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Importance The benefit of internal mammary node irradiation (IMNI) for treatment outcomes in node-positive breast cancer is unknown. Objective To investigate whether the inclusion of IMNI in regional nodal irradiation improves disease-free survival (DFS) in women with node-positive breast cancer. Design, Setting, and Participants This multicenter, phase 3 randomized clinical trial was conducted from June 1, 2008, to February 29, 2020, at 13 hospitals in South Korea. Women with pathologically confirmed, node-positive breast cancer after breast-conservation surgery or mastectomy with axillary lymph node dissection were eligible and enrolled between November 19, 2008, and January 14, 2013. Patients with distant metastasis and those who had received neoadjuvant treatment were excluded. Data analyses were performed according to the intention-to-treat principle. Interventions All patients underwent regional nodal irradiation along with breast or chest wall irradiation. They were randomized 1:1 to receive radiotherapy either with IMNI or without IMNI. Main Outcomes and Measures The primary end point was the 7-year DFS. Secondary end points included the rates of overall survival, breast cancer–specific survival, and toxic effects. Results A total of 735 women (mean [SD] age, 49.0 [9.1] years) were included in the analyses, of whom 373 received regional nodal irradiation without IMNI and 362 received regional nodal irradiation with IMNI. Nearly all patients underwent taxane-based adjuvant systemic treatment. The median (IQR) follow-up was 100.4 (89.7-112.1) months. The 7-year DFS rates did not significantly differ between the groups treated without IMNI and with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14; log-rankP = .22). However, an ad hoc subgroup analysis showed significantly higher DFS rates with IMNI among patients with mediocentrally located tumors. In this subgroup, the 7-year DFS rates were 81.6% without IMNI vs 91.8% with IMNI (HR, 0.42; 95% CI, 0.22-0.82; log-rankP = .008), and the 7-year breast cancer mortality rates were 10.2% without IMNI vs 4.9% with IMNI (HR, 0.41; 95% CI, 0.17-0.99; log-rankP = .04). No differences were found between the 2 groups in the incidence of adverse effects, including cardiac toxic effects and radiation pneumonitis. Conclusions and Relevance This randomized clinical trial found that including IMNI in regional nodal irradiation did not significantly improve the DFS in patients with node-positive breast cancer. However, patients with medially or centrally located tumors may benefit from the use of IMNI. Trial Registration ClinicalTrials.gov Identifier:NCT04803266

PURPOSE To identify the prognostic factors that could influence survival and to compare prognoses of the patients with the number of the risk factors that might assist in the adequate management of hepatocellular carcinoma (HCC) patients with bone metastases that showed a heterogeneous range of survival. MATERIALS AND METHODS A total of 41 patients, treated with radiotherapy (RT) for bone metastases from HCC from 2014 to 2017, were enrolled retrospectively. Survival was determined by the Kaplan-Meier method from the start of the RT for metastatic bone lesions. Pre-RT clinical features were evaluated and their influences on survival were analyzed. The significant factors were considered to compare survivals according to the number of prognostic factors. RESULTS Median follow-up was 6.0 months (range, 0.5 to 47.0 months). The median overall survival was 6.5 months, and the 1-year and 2-year survival rates were 35.5% and 13.5%, respectively. Multivariate analysis revealed that the Child-Pugh class A group, alpha-fetoprotein increased more than 30 ng/mL, and HCC size of more than 5 cm were associated with worse overall survival. The median survivals in HCC with none, 1, 2, and 3 of the aforementioned risk factors were 19.5, 9.0, 2.5, and 1.0 months, respectively (p < 0.05). CONCLUSION Our results show that the overall survivals were significantly different according to the number of the risk factors among HCC patients with bone metastases who showed various lengths of survival.

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.

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.

