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Tricholoma matsutake has been the most valuable ectomycorrhizal fungi in Asia because of its unique flavor and taste. However, due to the difficulty of artificial cultivation, the cultivation of T. matsutake has relied on natural growth in forests. To cultivate the T. matsutake artificially, microorganisms in fairy rings were introduced. In this study, we isolated 30 fungal species of microfungi from the soil of fairy rings. Among them, one single fungal strain showed a promoting effect on the growth of T. matsutake. The growth effect was confirmed by measuring the growth area of T. matsutake and enzyme activities including a-amylase, cellulase, and b-glucosidase. In comparison with control, microfungal metabolite increased the growth area of T. matsutake by 213% and the enzyme activity of T. matsutake by 110-200%. The isolated fungal strain was identified as Penicillium citreonigrum by BLAST on the NCBI database. The Discovery of this microfungal strain is expected to contribute to artificial cultivation of T. matsutake. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC). Materials and Methods Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity. Results Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin. Conclusion The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to evaluate prognosis of patients with level I/II axillary lymph node metastases from occult breast cancer (OBC). Materials and Methods: Data of 53 patients with OBC who received axillary lymph node dissection (ALND) positive/negative (+/-) breast-conserving surgery between 2001 and 2013 were retrospectively collected at seven hospitals in Korea. The median number of positive lymph nodes (+LNs) was 2. Seventeen patients (32.1%) had >3 +LNs. A total of 48 patients (90.6%) received radiotherapy. Extents of radiotherapy were as follows: whole-breast (WB; n = 11), regional lymph node (RLN; n = 2), and WB plus RLN (n = 35). Results: The median follow-up time was 85 months. Recurrence was found in four patients: two in the breast, one in RLN, and one in the breast and RLN. The 5-year and 7-year disease-free survival (DFS) rates were 96.1% and 93.5%, respectively. Molecular subtype and receipt of breast radiotherapy were significantly associated with DFS. Patients with estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) subtype had significantly lower 7-year DFS than those with non-ER-/PR-/HER2- tumor (76.9% vs. 100.0%; p = 0.03). Whole breast irradiation (WBI) was significantly associated with a higher 7-year DFS rate (94.7% for WBI group vs. 83.3% for non-WBI group; p = 0.01). Other factors including patient's age, number of +LNs, taxane chemotherapy, and RLN irradiation were not associated with DFS. Conclusion: Patients with OBC achieved favorable outcome after ALND and breast-targeting treatment. Molecular subtype and receipt of WBI was significant factors for DFS. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levels in improving the performance of magnetic resonance imaging (MRI) for the prediction of pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectal cancer. Materials and Methods We retrospectively reviewed the medical records of 524 rectal cancer patients who underwent NCRT and total mesorectal excision between January 2009 and December 2014. The performances of MRI with or without CEA parameters (initial CEA and CEA dynamics) for prediction of pathologic tumor response grade (pTRG) were compared by receiver-operating characteristic analysis with DeLong's method. Cox regression was used to identify the independent factors associated to pTRG and disease-free survival (DFS) after NCRT. Results The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis, poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) and the mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed association with poor pTRG. The mrTRG plus CEA parameters showed significantly improved performances in the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEA were also identified as independent factors associated with DFS. The initial CEA further discriminated DFS in the subgroups with good mrTRG or that without mrMFI. Conclusion The CEA parameters significantly improved the performance of MRI in the prediction of pTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initial CEA level in the groups with favorable MRI parameters. [ABSTRACT FROM AUTHOR]

Purpose This first Korean prospective study is to evaluate the feasibility of prone breast radiotherapy after breast conserving surgery for left breast cancer patients who have relatively small breast size and we present dosimetric comparison between prone and supine positions. Materials and Methods Fifty patients underwent two computed tomography (CT) simulations in supine and prone positions. Whole breast, ipsilateral lung, heart, and left-anterior-descending coronary artery were contoured on each simulation CT images. Tangential-fields treatment plan in each position was designed with total 50 Gy in 2-Gy fractions, and then one of the positions was designated for the treatment by comparing target coverage and dose to normal organs. Also, interfractional and intrafractional motion was evaluated using portal images. Results In total 50 patients, 32 cases were decided as prone-position–beneficial group and 