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Background: We developed a machine vision technology program that tracks patients’ realtime breathing and automatically analyzes their breathing patterns.Materials and Methods: To evaluate its potential for clinical application, the image tracking performance and accuracy of the program were analyzed using a respiratory motion phantom. Changes in the stability and regularity of breathing were observed in healthy adult volunteers according to whether the breathing pattern mirrored the breathing guidance.Results and Discussion: Displacement within a few millimeters was observed in real-time with a clear resolution, and the image tracking ability was excellent. This result was consistent even in the sections where breathing patterns changed rapidly. In addition, the respiratory gating method that reflected the individual breathing patterns improved breathing stability and regularity in all volunteers.Conclusion: The findings of this study suggest that this technology can be used to set the appropriate window and the range of internal target volume by reflecting the patient’s breathing pattern during radiotherapy planning. However, further studies in clinical populations are required to validate this technology.

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 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.

AIM Stereotactic-body radiotherapy (SBRT) is a treatment option for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Here, we report on our experience of treating PVTT using SBRT in patients with concomitant underlying chronic liver disease. METHODS This study included 24 patients. The initial prescription dose was 45 Gy in three fractions in 17 (70.8%) patients, but it was modified in the remaining seven (29.2%) patients, with the dose ranging from 39 to 42 Gy in 3-4 fractions. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients. RESULTS Of the 24 patients, 2 (8.3%) showed complete response, while 11 (45.8%) showed partial response. After a median follow-up of 8.4 months (range: 2.6-56.5 months), the 1-year overall survival (OS) and the median survival were 67.5% and 20.8 months, respectively. Both combined SBRT and TACE and grade ≥3 hepatic toxicity affected the 1-year OS (SBRT alone vs SBRT + TACE: 14.6% vs 71.4%, P

We investigated the relationship of physical activity with dietary habits and quality of life (QoL) in breast cancer survivors in accordance with the recommendations of the American Cancer Society. Data of 928 breast cancer survivors were obtained from the KROG 14-09 study to measure QoL in early phase after adjuvant radiotherapy. According to the extent of physical activity, survivors were divided into four groups: inactivity (0–149 min/week, N = 144), regular activity (150–450 min/week, N = 309), moderate activity (451–900 min/week, N = 229), and marked activity (901–1800 min/week, N = 164) excluding hyperactivity (> 1800 min/week, N = 82) as it is a difficult condition to recommend to survivors. Global physical activity questionnaire, 5-dimensional questionnaire by EuroQoL (EQ-5D-3L), QoL Questionnaire–breast cancer (QLQ-BR23) from EORTC, and dietary habits were surveyed. A linear-to-linear association test for EQ-5D-3L and Kruskal–Wallis analysis for QLQ-BR23 and dietary habit were conducted. Overall, 15.5% respondents (144/928) were classified as physically inactive. The trends of frequent intake of fruits (p = 0.001) and vegetable (p = 0.005) and reluctance toward fatty food (p

This study quantitatively analyzed the gain of the six-dimensional (6D) cone-beam CT (CBCT) correction method compared with the conventional set-up method in 60 patients who underwent radiation treatment of head and neck and brain tumors. The correction gain of CBCT was calculated for the translational and rotational motion components separately and in combination to evaluate the individual and overall effects of these motion components. Using a statistical simulation mimicking the actual set-up correction process, the effective gain of periodic CBCT correction during the entire treatment fraction was analyzed by target size and CBCT correction period under two different correction scenarios: translation alone and full 6D corrections. From the analyses performed in this study, the gain of CBCT correction was quantitatively determined for each situation, and the appropriate CBCT correction strategy was suggested based on treatment purpose and target size.

Objective: The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC. Methods: A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV). Results: In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05). Conclusions: CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.