This study evaluated the clinical significance of the lymph-node ratio (LNR) and its usefulness as an indicator of supraclavicular lymph-node radiation therapy (SCNRT) in pN1 breast cancer patients with disease-free survival (DFS) outcomes. We retrospectively analyzed the clinical data of patients with pN1 breast cancer who underwent partial mastectomy and taxane-based sequential adjuvant chemotherapy with postoperative radiation therapy in 12 hospitals (n = 1121). We compared their DFS according to LNR, with a cut-off value of 0.10. The median follow-up period was 66 months (range, 3&ndash, 112). Treatment failed in 73 patients (6.5%) and there was no significant difference in DFS between the SCNRT group and non-SCNRT group. High LNR (&gt, 0.10) showed significantly worse DFS in both univariate and multivariate analyses (0.010 and 0.033, respectively). In a subgroup analysis, the effect of SCNRT on DFS differed significantly among patients with LNR &gt, 0.10 (p = 0.013). High LNR can be used as an independent prognostic factor for pN1 breast cancer patients treated with partial mastectomy and postoperative radiotherapy. It may also be useful in deciding whether to perform SCNRT to improve DFS.

// Haeyoung Kim 1 , Won Park 2 , Jeong Il Yu 2 , Doo Ho Choi 2 , Seung Jae Huh 2 , Yeon-Joo Kim 3 , Eun Sook Lee 3 , Keun Seok Lee 3 , Han-Sung Kang 3 , In Hae Park 3 , Kyung Hwan Shin 4 , Kyubo Kim 5 , Kyung Ran Park 5 , Yong Bae Kim 6 , Sung Ja Ahn 7 , Jong Hoon Lee 8 , Jin Hee Kim 9 , Mison Chun 10 , Hyung-Sik Lee 11 , Jung Soo Kim 12 and Jong-Young Lee 13 1 Department of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi, South Korea 2 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea 3 Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea 4 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea 5 Department of Radiation Oncology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, South Korea 6 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea 7 Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, South Korea 8 Department of Radiation Oncology, St. Vincent’s Hospital, The Catholic University of Korea College of Medicine, Suwon, South Korea 9 Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea 10 Department of Radiation Oncology, Ajou University School of Medicine, Suwon, Gyeonggi, South Korea 11 Department of Radiation Oncology, Dong-A University Hospital, Dong-A University School of Medicine, Busan, South Korea 12 Department of Radiation Oncology, Chonbuk National University Medical School, Jeonju, Jeollabuk, South Korea 13 Department of Radiation Oncology, Wonju Severance Christian Hospital, Wonju, Kangwon, South Korea Correspondence to: Won Park, email: // Keywords : breast neoplasms, radiotherapy, dose-response relationship, prognosis Received : May 17, 2016 Accepted : August 25, 2016 Published : October 25, 2016 Abstract Background and Purpose: This study was performed to determine optimal radiation dose in pN1 breast cancer patients who received breast conserving surgery (BCS) and anthracycline plus taxane (AT)-based chemotherapy. Materials and Methods: Retrospective chart reviews were performed in 1,147 patients who were treated between January 2006 and December 2010. The impact of radiation dose on treatment outcomes was evaluated. Results: Median follow-up time was 66 months. The 5-year rate of disease-free survival (DFS) was 93.2%. Larger tumor size (> 20 mm), positive lymphovascular invasion, high histologic grade, and high ratio of positive nodes (> 0.1) were significantly associated with inferior DFS. By using the 4 factors related to DFS, patients were categorized into high-risk (with ≥ 3 factors) and low-risk (with 60.3 Gy EQD2 ) was significantly associated with better DFS than the lower dose (≤ 60.3 Gy EQD2 ). However, the radiation dose did not impact DFS in the low-risk group. Conclusions: Dosing of radiation affects the outcome of post-BCS radiotherapy in pN1 breast cancer. Doses of over 60.3 Gy EQD2 were associated with better outcome in the high-risk patients.