18 cases as supine-position–beneficial group based on dosimetric advantage. Target dose homogeneity was comparable, but target conformity in prone position was closer to optimal than in supine position. For both group, prone position significantly increased lung volume. However, heart volumewas decreased by prone position for prone-position–beneficial group but was comparable between two positions for supine-position–beneficial group. Lung and heart doses were significantly decreased by prone position for prone-position–beneficial group. However, prone position for supine-position–beneficial group increased heart dose while decreasing lung dose. Prone position showed larger interfractional motion but smaller intra-fractional motion than supine position. Conclusion Prone breast radiotherapy could be beneficial to a subset of small breast patients since it substantially spared normal organs while achieving adequate target coverage. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the treatment outcomes of radiotherapy (RT) for breast cancer with ipsilateral supraclavicular (SCL) and/or internal mammary (IMN) lymph node involvement. Materials and Methods A total of 353 patients from 11 institutions were included. One hundred and thirty-six patients had SCL involvement, 148 had IMN involvement, and 69 had both. All patients received neoadjuvant systemic therapy followed by breast-conserving surgery or mastectomy, and postoperative RT to whole breast/chest wall. As for regional lymph node irradiation, SCL RT was given to 344 patients, and IMN RT to 236 patients. The median RT dose was 50.4 Gy. Results The median follow-up duration was 61 months (range, 7 to 173 months). In-field progression was present in SCL (n=20) and/or IMN (n=7). The 5-year disease-free survival (DFS) and overall survival rates were 57.8% and 75.1%, respectively. On multivariate analysis, both SCL/IMN involvement, number of axillary lymph node ≥ 4, triple-negative subtype, and mastectomy were significant adverse prognosticators for DFS (p=0.022, p=0.001, p=0.001, and p=0.004, respectively). Regarding the impact of regional nodal irradiation, SCL RT dose ≥ 54 Gy was not associated with DFS (5-year rate, 52.9% vs. 50.9%; p=0.696) in SCL-involved patients, and the receipt of IMN RT was not associated with DFS (5-year rate, 56.1% vs. 78.1%; p=0.099) in IMN-involved patients. Conclusion Neoadjuvant chemotherapy followed by surgery and postoperative RT achieved an acceptable in-field regional control rate in patients with SCL and/or IMN involvement. However, a higher RT dose to SCL or IMN RT was not associated with the improved DFS in these patients. [ABSTRACT FROM AUTHOR]

Purpose We compared the oncologic outcomes of breast-conserving surgery plus radiation therapy (BCS+RT) and modified radical mastectomy (MRM) under anthracycline plus taxane-based (AT) regimens and investigated the role of adjuvant radiation therapy (RT) in patients with pathologic N1 (pN1) breast cancer treated by mastectomy. Materials and Methods We retrospectively reviewed the medical records of 2,011 patients with pN1 breast cancer who underwent BCS+RT or MRM alone at 12 institutions between January 2006 and December 2010. Two-to-one propensity score matching was performed for balances in variables between the groups. Results The median follow-up duration for the total cohort was 69 months (range, 1 to 114 months). After propensity score matching, 1,074 patients (676 in the BCS+RT group and 398 in the MRM-alone group) were analyzed finally. The overall survival, disease-free survival, locoregional failure-free survival, and regional failure-free survival (RFFS) curves of the BCS+RT group vs. MRM-alone group were not significantly different. The subgroup analysis revealed that in the group with both lymphovascular invasion (LVI) and histologic grade (HG) III, the BCS+RT showed significantly superior RFFS (p=0.008). Lymphedema (p=0.007) and radiation pneumonitis (p=0.031) occurred more frequently in the BCS+RT group than in the MRM-alone group, significantly. Conclusion There are no differences in oncologic outcomes between BCS+RT and MRM-alone groups under the AT chemotherapy regimens for pN1 breast cancer. However, BCS+RT group showed superior RFFS to MRM-alone group in the patients with LVI and HG III. Adjuvant RT might be considerable for pN1 breast cancer patients with LVI and HG III. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify prognostic factors for locoregional recurrence (LRR) in pT3N0 rectal cancer patients who were treated with surgery alone and had negative resection margin including circumferential resection margin (CRM) for optimal indication of adjuvant radiotherapy. Materials and Methods: We reviewed patients with pT3N0 rectal cancer who were treated via upfront surgery and had no other adjuvant treatment from January 2003 to December 2012. In total, 122 patients who had negative resection margin including negative CRM were included in the analysis. Results: The median follow-up period after surgery was 60 months (range, 3 to 161 months). During this time, 6 patients (4.9%) experienced LRR at the anastomotic site (4 patients), and regional lymphatic area (2 patients). The estimated 5-year rates of overall survival, recurrence-free survival, and LRR-free survival were 96.7%, 84.6%, and 94.0%, respectively. Multivariate analysis showed that level of tumor =5 cm was a significant prognostic factor for LRR-free survival (LRRFS) (p = 0.04; hazard ratio = 7.08; 95% confidence interval, 1.06-47.30). Patients with level of tumor =5 cm had an estimated 5-year LRRFS of 66.8%, which was much higher than 2.3% in patients with level of tumor >5 cm. There was no significant factor for recurrence-free survival or overall survival. Conclusion: In T3N0 rectal cancer, adjuvant chemoradiotherapy should be recommended in patients with level of tumor =5 cm for better local control. However, in patients with pT3N0 disease, negative resection margin, and level of tumor >5 cm, adjuvant chemoradiotherapy should be carefully suggested. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study is to compare the treatment outcomes of breast conserving surgery (BCS) plus radiotherapy (RT) versus mastectomy for patients with pT1-2N1 triple-negative breast cancer (TNBC). Materials and Methods Using two multicenter retrospective studies on breast cancer, a pooled analysis was performed among 320 patients with pT1-2N1 TNBC. All patients who underwent BCS (n=212) received whole breast RT with or without regional nodal RT, while none who underwent mastectomy (n=108) received it. All patients received taxane-based adjuvant chemotherapy. The median follow-up periods were 65 months in the BCS+RT group, and 74 months in the mastectomy group. Results The median age of all patients was 48 years (range, 24 to 70 years). Mastectomy group had more patients with multiple tumors (p < 0.001), no lymphovascular invasion (p=0.001), higher number of involved lymph node (p=0.028), and higher nodal ratio ≥ 0.2 (p=0.037). Other characteristics were not significantly different between the two groups. The 5-year locoregional recurrence-free, disease-free, and overall survival rates of BCS+RT group versus mastectomy group were 94.6% versus 87.7%, 89.5% versus 80.4%, and 95.0% versus 87.8%, respectively, and the differences were statistically significant after adjusting for covariates (p=0.010, p=0.006, and p=0.005, respectively). Conclusion In pT1-2N1 TNBC, breast conservation therapy achieved better locoregional recurrencefree, disease-free, and overall survival rates compared with mastectomy. [ABSTRACT FROM AUTHOR]

Purpose This study was conducted to validate the prognostic influence of treatment response among patients with positive circumferential resection margin for locally advanced rectal cancer. Materials and Methods Clinical data of 197 patients with positive circumferential resection margin defined as P 2 mm after preoperative chemoradiotherapy followed by total mesorectal excision between 2004 and 2009 were collected for this multicenter validation study. All patients underwent median 50.4 Gy radiation with concurrent fluoropyrimidine based chemotherapy. Treatment response was dichotomized to good response, including treatment response of grade 2 or 3, and poor response, including grade 0 or 1. Results After 52 months median follow-up, 5-year overall survival (OS) for good responders and poor responders was 79.1% and 48.4%, respectively (p < 0.001). In multivariate analysis, circumferential resection margin involvement and treatment response were a prognosticator for OS and locoregional recurrence-free survival. In subgroup analysis, good responders with close margin showed significantly better survival outcomes for survival. Good responders with involved margin and poor responders with close margin shared similar results, whereas poor responders with involved margin had worst survival (5-year OS, 81.2%, 57.0%, 50.0%, and 32.4%, respectively; p < 0.001). Conclusion Among patients with positive circumferential resection margin after preoperative chemoradiotherapy, survival of the good responders was significantly better than poor responders. Subgroup analysis revealed that definition of positive circumferential resection margin may be individualized as involvement for good responders, whereas ≤2 mm for poor responders. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to measure secondary neutron dose during proton therapy using a detector that covers the entire neutron energy range produced in proton therapy. We analyzed and compared the neutron dose during proton treatment with passive scattering and line scanning. The neutron ambient dose equivalents were measured with a 190 MeV wobbling and line-scanning proton beam. The center of a plastic water phantom (30 × 30 × 60 cm3) was placed at the isocenter. A Wide-Energy Neutron Detection Instrument (WENDI-2) was located 1m from the isocenter at four different angles (0°, 45°, 90° and 135°). Both wobbling and line-scanning modes of a multipurpose and pencil beam scanning dedicated nozzles were used to obtain a spread-out Bragg peak with 10-cm-width for the measurements. The ambient dose equivalent H*(10) value was normalized by the proton therapeutic dose at the isocenter. For wobbling mode and linescanning mode, the highest H*(10) values were 1.972 and 0.099 mSv/Gy, respectively. We successfully measured the neutron ambient dose equivalents at six positions generated by a 190MeV proton beam using wobbling and line-scanning mode with the WENDI-2. These reference data could be used for neutron dose reduction methods and other analysis for advanced proton treatment in the near future. [ABSTRACT FROM AUTHOR]

