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Stereotactic radiosurgery (SRS) is considered the initial treatment for lung cancer patients with small-sized and limited number of brain metastases. The objective of this study was to assess clinical outcomes of SRS treatment using CyberKnife (CK) for recursive partitioning analysis (RPA) class II/III patients with 1 to 3 brain metastases from lung cancer and identify which patients in the high RPA class could benefit from SRS. A total of 48 lung cancer patients who received CK-based SRS for their metastatic brain lesions from 2010 to 2017 were retrospectively analyzed. Radiographic response was evaluated during follow-up period. Overall survival (OS) and intracranial progression-free survival (IPFS) were calculated and prognostic variables associated with OS and IPFS were evaluated. Median follow-up time was 6.6 months. Local control rates at 6 months and 1-year following SRS were 98% and 92%, respectively. The median OS of all patients was 8 months. One-year and 2-year OS rates were 40.8% and 20.9%, respectively. In multivariate analysis, uncontrolled primary disease (P = .01) and Eastern Cooperative Oncology Group performance status of 2 or 3 (P = .001) were independent prognostic factors for inferior OS. These 2 factors were also significantly associated with inferior IPFS. In subgroup analysis according to RPA class, primary disease status was the only prognostic factor, showing statistically significant OS differences in both RPA class II and III (controlled vs uncontrolled: 41.1 vs 12.3 months in RPA class II, P = .03; 26.9 vs 4.1 months in RPA class III, P = .01). Our results indicated that SRS could be an effective treatment option for RPA class II/III patients with brain metastases from lung cancer in the modern treatment era. SRS might be particularly considered for patients with controlled primary disease.

The immunologic aspects of radiation pneumonitis (RP) are unclear. We analyzed variations in cytokine profiles between patients with grade (Gr) 0–1 and Gr ≥ 2 RP. Fifteen patients undergoing concurrent chemoradiotherapy for non-small cell lung cancer were included. Blood samples of 9 patients with Gr 0–1 and 6 with Gr ≥ 2 RP were obtained from the Biobank. Cytokine levels were evaluated using an enzyme linked immunosorbent assay at before radiotherapy (RT) initiation, 1, 3, and 6 weeks post-RT initiation, and 1 month post-RT completion. Concentrations of granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were analyzed, none were related to the occurrence of Gr ≥ 2 RP at pre-RT initiation. At 3 weeks, relative changes in the G-CSF, IL-6, and IFN-γ levels differed significantly between the groups (p = 0.026, 0.05 and 0.026, respectively). One month post-RT completion, relative changes of IL-17 showed significant differences (p = 0.045), however, relative changes in TNF-α, IL-10, IL-13, and TGF-β, did not differ significantly. Evaluation of changes in IL-6, G-CSF, and IFN-γ at 3 weeks after RT initiation can identify patients pre-disposed to severe RP. The mechanism of variation in cytokine levels in relation to RP severity warrants further investigation.

The cut-off value and prognostic significance of postoperative carcinoembryonic antigen (CEA) level in rectal cancer after preoperative chemoradiotherapy (CRT) and curative surgery are still unclear. 1559 rectal cancer patients staged with cT3-4N0-2M0 received preoperative CRT and total mesorectal excision (TME). CEA levels were measured before CRT and 3-4 weeks after surgery. Clinicopathologic factors that could be associated with tumor recurrence and patient survival were analyzed. The cumulative probability of tumor recurrence showed a steep increase with a cutoff value of 2.5 ng/mL for postoperative CEA level, and the gradient decreased as the CEA levels increased above 2.5 ng/mL. After a median follow-up time of 46.7 months, patients with postoperative CEA level 2.5 ng/mL had significantly lower relapse-free survival (RFS) (65.2 vs. 75.6 %, P 0.001) and overall survival (OS) (78.1 vs. 88.3 %, P 0.001) at 5 years than patients with postoperative CEA level ≤2.5 ng/mL. On the multivariate analysis, postoperative CEA level was a significant prognostic factor for RFS (HR 1.561; 95 % CI 1.221-1.996; P 0.001) and OS (HR 2.073; 95 % CI 1.498-2.869; P 0.001). Postoperative CEA level independently affected RFS irrespective of pre-CRT CEA level. Postoperative CEA level was a significant predictor for distant recurrence (P = 0.004), but not for locoregional recurrence (P = 0.472). Postoperative CEA level 2.5 ng/ml is a predictor of distant metastasis and a negative prognostic factor for survival in rectal cancer patients who receive preoperative CRT and curative surgery.

This study was aimed to evaluate the effectiveness of Monte Carlo (MC) method in stereotactic radiotherapy for brain tumor. The difference in doses predicted by the conventional Ray-tracing (Ray) and the advanced MC algorithms was comprehensively investigated through the simulations for phantom and patient data, actual measurement of dose distribution, and the retrospective analysis of 77 brain tumors patients. These investigations consistently showed that the MC algorithm overestimated the dose than the Ray algorithm and the MC overestimation was generally increased as decreasing the beams size and increasing the number of beams delivered. These results demonstrated that the advanced MC algorithm would be inaccurate than the conventional Raytracing algorithm when applied to a (quasi-) homogeneous brain tumors. Thus, caution may be needed to apply the MC method to brain radiosurgery or radiotherapy.

Previous studies suggest that cancer stem cells (CSCs) exist in solid tumors, and contribute to therapeutic resistance and disease recurrence. Therefore, the present study aimed to investigate whether radioresistant (RT‑R) breast cancer cells derived from breast cancer cells increase the number of CSCs, and whether these CSCs are responsible to increased invasiveness and therapeutic resistance. MCF‑7, T47D and MDA‑MB‑231 cells were irradiated 25 times (2 Gy each; 50 Gy total) to generate radioresistant breast cancer cells (RT‑R‑MCF‑7, RT‑R‑T47D and RT‑R‑MDA‑MB‑231). RT‑R‑breast cancer cells demonstrated increased cell viability against irradiation and increased colony forming abilities compared with parental breast cancer cells. Particularly, RT‑R‑MDA‑MB‑231 cells derived from highly metastatic MDA‑MB‑231 cells exhibited most radioresistance and chemoresistance of the three cell lines. In addition, MDA‑MB‑231 cells exhibited the most increased protein levels of CSCs markers cluster of differentiation 44, Notch‑4, octamer‑binding transcription factor 3/4 and aldehyde dehydrogenase 1, compared with RT‑R‑MCF‑7 cells, suggesting highly metastatic breast cancer cells MDA‑MB‑231 produce more CSCs. RT‑R‑MDA‑MB‑231 cells increased intercellular adhesion molecule‑1 and vascular cell adhesion molecule‑1 levels, resulting in enhanced migration and adhesion to endothelial cells (ECs), and enhanced invasiveness through ECs by inducing matrix metalloproteinase‑9, Snail‑1 and β‑catenin, and by downregulating E‑cadherin compared with MDA‑MB‑231 cells. These results suggest that highly metastatic breast cancer cells may increase the number of CSCs following radiation therapy, and CSCs present in RT‑R‑MDA‑MB‑231 cells contribute to the enhanced invasiveness by increasing migration, adhesion to ECs and invasion through ECs by promoting epithelial‑mesenchymal transition (EMT) via the upregulation of adhesion molecules and EMT‑associated proteins.

