Safety and Efficacy of Moderate-Intensity Stereotactic Body Radiation Therapy for Ultra-Central Lung Tumor.

Background and Objectives: Ultra-central (UC) lung tumors are defined as those abutting the proximal bronchial tree. Stereotactic body radiation therapy (SBRT) for UC tumors is difficult because of concerns about severe toxicities. Therefore, we report the safety and efficacy of moderate-intensity SBRT for UC tumors at our institution. Materials and Methods: From January 2017 to May 2021, we treated 20 patients with UC tumors with SBRT at a dose of 45-60 Gy in 10 fractions. The primary endpoints were local control (LC) and overall survival (OS). Results: The median follow-up time was 15.8 months (range: 2.7-53.8 months). Ten of the 20 patients (50.0%) showed a complete response, five (25.0%) had a partial response, two (10.0%) had stable disease, and three (15.0%) showed progressive disease (PD). The response and disease control rates were 75.0% and 85.0%, respectively. Patients with PD showed local progression at median 8.3 months (range: 6.8-19.1 months) after SBRT. One-year and 2-year OS rates were 79.4% and 62.4%, respectively. One-year and 2-year LC rates are 87.1% and 76.2%, respectively. Eight patients died due to a non-radiation therapy related cause. One patient experienced grade 5 massive hemoptysis 6 months after SBRT, resulting in death. One patient experienced grade 2 esophageal pain and two experienced grade 2 radiation pneumonitis. Otherwise, no grade 3 or higher toxicities were reported. Conclusions: Moderate-intensity SBRT offers effective control of UC tumors and is a well-tolerated treatment for such tumors.

A Potential Radiomics-Clinical Model for Predicting Failure of Lymph Node Control after Definite Radiotherapy in Locally Advanced Head and Neck Cancer.

Background and Objectives: To optimally predict lymph node (LN) failure after definite radiotherapy (RT) in head and neck cancer (HNC) with LN metastases, this study examined radiomics models extracted from CT images of different periods during RT. Materials and Methods: This study retrospectively collected radiologic and clinical information from patients undergoing definite RT over 60 Gy for HNC with LN metastases from January 2010 to August 2021. The same largest LNs in each patient from the initial simulation CT (CTpre) and the following simulation CT (CTmid) at approximately 40 Gy were indicated as regions of interest. LN failure was defined as residual or recurrent LN within 3 years after the end of RT. After the radiomics features were extracted, the radiomics alone model and the radiomics plus clinical parameters model from the set of CTpre and CTmid were compared. The LASSO method was applied to select features associated with LN failure. Results: Among 66 patients, 17 LN failures were observed. In the radiomics alone model, CTpre and CTmid had similar mean accuracies (0.681 and 0.697, respectively) and mean areas under the curve (AUC) (0.521 and 0.568, respectively). Radiomics features of spherical disproportion, size zone variance, and log minimum 2 were selected for CTpre plus clinical parameters. Volume, energy, homogeneity, and log minimum 1 were selected for CTmid plus clinical parameters. Clinical parameters including smoking, T-stage, ECE, and regression rate of LN were important for both CTpre and CTmid. In the radiomics plus clinical parameters models, the mean accuracy and mean AUC of CTmid (0.790 and 0.662, respectively) were more improved than those of CTpre (0.731 and 0.582, respectively). Conclusions: Both models using CTpre and CTmid were improved by adding clinical parameters. The radiomics model using CTmid plus clinical parameters was the best in predicting LN failure in our preliminary analyses.

Benefit of perioperative radiotherapy for hepatocellular carcinoma: a quality-based systematic review and meta-analysis.