Purpose This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. Materials and Methods We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. Results A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. Conclusion We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. Materials and Methods We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. Results We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [-]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081). Conclusion PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane- based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3. [ABSTRACT FROM AUTHOR]

Purpose: Hematotoxicity following anti-cancer treatment is known to be related to treatment efficacy in several malignancies. The purpose of this study was to examine the hematologic parameters related to the tumor response and survival in patients treated with curative surgery following preoperative chemoradiotherapy (CRT) for rectal cancer. Materials and Methods: Four hundred eighteen patients with rectal cancer who underwent preoperative CRT and curative surgery were analyzed, retrospectively. The main clinical factors and blood cell counts before and after CRT were investigated with respect to their relationships with tumor downstaging and patient survival. Results: The post-CRT leukocyte count was significantly different between the tumor downstaging group and the nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate analysis showed that histological grade, circumferential extent, and post-CRT leukocyte count were related to tumor downstaging. In addition, histological grade, post-CRT leukocyte count, and tumor downstaging were related to disease-free survival. The 5-year disease-free survival and overall survival in patients with post-CRT leukocyte count ≤3730/uL, which is the cut-off value derived from the receiver operation characteristic (ROC) curve analysis, were significantly higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs. 84.1%, p = 0.024). Conclusion: Post-CRT leukocyte count of ≤3730/uL could be regarded as a good prognostic factor for tumor response and survival in rectal cancer patients treated with preoperative CRT. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods: We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results: Average rectal volume and ARA were 11.3 mL and 2.9 cm?. After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion: Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation. Materials and Methods: Overall, 235 Korean patients with BRCA1/2 mutation-negative high-risk breast cancer were screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT. Results: A total of 20 sequence alterations including 12 exonic and eight intronic variants were found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein- truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1. Conclusion: No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Materials and Methods: Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. Results: A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Conclusion: Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. Materials and Methods: We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). Results: The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (≥50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (≤1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. Conclusion: High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC. [ABSTRACT FROM AUTHOR]

Purpose: In proton therapy, collisions between the patient and nozzle potentially occur because of the large nozzle structure and efforts to minimize the air gap. Thus, software was developed to predict such collisions between the nozzle and patient using treatment virtual simulation. Methods: Three-dimensional (3D) modeling of a gantry inner-floor, nozzle, and robotic-couch was performed using SolidWorks based on the manufacturer's machine data. To obtain patient body information, a 3D-scanner was utilized right before CT scanning. Using the acquired images, a 3D-image of the patient's body contour was reconstructed. The accuracy of the image was confirmed against the CT image of a humanoid phantom. The machine components and the virtual patient were combined on the treatment-room coordinate system, resulting in a virtual simulator. The simulator simulated the motion of its components such as rotation and translation of the gantry, nozzle, and couch in real scale. A collision, if any, was examined both in static and dynamic modes. The static mode assessed collisions only at fixed positions of the machine's components, while the dynamic mode operated any time a component was in motion. A collision was identified if any voxels of two components, e.g., the nozzle and the patient or couch, overlapped when calculating volume locations. The event and collision point were visualized, and collision volumes were reported. Results: All components were successfully assembled, and the motions were accurately controlled. The 3D-shape of the phantom agreed with CT images within a deviation of 2 mm. Collision situations were simulated within minutes, and the results were displayed and reported. Conclusions: The developed software will be useful in improving patient safety and clinical efficiency of proton therapy. [ABSTRACT FROM AUTHOR]