Stereotactic radiosurgery (SRS) is considered the initial treatment for lung cancer patients with small-sized and limited number of brain metastases. The objective of this study was to assess clinical outcomes of SRS treatment using CyberKnife (CK) for recursive partitioning analysis (RPA) class II/III patients with one to three brain metastases from lung cancer and identify which patients in the high RPA class could benefit from SRS. A total of 48 lung cancer patients who received CK-based SRS for their metastatic brain lesions from 2010 to 2017 were retrospectively analyzed. Radiographic response was evaluated during follow-up period. Overall survival (OS) and intracranial progression-free survival (IPFS) were calculated and prognostic variables associated with OS and IPFS were evaluated. Median follow-up time was 6.6 months. Local control rates at 6 months and 1-year following SRS were 98% and 92%, respectively. The median OS of all patients was 8 months. One-year and 2-year OS rates were 40.8% and 20.9%, respectively. In multivariate analysis, uncontrolled primary disease (p = 0.008) and ECOG performance status of 2 or 3 (p = 0.001) were independent prognostic factors for inferior OS. These two factors were also significantly associated with inferior IPFS. In subgroup analysis according to RPA class, primary disease status was the only prognostic factor, showing statistically significant OS differences in both RPA class II and III (controlled vs. uncontrolled: 41.1 vs. 12.3 months in RPA class II, p = 0.031; 26.9 vs. 4.1 months in RPA class III, p = 0.011). Our results indicated that SRS could be an effective treatment option for RPA class II/III patients with brain metastases from lung cancer in the modern treatment era. SRS might be particularly considered for patients with controlled primary disease.

Background Pulmonary emphysema is a major component of chronic obstructive pulmonary disease and lung cancer. However the prognostic significance of quantitative emphysema severity in patients with lung cancer is unclear. We analyzed whether numerical emphysema value is a prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer. Methods We quantified emphysema severity of the whole lung and regional lobes in 45 patients (mean age 68.0 years) using an automated chest computed tomography-based program. Predictive factors for recurrence were investigated using a Cox proportional hazards model. Recurrence-free and overall survival was compared after dichotomization of patients according to whole lung emphysema severity. Results The mean percentage emphysema ratio of the whole lung was 1.21 ± 2.04. Regional lobar emphysema severity was highest in the right middle lobe (1.93 ± 0.36), followed by right upper (1.35 ± 2.50), left upper (1.34 ± 2.12), left lower (1.05 ± 2.52), and right lower (0.78 ± 2.28) lobes. The low severity group showed significantly longer overall survival compared to the high severity group (log-rank test, P = 0.018). Quantitative emphysema severity of the whole lung (hazard ratio 1.36; 95% confidence interval 1.0-1.73) and stage III (hazard ratio 6.17; 95% confidence interval 1.52-25.0) were independent predictors of recurrence after adjusting for age, gender, smoking status, and forced expiratory volume in one second. Conclusion The severity of whole lung emphysema was independently associated with recurrence. Patients with non-small cell lung cancer and marginal pulmonary emphysema at lower severity survive longer after curative-intent surgery.

Background The role of adjuvant radiotherapy (RT) and setting proper RT target volumes have not been clearly demonstrated for extrahepatic bile duct (EHBD) cancer, due to the rarity of the disease and the lack of randomized trials. This study was conducted to evaluate the indication and treatment volume for adjuvant RT in EHBD cancer patients by identifying the prognostic factors for loco-regional (LR) failure, and analyze the patterns of LR failure. Methods Ninety-three patients with EHBD cancer, who underwent resection without adjuvant RT, at 2 medical centers, between 2001 and 2016, were analyzed retrospectively. Univariable and multivariable analyses were performed to find the prognostic factors for LR recurrence. The initial patterns of failure were recorded, especially those of LR recurrence, and categorized according to the Japanese classification. Results The median follow-up duration was 30 months, and 38 (40.9%) patients experienced LR recurrence during this period. With regards to LR recurrence, close or positive resection margin (RM) status (p

Background Although intracavitary radiotherapy (ICR) is essential for the radiation therapy of cervical cancer, few institutions in Korea perform 3-dimensional (3D)-based ICR. To identify patients who would benefit from 3D-based ICR, dosimetric parameters for tumor targets and organs at risk (OARs) were compared between 2-dimensional (2D)- and 3D-based ICR. Methods Twenty patients with locally advanced cervical cancer who underwent external beam radiation therapy (EBRT) following 3D-based ICR were retrospectively evaluated. New 2D-based plans based on the Manchester system were developed. Tumor size was measured by magnetic resonance imaging. Results The mean high risk clinical target volume (HR-CTV) D90 value was about 10% lower for 2D- than for 3D-based plans (88.4% vs. 97.7%; P = 0.068). Tumor coverage did not differ between 2D- and 3D-based plans in patients with tumors ≤ 4 cm at the time of brachytherapy, but the mean HR-CTV D90 values in patients with tumors > 4 cm were significantly higher for 3D-based plans than for 2D-based plans (96.0% vs. 78.1%; P = 0.017). Similar results were found for patients with tumors > 5 cm initially. Other dosimetric parameters for OARs were similar between 2D- and 3D-based plans, except that mean sigmoid D2cc was higher for 2D- than for 3D-based plans (67.5% vs. 58.8%; P = 0.043). Conclusion These findings indicate that 3D-based ICR plans improve tumor coverage while satisfying the dose constraints for OARs. 3D-based ICR should be considered in patients with tumors > 4 cm size at the time of brachytherapy or > 5 cm initially., Graphical Abstract

In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). The data from the patients participating in two South Korean multi-institutional studies (KROG 14–22; N = 1842 and KROG 14–23; N = 1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. The median follow-up time was 72.2 months (range 0.8–125.2 months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.