Emerging evidence suggests that breast cancer stem cells (BCSCs), and epithelial–mesenchymal transition (EMT) may be involved in resistance to doxorubicin. However, it is unlear whether the doxorubicin-induced EMT and expansion of BCSCs is related to cancer dormancy, or outgrowing cancer cells with maintaining resistance to doxorubicin, or whether the phenotypes can be transferred to other doxorubicin-sensitive cells. Here, we characterized the phenotype of doxorubicin-resistant TNBC cells while monitoring the EMT process and expansion of CSCs during the establishment of doxorubicin-resistant MDA-MB-231 human breast cancer cells (DRM cells). In addition, we assessed the potential signaling associated with the EMT process and expansion of CSCs in doxorubicin-resistance of DRM cells. DRM cells exhibited morphological changes from spindle-shaped MDA-MB-231 cells into round-shaped giant cells. They exhibited highly proliferative, EMT, adhesive, and invasive phenotypes. Molecularly, they showed up-regulation of Cyclin D1, mesenchymal markers (β-catenin, and N-cadherin), MMP-2, MMP-9, ICAM-1 and down-regulation of E-cadherin. As the molecular mechanisms responsible for the resistance to doxorubicin, up-regulation of EGFR and its downstream signaling, were suggested. AKT and ERK1/2 expression were also increased in DRM cells with the advancement of resistance to doxorubicin. Furthermore, doxorubicin resistance of DRM cells can be transferred by autocrine signaling. In conclusion, DRM cells harbored EMT features with CSC properties possessing increased proliferation, invasion, migration, and adhesion ability. The doxorubicin resistance, and doxorubicin-induced EMT and CSC properties of DRM cells, can be transferred to parental cells through autocrine signaling. Lastly, this feature of DRM cells might be associated with the up-regulation of EGFR.

Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed to evaluate the anticancer effect of mebendazole (MBZ) and radiotherapy (RT) concomitant use in triple-negative breast cancer (TNBC) cells and elucidate the underlying mechanisms of action. Breast cancer mouse models and several types of breast cancer cells, including TNBC-derived RT-resistant (RT-R) MDA-MB-231 cells, were treated with MBZ and/or RT. In mice, changes in body weight, renal and liver toxicity, tumor volume, and number of lung metastases were determined. In cells, cell viability, colony formation, scratch wound healing, Matrigel invasion, and protein expression using western blotting were determined. Our findings showed that MBZ and RT combined treatment increased the anticancer effect of RT without additional toxicity. In addition, we noted that cyclin B1, PH2AX, and natural killer (NK) cell-mediated cytotoxicity increased following MBZ + RT treatment compared to unaided RT. Our results suggest that MBZ + RT have an enhanced anticancer effect in TNBC which acquires radiation resistance through blocking cell cycle progression, initiating DNA double-strand breaks, and promoting NK cell-mediated cytotoxicity.

Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.

We evaluated whether there is a difference in the local recurrence and survival after pelvic external radiotherapy (ERT) with and without boost vaginal brachytherapy (VB) in cervical cancer patients with positive or close vaginal resected margins (RM). We retrospectively reviewed FIGO stage IA-IIB cervical cancer patients treated with postoperative ERT between 1997 and 2018. The sixty patients showing close (safety margin

Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. In this study, we performed antibody array analysis to identify the hub signaling mechanism for the radiation resistance of RT-R-MDA-MB-231 cells by comparing parental MDA-MB-231 (p-MDA-MB-231) and RT-R-MDA-MB-231 cells. Antibody array analysis unveiled that the MAPK1 protein was the most upregulated protein in RT-R-MDA-MB-231 cells compared to in p-MDA-MB-231 cells. The pathway enrichment analysis also revealed the presence of MAPK1 in almost all enriched pathways. Thus, we used an MEK/ERK inhibitor, PD98059, to block the MEK/ERK pathway and to identify the role of MAPK1 in the radio-resistance of RT-R-MDA-MB-231 cells. MEK/ERK inhibition induced cell death in both p-MDA-MB-231 and RT-R-MDA-MB-231 cells, but the death mechanism for each cell was different, p-MDA-MB-231 cells underwent apoptosis, showing cell shrinkage and PARP-1 cleavage, while RT-R-MDA-MB-231 cells underwent necroptosis, showing mitochondrial dissipation, nuclear swelling, and an increase in the expressions of CypA and AIF. In addition, MEK/ERK inhibition reversed the radio-resistance of RT-R-MDA-MB-231 cells and suppressed the increased expression of CSC markers (CD44 and OCT3/4) and the EMT phenotype (β-catenin and N-cadherin/E-cadherin). Taken together, this study suggests that activated ERK signaling is one of the major hub signals related to the radio-resistance of MDA-MB-231 breast cancer cells.

Purpose: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes. Methods and Materials: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates. Results: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524–0.588, p &lt, 0.001). Gleason score, iPSA &lt, 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy1.5 (EQD2, 77 Gy) were independently significant for BCFFS (all p &lt, 0.05). IMRT and ≥179 Gy1.5 were significant factors in the high-risk group, whereas ≥170 Gy1.5 (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy1.5 was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities. Conclusions: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited.

