary HCC; (2) no prior treatment for HCC; (3) Child–Turcotte–Pugh score of seven or less; and (4) unsuitability for or refusal of surgery and radiofrequency ablation (RFA). The prescribed dose of SBRT was 40 Gy in five fractions. The primary endpoint was 3-year overall survival (OS); the secondary endpoints included local progression-free survival (LPFS), local control (LC), and adverse events. The accrual target was 60 patients, expecting a 3-year OS of 70% with a 50% threshold. Results: Between 2014 and 2018, 36 patients were enrolled; enrollment was closed early because of slow accrual. The median tumor size was 2.3 cm. The median follow-up at the time of evaluation was 20.8 months. The 3-year OS was 78% (95% confidence interval [CI]: 53%–90%). The 3-year LPFS and LC proportion were 73% (95% CI: 48%–87%) and 90% (95% CI: 65%–97%), respectively. Grade 3 or higher SBRT-related toxicities were observed in four patients (11%), and grade five toxicities were not observed. Conclusions: This study showed acceptably low incidence of SBRT-related toxicities. LC and OS after SBRT were comparable for previously untreated solitary HCC for patients unfit for resection and RFA. Although a definitive conclusion cannot be drawn by this study, the promising results indicate that SBRT may be an alternative option in the management of early HCC.

Background: In clinical practice, many hepatocellular carcinoma (HCC) patients in Barcelona Clinical Liver Cancer (BCLC) stage A4–B1 cannot receive the curative treatments of liver transplantation, resection, and radiofrequency ablation (RFA), which are the recommended options according to liver cancer guidelines. Our aim is to study the feasibility of RFA and stereotactic body radiotherapy (SBRT) as a curative treatment for different multifocal HCCs in BCLC stage A4–B1 patients. Methods: From September 2014 to August 2019, 39 multifocal HCC lesions (median diameter: 16.6 mm) from 15 patients (median age: 73 years) were retrospectively selected. Among them, 23 were treated by RFA and the other 16 by SBRT because of predictable insufficiency and/or risk related to RFA performance. The indicators for evaluating this novel therapy were the tumor response, prognosis (recurrence and survival), and adverse effects (deterioration of laboratory test values and severe complications). Results: The median follow-up duration was 31.3 months (range: 15.1–71.9 months). The total patients with a one-year complete response, stable disease, or disease progression were 11, 1, and 3, respectively. In total, 8 and 2 patients had confronted intrahepatic or local recurrence, respectively. The one-year progression-free survival rate and local control rate were 80% (12/15 patients) and 97.4% (38/39 lesions), respectively. The median time to progression was 20.1 (2.8–45.1) months. The one- and two-year survival rates were 100 and 88.9%, respectively. In up to five months’ observation, no patient showed severe complications. Seven, four, and two patients had slight changes in their white blood cells, platelet count, or albumin–bilirubin grade, respectively. Conclusions: For patients with BCLC stage A4–B1, RFA and SBRT treatment for different multifocal HCCs may be a potential option because of the favorable prognosis and safety. However, before its application in clinical practice, prospective, controlled, large-scale studies are needed to further confirm our conclusions.

We studied five pathological specimens from five patients at 1.5, 3.0, 4.0, 13.5, and 14.0 months after radiotherapy for HCC. Four needle biopsies were obtained to investigate liver parenchyma of focal liver reaction (FLR) around treated HCC, when patients had newly developed HCC or local recurrence appeared in the liver. Liver resection was performed in one case where insufficient radiotherapy effect for HCC was suspected. In all patients, FLR was recognized as a hypervascular area around the HCC on enhanced CT and enhanced Gd-EOB-DTPA (EOB-MRI). Liver specimens were analyzed to assess thepathological characteristics of FLR. FLR was recognized as prolonged liver enhancement in enhanced CTand EOB-MRI. From pathological understanding, sinusoidal dilatation with degeneration and desquamation was caused by direct endothelial cell injury following radiotherapy. Hepatocytes and endothelium fell off, and so the portal tract came close, and hepatic arteries increase simultaneously, resultinginFLR around HCC after radiotherapy. In conclusion, the prolapse of hepatocytes and sinusoidal endothelium induced neovascularization of hepatic arteries due to the repair mechanisms; in addition, these prolapse may shorten the distance between each portal region and the hepatic arteries flowing through the portal region become more prominent in FLR.

Introduction: Our systematic review and meta-analysis aimed to evaluate the effect of postoperative radiotherapy (PORT) on completely resected Masaoka/Masaoka-Koga (M/MK) stage II/III thymomas. Methods: We systematically searched four online databases and included studies that compared surgery alone versus surgery plus a PORT for completely resected M/MK stage II/III thymoma. The multivariate-adjusted hazard ratios (HRs) of overall survival (OS) and disease-free survival were evaluated as the primary and secondary end points, respectively. We performed a subgroup analysis for OS with respect to M/MK stage II, III, and inseparable II/III cases. A generic inverse variance meta-analysis using a random model was conducted. Results: Five studies including 4746 patients (among them, 2408 patients received PORT) met our selection criteria. A meta-analysis of these five studies revealed that PORT was associated with a significantly better OS (HR = 0.68, 95% confidence interval [CI]: 0.57–0.83, p < 0.001, I2 = 0%, p for heterogeneity = 0.97). Subgroup analyses for M/MK stage II disease (HR = 0.63, 95% CI: 0.44–0.91, p = 0.01, I2 = 0%, p for heterogeneity = 0.80) and M/MK stage III disease (HR = 0.72, 95% CI: 0.55–0.95, p = 0.02, I2 = 0%, p for heterogeneity = 0.84) revealed similar results. PORT was not associated with an improved disease-free survival (HR = 0.96, 95% CI: 0.70–1.33, p = 0.83, I2 = 0%, p for heterogeneity = 0.72). Conclusions: Currently available evidence from observational studies suggests PORT for patients with completely resected M/MK stage II/III thymoma. A randomized trial is warranted.

