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

Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM >4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p=0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p=0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 >37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS. Citation Format: Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki Chung, Kyung Su Kim, Won Sup Yoon, Jin Hee Kim, Jihye Cha, Yoon Kyeong Oh, In Ah Kim. Multicenter study for brain metastasis from breast cancer in Korea: The significance of molecular subtype (KROG 1612) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-01.

Background To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients. Materials and methods We identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000–2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT. Results The median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/β of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P, Highlights • Multicenter retrospective study of salvage WBRT for recurrent brain metastasis. • Subsequent use of systemic treatment after salvage WBRT showing better OS. • Limitations of previous graded prognostic assessments for recurrent brain metastasis. • Novel RPA classification consisting of four simple clinical factors predicts OS.

To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2−, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p 4) (p

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

Background Incurable inflammatory breast cancer (IBC) patients occasionally suffer from general symptoms such as breast pain, bleeding, ulceration, and discharge, and thus require palliative radiotherapy (RT). Hypofractionated RT has many advantages in palliative settings, but very few studies on IBC have been conducted. This study was conducted to evaluate the effects of hypofractionated RT on symptomatic IBC patients. Methods Twenty-two patients with IBC who underwent hypofractionated palliative RT between 2010 and 2016 were retrospectively analyzed. RT was performed at a total dose of 42.5–55 Gy with 2.5–3 Gy per fraction. The treatment effects were evaluated with respect to symptom improvement, tumor response, and treatment-related toxicity. Results The main symptoms that the patients complained of before RT were pain, bleeding, and discharge. According to the percentage of symptom relief compared with pre-RT symptoms, the number of patients with

To investigate the prognostic significance of lymphovascular space invasion (LVI) and perineural invasion (PNI) in rectal cancer.Clinical data of 1,232 stage II-III rectal cancer patients from six tertiary institutions were analyzed. All patients were treated by long-course preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Adjuvant systemic chemotherapy was performed for 962 (78.1%) patients according to the multidisciplinary team's decision. Treatment outcomes and prognostic factors were evaluated according to the lymphovascular invasion (LVI) and perineural invasion (PNI) status.Five-year overall survival (OS) and recurrence-free survival (RFS) rates of the entire cohort were 84.1% and 71.1%, respectively. There is a significant difference in 5-year OS among both-absent, LVI+ only, PNI+ only, and both-present groups (89.1% vs. 77.9% vs. 67.6% vs. 56.2%; p 0.001). RFS at five years was significantly different among both-absent, LVI+ only, PNI+ only, and both-present groups (78.7% vs. 58.7% vs. 44.6% vs. 38.6%; p 0.001). The 5-year distant failure-free survival (DFFS) rate was also significantly different among four groups (84.6% vs. 61.4% vs. 54.2% vs 48.6%; p 0.001). Although adjuvant chemotherapy did not affect 5-year DFFS in the entire cohort, adjuvant chemotherapy significantly reduced the distant failure rate in patients with PNI+ patients (44.9% vs. 54.6%, p = 0.048), not LVI+ patients (65.0% vs. 56.1%, p = 0.487).Compared to LVI, PNI is a more significant prognostic factor in stage II-III rectal patients treated by preoperative CRT and TME surgery. The status of PNI rather than LVI could be an indicator for identifying patients who could benefit from adjuvant systemic chemotherapy.

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

Background/aim To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers. Patients and methods We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation. Results Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case. Conclusion There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.

Purpose: The purpose of this study is to evaluate the effects of Vitamin E (VE) on the immune system and tumor growth during radiotherapy (RT) in mice model. Methods: C57BL/6NCrSlc mice were randomly distributed in four groups (control, VE alone, RT alone, and VE + RT). In the VE and VE + RT groups, VE was administered in the diet at 500 mg/kg. Radiation was delivered at 2 Gy in a single fraction on the whole body or at 6 Gy in three fractions locally in the RT and VE + RT groups. Changes in leukocytes and T lymphocytes were counted and compared between the four groups. To evaluate the effects on tumor growth, Ehrlich carcinoma cells were injected into the thighs of mice, and tumor volumes and growth inhibition rates were compared. Results: The number of leukocytes was increased in the VE group compared with that in the control group. The magnitude of leukocyte recovery after RT was also increased by VE. This change was affected largely by alterations in lymphocytes and monocytes rather than that in granulocytes. Both CD4+ and CD8+ T lymphocytes were positively affected by VE. The tumor growth was inhibited not only by RT but also by VE alone. If RT was delivered with VE, tumor growth was markedly inhibited. Conclusion: VE could increase the number of leukocytes, primarily lymphocytes, even after RT was delivered. VE also inhibited the tumor growth in addition to RT. Thus, VE may be a useful radioprotective supplement in radiotherapy without inducing tumor growth.