To evaluate the role of adjuvant radiotherapy (RT) after curative resection in patients with extrahepatic bile duct (EHBD) cancer.Between January 2000 and December 2015, 1475 patients with EHBD cancer who underwent curative resection were accrued from 14 institutions in Korea. Among these, 959 patients did not receive any adjuvant therapy (RT(-) group), while 516 underwent postoperative RT with or without chemotherapy (RT(+) group).The median age was 67 years. Nodal involvement was present in 482 patients (32.7%), and resection margin was involved in 293 patients (19.9%). RT(+) group had more patients with proximal tumours, advanced tumours, nodal involvement, perineural invasion, and involved resection margin than RT(-) group (all p 0.001). With a median follow-up of 36 months, there were 211 locoregional recurrences, 307 distant metastases and 322 combined locoregional and distant failures. On multivariate analysis incorporating age, tumour location, differentiation, pT classification, pN classification, perineural invasion and resection margin, adjuvant RT was associated with improved overall survival (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p 0.001). When RT(+) group was separated into RT alone, concurrent chemoradiotherapy (CCRT) and CCRT followed by chemotherapy, the greatest benefit was observed in patients treated with CCRT followed by chemotherapy (hazard ratio, 0.52; 95% confidence interval, 0.41-0.68).Adjuvant RT combined with chemotherapy improved survival outcomes of resected EHBD cancer patients. Considering the greatest benefit observed in patients receiving CCRT followed by chemotherapy, a randomised controlled trial comparing chemotherapy alone and CCRT followed by chemotherapy is urgently needed.

Purpose To investigate the safety and efficacy of intensity-modulated radiation therapy (IMRT) for early breast cancer compared with 3-dimensional conformal radiotherapy (3D-CRT) in a prospective and randomized trial. Methods and materials From March 2015 to February 2018, 693 patients with pT1-2N0M0 early breast cancer who underwent breast-conserving surgery were enrolled and randomly assigned into IMRT and 3D-CRT. The primary endpoint was 3-year locoregional recurrence-free survival (LRRFS). The secondary endpoints were recurrence-free survival, overall survival, acute toxicity, target coverage index, irradiation dose to organs at risk, and fatigue inventory. The radiation dose for the 3D-CRT arm was 59.4 Gy in 33 fractions for 6.5 weeks. It was 57.4 Gy in 28 fractions with simultaneous integrated boost for 5.5 weeks for the IMRT arm. Results Of 693 patients, 349 and 344 patients received 3D-CRT and IMRT, respectively. There was no significant difference in LRRFS between the two arms. Conformity index of planning target volume was significantly superior in the IMRT arm than the 3D-CRT arm (p Conclusion Compared to 3D-CRT, IMRT showed similar results in locoregional tumor control but superior results in planning target volume coverage. When IMRT is used in breast cancer, the irradiation dose to an ipsilateral lung and skin toxicity can be reduced.

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control, group II, ALA alone (100 mg/kg), group III, RI alone (0.01 mCi/g body weight, orally), and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.

Purpose In pulmonary oligometastases from colorectal cancer (POM-CRC), the primarily recommended local therapy is metastasectomy. Stereotactic body radiotherapy (SBRT) is another local therapy modality that is considered as an alternative option in patients who cannot undergo surgery. The purpose of this meta-analysis is to demonstrate the effects of SBRT on POM-CRC by integrating the relevant studies. Materials and methods The authors explored MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS, and selected studies including patients treated with SBRT for POM-CRC and availability of local control (LC) or overall survival (OS) rate. In this meta-analysis, the effect of SBRT was presented in the form of the LC and OS rates for 1, 2, 3, and 5 years after SBRT as pooled estimates, and the frequency of pulmonary toxicity of grade 3 or higher after SBRT (PTG3-SBRT). Results Fourteen full texts among the searched 4,984 studies were the objects of this meta-analysis. The overall number of POM-CRC patients was 495 as per the integration of 14 studies. The pooled estimate LC rate at 1, 2, 3, and 5 years after SBRT was 81.0%, 71.5%, 56.0%, and 61.8%, and the OS rate was 86.9%, 70.1%, 57.9%, and 43.0%, respectively. The LC and OS rates gradually declined until 3 years after SBRT in a similar pattern. Among the 14 studies, only two studies reported PTG3-SBRT as 2.2% and 10.8%, respectively. Conclusion For POM-CRC, SBRT is an ablative therapy with a benefit on LC and OS rates and less adverse effects on the lung.