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable.

In the treatment of colorectal cancer patients with distant metastases, the development of new anticancer agents has considerably prolonged progression-free survival. Such survival benefits attributed to chemotherapy have increased the relative significance of local therapy in patients with limited metastases. The liver is recognized as the most common site of metastasis of colorectal cancer because of the intestinal mesenteric drainage to the portal veins. Hepatic resection of isolated liver metastases of colorectal cancer is the only option for a potential cure. However, hepatic metastases are resectable in only approximately 20% of the patients. For remaining patients with high-risk resectable liver metastases or those who are unfit for surgery, less invasive, local therapies including radiation therapy (stereotactic body radiation therapy, SBRT) may have a potential role in treatment. Although the local control rate of SBRT for colorectal liver metastases has room for improvement, its less-invasive nature and broad indications deserve consideration. Future research should include SBRT dose escalation or the selection of patients who benefit from local ablative therapies. SBRT may offer an alternative, non-invasive approach for the treatment of colorectal liver metastases in a multidisciplinary treatment strategy.

Aim To evaluate the safety and efficacy of the administration of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in the short term to the same patients in Barcelona Clinical Liver Cancer (BCLC) stages 0–B1. Methods From April 2014 to June 2019, we retrospectively reviewed BCLC stage 0–B1 patients with fresh hepatocellular carcinoma (HCC) lesions that were repeatedly treated by RFA (control group, n = 72), and by RFA and subsequent SBRT (case group, n = 26). Propensity score matching (PSM) was performed to reduce the selection bias between two groups. Recurrence, survival, Child–Pugh scores and short-term side effects (fever, bleeding, skin change, abdominal pain and fatigue) were recorded and analyzed. Results After PSM, 21 patients remained in each group. Seventeen and 20 patients in the case and control groups experienced recurrence. For these patients, the median times to progression and follow-up were 10.7 and 35.8 months, respectively. After PSM, the 1-year progression-free survival rate in case and control groups were 66.7% and 52.4%, respectively (P = 0.313). The inter-group overall survival (OS) was comparable (3 and 5-year OS rates in case groups were 87.3% and 74.8%, while rates in control groups were 73.7% and 46.3%, respectively; P = 0.090). The short-term side effects were mild, and the incidence showed no inter-group difference. The 1-year rates of the Child–Pugh score deterioration of ≥2 in case and control groups were 23.8% and 33.3% (P > 0.05), respectively. Conclusion The short-term administration of RFA and SBRT to the same BCLC stage 0–B1 patients may be feasible and effective because of their good prognosis and safety.

Purpose: We investigated whether delivery of a high biologically effective dose (BED) to primary tumors affects systemic outcomes of cancer-specific death (CSD) and overall survival (OS) rates after stereotactic body radiation therapy (SBRT) in patients with early-stage non-small cell lung cancer (ES-NSCLC). Methods and Materials: Among consecutive ES-NSCLC patients treated with SBRT between 2005 and 2019, we retrospectively identified patients who received a prescription of 50 to 60 Gy in 5 fractions with maximum doses of 62.5 to 100 Gy. Patients were categorized by maximum BED within the planning target volume with a threshold dose of 200 Gy. Outcomes were analyzed in all and matched patients. Results: Overall, 433 patients were eligible, and 262 and 171 patients were categorized into HighBED and LowBED groups, respectively. After propensity score matching, pairs of 154 patients were selected. Median follow-up times for the HighBED and LowBED groups were 52.3 months (range, 0.8-107.2 months) and 121.6 months (range, 3.0-162.8 months), respectively. The local recurrence rate in the HighBED group was significantly lower than that in the LowBED group (5-year rate, 1.3% and 7.2%; hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.03-0.65; P = .011). Rates of any recurrence and CSD in the HighBED group were significantly lower (5-year any recurrence: 18.1% and 32.1%; HR, 0.52; 95% CI, 0.33-0.83; P = .0058; 5-year CSD: 9.5% and 21.8%; HR, 0.38; 95% CI, 0.20-0.70; P = .002), and OS in the HighBED group was significantly better compared with the LowBED group (5-year rate: 61.7% and 51.8%; HR, 0.71; 95% CI, 0.50-1.00; P = .047). Conclusion: In patients with peripheral ES-NSCLC, SBRT with a high maximum dose may improve not only local control, but also any recurrence, CSD, and OS rates without increased toxicity. Further trials designed to evaluate whether higher intensity SBRT increases local control rates and contributes to improved CSD and OS outcomes are anticipated.

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.