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.

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.

Purpose: There is uncertainty over the effect of systemic inflammatory response on oncologic outcomes in patients who underwent neoadjuvant chemoradiotherapy and surgery for rectal cancer. We investigated the association between neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as markers of systemic inflammation and tumor response and prognosis after treatment. Methods: A total of 176 patients who underwent neoadjuvant chemoradiotherapy and curative surgery for rectal cancer were analyzed retrospectively. Pretreatment hematologic parameters and the main clinical factors for patients and tumors were investigated with respect to their relationship with tumor regression and survival. Results: In the receiver operating characteristic analysis, NLR 2.0 and PLR 133.4 had the highest sensitivity and specificity in predicting tumor response. NLR Conclusions: Elevated NLR and PLR levels can be considered as predictors of poor pathologic response, and NLR can be considered a prognosticator in patients who underwent neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

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

// 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.

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.

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.

e14008 Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM > 4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p = 0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis showed that shorter time interval to BM, TNBC subtype, extracranial systemic disease, number of BM > 4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p = 0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 > 37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS.

BackgroundAlthough radical cystectomy is a standard treatment in muscle-invasive bladder cancer, bladder preservation therapy including transurethral resection of bladder tumor, radiotherapy, and concurrent chemotherapy has been widely adopted, recently. This retrospective analysis was performed to evaluate the survival rates and prognostic factors related to treatment outcomes following bladder-preserving therapy including radiotherapy (RT) in bladder cancer with a curative intent.Materials and methodsWe conducted a multi-institutional retrospective study of 152 patients with stage II-IV bladder cancer treated with curative RT between 2000 and 2010. There were 72 patients in stage II, 49 in stage III, and 31 in stage IV. Ninety-seven patients were treated with concurrent chemoradiotherapy and fifty-five with RT alone. Radiation was delivered to the pelvis (median 63 Gy), mainly with cisplatin. The median follow-up time was 35.5 months.ResultsSixty-nine patients (45.4%) showed a complete response to RT. The 5-year overall survival (OS) rate was 45.8%, the 5-year cause-specific survival (CSS) rate was 48.9%, and the 5-year disease-free survival (DFS) rate was 20.8%. Univariate analysis revealed significant differences in the following factors according to the survival rates: patient age, initial hemoglobin level, clinical T stage, clinical N stage, clinical stage group, tumor response to RT, hydronephrosis, and concurrent chemotherapy. Multivariate analysis also revealed a significant difference in patient age (p = 0.003 in OS, pConclusionsThe survival rates reported herein are comparable to those from other studies, and tumor response and concurrent chemoradiotherapy were significant prognostic factors for better survival rates. Further randomized studies are needed to elucidate the impact of RT in bladder cancer.

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 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

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.

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.

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.

// 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.

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

Background and purpose To prospectively investigate the effect of radiotherapy fraction size on clinical outcomes in early glottic carcinoma Methods and materials Patients with T1–2 glottic carcinoma were eligible for the protocol. Although 282 patients were required, the study was closed prematurely due to poor accrual with only 156 patients. Of these, 82 patients were allocated to conventional fractionation (CONV) arm (66Gy/33 fractions for T1 and 70Gy/35 fractions for T2), with 74 patients to hypofractionation (HYPO) arm (63Gy/28 fractions for T1 and 67.5Gy/30 fractions for T2). The primary objective was local progression-free survival (LPFS). Results With a median follow-up of 67months (range, 2–122months), the 5-year LPFS was 77.8% for CONV arm and 88.5% for HYPO arm (HR 1.55, p =0.213). No significant difference was observed in the toxicity profile between the two arms. In a subgroup exploratory analysis for T1a disease, the 5-year LPFS trended positively in HYPO arm (76.7% vs. 93.0%, HR 3.65, p =0.056). Conclusions Given that HYPO is at least not inferior to CONV with a similar toxicity profile, the hypofractionation scheme used in this study can be offered to patients with T1–2 glottic carcinoma with potential advantages in terms of local control and a shortened overall treatment time.

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

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.