Purpose To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma. Methods and Materials Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated. Results With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm). Conclusion Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.

Artemisia annua L. has been reported to show anti-cancer activities. Here, we determined whether polyphenols extracted from Artemisia annua L. (pKAL) exhibit anti-cancer effects on radio-resistant MDA-MB-231 human breast cancer cells (RT-R-MDA-MB-231 cells), and further explored their molecular mechanisms. Cell viability assay and colony-forming assay revealed that pKAL inhibited cell proliferation on both parental and RT-R-MDA-MB-231 cells in a dose-dependent manner. The anti-proliferative effects of pKAL on RT-R-MDA-MB-231 cells were superior or similar to those on parental ones. Western blot analysis revealed that expressions of cluster of differentiation 44 (CD44) and Oct 3/4, matrix metalloproteinase-9 (MMP-9) and signal transducer and activator of transcription-3 (STAT-3) phosphorylation were significantly increased in RT-R-MDA-MB-231 cells compared to parental ones, suggesting that these proteins could be associated with RT resistance. pKAL inhibited the expression of CD44 and Oct 3/4 (CSC markers), and &beta, catenin and MMP-9 as well as STAT-3 phosphorylation of RT-R-MDA-MB-231. Regarding upstream signaling, the JNK or JAK2 inhibitor could inhibit STAT-3 activation in RT-R-MDA-MB-231 cells, but not augmented pKAL-induced anti-cancer effects. These findings suggest that c-Jun N-terminal kinase (JNK) or Janus kinase 2 (JAK2)/STAT3 signaling are not closely related to the anti-cancer effects of pKAL. In conclusion, this study suggests that pKAL exhibit anti-cancer effects on RT-R-MDA-MB-231 cells by suppressing CD44 and Oct 3/4, &beta, catenin and MMP-9, which appeared to be linked to RT resistance of RT-R-MDA-MB-231 cells.

Background Significant proportion of lung cancer patients suffer from malignant airway obstruction (MAO). Palliative external beam radiotherapy (EBRT) is often attempted to control symptoms caused by MAO. In this study, we report the effect of palliative EBRT on lung cancer with MAO and analyze the factors that influence it. Methods This study included 75 patients with MAO in lung cancer who underwent palliative EBRT, between 2009 and 2018 and were analyzed retrospectively. Change of dyspnea, tumor response, and overall survival (OS) were recorded. Univariate and multivariate analyses were done to find the prognostic factors for treatment outcomes. Results The median follow-up duration was 2.5 months, and the median OS was 2.3 months. Out of 75 patients, dyspnea was improved in 46 patients (61.3%), and tumor was partially decreased in 39 patients (52%). The symptom improvement was significantly affected by tumor response and radiation dose. The tumor response was significantly affected by disease status, radiation dose, and time to EBRT.Conclusions Palliative EBRT is an effective and safe treatment option for patients with MAO in lung cancer. Especially, high-dose irradiation and prompt treatment can improve treatment results.

Background A significant proportion of lung cancer patients suffer from malignant airway obstruction (MAO). Palliative external beam radiotherapy (EBRT) is often used to control the symptoms caused by MAO. In this study, we report the effect of palliative EBRT on lung cancer with MAO and analyze the factors that influence it. Methods This study included 75 patients with MAO in lung cancer who underwent palliative EBRT, between 2009 and 2018 and were analyzed retrospectively. Change of dyspnea, tumor response, and overall survival (OS) were recorded. Univariate and multivariate analyses were performed to determine the prognostic factors for treatment outcomes. Results The median follow-up duration was 2.5 months, and median OS was 2.3 months. Out of 75 patients, dyspnea was improved in 46 patients (61.3%), and tumor was partially decreased in 39 patients (52%). Symptoms improved in all tumor responding patients. The symptom improvement was significantly affected by radiation dose and time to EBRT. The tumor response was significantly affected by pathology, radiation dose, and time to EBRT. Conclusions Palliative EBRT is an effective and safe treatment option for patients with MAO in lung cancer. In particular, high-dose irradiation and prompt treatment can improve treatment results. Key points SIGNIFICANT FINDINGS OF THE STUDY: In MAO patients, tumor response is an important factor for resolving dyspnea and improving survival rate. In order to increase the tumor response, high-dose irradiation and prompt treatment after symptoms occur are necessary. What this study adds Our study reported the effects of EBRT and prognostic factors in MAO patients. We emphasize that palliative EBRT is a relatively safe and effective treatment in MAO patients, which is a complement to previous studies.