Purpose: We performed exome sequencing in a breast cancer family without BRCA mutations. Materials and Methods: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members. Results: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined. Conclusion: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the appropriateness of prophylactic inguinal nodal irradiation (PINI), we analyzed patterns of failure in anal cancer patients who were inguinal node-negative at presentation and did not receive PINI. Materials and Methods: We retrospectively reviewed the records of 33 anal cancer patients treated by definitive concurrent chemoradiation therapy (CCRT) between 1994 and 2013. Radiotherapy consisted of a total dose of 44-45 Gy (22-25 fractions in 5 weeks) on the whole pelvis, anus, and perineum. Except inguinal lymphadenopathy was present at initial diagnosis, the entire inguinal chain was not included in the radiation field. In other words, there was no PINI. Results: The median follow-up duration was 50 months (range, 4 to 218 months). Median survival and progression-free survival (PFS) were 57 months (range, 10 to 218 months) and 50 months (range, 4 to 218 months), respectively. Among the survival, the median follow-up duration was 51 months (range, 12 to 218 months). The 5-year overall survival and PFS rates were 93.4% and 88.8%, respectively. Although none of the patients received inguinal node irradiation for prophylactic purposes, there was no inguinal recurrence. Conclusion: Treatment of anal cancer by omitting PINI might be considered in selected patients with clinically uninvolved inguinal nodes. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to evaluate the efficacy and safety of topically applied recombinant human epidermal growth factor (rhEGF) for the prevention of radiation-induced dermatitis in cancer patients. Materials and Methods: From December 2010 to April 2012, a total of 1,172 cancer patients who received radiotherapy (RT) of more than 50 Gy were prospectively enrolled and treated with EGF-based cream. An acute skin reaction classified according to the Radiation Therapy Oncology Group 6-point rating scale was the primary end point and we also assessed the occurrence of edema, dry skin, or pruritus. Results: The percentage of radiation dermatitis with maximum grade 0 and grade 1 was 19% and 58% at the time of 50 Gy, and it became 29% and 47% after completion of planned RT. This increment was observed only in breast cancer patients (from 18%/62% to 32%/49%). Adverse events related to the EGF-based cream developed in 49 patients (4%) with mild erythema the most common. Skin toxicity grade >2 was observed in 5% of the patients. Edema, dry skin, and pruritus grade ≥3 developed in 9%, 9%, and 1% of the patients, respectively. Conclusion: Prophylactic use of an EGF-based cream is effective in preventing radiation dermatitis with tolerable toxicity. Further studies comparing EGF cream with other topical agents may be necessary. [ABSTRACT FROM AUTHOR]

Background: Large genomic rearrangements (LGRs) in the BRCA1/2 genes are frequently observed in breast cancer patients who are negative for BRCA1/2 small mutations. Here, we examined 221 familial breast cancer patients from 37 hospitals to estimate the contribution of LGRs, in a nationwide context, to the development of breast cancer. Methods: Direct sequencing or mutation scanning followed by direct sequencing was performed to screen small mutations. BRCA1/2 small mutation-negative patients were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay. Results: Using a combined strategy to detect the presence of small mutations and LGRs, we identified BRCA1/2 small mutations in 78 (35.3%) out of 221 familial breast cancer patients and BRCA1 LGRs in 3 (2.1%) out of 143 BRCA1/2 small mutation-negative patients: the deletion of exons 11-13, the deletion of exons 13-15, and whole gene deletion of exons 1-24. The novel deletion of exons 11-13 is thought to result from a non-homologous recombination event mediated by a microhomology sequence comprised of 3 or 4 base pairs: c.3416_4357 + 1863delins187 (NG_005905.2: g.33369_44944delins187). Conclusions: In this study, we showed that LGRs were found in 3.7% (3/81) of the patients who had mutations in BRCA1 or BRCA2, and 7.5% (3/40) of patients with mutations in BRCA1. This suggests that the contribution of LGRs to familial breast cancer in this population might be comparable to that in other ethnic populations. Given these findings, an MLPA to screen for mutations in the BRCA1 gene is recommended as an initial screening test in highly selective settings. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to examine the clinical implications of a pathologically complete response after neoadjuvant chemoradiotherapy (CRT) followed by local excision for patients with cT2 rectal cancer who refused radical surgery. Materials and Methods Seventeen patients with cT2 primary rectal cancer within 6 cm from the anal verge who received neoadjuvant CRT and local excision because of patient refusal of radical surgery or poor performance status were included. Two patients had clinical involvement of a regional lymph node. Preoperative radiotherapy was delivered to the whole pelvis at a dose of 44 to 50.4 Gy in 22 to 28 fractions. All patients underwent transanal excision and eight patients (47%) received postoperative chemotherapy. Results Ten patients (59%) achieved ypT0. At a median follow-up period of 75 months (range, 22 to 126 months), four (24%) patients developed recurrence (two locoregional and two distant). The 5-year disease-free survival of all patients was 82%, and was higher in patients with ypT0 (90%) than in patients with ypT1-2 (69%, p=0.1643). Decreased disease-free survival was also observed in patients receiving capecitabine compared with 5-fluorouracil (54% vs. 100%, p=0.0298). Conclusion Local excision could be a feasible alternative to radical surgery in patients with ypT0 after neoadjuvant CRT for cT2 distal rectal cancer without further radical surgery. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Materials and Methods: Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. Results: The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). Conclusion: A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the treatment outcomes of local excision following preoperative chemoradiotherapy in patients with locally advanced rectal cancer who have not undergone radical surgery for any reason. Materials and Methods: The data of 27 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by local excision were analyzed retrospectively. The primary endpoint was the 5-year relapse-free survival rate, and the secondary endpoint was the pattern of recurrence. Results: The median follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and 85.0%, respectively. Six (22%) patients developed treatment failure; one (4%) patient had local recurrence only, three (11%) patients had distant recurrence only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1% vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073), respectively. Conclusion: Local excision following preoperative chemoradiotherapy may be an alternative treatment for highly selected patients with locally advanced rectal cancer who have achieved ypT0-1 after preoperative chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This study was performed to evaluate prognostic factors for survival from first relapse (SFFR) in stage I-III breast cancer patients. Materials and Methods: From June 1994 to June 2008, 3,835 patients were treated with surgery plus postoperative radiotherapy and adjuvant chemotherapy for stage I-III breast cancer at Samsung Medical Center. Among them, a total of 224 patients died by June 2009, and 175 deaths were of breast cancer. Retrospective review was performed on medical records of 165 patients who met the inclusion criteria of this study. Univariate and multivariate analysis were done on survivals according to variables, such as age, stage, hormone status of tumor, disease-free interval (DFI), sites of first failure, number of organs involved by recurrent disease (NOR), application of salvage treatments, and existence of brain or liver metastasis (visceral metastasis). Results: Patients' median overall survival time was 38 months (range, 8 to 123 months). Median SFFR was 17 months (range, 5 to 87 months). Ninety percent of deaths occurred within 40 months after first recurrence. The patients with SFFR ≤1 year had tendency of triple-negativity, shorter DFI (≤2 years), larger NOR (>3), visceral metastasis for first relapse than the patients with SFFR >1 year. In multivariate analysis, longer DFI (>2 vs. ≤2 years), absence of visceral metastasis, and application of salvage treatments were statistically significant prognosticators for longer SFFR. Conclusion: The DFI, application of salvage treatments, and visceral metastasis were significant prognostic factors for SFFR in breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: We designed this study to identify and suggest the reasonable timing of adjuvant radiotherapy in the treatment of uterine carcinosarcoma according to the surgical intent and patterns of progression. Materials and Methods: We retrospectively analyzed a total of 50 carcinosarcoma patients diagnosed between 1995 and 2010. Among these 50 patients, 32 underwent curative surgery and 13 underwent maximal tumor debulking surgery. The remaining ive patients underwent biopsy only. Twenty-six patients received chemotherapy, and 15 patients received adjuvant radiotherapy. Results: The median follow-up period was 17.3 months. Curative resection (p < 0.001) and stage (p < 0.001) were statistically significant factors affecting survival. During follow-up, 30 patients showed progression. Among these, eight patients (16.0%) had loco-regional progression only. The patients who had received adjuvant radiotherapy did not show loco-regional progression, and radiotherapy was a significant negative risk factor for loco-regional progression (p = 0.01). The time to loco-regional progression was much earlier for non-curative than curative resection (range, 0.7 to 7.6 months vs. 7.5 to 39.0 months). Conclusion: Adjuvant radiotherapy in the treatment of carcinosarcoma might be related to a low loco-regional progression rate. Radiotherapy should be considered in non-curatively resected patients as soon as possible. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Although anemia is considered to be a contributor to intra-tumoral hypoxia and tumor resistance to ionizing radiation in cancer patients, the impact of pretreatment anemia on local control after neoadjuvant concurrent chemoradiotherapy (NACRT) and surgery for rectal cancer remains unclear. Materials and Methods: We reviewed the records of 247 patients with locally advanced rectal cancer who were treated with NACRT followed by curative-intent surgery. Results: The patients with anemia before NACRT (36.0%, 89/247) achieved less pathologic complete response (pCR) than those without anemia (p = 0.012). The patients with pretreatment anemia had worse 3-year local control than those without pretreatment anemia (86.0% vs. 95.7%, p = 0.005). Multivariate analysis showed that pretreatment anemia (p = 0.035), pathologic tumor and nodal stage (p = 0.020 and 0.032, respectively) were independently significant factors for local control. Conclusion: Pretreatment anemia had negative impacts on pCR and local control among patients who underwent NACRT and surgery for rectal cancer. Strategies maintaining hemoglobin level within normal range could potentially be used to improve local control in rectal cancer patients. [ABSTRACT FROM AUTHOR]

Since card-type one-time password (OTP) generators became available, power and area consumption has been one of the main issues of hardware OTPs. Because relatively smaller batteries and smaller chip areas are available for this type of OTP compared to existing token-type OTPs, it is necessary to implement power-efficient and compact dedicated OTP hardware modules. In this paper, we design and implement a low-power small-area hardware OTP generator based on the Advanced Encryption Standard (AES). First, we implement a prototype AES hardware module using a 350 nm process to verify the effectiveness of our optimization techniques for the SubBytes transform and data storage. Next, we apply the optimized AES to a real-world OTP hardware module which is implemented using a 180 nm process. Our experimental results show the power consumption of our OTP module using the new AES implementation is only 49.4% and 15.0% of those of an HOTP and software-based OTP, respectively. [ABSTRACT FROM AUTHOR]

Background: To evaluate the palliative role of radiotherapy (RT) and define the effectiveness of chemotherapy combined with palliative RT (CCRT) in patients with a symptomatic pelvic mass of metastatic colorectal cancer. Methods: From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases), bleeding (18 cases), and obstruction (nine cases). The pelvic mass originated from rectal cancer in 58 patients (73%) and from colon cancer in 22 patients (27%). Initially 72 patients (90%) were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8- 60 Gy (median: 36 Gy) with 1.8-8 Gy per fraction. When the α/β for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the median RT dose was 46.8 Gy10 (14.4-78). Twenty one patients (26%) were treated with CCRT. Symptom palliation was assessed one month after the completion of RT. Results: Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months), 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED≥40 Gy10 (p < 0.05), and CCRT was a marginally significant factor (p = 0.0644). On multivariate analysis, BED and CCRT were significant prognostic factors for symptom control duration (p < 0.05). Conclusions: RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (GNPs) injected in a body for dose enhancement in radiation therapy are known to form clusters. We investigated the dependence of dose enhancement on the GNP morphology using Monte-Carlo simulations and compared the model predictions with experimental data. The cluster morphology was approximated as a body-centred cubic (BCC) structure by placing GNPs at the 8 corners and the centre of a cube with an edge length of 0.22–1.03 µm in a 4  ×  4  ×  4 µm3 water-filled phantom. We computed the dose enhancement ratio (DER) for 50 and 260 kVp photons as a function of the distance from the cube centre for 12 different cube sizes. A 10 nm-wide concentric shell shaped detector was placed up to 100 nm away from a GNP at the cube centre. For model validation, simulations based on BCC and nanoparticle random distribution (NRD) models were performed using parameters that corresponded to the experimental conditions, which measured increases in the relative biological effect due to GNPs. We employed the linear quadratic model to compute cell surviving fraction (SF) and sensitizer enhancement ratio (SER). The DER is inversely proportional to the distance to the GNPs. The largest DERs were 1.97 and 1.80 for 50 kVp and 260 kVp photons, respectively. The SF predicted by the BCC model agreed with the experimental value within 10%, up to a 5 Gy dose, while the NRD model showed a deviation larger than 10%. The SERs were 1.21  ±  0.13, 1.16  ±  0.11, and 1.08  ±  0.11 according to the experiment, BCC, and NRD models, respectively. We most accurately predicted the GNP radiosensitization effect using the BCC approximation and suggest that the BCC model is effective for use in nanoparticle dosimetry. [ABSTRACT FROM AUTHOR]

Discusses the role of c-Jun N-terminal kinase (JNK) in radiation-induced lung fibrosis (RTLF). Focus of the role of transforming growth factor-beta on the generation of RTLF; Evaluation of the activity of JNK in alveolar macrophages after radiation; Examination of the role of JNK in increasing the transcription of fibrogenic cytokines through the transcription factor.