Background To analyze clinical outcome of CyberKnife (CK) tumor-tracking stereotactic body radiotherapy (SBRT) for prostate cancer (Pca) according to the magnitude of intra-fractional prostate motion. Methods Medical records and daily treatment logs for 71 patients who received CK tumor-tracking SBRT were retrospectively analyzed. Statistical relationships between prostate motion and various outcome results, including local recurrence (LR), biochemical failure (BF), and treatment-related toxicity, were investigated in order to evaluate motion-dependent efficacy of tumor-tracking SBRT for Pca. Results In a total 71 patients, 3 (4.2%) patients with LR, 12 (16.9%) patients with BF, and 22 (31%) patients with grade-II or worse toxicities to rectal or bladder (22 to rectal, 22 to bladder and 8 patients to both) were observed in a median follow-up of 47 months. Magnitudes of intra-fractional tumor motion along superior-inferior, right-left, and anterior-posterior (AP) axes were 0.15 ± 0.31, 0.12 ± 0.19, and 0.73 ± 0.32 mm, respectively. Radial magnitude was estimated to be 1.0 ± 0.35 mm. Intra-fractional movement was not significantly correlated with tumor control. However, it was significant correlated with the incidence of grade-II or worse toxicity to rectum or bladder particularly when tumor motion was in the AP axis. Conclusion Our quantitative results revealed that toxicity related to SBRT treatment was highly sensitive to intra-fractional prostate movements, although local-tumor control was not affected by such movements. Our results demonstrate that precise motion correction is essential in prostate SBRT, even if it seems to be small., Graphical Abstract

Background The eighth tumor, node, metastasis (TNM) staging system (8-TNM) for non-small cell lung cancer (NSCLC) was newly released in 2015. This system had limitation because most patients included in the analysis were treated with surgery. Therefore, it might be difficult to reflect prognosis of patients treated with curative concurrent chemoradiotherapy (CCRT). Purpose of this study was to investigate clinical impact of the newly published 8-TNM compared to the current seventh TNM staging system (7-TNM) for locally advanced NSCLC patients treated with CCRT. Methods New 8-TNM was applied to 64 patients with locally advanced NSCLC who were treated with CCRT from 2010 to 2015. Changes in T category and stage group by 8-TNM were recorded and patterns of change were evaluated. Survival was analyzed according to T category, N category, and stage group in each staging system, respectively. Results Among the total of 64 patients, 38 (59.4%) patients showed change in T category while 22 (34.4%) patients showed change in stage group using 8-TNM compared to 7-TNM. Survival curves were significantly separated in the 8-TNM stage group (p = 0.001) than those in the 7-TNM (p > 0.05). Especially, survival of newly introduced stage IIIC by 8-TNM was significantly lower than that of others. On the other hand, there was no significant survival difference between T categories in each staging system. Conclusions Subdivision of stage III into IIIA, IIIB, and IIIC by 8-TNM for patients treated with CCRT better reflected prognosis than 7-TNM. However, subdivision of T category according to tumor size in 8-TNM might be less significant.

Purpose We aimed to assess prognostic value of metastatic pelvic lymph node (mPLN) in early-stage cervical cancer treated with radical surgery followed by postoperative chemoradiotherapy. Also, we sought to define a high-risk group using prognosticators for recurrence. Materials and methods A multicenter retrospective study was conducted using the data from 13 Korean institutions from 2000 to 2010. A total of 249 IB-IIA patients with high-risk factors were included. We evaluated distant metastasis-free survival (DMFS) and disease-free survival (DFS) in relation to clinicopathologic factors including pNstage, number of mPLN, lymph node (LN)ratio (number of positive LN/number of harvested LN), and log odds of mPLNs (log(number of positive LN+0.5/number of negative LN+0.5)). Results In univariate analysis, histology (squamous cell carcinoma [SqCC] vs. others), lymphovascular invasion (LVI), number of mPLNs (≤ 3 vs. g 3), LN ratio (≤ 17% vs. g 17%), and log odds of mPLNs (≤ ‒0.58 vs. g ‒0.58) were significant prognosticators for DMFS and DFS. Resection margin involvement only affected DFS. No significant survival difference was observed between pN0 patients and patients with 1-3 mPLNs. Multivariate analysis revealed that mPLN g 3, LVI, and non-SqCC were unfavorable index for both DMFS (p l 0.001, p=0.020, and p=0.031, respectively) and DFS (p l 0.001, p=0.017, and p=0.001, respectively). A scoring system using these three factors predicts risk of recurrence with relatively high concordance index (DMFS, 0.69; DFS, 0.71). Conclusion mPLN g 3 in early-stage cervical cancer affects DMFS and DFS. A scoring system using mPLNs g 3, LVI, and non-SqCC could stratify risk groups of recurrence in surgically resected early-stage cervix cancer with high-risk factors.

We evaluated the dietary habits of breast cancer survivors and investigated the relationship with quality of life (QoL), with 1,156 survivors recruited from 17 institutions. We used the Questionnaire Survey of Dietary Habits of Korean Adults (Q-DH-KOR) comprising 25 questions. The following indices were derived as follows: (1) quality of healthy dietary habits (Q-HD)-eight questions on number of meals, regularity, quantity, duration, skipping breakfast, dinner with companion(s), overeating and late-night snacks; (2) habits of nutritional balance (H-NB)-questions on consuming five food categories (grains, fruits, proteins, vegetables and dairy products); and (3) habits of unhealthy foods (H-UF)-questions on consuming three food categories (fatty, instant and fast foods). The times and regularity of meals, frequency of skipping breakfast, dinner with companion(s) and overeating were better in groups with high symptomatic and functional QoL. Symptomatic QoL positively affected Q-HD and H-NB (p < 0.001 and p = 0.024 respectively) and negatively affected H-UF (p = 0.02). Breast cancer survivors more frequently ate from the fruit, protein and vegetable categories than did the control group, with lower H-UF and higher Q-HD values (p < 0.001 and p < 0.001 respectively). Our findings supported the relationship between QoL and dietary habit and showed healthier dietary habits of breast cancer survivors than controls.

The definition and criteria of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients vary among studies. Therefore, the reported rates of RIHT differ among studies, and this causes confusion. In this study, we evaluated RIHT using several laboratory and clinical parameters, and analyzed which criterion is more correlated with RT and survival. Forty-five HCC patients treated with stereotactic body radiotherapy were included for the analysis. All patients had unresectable HCC and Child-Pugh (CP) class A or B baseline liver function. A median total dose of 45 Gy was delivered by CyberKnife in 3 fractions. For individual laboratory parameter, ≥ grade 2 toxicity development of bilirubin, albumin, or prothrombin time by Common Terminology Criteria of Adverse Effects (CTCAE) was correlated with mean liver dose and survival. However, serum transaminases had no correlation with liver mean dose and survival, and were rather affected by other local treatments. Compared to the CTCAE, the increase in the CP score of 2 points or more was better correlated with liver failure and overall survival, and it was not affected by other local treatments or tumor progression. We concluded RIHT was better defined by the change in the CP score rather than the CTCAE in patients treated by stereotactic body radiotherapy for HCC.