There has been increasing use of external beam radiotherapy for localized treatment of hepatocellular carcinoma (HCC) with both palliative and curative intent. Quality control of target delineation in primary HCC is essential to deliver adequate doses of radiation to the primary tumor while preserving adjacent healthy organs. We analyzed interobserver variability in gross tumor volume (GTV) delineation for HCC. Twelve radiation oncologists specializing in liver malignancy participated in a multi-institutional contouring dummy-run study of nine HCC cases and independently delineated GTV on the same set of provided computed tomography images. Quantitative analysis was performed using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE) with kappa statistics calculating agreement between physicians. To quantify the interobserver variability of GTV delineations, the ratio of the actual delineated volume to the estimated consensus volume (STAPLE), the ratio of the common and encompassing volumes, and the coefficient of variation were calculated. The median kappa agreement level was 0.71 (range 0.28–0.86). The ratio of the actual delineated volume to the estimated consensus volume ranged from 0.19 to 1.93 (median 0.94) for all cases. The ratio of the common and encompassing volumes ranged from 0.001 to 0.56 (median 0.25). The coefficient of variation for GTV delineation ranged from 8 to 57 % (median 26 %). The interobserver variability in target delineation of HCC GTV in this study is noteworthy. Multi-institution studies involving radiotherapy for HCC require appropriate quality assurance programs for target delineation.

The purpose of the current in silico planning study is to compare radiation doses of whole-breast irradiation (WBI) and whole-breast plus regional lymph node irradiation (WBI+RNI) administered to the regional lymph nodes (RLN) in pN1 breast cancer. Twenty-four participating institutions were asked to create plans of WBI and WBI+RNI for two dummy cases. To compare target coverage between the participants, an isodose line equal to 90% of the prescribed dose was converted to an isodose contour (contour90% iso). The relative nodal dose (RND) was obtained using the ratio of RLN dose to the target dose. The Fleiss&rsquo, s kappa values which represent inter-observer agreement of contour90% iso were over 0.68. For RNI, 6 institutions included axillary lymph node (ALN), supraclavicular lymph node (SCN), and internal mammary lymph node (IMN), while 18 hospitals included only ALN and SCN. The median RND between the WBI and WBI+RNI were as follows: 0.64 vs. 1.05 (ALN level I), 0.27 vs. 1.08 (ALN level II), 0.02 vs. 1.12 (ALN level III), 0.01 vs. 1.12 (SCN), and 0.54 vs. 0.82 (IMN). In all nodal regions, the RND was significantly lower in WBI than in WBI+RNI (p &lt, 0.01). In this study, we could identify the nodal dose difference between WBI and WBI+RNI.

PURPOSE This multi-institutional study intended to investigate the effect of tumor bed boost in patients who achieved pathologic complete response (ypCR) following neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). MATERIALS AND METHODS We identified 180 patients who initially had lymph node (LN) metastasis and achieved ypCR (ypT0/isN0) following NAC and BCT from the 13 institutions of the Korean Radiation Oncology Group (KROG) 16-16 and KROG 12-05. The effect of tumor bed boost on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates was analyzed. RESULTS In all patients, five-year LRC, DFS and OS rates were 97.5%, 95.4%, and 99.4%, respectively. Tumor bed boost was performed in 158 (87.8%) patients. Advanced N-stage (cN2-3, p = 0.036), close resection margin (p

The Korean Radiation Oncology Group (KROG) 08-06 study protocol allowed radiation therapy (RT) technique to include or exclude breast cancer patients from receiving radiation therapy to the internal mammary lymph node (IMN). The purpose of this study was to assess dosimetric differences between the 2 groups and potential influence on clinical outcome by a dummy run procedure.All participating institutions were asked to produce RT plans without irradiation (Arm 1) and with irradiation to the IMN (Arm 2) for 1 breast-conservation treatment case (breast-conserving surgery [BCS]) and 1 mastectomy case (modified radical mastectomy [MRM]) whose computed tomography images were provided. We assessed interinstitutional variations in IMN delineation and evaluated the dose-volume histograms of the IMN and normal organs. A reference IMN was delineated by an expert panel group based on the study guidelines. Also, we analyzed the potential influence of actual dose variation observed in this study on patient survival.Although physicians intended to exclude the IMN within the RT field, the data showed almost 59.0% of the prescribed dose was delivered to the IMN in Arm 1. However, the mean doses covering the IMN in Arm 1 and Arm 2 were significantly different for both cases (P.001). Due to the probability of overdose in Arm 1, the estimated gain in 7-year disease-free survival rate would be reduced from 10% to 7.9% for BCS cases and 7.1% for MRM cases. The radiation doses to the ipsilateral lung, heart, and coronary artery were lower in Arm 1 than in Arm 2.Although this dummy run study indicated that a substantial dose was delivered to the IMN, even in the nonirradiation group, the dose differences between the 2 groups were statistically significant. However, this dosimetric profile should be studied further with actual patient samples and be taken into consideration when analyzing clinical outcomes according to IMN irradiation.