INTRODUCTION: Although surgery is the standard curative modality for hepatocellular carcinoma, more than two-thirds experience intrahepatic recurrence. Since no standard perioperative treatment has been established, the authors performed a meta-analysis to evaluate the benefits of perioperative radiotherapy (RT). METHODS: The PubMed, MEDLINE, EMBASE, and Cochrane Library were searched until May 2023. Randomized or propensity-matched studies evaluating at least five major clinical factors investigating benefit of perioperative RT, were included. The main effect measure were the pooled odds ratios (OR) regarding the benefit of perioperative RT using 2-year overall survival (OS) and 1-year disease-free survival (DFS) data. RESULTS: Seven studies (five randomized and two propensity-matched studies) involving 815 patients were included. The pooled ORs for 1-year DFS and 2-year OS were 0.359 (95% CI: 0.246-0.523) and 0.371 (95% CI: 0.293-0.576), respectively, favoring perioperative RT, with very low heterogeneity. In the subgroup analyses, the benefits of OS and DFS were consistent between the two subgroups [portal vein thrombosis (PVT) and narrow resection margin (RM) groups]. In the PVT subgroup, the pooled OS rates at both 1-year and 2-year (75.6 vs. 36.9%, P <0.001; 25.6 vs. 9.9%, P =0.004) and DFS rates at both 1-year and 2-year (25.2 vs. 10.3%, P =0.194; 11.9 vs. 3.0%, P =0.022) were higher in the perioperative RT group. In the narrow RM subgroup, the surgery and RT groups showed higher pooled OS rates for both 1-year and 2-year (97.3 vs. 91.9%, P =0.042; 90.4 vs. 78.7%, P =0.051) and DFS (88.1 vs. 72.6%, P <0.001; 70.1 vs. 51.7%, P <0.001). Grade 5 toxicity was not reported, and three studies reported grade ≥3 or higher liver function test abnormalities, ranging from 4.8-19.2%. CONCLUSION: The present study supports the oncological benefits of perioperative RT, for cases with high-risk of recurrence. Oncologic outcomes between subgroups differed according to clinical indications.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Role of local ablative treatment in oligometastatic non-small cell lung cancer: a meta-analysis.

INTRODUCTION: This meta-analysis analyzed the oncologic role of local ablative treatment (LAT) in oligometastatic nonsmall cell lung cancer. METHOD: Pubmed, MEDLINE, Embase, and Cochrane Library were searched until October, 2022. Studies comparing LAT with standard care (control) were included. Sensitivity analyses were performed including randomized controlled studies (RCTs). Subgroup analyses were performed according to specific categories and metastatic burden. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Considering the median OS and PFS from landmark studies, 2-year OS and 1-year PFS rates were used to calculate pooled odds ratios (ORs). RESULTS: A total of 20 studies (four RCTs) encompassing 1750 patients were included. Surgery and radiotherapy (60 and 90% of studies) were mainly used as LATs. Pooled ORs of OS and PFS were 3.492 (95% CI:2.612-4.699, P <0.001) and 3.743 (95% CI: 2.586-5.419, P <0.001), favoring LAT, respectively. Sensitivity analyses, including RCTs showed ORs of 4.111 ( P <0.001) and 4.959 ( P =0.001) regarding OS and PFS, favoring LCT, respectively. Pooled 1-year and 2-year OS rates were 83.8 and 58.4% in LAT arms, whereas 64.4 and 31% in control arms; pooled 1-year and 2-year PFS rates were 64.6 and 32.8% in LAT arms, and 36.1 and 10% in control arms. In subgroup analyses, the pooled ORs were 3.981 ( P <0.001), 3.355 ( P <0.001), and 1.726 ( P =0.373) in synchronous, oligopersistence, and oligoprogression/recurrence subgroups, respectively. Regarding PFS comparison, pooled ORs were 5.631 ( P <0.001), 3.484 ( P <0.001), and 1.777 ( P =0.07), respectively. According to metastatic burden categories, pooled ORs favored LAT arms in both analyses including low-metastatic and high-metastatic burden subgroups. CONCLUSION: The present study supports the role of LAT in treating nonsmall cell lung cancer oligometastasis. The oligoprogression/recurrence disease could have less LAT benefit than synchronous or oligopersistent disease.

Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish.

PURPOSE: The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish. METHODS: Wild-type adult AB zebrafish were exposed to 45-50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi. RESULTS: The median follow-up period was 10 d post-irradiation (range: 7-11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20-54.3) and 68.4% (95% CI:53.8-86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1ß and IL-6) compared to the radiation alone group (p<.05). CONCLUSION: The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.

Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses.

INTRODUCTION: External beam radiation therapy (EBRT) is commonly used as a palliative treatment for bone metastases of hepatocellular carcinoma (HCC). We planned a hybrid systematic review that meta-analyzed the efficacy and feasibility of EBRT and reviewed the literature to answer specific clinical questions. METHODS: The PubMed, Medline, Embase, and Cochrane Library databases were searched through 1 December 2021. Primary endpoints were overall survival (OS) and response rate (RR). Secondary endpoints were comparative data, including treatment response and survival related to dose escalation, number of metastases, and fractionation scheme. Formal pooled analyses were performed on the primary endpoints, and the secondary endpoints were systematically reviewed. Complications were also reviewed. RESULTS: Nineteen studies involving 1613 patients with HCC and bone metastases were included. The median OS was 6 months (range: 3-13 months). The pooled one-year OS was 23.1% (95% confidence interval [CI]: 18.4-28.6); pooled pain RR was 81.5% (95% CI: 76.4-85.7) and of pain complete remission was 26.5% (95% CI: 21.7-32.0). Pain response might be related to dose escalation, considering the moderate consistency of results and plausibility, with a low-quality grade of evidence†. Considering the indeterminate results, we cannot suggest that dose escalation is correlated with OS. The oligometastasis status might be related to better OS, considering the high consistency of results and plausibility with low to moderate quality of evidence. Hypofractionated EBRT might yield comparable efficacy to conventional EBRT, with a low-quality grade of evidence. There were few complications of grade ≥3, except for hematologic complications, which ranged from 11.5to 34%. CONCLUSION: EBRT is an efficient and feasible palliative option. Clinical consideration of hematologic complications is necessary. Future studies are needed to increase the quality of evidence for actual clinical questions. †Reference to a system of the American Society for Radiation Oncology primary liver cancer clinical guidelines.

Efficacy and feasibility of surgery and external radiotherapy for hepatocellular carcinoma with portal invasion: A meta-analysis.

BACKGROUND: External beam radiation therapy (EBRT) and surgery are local treatment modalities for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). This meta-analysis aims to evaluate the effectiveness and feasibility of these treatment modalities. METHODS: PubMed, Medline, Embase, and Cochrane Library databases were systematically searched until April 2021. The primary endpoint was overall survival (OS) of the patients; the adverse effects of the treatment were also investigated. RESULTS: A total of 59 studies involving 9525 patients with HCC and PVT were included in this meta-analysis. All studies were non-randomized series, including seven comparative studies, and the remainder were single-arm studies or studies with comparative groups other than surgery or EBRT. The pooled rates of Child-Pugh class A were 74.6% and 95.3% in the EBRT and surgery arms, respectively, and the pooled main PVT rates were 40.7% and 15.5% in the EBRT and surgery arms, respectively (p < 0.001). Pooled 1- and 2-year OS rates of the EBRT arm were 44.1% (95% CI:40.3-48.0) and 21.7% (95% CI:18.9-24.8), respectively. In the subgroup of EBRT studies without main PVT, pooled 1- and 2-year OS rates were 59.9% (95% CI:48.9-70.1) and 30.5% (95% CI:15.2-51.8), respectively. In the surgery arm, the correlation rates were 62.8% (95% CI:55.0-70.0) and 42.5% (95% CI:34.4-51.0), respectively. The pooled 1-, and 2-year OS rates of surgery arm were significantly higher than those of EBRT arm (ps < 0.001), and not significantly different with the EBRT subgroup without main PVT (p = 0.762, 0.353, respectively). In studies of surgery accompanied by EBRT, the 1- and 2-year OS rates were 77.1% (95% CI:69.6-83.2) and 45.4% (95% CI:19.8-73.7), respectively. The pooled rates of grade≥3 toxicities ranged from 1.8 to 4.3%, depending on the type. CONCLUSION: Surgery can yield a favorable survival outcome, whereas EBRT can be widely considered for patients, including those with inferior clinical profiles. Further studies are warranted to determine the possibility of improving the clinical outcomes of surgery accompanied by EBRT.