Definitive chemoradiotherapy (CRT) followed by brachytherapy is a standard treatment for locally advanced cervical cancer. During CRT, marked reduction of cervical tumor is often observed in magnetic resonance imaging (MRI). The primary aim of this study was to assess the association between tumor response in MRI using FIGO classification and clinical outcomes.Multi-institutional data were retrospectively reviewed to identify the significance of MR tumor response on tumor recurrence and patient survival. 225 patients with histologically confirmed squamous cell carcinoma of the cervix, staged as FIGO Ib2-IVa on initial pelvic MRI, were included. Post-CRT MRI was performed median 35days after the beginning of CRT and before brachytherapy. A median 54Gy of external radiation was given with weekly cisplatin during CRT.112 (49.7%) of the 225 patients showed a positive response in post-CRT MRI and were named the responsive arm. After a median follow-up time of 36.2months, the responsive arm had significantly lower para-aortic recurrence (7.5% vs. 12.4%; p=0.04) and distant metastasis (13.2% vs. 27.6%; p=0.03) rates than did the non-responsive arm. The responsive arm had significantly higher 3-year cause-specific survival rate (94.6% vs. 81.1%, p0.01) than did the non-responsive arm. In the multivariate analysis, tumor size (hazard ratio, 1.91 and 95% confidence interval, 1.07-3.43; p=0.028) and positive MR response (hazard ratio, 1.75 and 95% confidence interval, 1.06-2.27; p=0.045) were significant factors for recurrence-free survival CONCLUSION: Early tumor response evaluation with MRI using FIGO classification effectively predicted distant tumor metastasis and disease-specific survival in locally advanced cervical cancer.

// Jin Hyun Kim 1, 2 , Myeong Hee Jung 1 , Jin Pyeong Kim 2, 3 , Hyun-Jung Kim 2, 4 , Jung Hwa Jung 2, 4 , Jong Ryeal Hahm 2, 4 , Ki Mun Kang 2, 5 , Bae-Kwon Jeong 2, 5 and Seung Hoon Woo 2, 3, 6 1 Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Gyeongnam, Republic of Korea 2 Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea 3 Department of Otolaryngology, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea 4 Department of Internal Medicine, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea 5 Department of Radiation Oncology, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea 6 Beckman Laser Institute, University of California, Irvine, California, USA Correspondence to: Seung Hoon Woo, email: lesaby@hanmail.net Keywords: alpha lipoic acid, oral mucosa, radiation, Hif-1a, complications Received: May 05, 2017 Accepted: July 25, 2017 Published: August 16, 2017 ABSTRACT Purpose: Radiotherapy is currently one of the main treatment modalities for head and neck cancer; however, it also results in severe toxicity to the normal tissue, to the detriment of patients. This study aimed to investigate whether alpha lipoic acid (ALA) could protect against radiation-induced oral mucositis in a rat model. Results: On post-irradiation days 4 and 7, the epithelial layer on oral mucosa showed pronounced injury (shortening of the layer) and it is diminished by ALA pretreatment before radiation. Hif-1a expression was significantly induced in the radiation group on days 4, 7, and 28. GLUT1 expression was also induced by radiation at all time points, and the expression levels peaked on day 28. Phosphorylated p53 level was significantly higher in the radiation group on days 4 and 7, and Bax protein expression was significantly higher in the same group on day 4 than ALA-pretreated radiation group. TUNEL-positive staining was significantly lower in the ALA-pretreated radiation group. Materials and methods: Rats were assigned to one of the following four groups: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation, with the neck area including the oral mucosa evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were sacrificed 4, 7, 28, or 56 days after radiation. Conclusions: The results show that ALA can be used to ameliorate radiation-induced oral mucositis with head and neck cancer.

Aim This study aimed to determine predictive values for volumetric measures in patients with oropharyngeal cancer who received definitive chemoradiotherapy (CCRT). Methods Contrast-enhanced computed tomography (CT) scans were obtained before radiotherapy (RT) (I), after delivering a median RT of 50.6 Gy (R) and three months after RT (F). Primary site gross tumor volumes (GTV) were assessed using these scans (GTVI, GTVR and GTVF). The percentage volume change between GTVI and GTVR (GTV change) was calculated. Volumetric analyses of primary site local control (LC) and progression-free survival (PFS) were performed. Results In total, 35 patients were evaluated, with a median 31 months of follow-up. The 2-year LC rates (LCRs) were 95.0% for patients with GTVI

Backgrounds Quality of life (QoL) has become a major concern as the survival time of breast cancer increases. We investigated the changes in QoL through comprehensive categorical analysis, for the first three years after breast cancer treatment including radiotherapy. Methods A total of 1156 patients were enrolled from 17 institutions. All survivors were grouped according to a surveillance period of 9–15 months (first year), 21–27 months (second year), and 33–39 months (third year) from the end of radiotherapy. The 5-dimensional questionnaire by the EuroQol group (EQ-5D) and the EORTC Quality of Life Questionnaire; breast cancer specific module (QLQ-BR23) were checked by self-administrated method. Results First, second and third year groups comprised 51.0, 28.9, and 21.0%. In EQ-5D-3 L (3-Likert scale) analysis, pain/discomfort and anxiety/depression categories showed lower QoL. In multivariate analyses of EQ-5D-VAS (visual-analogue scale), categories of pain/discomfort and self-care were improved with time; axillary dissection was a significant clinical factor deteriorates pain/discomfort, self-care and usual activities. In QLQ-BR23 analysis, the lowest scored category was sexual activity, followed by sexual enjoyment, future perspective, and hair loss, and the best scored category was breast symptoms. In multivariate analyses, arm symptoms, breast symptoms and body image were improved with time. Conclusions Categories of pain/discomfort and self-care in EQ-5D-VAS, arm/breast symptoms and body image in QLQ-BR23 were improved, while categories of anxiety/depression and future perspective BR23 were not, suggesting necessity of psychosocial support. This research provides comprehensive information on the categorical aspects of QoL and changes during early follow-up after breast cancer treatment.

We evaluated the changes in the dose distribution of radiation during volumetric arc radiotherapy (VMAT), to determine the right time for adaptive replanning in prostate cancer patients with progressive weight (WT) changes. Five prostate cancer patients treated with VMAT were selected for dosimetric analysis. On the original computed tomography images, nine artificial body contours were created to reflect progressive WT changes. Combined with three different photon energies (6, 10, and 15-MV), 27 comparable virtual VMAT plans were created per patient. The dosimetric analysis included evaluation of target coverage (D95%,Dmax), conformity index, homogeneity index, and organs at risk doses. The dose differences among the plans were determined using the gamma index analysis and were compared with the dosimetric analysis. Mean D95% became lower than 98% when body contour expanded by 2.0 cm or more and Dmax became higher than 107% when body contour contracted by 1.5 cm or more in 10-MV plans. This cut-off values correlated well with gamma index analysis results. Adaptive replanning should, therefore, be considered if the depth of body contour becomes 1.5 cm smaller (WT loss) or 2.0 cm larger (WT gain) in patients treated by VMAT with 10-MV photons.