Aims and background Little is known about chemoradiotherapy in elderly patients with locally advanced esophageal cancer. We compared the efficacy and toxicity of chemoradiotherapy in elderly and non-elderly patients with locally advanced esophageal cancer and determined the variables affecting the treatment outcome in the elderly patients with locally advanced esophageal cancer who had received chemoradiotherapy. Methods Fifty-seven elderly patients (age ≥65 years) and 30 non-elderly patients (age Results The median age of the elderly group was 69 years and in the non-elderly group, 56.5 years. Although treatment compliance appeared to be poor, the response rate and median survival were similar in both the groups (elderly versus non-elderly; 84.4% vs 87.5%, and 11.2 months vs11.3 months) and so were G3/4 hematologic and non-hematologic toxicities. The treatment-related mortality of the elderly patients appeared to be higher than that of the non-elderly group (7.0% vs 3.3%), but did not reach statistical significance. In prognostic factor analysis, a major response to chemoradiotherapy was a good prognostic indicator in the elderly group (response versus non-response; median overall survival times of 19.5 vs 5.4 months, respectively, P Conclusions The study suggests that chemoradiotherapy for locally advanced esophageal cancer in elderly patients, even though treatment compliance appears to be poor, is as safe and effective as in non-elderly patients and that the response to chemoradiotherapy is related to prognosis in elderly patients.

Purpose On the basis of the benefits of frontline radiation in early-stage, extranodal, natural killer (NK)/T-cell lymphoma (ENKTL), we conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of etoposide, ifosfamide, cisplatin, and dexamethasone (VIPD). Patients and Methods Thirty patients with newly diagnosed, stages IE to IIE, nasal ENKTL received CCRT (ie radiation 40 to 52.8 Gy and cisplatin 30 mg/m2 weekly). Three cycles of VIPD (etoposide 100 mg/m2 days 1 through 3, ifosfamide 1,200 mg/m2 days 1 through 3, cisplatin 33 mg/m2 days 1 through 3, and dexamethasone 40 mg days 1 through 4) were scheduled after CCRT. Results All patients completed CCRT, which resulted in 100% response that included 22 complete responses (CRs) and eight partial responses (PRs). The CR rate after CCRT was 73.3% (ie, 22 of 30 responses; 95% CI, 57.46 to 89.13). Twenty-six of 30 patients completed the planned three cycles of VIPD, whereas four patients did not because they withdrew (n = 2) or because they had an infection (n = 2). The overall response rate and the CR rate were 83.3% (ie; 25 of 30 responses; 95% CI, 65.28 to 94.36) and 80.0% (ie, 24 of 30 responses; 95% CI, 65.69 to 94.31), respectively. Only one patient experienced grade 3 toxicity during CCRT (nausea), whereas 12 of 29 patients experienced grade 4 neutropenia. The estimated 3-year, progression-free and overall survival rates were 85.19% (95% CI, 72.48 to 97.90) and 86.28% (95% CI, 73.97 to 98.59), respectively. Conclusion Patients with newly diagnosed, stages IE to IIE, nasal ENKTL are best treated with frontline CCRT.

// 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.

// 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.

To evaluate the pre-treatment clinical factors affecting recurrence and survival in rectal cancer patients who receive preoperative chemoradiotherapy (CRT) and curative surgery.The clinical data of 1782 patients from 8 institutions in Korea were analyzed. The potential prognostic factors that could be acquired before radical surgery were patient age, gender, clinical T and N stages, tumor size and location, tumor grade, carcinoembryonic antigen (CEA) level, and the concurrent chemotherapy regimen. The relapse-free survival (RFS), overall survival (OS), and cumulative incidence of locoregional and distant recurrence were analyzed according to the clinical factors.Among the pre-treatment clinical factors, tumor grade, pre-CRT CEA level, tumor location, and clinical N stage were significant prognostic factors affecting the RFS. The high-grade tumor was the hazardous factor for RFS on the multivariate analysis [Hazard ratio (HR), 1.83; 95% confidence interval (CI), 1.29-2.58; p=0.001]. The 5-year RFS rate for high-grade tumors was significantly lower than that for low-grade tumors (63.8% vs. 78.8%, p0.001). The tumor grade was a significant prognostic factor for distant recurrence (HR, 1.83, 95% CI, 1.29-2.58; p0.001), but not for locoregional recurrence (HR, 1.49, 95% CI, 0.68-3.26; p=0.320) on the multivariate analysis. The 5-year OS rate for high-grade tumors was significantly lower than that for low-grade tumors (70.6% vs. 85.5%, p0.001).The tumor grade is the significant pre-treatment clinical factor for recurrence and survival in rectal cancer patients who receive preoperative CRT and curative surgery.

// 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.