Radiation therapy is a standard treatment for patients with head and neck cancer. However, radiation exposure to the head and neck induces salivary gland (SG) dysfunction. Alpha lipoic acid (ALA) has been reported to reduce radiation-induced toxicity in normal tissues. In this study, we investigated the effect of ALA on radiation-induced SG dysfunction. Male Sprague&ndash, Dawley rats were assigned to the following treatment groups: control, ALA only (100 mg/kg, intraperitoneally), irradiation only, and ALA administration 24 h or 30 min prior to irradiation. The neck area, including SGs, was irradiated evenly at 2 Gy/min (total dose, 18 Gy) using a photon 6 MV linear accelerator. The rats were sacrificed at 2, 6, 8, and 12 weeks after irradiation. Radiation decreased SG weight, saliva secretion, AQP5 expression, parasympathetic innervation (GFR&alpha, 2 and AchE expression), regeneration potentials (Shh and Ptch expression), salivary trophic factor levels (brain-derived neurotrophic factor and neurturin), and stem cell expression (Sca-1). These features were restored by treatment with ALA. This study demonstrated that ALA can rescue radiation-induced hyposalivation by preserving parasympathetic innervation and regenerative potentials.

Purpose: Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) can affect systemic circulation, causing fatal complications. Standard treatment is yet to be...

Background To evaluate the treatment outcome and prostate-specific antigen (PSA) change after stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods Patients with localized prostate cancer treated with SBRT at three academic hospitals were enrolled. Treatment was delivered using Cyberknife with dose range from 35 to 37.5 Gy in 5 fractions. Biochemical failure (BCF) was assessed with Phoenix definition and toxicities were scored with Radiation Therapy Oncology Group (RTOG) toxicity criteria. The PSA kinetics were analyzed in patients who received no androgen deprivation therapy (ADT) and showed no recurrence. Results Of the total 88 patients, 14 patients (15.9%) received ADT. After median follow-up of 63.8 months, the 5-year BCF free survival (BCFFS) was 94.7%. Two patients experienced late grade ≥ 3 GI toxicities (2.2%). The median nadir PSA was 0.12 ng/mL (range, 0.00–2.62 ng/mL) and the median time to nadir was 44.8 months (range, 0.40–85.7 months). Patients who reached nadir before 24 months showed poorer BCFFS than the others. The rate of PSA decline was maximum in the first year after treatment and gradually decreased with time. The pattern of PSA change was significantly different according to the risk groups (p = 0.011) with the slope of − 0.139, − 0.161 and − 0.253 ng/mL/month in low-, intermediate- and high-risk groups, respectively. Conclusion SBRT for localized prostate cancer showed favorable efficacy with minimal toxicities. The time to PSA nadir was significantly associated with treatment outcome. PSA revealed rapid initial decline and slower decrease with longer follow-up and the patterns of PSA changes were different according to the risk groups.

Background We compared the treatment outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy in patients with pulmonary metastases. Methods Twenty-one patients received SBRT (total radiation doses 60 Gy in 3 fractions or 48 Gy in 4 fractions) and 30 underwent metastasectomy, most (93.3%) with wedge resection. The patients were followed for a median of 13.7 months. The tumor size in the SBRT group was larger than in the metastasectomy group (median 2.5 vs. 1.25 cm; P = 0.015). Patients with synchronous metastases were more likely to be treated with SBRT than with metastasectomy (P = 0.006). Results There was no significant difference in the local control rates of the treatment groups (P = 0.163). Progression-free survival (PFS) was longer in the metastasectomy than in the SBRT group (P = 0.02), with one and two-year PFS rates of 51.1% and 46% versus 23.8% and 11.9%, respectively. The one and two-year overall survival (OS) rates were 95% and 81.8% in the metastasectomy group and 79.5% and 68.2%, in the SBRT group, respectively. In multivariate analysis, synchronous metastasis was related to poor PFS, and tumor size was the most significant factor affecting OS. There were no significant differences in PFS and OS between treatment groups after dividing patients according to the presence or absence of synchronous metastases. Conclusions SBRT is considered a suitable local modality against pulmonary metastases; however, patients with synchronous metastases are only likely to obtain a small benefit from local treatment with either SBRT or surgery.