Purpose Concurrent chemoradiation (CRT) with 3-weekly doses of cisplatin is a standard treatment for loco-regionally advanced head and neck squamous cell carcinoma (HNSCC). However, treatment with 3-weekly doses of cisplatin is often associated with several adverse events. Therefore, we conducted this retrospective analysis to determine the efficacy and tolerance of CRT with a low weekly dose of cisplatin in stage IV HNSCC patients. Materials and methods Medical records of patients who were diagnosed with stage IV HNSCC and received concurrent CRT were analyzed. All patients were treated weekly with cisplatin at 20-30 mg/m(2) until radiotherapy was completed. Results A total of 35 patients were reviewed. Median follow up was 10.7 months (range, 1.7 to 90.5 months), the median radiation dose was 7,040 cGy, and the median dose of cisplatin received was 157 mg/m(2). Eleven patients received docetaxel combination chemotherapy. Overall, 25 patients (71.4%) achieved complete response (CR), eight (22.9%) showed partial response. The median overall survival was 42.7 months, the 3-year survival rate was 51.2% and the 3 year disease-free survival rate was 72.8%. Overall survival was improved in patients who achieved CR relative to others (59.7 months vs. 13.4 months; p=0.008). There were significant differences in survival between patients who received docetaxel combination and cisplatin alone (51.8 months vs. 7.9 months; p=0.009). Grade 3-4 adverse events included stomatitis (82.9%), dermatitis (22.9%), infection (11.4%), dysphagia (8.6%), and neutropenia (5.7%). Conclusion CRT with low dose weekly cisplatin is likely effective and tolerable, even in patients with locally advanced-stage IV HNSCC.

Background. The purpose of this study was to examine the predictive value of hypoxia-inducible factor (HIF)21a, carbonic anhy- drase (CA)-IX, glucose transporter (GLUT)21, cyclooxygenase (COX)22, Ki-67, and erythropoietin receptor (EPOR) as immunohistochemical markers for determining the optimal treatment modality for early stage laryngeal carcinoma. Methods. Tissue samples from 42 early stage laryngeal carcinomas treated with radiotherapy alone were analyzed immunohistochemically for the expression of 6 markers. The Kaplan-Meier method, univariate and multivariate analyses, and the Cox proportional hazards model were used to analyze the associations between patient and tumor characteris- tics and immunohistochemical results, and locoregional control. Results. Increased expression of HIF-1a and CA-IX was significantly cor- related with residual tumor; no correlations were observed for the other immunohistochemical markers. Conclusion. High levels of HIF-1a or CA-IX expression were significantly correlated with residual tumor after radiotherapy for early stage laryngeal carcinomas. Alternative treatment modalities to primary radiotherapy should be considered for early stage laryngeal carcinomas showing high HIF-1a or CA-IX expression. V C 2014 Wiley Periodicals, Inc. Head Neck 00: 000-000, 2014 50%. 2 Patients with HNSCC with similar histological grade and clinical stage often have different prognosis; these differences may be associated with the expression of spe- cific immunohistochemical markers. Therefore, the identi- fication of immunohistochemical markers associated with the clinicopathological features of HNSCC is very impor- tant. Endogenous hypoxia-related markers are associated with the prognoses of patients with different types of car- cinoma. Clinically relevant hypoxia is detected in approx- imately 50% of all solid tumors. 3 Hypoxia is the result of an imbalance between oxygen delivery and oxygen con- sumption, and is one of the most important events during

Purpose In some unusual cases, in patients with cervical cancer, an elevation of squamous cell carcinoma antigen (SCC-Ag) was not observed at diagnosis but was observed on recurrence, or vice versa. The objective of this study was to identify patient-, disease-, and treatment-related factors associated with this unusual level of SCC-Ag, and to determine whether SCC-Ag is a useful tumor marker in such patients. Materials and Methods Among 129 patients with recurrence, 14 who showed a normal SCC-Ag level at diagnosis but an elevated level at recurrence were classified as group I; 22 patients with an elevated SCC-Ag level at diagnosis but not at recurrence were classified as group II; and 76 patients with an elevated SCC-Ag level at both diagnosis and recurrence were classified as group III. Results In univariate analysis, unusual SCC-Ag showed statistically significant relationships with pathology and biochemical response to treatment. However, in the multivariate analysis, none of the clinicopathologic factors showed a statistical relationship with unusual levels of SCC-Ag. The 5-year disease-free survival rates for groups I, II, and III were 7.1%, 9.1%, and 0% (p=0.418), and the 5-year overall survival rates were 34.3%, 58.4%, and 33.3% (p=0.142), respectively. Conclusion The value of SCC-Ag has been confirmed in all patients; thus, check of SCC-Ag level at follow-up should be considered. Although no statistically significant differences were observed among the groups, we conclude that patients with a high initial SCC-Ag and elevated SCC-Ag at relapse have poor prognosis due to high SCC-Ag level.

Rectal cancer patients with a pathological complete response (pCR) after neoadjuvant concurrent chemoradiotherapy (CCRT) have a better prognosis compared to those without a pCR. Therefore, the "Wait and See" (WS) approach in those who achieved clinically complete response (cCR) after CCRT was introduced as an alternative modality to the total mesorectal excision (TME). The aim of this study was to compare the oncological outcomes between WS and TME via meta-analysis.We performed a comprehensive literature search on January 14, 2016, using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. In addition, the references of all articles obtained were searched manually. The qualities of each study were assessed using the Newcastle-Ottawa quality assessment scale. The main outcomes were recurrence, disease-free survival (DFS), and overall survival (OS). We calculated the risk ratio (RR) and hazard ratio (HR) for the recurrence and survival rates, respectively.The RR of patients whose initial recurrences was local recurrence (LR), distant metastasis (DM), LR + DM, or overall recurrences were 0.18, 1.00, 0.61, and 0.49, respectively. There was no heterogeneity in the results. The HR of DFS was 0.59 and indicated that DFS in the TME group was superior compared with that in the WS group. The OS has no significant difference between the studies.Although the WS approach seemed feasible for rectal cancer patients with a cCR after neoadjuvant CCRT, concrete evidence obtained in well-controlled randomized trials with a long-term follow-up is required to validate potential treatment options.