Benefit of adjuvant radiotherapy for gallbladder cancer: a comparability-based meta-analysis.

BACKGROUND AND PURPOSE: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies. METHODS: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm). RESULTS: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted. CONCLUSION: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment. PROTOCOL REGISTRATION: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).

Stereotactic ablative radiotherapy for pulmonary oligometastases from primary hepatocellular carcinoma: a multicenter and retrospective analysis (KROG 17-08).

OBJECTIVE: Hypofractionated radiotherapy has recently been applied to treat pulmonary metastases of hepatocellular carcinoma. However, there is no definite evidence on its safety and efficacy. We evaluate the clinical outcomes of hypofractionated radiotherapy for oligo pulmonary metastases of hepatocellular carcinoma in the multicenter and retrospective study. METHODS: From March 2011 to February 2018, 58 patients with fewer than five pulmonary metastases of hepatocellular carcinoma who underwent hypofractionated radiotherapy in nine tertiary university hospitals were analyzed retrospectively. The primary endpoint was the local control rate. The secondary endpoints were overall survival, progression-free survival, prognostic factors affecting the treatment outcomes and treatment-related side effects. RESULTS: The local tumor response rate including complete and partial response was 77.6% at 3 months after hypofractionated radiotherapy. The median survival and progression-free survival times were 20.9 and 5.3 months, respectively. The 1-year overall survival and progression-free survival rates were 65.5 and 22.4%, respectively. The good treatment response after hypofractionated radiotherapy (P = 0.001), the absence of intrahepatic tumor (P = 0.004) and Child-Pugh class A (P = 0.010) were revealed as significant prognostic factors for overall survival in the multivariate analysis. A progression-free interval of <6 months (P = 0.009) was a negative prognostic factor for overall survival in the multivariate analysis. Of 58 patients, five (8.6%) had grade 2 or higher radiation pneumonitis after hypofractionated radiotherapy. CONCLUSIONS: The favorable local control rate and acceptable toxicity indicate the clinical usefulness of hypofractionated radiotherapy for hepatocellular carcinoma patients who have less than five pulmonary metastases.

Oncologic outcomes according to the level of disease burden in patients with metachronous distant metastases from uterine cervical cancer: a Korean Radiation Oncology Group study (KROG 18-10).

OBJECTIVE: This study aimed to evaluate the oncologic outcomes according to disease burden in uterine cervical cancer patients with metachronous distant metastases. METHODS: Between 2005 and 2015, 163 patients with metachronous distant metastases from uterine cervical cancer after receiving a definitive therapy were evaluated at seven institutions in Korea. Low metastatic burden was defined as less than 5 metastatic sites, whereas high metastatic burden was others. Each metastasis site was divided based on the lymph node (LN) and organs affected. The overall survival (OS) and progression-free survival (PFS) were assessed. Cox proportional hazards models, including other clinical variables, were used to evaluate the survival outcomes. RESULTS: The median follow-up duration was 22.2 months (range: 0.3-174.8 months). Para-aortic LNs (56.4%), lungs (26.4%), supraclavicular LNs (18.4%), and peritoneum (13.5%) were found to be the common metastasis sites. Among 37 patients with a single metastasis, 17 (45.9%) had LN metastases and 20 (54.1%) had organ metastases. The 1- and 2-year OS rates were 73.9% and 55.0%, respectively, whereas the PFS rates were 67.2% and 42.9%, respectively. SCC Ag after recurrence and high metastatic burden were significant factors affecting the OS (p=0.004 and p<0.001, respectively). Distant organ recurrence, short disease-free interval (≤2 years), and high metastatic burden were unfavorable factors for PFS (p=0.003, p=0.011, and p=0.002, respectively). CONCLUSION: A favorable oncologic outcome can be expected by performing salvage treatments in selected patients with a long disease-free interval, low metastatic burden, and/or lymphatic-only metastasis.