Background/Aims: To evaluate the technical feasibility of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) with the major portal vein tumor thrombosis (PVTT). Methods: Ten institutions affiliated with the Korean Stereotactic Radiosurgery Group were provided the contours of four cases: the first case was the first branch PVTT with sufficient normal liver volume (NLV), the second was the first branch PVTT with insufficient NLV, the third was the main trunk PVTT at confluence level, and the fourth was the main trunk PVTT with entire length. The institutions were asked to make SBRT plans according to their current treatment protocols and to complete facility questionnaires. Results: Based on institutional protocols, SBRT was feasible in nine institutions for the first case (32-60 Gy in 3-5 fractions), in eight institutions for the second case (32-50 Gy in 3-5 fractions), in seven institutions for the third case (35-60 Gy in 3-5 fractions), and in four institutions for the fourth case (35-42 Gy in 4-5 fractions). The other institutions recommended hypo- or conventional fractionation due to insufficient NLV or gastrointestinal organ proximity. With analysis of the SBRT dose to the central hepatobiliary tract, the major PVTT could theoretically be associated with a high risk of hepatobiliary toxicity. Conclusions: Although SBRT is a technically feasible option for HCC with the major PVTT, there was a variability among the participating institutions. Therefore, further studies will be necessary to standardize the practice of SBRT for the major PVTT. (J Liver Cancer 2018;18:130-141)

The aim of this study was to evaluate the protective effects of anthocyanins from the black soybean seed coat against radiation injury in dermal fibroblasts and mouse skin. Dermal fibroblasts treated with 50 and 100 µg/mL anthocyanins were irradiated with single doses of 20 Gy. Cell viability, intracellular reactive oxygen species (ROS) production, and mRNA expression were measured. A total of 60 mice were used for an in vivo study. A dose of 100 µg/mL anthocyanins was administered daily for 5 days before or after radiation therapy. Following irradiation (45 Gy), mice were inspected for gross pathology twice per wk for 8 weeks. At 4 and 8 weeks post-irradiation, dorsal skin was harvested for histopathologic examination and protein isolation. In dermal fibroblasts, treatment with 50 and 100 µg/mL anthocyanins significantly reduced radiation-induced apoptosis at 72 h and intracellular reactive oxygen species generation at 48 h. Furthermore, 100 µg/mL anthocyanins markedly decreased Smad3 mRNA expression and increased Smad7 mRNA expression at 72 h post-irradiation. In mice, treatment with 100 µg/mL anthocyanins resulted in a significant reduction in the level of skin injury, epidermal thickness, and collagen deposition after irradiation. Treatment with 100 µg/mL anthocyanins significantly decreased the number of α-SMA-, TGF-β-, and Smad3-positive cells after irradiation. Our study demonstrated that black soybean anthocyanins inhibited radiation-induced fibrosis by downregulating TGF-β and Smad3 expression. Therefore, anthocyanins may be a safe and effective candidate for the prevention of radiation-induced skin fibrosis.

It is our great honor to receive valuable opinions from the world-wide experts on our published article entitled “ Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in patients with pulmonary metastases ” (1). This published paper was the retrospective study for outcomes in 51 patients underwent local ablative treatments for them up to three pulmonary oligometastases.

In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.

Objective The aim of this multi-institutional study was to determine the prognostic impact of tumour parameters, such as tumour size (TS), tumour volume (TV), and marker expression, on survival during radiation therapy (RT) for cervical cancer patients. Methods A total of 231 patients with histologically confirmed cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) Ib2-IVa, were enrolled in this study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) and squamous cell carcinoma antigen (SCC-ag) analysis were performed twice, during RT and just before brachytherapy. Results The median follow-up time was 27.8months (range, 2–116months). Multivariate analysis revealed that stage (odds ratio [OR], 2.936 and 95% confidence interval [CI], 1.119–7.707; P =0.029), tumour volume reduction rate (TVRR) (OR, 3.435 and 95% CI, 1.062–11.106; P =0.039), and SCC-ag reduction rate (SCCRR) (OR, 5.104 and 95% CI, 1.769–14.727; P =0.003) were independently associated with overall survival (OS), while pre-RT TS (OR, 2.148 and 95% CI, 1.221–3.810; P =0.009), mid-RT TV (OR, 3.106 and 95% CI, 1.685–5.724; P P =0.016) were associated with progression-free survival (PFS). Based on the prognostic factor analysis, patients with the highest prognostic risk score of 3 showed poorer overall survival and progression free survival than patients with lower prognostic risk scores. Conclusion We identified that tumour parameters such as TVRR, SCCRR, pre-RT TS, and mid-RT TV areindependent and strong prognostic parameters for patients with cervical cancer receiving RT. This scoring system-based prognostic factor analysis could be used to help develop optimized treatment plans for cervical cancer patients during RT.