OBJECTIVE A recent revision of the FIGO staging system does not recommend the mandatory use of cystoscopy and sigmoidoscopy. The objective of this study was to assess the clinical utility of CT or MRI scans for ruling out bladder or rectal invasion and determine the indication for endoscopy in patients with cervical cancer. METHODS We retrospectively reviewed 769 patients with cervical cancer, who underwent imaging and endoscopic work-up between January 1997 and December 2010. Using endoscopy as the standard reference for comparison, we calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the imaging modality for bladder or rectal invasion. RESULTS The CT scan showed 68.2% and 85.7% for sensitivity and 96.4% and 98.9% for specificity in detecting bladder and rectal invasion, respectively. CT scan provided a low PPV (51.7%, 54.5%) and a high NPV (98.2%, 99.8%). MRI scan showed 88.0% and 75.0% for sensitivity and 93.1% and 98.9% for specificity in detecting bladder and rectal invasion, respectively. MRI scan provided a low PPV (35.6%, 42.9%) and a high NPV (99.4%, 99.7%). The accuracies of CT and MRI scans in identifying bladder invasion were 94.9% and 92.8%, respectively. The accuracies of CT and MRI in identifying rectal invasion were 98.7% and 98.6%, respectively. CONCLUSION The results of this study demonstrate that additional invasive endoscopy is not necessary for patients who present with no invasion on imaging work-up, and therefore, endoscopy should be considered a tool for confirming cases that are positive for invasion based on imaging work-up.

442 Background: Portal vein tumor thrombosis (PVTT) is commonly accompanied by hepatocellular carcinoma (HCC) patients, and in these cases the treatment options became limited and treatment outcome was poor. Stereotactic body radiotherapy (SBRT) is one of the possible treatment options, which can deliver higher doses with highly conformal target have conducted for treatment of PVTT. However, only few studies about the SBRT have reported, even treatment schedules were not consistent. In this study, we report our institutional experience of treating PVTT in HCC patients using SBRT. Methods: 24 HCC patients with PVTT were treated with SBRT at our institution. All patients had unresectable HCC with PVTT, baseline liver function of Child-Pugh class A or B. SBRT was performed by Cyberknife based on 4D-simulation and 4D-planning. The prescription dose was 45 Gy in 3 fractions in 17 (70.8%) patients, and was modified to 39 to 42 Gy in 3 to 4 fractions in 7 (29.2%) patients whose target was large or adjacent to the bowel. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients within 3 months. Results: There were 2 (8.3%) patients of PVTT showed complete response, and 11 (45.8%) patients showed partial response. Stable disease was found in 7 (29.2%) patients, and progression in 4 (16.7%) patients. The response rate was lower in patients with tumor thrombus at main portal vein than those at branch of portal vein (main, 30% vs. branch, 71.4%, p = 0.052). The 1- and 2-year overall survival (OS) was 67.5%, 48.2%, respectively, with median survival of 20.8 months. The combination SBRT followed by TACE, and presence of grade 3 hepatic toxicities impacted on survival. The 1-year OS was 71.4% in patients whom TACE was combined after SBRT, which was higher than that of 14.6% who were treated with SBRT alone (p < 0.001). The 1-year OS was 81.1% in patients who did not occur grade 3 hepatic toxicity, while 0% in patients who had grade 3 hepatic toxicity (p = 0.002). Conclusions: SBRT is a relatively effective treatment option for HCC patients of PVTT. Especially combined with TACE. Finding an optimal dose schedule which can reduce hepatic toxicity, while keeping the response seems important to increase the survival.

// Jin Hyun Kim 1, 2 , Kyung Mi Kim 3 , Myeong Hee Jung 1 , Jung Hwa Jung 2, 4 , Ki Mun Kang 2, 5 , Bae Kwon Jeong 2, 5 , Jin Pyeong Kim 2, 3 , Jung Je Park 2, 3 , Seung Hoon Woo 2, 3 1 Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Gyeongnam, Republic of Korea 2 Institute of Health Science, Jinju, Gyeongnam, Republic of Korea 3 Department of Otolaryngology, Jinju, Gyeongnam, Republic of Korea 4 Department of Internal Medicine, Jinju, Gyeongnam, Republic of Korea 5 Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Gyeongnam, Republic of Korea Correspondence to: Seung Hoon Woo, email: lesaby@hanmail.net Keywords: alpha lipoic acid, salivary gland, radiation, Nox-2, complication Received: December 27, 2015 Accepted: March 16, 2016 Published: April 09, 2016 ABSTRACT Purpose: Radiation therapy is a treatment for patients with head and neck (HN) cancer. However, radiation exposure to the HN often induces salivary gland (SG) dysfunction. We investigated the effect of α-lipoic acid (ALA) on radiation-induced SG injury in rats. Results: ALA preserved acinoductal integrity and acinar cell secretary function following irradiation. These results are related to the mechanisms by which ALA inhibits oxidative stress by inhibiting gp91 mRNA and 8-OHdG expression and apoptosis of acinar cells and ductal cells by inactivating MAPKs in the early period and expression of inflammation-related factors including NF-κB, IκB-α, and TGF-β1 and fibrosis in late irradiated SG. ALA effects began in the acute phase and persisted for at least 56 days after irradiation. Materials and Methods: Rats were assigned to followings: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation. The neck area including the SG was evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were killed at 4, 7, 28, and 56 days after radiation. Conclusions: Our results show that ALA could be used to ameliorate radiation-induced SG injury in patients with HN cancer.

We compared the patterns of failure between 3-dimensional radiotherapy (3D-RT) and intensity-modulated radiotherapy (IMRT) for head and neck squamous cell carcinoma (HNSCC).We reviewed the medical records of 49 patients with stage III-IV HNSCC treated with concurrent chemoradiotherapy. The treatment outcome, patterns of failure, and toxicities were compared between 3D-RT and IMRT.There were 13 locoregional recurrences as initial failure sites. Eight recurrences were local, three were regional, and two were both local and regional. The recurrence pattern did not differ between the 3D-RT- and IMRT-treated groups, while toxicities were reduced in the IMRT-treated group. All recurrences were within the high-risk planning target volume except for one case in IMRT.IMRT did not increase the risk of locoregional recurrence neither did it change the pattern of failure in patients with stage III-IV locally advanced HNSCC, although it did reduce toxicities.