The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12).

PURPOSE: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. MATERIALS AND METHODS: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). RESULTS: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. CONCLUSION: The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Adjuvant Radiotherapy for Extrahepatic Cholangiocarcinoma: A Quality Assessment-Based Meta-Analysis.

INTRODUCTION: The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. METHODS: PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). RESULTS: Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10-21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, p = 0.035; 34.3% versus 44.7%, p = 0.025; 25.6% versus 31.7%, p = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (p = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, p = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, p = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, p = 0.143; 38.5% versus 49.2%, p = 0.026; and 27.8% versus 34.5%, p = 0.11, respectively. CONCLUSIONS: ART was shown to improve OS in all studies and in those selected for their reliable comparability.

Salvage External Beam Radiotherapy after Incomplete Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review.

Background and objective: Although transarterial chemoembolization (TACE) has been the commonest local modality for hepatocellular carcinoma (HCC), incomplete repsonse occurs especially for tumors with a large size or difficult tumor accessment. The present meta-analysis assessed the efficacy and feasibility of external beam radiotherapy (EBRT) as a salvage modality after incomplete TACE. Materials and Methods: We systematically searched the PubMed, Embase, Medline, and Cochrane databases. The primary endpoint was overall survival (OS), and the secondary endpoints included the response ratem toxicity of grade 3, and local control. Results: Twelve studies involving 757 patients were included; the median of portal vein thrombosis rate was 25%, and the pooled median of tumor size was 5.8 cm. The median prescribed dose ranged from 37.3 to 150 Gy (pooled median: 54 Gy in *EQD2). The pooled one- and two-year OS rates were 72.3% (95% confidence interval (CI): 60.2-81.9%) and 50.5% (95% CI: 35.6-65.4%), respectively; the pooled response and local control rates were 72.2% (95% CI: 65.4-78.1%) and 86.6 (95% CI: 80.1-91.2%) respectively. The pooled rates of grade ≥3 gastrointestinal toxicity, radiation-induced liver disease, hepatotoxicity, and hematotoxicity were 4.1%, 3.5%, 5.7%, and 4.9%, respectively. Local control was not correlated with intrahepatic (p = 0.6341) or extrahepatic recurrences (p = 0.8529) on meta-regression analyses. Conclusion: EBRT was feasible and efficient in regard to tumor response and control; after incomplete TACE. Out-field recurrence, despite favorable local control, necessitates the combination of EBRT with systemic treatments. *Equivalent dose in 2 Gy per fraction scheme.

Is the Concurrent Use of Sorafenib and External Radiotherapy Feasible for Advanced Hepatocellular Carcinoma? A Meta-Analysis.