We analyzed patterns of care and outcomes for patients with primary central nervous system lymphoma (PCNSL) in this multi-institutional retrospective study. Between January 2000 and December 2011, 220 patients with PCNSL received radiotherapy (RT). Among these patients, 26 patients received RT alone; 179 patients were treated with chemotherapy and radiotherapy; the rest of the patients (N = 15) initially underwent chemotherapy alone, then received RT as a salvage treatment. Most of the patients (N = 188) received methotrexate-based chemotherapy. The median follow up duration was 38 months (range 3-179 months). The median RT dose and whole brain RT (WBRT) dose were 45.0 Gy (range 20.0-59.4) and 30.6 Gy (range 18.0-45.0), respectively. Seventy-seven (35%) patients received WBRT alone, and 143 patients (65%) underwent WBRT plus boost RT. Total RT dose and WBRT dose decreased during the study period. The median survival was 64 months and actuarial 5-year overall survival was 51.4%. In multivariate analysis, age (P

Purpose In a recent meta-analysis, post-mastectomy radiotherapy (PMRT) reduced any first recurrence (AFR) and improved survival in N1 and N2 patients. We investigated risk factors for AFR in N1 after optimal systemic therapy without PMRT, to define a subgroup of patients who may benefit from PMRT. Materials and Methods One thousand three hundred eighty-two pT1-2N1M0 breast cancer patients treated with mastectomy without PMRT between 2005 and 2010 were retrospectively analyzed. Only 0.6% had no systemic therapy. Results After a median follow-up of 5.9 years, there were 173 AFR (53 loco-regional recurrence [LRR] without distant metastases [DM], 38 LRR with DM, and 82 DM without LRR). The 5-year LRR and AFR rates were 6.1% and 12.0%, respectively. Multivariate analysis revealed that close resection margin (p=0.001) was the only independent risk factor for LRR. Multivariate analysis for AFR revealed that age < 35 years (p=0.025), T2 stage (p=0.004), high tumor grade (p=0.032), close resection margin (p=0.035), and triple-negative biological subtype (p=0.031) were independent risk factors. Two or three positive lymph nodes (p=0.078) were considered a marginally significant factor. When stratified by these six factors, the 5-year LRR rates were 3.6% with 0-1 (n=606), 7.5% with 2-3 (n=655), and 12.7% with 4-6 (n=93) risk factors. The 5-year AFR rates were 7.1% with 0-1, 15.0% with 2-3, and 24.5% with 4-6 risk factors. Conclusion Patients with pT1-2N1M0 breast cancer who underwent mastectomy and optimal systemic therapy showed excellent loco-regional control and disease control. The patients with four or more risk factors may benefit from PMRT, and those with two or three risk factors merit consideration of PMRT.

Objectives: To identify the factors that predict the progression of radiological radiation pneumonitis (RP) to symptomatic RP, and to evaluate the usefulness of the neutrophil-lymphocyte ratio (NLR) as a marker of RP severity and prognosis in stage III non-small cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (CCRT). Materials and Methods: We retrospectively reviewed 61 patients treated between January 2010 and December 2015. Patients' demographic characteristics, clinical data, laboratory findings, and treatment parameters were analyzed to determine the predictive factors associated with progression from radiological RP to symptomatic RP. Results: Forty-seven patients (77%) exhibited radiological RP at a median of 78 days after radiation therapy (RT) completion, and 15 (32%) of these patients developed symptomatic RP. The interval between RT completion and radiological RP presentation was shorter in patients who progressed to symptomatic RP (p=0.001); progression was highly probable if this latency period was ≤2 months (p=0.002). Stage and RT technique correlated with symptomatic RP development (p=0.046 and p=0.046, respectively). Among dosimetric factors, a V20 (defined as the lung volume receiving ≥20 Gy) of >30% was the most significant predictor of symptomatic RP (p=0.001). The NLR and C-reactive protein level at radiological RP were higher in patients who developed symptomatic RP (p=0.067 and p=0.012, respectively). On multivariate analysis, a V20 >30% and an NLR at radiological RP >6 were associated with symptomatic RP development. Conclusion: The NLR at radiological RP is a useful biomarker for predicting symptomatic RP development after CCRT in stage III NSCLC patients. This article is protected by copyright. All rights reserved.