// Bae Kwon Jeong 1, 4 , Jin Ho Song 1, 4 , Hojin Jeong 1, 4 , Hoon Sik Choi 1 , Jung Hwa Jung 2, 4 , Jong Ryeal Hahm 2, 4 , Seung Hoon Woo 3, 4 , Myeong Hee Jung 5 , Bong-Hoi Choi 6 , Jin Hyun Kim 4, 5 , Ki Mun Kang 1, 4 1 Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea 2 Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea 3 Department of Otolaryngology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea 4 Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea 5 Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Republic of Korea 6 Department of Nuclear Medicine and Molecular Imaging, Gyeongsang National University, Jinju, Republic of Korea Correspondence to: Ki Mun Kang, e-mail: jsk92@gnu.ac.kr Jin Hyun Kim, e-mail: ajini7044@hanmail.net Keywords: radiation therapy, alpha-lipoic acid, small intestine, oxidative stress, inflammation Received: October 05, 2015 Accepted: January 23, 2016 Published: March 03, 2016 ABSTRACT Purpose: Radiation therapy is a highly effective treatment for patients with solid tumors. However, it can cause damage and inflammation in normal tissues. Here, we investigated the effects of alpha-lipoic acid (ALA) as radioprotection agent for the small intestine in a mouse model. Materials and Methods: Whole abdomen was evenly irradiated with total a dose of 15 Gy. Mice were treated with either ALA (100 mg/kg, intraperitoneal injection [i.p.]) or saline (equal volume, i.p.) the prior to radiation as 100 mg/kg/day for 3 days. Body weight, food intake, histopathology, and biochemical parameters were evaluated. Results: Significant differences in body weight and food intake were observed between the radiation (RT) and ALA + RT groups. Moreover, the number of crypt cells was higher in the ALA + RT group. Inflammation was decreased and recovery time was shortened in the ALA + RT group compared with the RT group. The levels of inflammation-related factors (i.e., phosphorylated nuclear factor kappa B and matrix metalloproteinase-9) and mitogen-activated protein kinases were significantly decreased in the ALA + RT group compared with those in the RT group. Conclusions: ALA treatment prior to radiation decreases the severity and duration of radiation-induced enteritis by reducing inflammation, oxidative stress, and cell death.

// Jin Ho Song 1, 4 , Ki Mun Kang 1, 4 , Hoon-Sik Choi 1 , Hojin Jeong 1, 4 , In Bong Ha 1, 4 , Jong Deog Lee 2 , Ho Cheol Kim 2 , Yi Yeong Jeong 2 , Yu Ji Cho 2 , Seung Jun Lee 2 , Sung Hwan Kim 3 , In-Seok Jang 3 , Bae Kwon Jeong 1, 4 1 Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea 2 Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea 3 Department of Thoracic and Cardiovascular Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea 4 Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea Correspondence to: Bae Kwon Jeong, e-mail: blue129j@gnu.ac.kr Keywords: stereotactic body radiotherapy, lung cancer, calculation algorithm, CyberKnife, Monte Carlo Received: August 10, 2015 Accepted: October 01, 2015 Published: October 26, 2015 ABSTRACT Purpose: The purpose of this study was to compare the clinical outcomes between the groups using Ray-Tracing (RAT) and Monte-Carlo (MC) calculation algorithms for stereotactic body radiotherapy (SBRT) of lung tumors. Materials and Methods: Thirty-five patients received SBRT with CyberKnife for 47 primary or metastatic lung tumors. RAT was used for 22 targets in 12 patients, and MC for 25 targets in 23 patients. Total dose of 48 to 60 Gy was prescribed in 3 to 5 fractions on median 80% isodose line. The response rate, local control rate, and toxicities were compared between RAT and MC groups. Results: The response rate was lower in the RAT group (77.3%) compared to the MC group (100%) ( p = 0.008). The response rates showed an association with the mean dose to the gross tumor volume, which the doses were re-calculated with MC algorithm in both groups. However, the local control rate and toxicities did not differ between the groups. Conclusions: The clinical outcome and toxicity of lung SBRT between the RAT and MC groups were similar except for the response rate when the same apparent doses were prescribed. The lower response rate in the RAT group, however, did not compromise the local control rates. As such, reducing the prescription dose for MC algorithm may be performed but done with caution.

The Korean Radiation Oncology Group evaluated the significance of carcinoembryonic antigen (CEA) levels both as a predictor of tumor response after CRT and as a prognosticator for recurrence-free survival.1804 rectal cancer patients, staged cT3-4N0-2M0, participated in a multicenter study. The patients were administered preoperative radiation of 50.4 Gy in 28 fractions with 5-FU or capecitabine, followed by total mesorectal excision. Patients with elevated CEA levels (5 ng/mL) were matched at a 1 (n=595):1 (n=595) ratio with patients with normal CEA (⩽5 ng/mL). The tumor response after CRT and the recurrence-free survival (RFS) rates were evaluated and compared between two arms.An elevated CEA level (p0.001) was determined to be a significant negative predictor of downstaging after CRT. The downstaging rate was 42.9% for normal CEA and 23.4% for elevated CEA. A multivariate analysis also revealed that cT (p=0.021) and cN classification (p=0.001), tumor size (p=0.002), and tumor location from the anal verge (p=0.006) were significant predictors for tumor downstaging. The 5-year RFS rates were significantly higher for the normal CEA arm than for the elevated CEA arm (74.2 vs. 63.5%, p0.001).Elevated CEA (5 ng/mL) is a negative predictor of tumor downstaging after CRT and also has a negative impact on RFS in rectal cancer.

We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ∼21%, whereas the overestimation were markedly lower in GTV by ∼12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer. PACS numbers: 87.55.D, 87.55.kh, 87.53.Ly, 87.55.‐x

The aim of the present study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for low- to intermediate-risk prostate adenocarcinoma. Thirty-nine patients were retrospectively reviewed. The SBRT was delivered using the CyberKnife with the fiducial tracking method combined with In-tempo imaging. The gross target volume, which included the prostate only, was delineated on the fused CT/MRI scans. The prescription dose was delivered every other day as 5 fractions of 7.5 Gy. Venous blood was obtained before and after SBRT to assess the prostate-specific antigen (PSA) level. Toxicity was evaluated using the CTCAE, v4.03. The median follow-up time was 30.0 months. The median initial PSA level was 7.7 ng/mL. PSA levels decreased in all patients treated with SBRT, and after 5 months, the median PSA was less than 2 ng/mL. The rate of overall 3-yr actuarial biochemical failure free survival was 93.9%. Acute side effects were generally comparable with those of previous studies. The PSA change and toxicity after SBRT for low- to intermediate-risk prostate adenocarcinoma indicates favorable biochemical responses and tolerable levels of toxicity. Additionally short course treatment may produce cost benefit and convenience to patients.