We evaluate the feasibility of a concurrent application of sorafenib and external beam radiation therapy (EBRT) for advanced hepatocellular carcinoma (HCC). PubMed, Embase, Medline, and Cochrane Library were searched up to 9 April 2021. The primary endpoint was grade ≥3 complications, and the secondary endpoint was overall survival (OS). Subgroup analyses were performed for studies with the EBRT targets, intrahepatic vs. non-intrahepatic lesions (e.g., extrahepatic metastases or malignant vessel involvement only). Eleven studies involving 512 patients were included in this meta-analysis. Pooled rates of gastrointestinal, hepatologic, hematologic, and dermatologic grade ≥3 toxicities were 8.1% (95% confidence interval (CI): 4.8-13.5, I2 = ~0%), 12.9% (95% CI: 7.1-22.1, I2 = 22.4%), 9.1% (95% CI: 3.8-20.3, I2 = 51.3%), and 6.8% (95% CI: 3.8-11.7, I2 = ~0%), respectively. Pooled grade ≥3 hepatologic and hematologic toxicity rates were lower in studies targeting non-intrahepatic lesions than those targeting intrahepatic lesions (hepatologic: 3.3% vs. 17.1%, p = 0.041; hematologic: 3.3% vs. 16.0%, p = 0.078). Gastrointestinal and dermatologic grade ≥3 complications were not significantly different between the subgroups. Regarding OS, concurrent treatment was more beneficial than non-concurrent treatment (odds ratio: 3.3, 95% CI: 1.3-8.59, p = 0.015). One study reported a case of lethal toxicity due to tumor rupture and gastrointestinal bleeding. Concurrent treatment can be considered and applied to target metastatic lesions or local vessel involvement. Intrahepatic lesions should be treated cautiously by considering the target size and hepatic reserve.

Implications of Radiotherapy Utilization in Korea from 2010 to 2019.

BACKGROUND: This study was to assess the rate of radiotherapy (RT) utilization according to the modality in South Korea to identify the implications of contemporary RT patterns. METHODS: We collected information from claims and reimbursement records of the National Health Insurance Service from 2010 to 2019. We classified the location of each institution as capital (Seoul, Incheon, and Gyeonggi-do) and non-capital areas. RESULTS: The rate of RT utilization in total cancer patients nationwide was 24.5% in 2010, which consistently has increased to 36.1% in 2019 (annual increase estimate [AIE], 4.5%). There was an abrupt increase in patients receiving intensity-modulated RT (IMRT), with an AIE of 33.5%, and a steady decline in patients receiving three-dimensional conformal RT (3DCRT), with an AIE of -7.1%. The commonest RT modality was IMRT (44.5%), followed by 3DCRT and stereotactic RT (SRT) (37.2% and 13.5%) in 2019. An increasing trend of advanced RT (such as IMRT and SRT) utilization was observed regardless of the region, although the AIE in the capital areas was slightly higher than that in non-capital areas. CONCLUSION: The utilization of overall RT application and especially of advanced modalities remarkably increased from 2010 to 2019. We also found gaps in their AIEs between capital and non-capital areas. We should ensure that advanced RT is accessible to all cancer patients across South Korea.

Benefits of Local Treatment Including External Radiotherapy for Hepatocellular Carcinoma with Portal Invasion.

We aimed to identify the oncologic benefits of local treatment including radiotherapy (LRT) in hepatocellular carcinoma (HCC) invading the portal vein. We used clinical data of patients with HCC invading the portal vein from 2008 to 2014 provided by 50 hospitals nationwide. A total of 1163 patients were included in the analysis. The LRT group was younger than the best supportive care (BSC) group (p < 0.001). The mean Child-Pugh score of the LRT group (6.1) was significantly lower than that of the BSC group (7.7) (p < 0.001). Propensity score-matched analysis generated 222 pairs. The median survival of all patients, LRT, and BSC groups were 5.0, 8.0, and 2.0 months, respectively. The overall survival (OS) rates in the LRT and BSC groups were 34.2% and 16.2% at one year, and 12.6% and 6.8% at two years, respectively (p < 0.001). Multivariate analysis showed that LRT (HR 0.41, 95% CI 0.32-0.52), age >60 years, extrahepatic metastases, tumor size ≥10 cm, and Child-Pugh class (CPC) B or C were independent predictors of higher mortality (all p < 0.05). Statistical differences in survival were maintained in all CPC-albumin-bilirubin classes (all p < 0.05). LRT was significant in patients with HCC with portal invasion, valid for patients with CPC A and B.