Objective: The purpose of our study was to evaluate the feasibility and treatment outcomes of fractionated stereotactic radiotherapy (SRT) for primary hepatocellular carcinoma (HCC). Methods: We enrolled 20 patients who had been histologically diagnosed as HCC patients and treated by fractionated SRT. Tumor size was 2-6.5 cm (average: 3.8 cm). We prescribed 50 Gy in 5 or 10 fractions at the 85-90% isodose line of the planning target volume for 2 weeks. The follow-up period was 3-55 months (median: 23 months). Results: The overall response rate was 80%, with 4 patients showing complete response (20%), 14 patients showing partial response (60%) and 4 patients showing stable disease (20%). The 1-year and 2-year survival rates were 70.0 and 43.1%, respectively (median: 20 months). The 1-year and 2-year disease-free survival rates were 65.0 and 32.5%, respectively (median: 19 months). The fractionated SRT was well tolerated, because grade 3 or grade 4 toxicity was not observed. Conclusion: These results suggest that fractionated SRT is a relatively safe and effective method for treating small primary HCC. Thus, fractionated SRT may be suggested as a local treatment of choice for small HCC when the patients are inoperable or when the patients refuse operation.

Purpose: To investigate the feasibility of intensity-modulated radiotherapy (IMRT) as a method of boost radiotherapy after the initial irradiation by the conventional anterior/posterior opposed beams for centrally located non–small-cell lung cancer through the evaluation of dose distributions according to the various boost methods. Methods and Materials: Seven patients with T3 or T4 lung cancer and mediastinal node enlargement who previously received radiotherapy were studied. All patients underwent virtual simulation retrospectively with the previous treatment planning computed tomograms. Initial radiotherapy plans were designed to deliver 40 Gy to the primary tumor and involved nodal regions with the conventional anterior/posterior opposed beams. Two radiation dose levels, 24 and 30 Gy, were used for the boost radiotherapy plans, and four different boost methods (a three-dimensional conformal radiotherapy [3DCRT], five-, seven-, and nine-beam IMRT) were applied to each dose level. The goals of the boost plans were to deliver the prescribed radiation dose to 95% of the planning target volume (PTV) and minimize the volumes of the normal lungs and spinal cord irradiated above their tolerance doses. Dose distributions in the PTVs and lungs, according to the four types of boost plans, were compared in the boost and sum plans, respectively. Results: The percentage of lung volumes irradiated >20 Gy (V20) was reduced significantly in the IMRT boost plans compared with the 3DCRT boost plans at the 24- and 30-Gy dose levels ( p = 0.007 and 0.0315 respectively). Mean lung doses according to the boost methods were not different in the 24- and 30-Gy boost plans. The conformity indexes (CI) of the IMRT boost plans were lower than those of the 3DCRT plans in the 24- and 30-Gy plans ( p = 0.001 in both). For the sum plans, there was no difference of the dose distributions in the PTVs and lungs according to the boost methods. Conclusions: In the boost plans the V20s and CIs were reduced significantly by the IMRT plans, but in the sum plans the effects of IMRT on the dose distributions in the tumor and lungs, like CI and V20, were offset. Therefore, to keep the beneficial effect of IMRT in radiotherapy for lung cancer, it would be better to use IMRT as a whole treatment plan rather than as a boost treatment.

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.

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.

Background The purpose of this study was to evaluate the technical feasibility of an image-guided intensity modulated radiotherapy (IG-IMRT) using involved-field technique to perform a hypofractionated schedule for patients with locally advanced or recurrent pancreatic cancer. Methods From May 2009 to November 2011, 12 patients with locally advanced or locally recurrent pancreatic cancer received hypofractionated CCRT using TomoTherapy Hi-Art with concurrent and sequential chemotherapy at Seoul St. Mary’s Hospital, the Catholic University of Korea. The total dose delivered was 45 Gy in 15 fractions or 50 Gy in 20 fractions. The target volume did not include the uninvolved regional lymph nodes. Treatment planning and delivery were performed using the IG-IMRT technique. The follow-up duration was a median of 31.1 months (range: 5.7-36.3 months). Results Grade 2 or worse acute toxicities developed in 7 patients (58%). Grade 3 or worse gastrointestinal and hematologic toxicity occurred in 0% and 17% of patients, respectively. In the response evaluation, the rates of partial response and stable disease were 58% and 42%, respectively. The rate of local failure was 8% and no regional failure was observed. Distant failure was the main cause of treatment failure. The progression-free survival and overall survival durations were 7.6 and 12.1 months, respectively. Conclusion The involved-field technique and IG-IMRT delivered via a hypofractionated schedule are feasible for patients with locally advanced or recurrent pancreatic cancer.