// Ki Mun Kang 1, 2 , Hoon Sik Choi 2, 3 , Bae Kwon Jeong 1, 2 , Jin Ho Song 2, 3 , In-Bong Ha 1, 2 , Yun Hee Lee 1, 2 , Chul Hang Kim 3 and Hojin Jeong 1, 2 1 Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea 2 Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea 3 Department of Radiation Oncology, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea Correspondence to: Hojin Jeong, email: jeong3023@gmail.com Keywords: MRI-based radiotherapy, rigid image registration, brain tumor, radiotherapy planning Received: March 24, 2017 Accepted: April 24, 2017 Published: May 07, 2017 ABSTRACT An alternative pseudo CT generation method for magnetic resonance image (MRI)-based radiotherapy planning was investigated in the work. A pseudo CT was initially generated using the rigid image registration between the planning MRI and previously acquired diagnostic CT scan. The pseudo CT generated was then refined to have the same morphology with that of the referenced planning image scan by applying the outer body correction scheme. This method was applied to some sample of brain image data and the feasibility of the method was assessed by comparing dosimetry results with those from the current gold standard CT-based calculations. Validation showed that nearly the entire pixel doses calculated from pseudo CT were agreed well with those from actual planning CT within 2% in dosimetric and 1mm in geometric uncertainty ranges. The results demonstrated that the method suggested in the study was sufficiently accurate, and thus could be applicable to MRI-based brain radiotherapy planning.

// Hae Jin Park 1 , Kyung Hwan Shin 2 , Jin Ho Kim 3 , Seung Do Ahn 4 , Su Ssan Kim 4 , Yong Bae Kim 5 , Won Park 6 , Yeon-Joo Kim 7 , Hyun Soo Shin 8 , Jin Hee Kim 9 , Sun Young Lee 10 , Kyubo Kim 11 , Kyung Ran Park 12 and Bae Kwon Jeong 13 1 Departments of Radiation Oncology, Hanyang University Hospital, Seoul, Korea 2 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea 3 Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea 4 Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul, Korea 5 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea 6 Department of Radiation Oncology, Sungkyunkwan University School of Medicine, Seoul, Korea 7 Department of Radiation Oncology, Proton Therapy Center, National Cancer Center, Goyang, Korea 8 Department of Radiation Oncology, CHA University School of Medicine, Pocheon, Korea 9 Department of Radiation Oncology, Keimyung University School of Medicine, Daegu, Korea 10 Department of Radiation Oncology, Chonbuk National University Hospital, Jeonju, Korea 11 Department of Radiation Oncology, Ewha Womans University School of Medicine, Seoul, Korea 12 Department of Radiation Oncology, Ewha Womans University Mokdong Hospital, Seoul, Korea 13 Department of Radiation Oncology, Gyeongsang National University School of Medicine, Jinju, Korea Correspondence to: Kyung Hwan Shin, email: // Keywords : breast cancer, post-mastectomy radiotherapy, risk factors Received : January 02, 2017 Accepted : February 20, 2017 Published : March 15, 2017 Abstract Purpose: This study was performed to identify a subset of patients who may benefit from post-mastectomy radiotherapy (PMRT) among node-negative breast cancer patients. Materials and Methods: We retrospectively reviewed 1,828 patients with pT1-2N0 breast cancer, treated with mastectomy without PMRT from 2005 to 2010 at 10 institutions. Univariate and multivariate analyses for locoregional recurrence (LRR) and any first recurrence (AFR) were performed according to clinicopathologic factors and biologic subtypes. Results: During a median follow-up period of 5.9 years (range: 0.7-10.4 years), 98 patients developed AFR (39 isolated LRR, 13 LRR with synchronous distant metastasis, and 46 isolated distant metastasis), and 52 patients developed LRR. The 7-year LRR and AFR rates were 3.8% and 6.7%, respectively. Multivariate analysis revealed that age of ≤ 40 years ( p