Exposure of the thyroid to radiation during radiotherapy of the head and neck is often unavoidable. The present study aimed to investigate the protective effect of alpha-lipoic acid (ALA) on radiation-induced thyroid injury in rats. Rats were randomly assigned to four groups: healthy controls (CTL), irradiated (RT), received ALA before irradiation (ALA + RT), and received ALA only (ALA, 100 mg/kg, i.p.). ALA was treated at 24 h and 30 minutes prior to irradiation. The neck area including the thyroid gland was evenly irradiated with 2 Gy per minute (total dose of 18 Gy) using a photon 6-MV linear accelerator. Greater numbers of abnormal and unusually small follicles in the irradiated thyroid tissues were observed compared to the controls and the ALA group on days 4 and 7 after irradiation. However, all pathologies were decreased by ALA pretreatment. The quantity of small follicles in the irradiated rats was greater on day 7 than day 4 after irradiation. However, in the ALA-treated irradiated rats, the numbers of small and medium follicles were significantly decreased to a similar degree as in the control and ALA-only groups. The PAS-positive density of the colloid in RT group was decreased significantly compared with all other groups and reversed by ALA pretreatment. The high activity index in the irradiated rats was lowered by ALA treatment. TGF-beta 1 immunoreactivity was enhanced in irradiated rats and was more severe on the day 7 after radiation exposure than on day 4. Expression of TGF-beta 1 was reduced in the thyroid that had undergone ALA pretreatment. Levels of serum pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) did not differ significantly between the all groups. This study provides that pretreatment with ALA decreased the severity of radiation-induced thyroid injury by reducing inflammation and fibrotic infiltration and lowering the activity index. Thus, ALA could be used to ameliorate radiation-induced thyroid injury.

We investigated the relationship between the time of radiotherapy (RT) and treatment outcomes in breast cancer. Patients with pathologic T1–2N0–1 breast cancer who received adjuvant RT in the morning (before 10:00 AM) or late afternoon (after 3:00 PM) were eligible for inclusion in this study. We retrospectively compared the clinicopathologic characteristics, acute skin reaction, and survival outcomes according to the time of RT. The median follow-up duration was 83 months (range, 10–131 months). From the 395 eligible patients, 190 (48.1%) and 205 (51.9%) patients were classified into the morning RT group and the afternoon RT group, respectively. The clinicopathologic characteristics were relatively well balanced between the treatment groups, except for pathologic N-stage (P = 0.0409). Grade 2 or higher acute skin reaction according to the Radiation Therapy Oncology Group criteria was observed in 39 (9.9%) patients, with a higher frequency in the afternoon RT group than the morning RT group (13.7% vs 5.8%, respectively; P = 0.0088). There was no difference in the failure patterns or survival outcomes between the treatment groups. RT in late afternoon was associated with increased Grade 2 or more skin reaction after RT for breast cancer patients, but treatment outcomes did not differ according to the time of RT. Individualized considerations for treatment should be taken into account to reduce the risk of skin reactions.

The purpose of this study was to examine the predictive value of hypoxia-inducible factor (HIF)-1α, carbonic anhydrase (CA)-IX, glucose transporter (GLUT)-1, cyclooxygenase (COX)-2, Ki-67, and erythropoietin receptor (EPOR) as immunohistochemical markers for determining the optimal treatment modality for early stage laryngeal carcinoma.Tissue samples from 42 early stage laryngeal carcinomas treated with radiotherapy alone were analyzed immunohistochemically for the expression of 6 markers. The Kaplan-Meier method, univariate and multivariate analyses, and the Cox proportional hazards model were used to analyze the associations between patient and tumor characteristics and immunohistochemical results, and locoregional control.Increased expression of HIF-1α and CA-IX was significantly correlated with residual tumor; no correlations were observed for the other immunohistochemical markers.High levels of HIF-1α or CA-IX expression were significantly correlated with residual tumor after radiotherapy for early stage laryngeal carcinomas. Alternative treatment modalities to primary radiotherapy should be considered for early stage laryngeal carcinomas showing high HIF-1α or CA-IX expression.

To examine the dosimetric effect of intrafraction movements occurred during image-guided frameless brain radiosurgery and to derive the optimal margin recipe to compensate the movement.The patients' movements during image-guided radiosurgeries were measured using skull-tracking method incorporated in the CyberKnife system. The dosimetric changes with the movements were computed using the six different dynamic-arc treatment plans based on the dose-grid analysis method. The authors extensively searched the proper relationship between the dose variations and the intrafraction geometric errors. The optimal margin for intrafraction movement was estimated via statistical analysis of the dosimetric changes with 262 actual patients' data.The overall geometric effect of intrafraction movements was approximated as 1.0 r+0.2σ, where r and σ are the average and standard deviation of the movements, respectively. The authors computed the required margins to compensate the movements with various confidence levels and with various estimated times for completing the treatments. The computed optimal margins were calculated as 2.1, 3.2, and 4.2 mm at 90% confidence level when the authors assumed the estimated treatment times of 10, 20, and 30 min, respectively.The authors provide a quantitative relationship for dosimetric change with the intrafraction movement and derived appropriate margin recipes to ensure the prescribed dose delivery to targeted area for frameless brain radiosurgery.

External-beam radiation therapy with intracavitary high-dose-rate brachytherapy is the standard treatment modality for advanced cervical cancer; however, late gastrointestinal complications are a major concern after radiotherapy. While radiation proctitis is a well-known side effect and radiation oncologists make an effort to reduce it, the sigmoid colon is often neglected as an organ at risk. Herein, we report two cases of radiation sigmoiditis mimicking sigmoid colon cancer after external-beam radiation therapy with intracavitary high-dose-rate brachytherapy for uterine cervical cancer with dosimetric consideration.

Purpose Intensity modulated radiation therapy (IMRT) is a high precision therapy technique that can achieve a conformal dose distribution on a given target. However, organ motion induced by respiration can result in significant dosimetric error. Therefore, this study explores the dosimetric error that result from various patterns of respiration. Materials and Methods Experiments were designed to deliver a treatment plan made for a real patient to an in-house developed motion phantom. The motion pattern; the amplitude and period as well as inhale-exhale period, could be controlled by in-house developed software. Dose distribution was measured using EDR2 film and analysis was performed by RIT113 software. Three respiratory patterns were generated for the purpose of this study; first the 'even inhale-exhale pattern', second the slightly long exhale pattern (0.35 seconds longer than inhale period) named 'general signal pattern', and third a 'long exhale pattern' (0.7 seconds longer than inhale period). One dimensional dose profile comparisons and gamma index analysis on 2 dimensions were performed Results In one-dimensional dose profile comparisons, 5% in the target and 30% dose difference at the boundary were observed in the long exhale pattern. The center of high dose region in the profile was shifted 1 mm to inhale (caudal) direction for the 'even inhale-exhale pattern', 2 mm and 5 mm shifts to exhale (cranial) direction were observed for 'slightly long exhale pattern' and 'long exhale pattern', respectively. The areas of gamma index >1 were 11.88%, 15.11%, and 24.33% for 'even inhale-exhale pattern', 'general pattern', and 'long exhale pattern', respectively. The long exhale pattern showed largest errors. Conclusion To reduce the dosimetric error due to respiratory motions, controlling patient's breathing to be closer to even inhaleexhale period is helpful with minimizing the motion amplitude.

In the Funding section, the grant number from funder Ministry of Education Science and Technology is listed incorrectly. The correct grant number is [2012R1A1A4A01015109].