Variation of heart and lung radiation doses according to setup uncertainty in left breast cancer.

PURPOSE: Breast radiotherapy set-up is often uncertain. Actual dose distribution to normal tissues could be different from planned dose distribution. The objective of this study was to investigate such difference in dose distribution according to the extent of set-up error in breast radiotherapy. MATERIALS AND METHODS: A total of 50 Gy with fraction size of 2 Gy was given to 30 left breasts with different set-ups applying a deep inspiration breath holding (DIBH) or a free breathing (FB) technique. Under the assumption that errors might come from translational axes of deep or caudal directions, the isocenter was shifted from the original tangential alignment every 2.5 mm to simulate uncertainty of deep and caudal tangential set-up in DIBH and FB. Changes were evaluated for dosimetric parameters for the heart, the left ventricle (LV), the left anterior descending coronary artery (LAD), and the ipsilateral lung. RESULTS: On the original plan, mean doses of heart and ipsilateral lung were 2.0 ± 1.1 Gy and 3.7 ± 1.4 Gy in DIBH and 8.4 ± 1.3 Gy and 7.8 ± 1.5 Gy in FB, respectively. The change of dose distribution for the heart in DIBH was milder than that in FB. The deeper the tangential set-up, the worse the heart, LV, LAD, and ipsilateral lung doses, showing as much as 49.4%, 56.4%, 90.3%, and 26.1% shifts, respectively, in 5 mm DIBH setup. The caudal set-up did not show significant dose difference. In multiple comparison of DIBH, differences of mean dose occurred in all 7.5 mm deep set-ups for the heart (p = 0.025), the LV (p = 0.049), and LAD (p = 0.025) in DIBH. CONCLUSIONS: To correct set-up error over indicated limitation for deep tangential set-up in DIBH at 5 mm action level, mean heart and ipsilateral lung doses are expected to increase approximately 50% and 25%, respectively.

Clinical Impact of Supraclavicular Lymph Node Involvement of Stage IIIC Non-Small Cell Lung Cancer Patients.

Background and Objective: Investigations on the clinical impact of supraclavicular lymph node (SCN) involvement in stage IIIC non-small cell lung cancer (NSCLC) remain scarce. We evaluated the oncological outcomes of definitive radiochemotherapy and the clinical significance of SCN involvement. Materials and Methods: Between November 2009 and June 2019, a total of 40 patients with N3-positivity and NSCLC were evaluated. Most patients received concomitant chemotherapy, but six patients who received radiotherapy (RT) alone were also included. Twenty-one patients (52.5%) received 3D-conformal RT (3DCRT), and the remainder received intensity-modulated RT (IMRT). Results: The median follow-up duration was 10.7 months (range: 1.7-120.6 months). Median overall survival (OS) and cause-specific survival (CSS) times were 10.8 months and 16.3 months, respectively. Among the 40 patients, 17 (42.5%) had SCN involvement. SCN involvement negatively affected progression-free survival (hazard ratio (HR): 2.08, 95% confidence interval (CI): 1.04-4.17, p = 0.039) and local control (HR: 3.05, 95% CI: 1.09-8.50, p = 0.034). However, IMRT use was correlated with higher local control (HR: 0.28, 95% CI: 0.09-0.86, p = 0.027). Grade ≥3 esophagitis and pneumonitis accounted for 7.5% and 15.0% of all cases, respectively. A higher RT dose (mean dose: 66.6 vs. 61.7 Gy) was significantly correlated with grade ≥3 pneumonitis (p = 0.001). RT modality was a significant factor (p = 0.042, five of six cases occurred in the IMRT group). Conclusions: SCN involvement could negatively affect oncologic outcomes of stage IIIC NSCLC patients. High-dose irradiation with IMRT could increase local control but may cause lung toxicities.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.