PURPOSE To explore the feasibility of maximum diameter as a response assessment method for vestibular schwannomas (VS) after stereotactic radiosurgery or fractionated stereotactic radiotherapy (RT), we analyzed the concordance of RT responses between maximum diameters and volumetric measurements. Materials and. METHODS Forty-two patients receiving curative stereotactic radiosurgery or fractionated stereotactic RT for VS were analyzed retrospectively. Twelve patients were excluded: 4 did not receive follow-up magnetic resonance imaging (MRI) scans and 8 had initial MRI scans with a slice thickness >3 mm. The maximum diameter, tumor volume (TV), and enhanced tumor volume (ETV) were measured in each MRI study. The percent change after RT was evaluated according to the measurement methods and their concordances were calculated with the Pearson correlation. The response classifications were determined by the assessment modalities, and their agreement was analyzed with Cohen kappa statistics. RESULTS Median follow-up was 31.0 months (range, 3.5 to 86.5 months), and 90 follow-up MRI studies were analyzed. The percent change of maximum diameter correlated strongly with TV and ETV (r(p) = 0.85, 0.63, p = 0.000, respectively). Concordance of responses between the Response Evaluation Criteria in Solid Tumors (RECIST) using the maximum diameters and either TV or ETV were moderate (kappa = 0.58; 95% confidence interval, 0.32-0.85) or fair (kappa = 0.32; 95% confidence interval, 0.05-0.59), respectively. Conclusions: The percent changes in maximum diameter and the responses in RECIST were significantly concordant with those in the volumetric measurements. Therefore, the maximum diameters can be used for the response evaluation of VS following stereotactic RT.

Introduction Rectal volume and movement are major factors that influence prostate location. The aim of this study was to assess the effect of a rectal enema on intrafraction prostate motion. Methods The data from 12 patients with localised prostate cancer were analysed. Each patient underwent image-guided radiotherapy (RT), receiving a total dose of 70 Gy in 28 fractions. Rectal enemas were administered to all of the patients before each RT fraction. The location of the prostate was determined by implanting three fiducial markers under the guidance of transrectal ultrasound. Each patient underwent preparation for IGRT twice before an RT fraction and in the middle of the fraction. The intrafraction displacement of the prostate was calculated by comparing fiducial marker locations before and in the middle of an RT fraction. Results The rectal enemas were well tolerated by patients. The mean intrafraction prostate movement in 336 RT fractions was 1.11 ± 0.77 mm (range 0.08–7.20 mm). Intrafraction motions of 1, 2 and 3 mm were observed in 56.0%, 89.0% and 97.6% of all RT fractions, respectively. The intrafraction movements on supero-inferior and anteroposterior axes were larger than on the right-to-left axes (P

Background: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II–III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). Methods: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. Results: After a median follow-up period of 66.2 months (range, 15.6–127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0−is vs 1 vs 2–4) and the number of LNs sampled (

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.

Background Postmastectomy adjuvant therapy is used to prevent locoregional recurrence and improve overall breast cancer specific survival rates. However, it can adversely affect the cosmetic results of reconstruction. Therefore, the authors examined flap stability and patients' satisfaction with immediate breast reconstruction after adjuvant therapy. Methods We retrospectively reviewed the medical records of 204 patients from January 2006 to November 2011. For complication rates, the authors categorized the patients who underwent the immediate breast reconstruction into 4 groups: adjuvant chemotherapy and radiotherapy group, adjuvant chemotherapy only group, adjuvant radiotherapy only group, and the group that did not undergo adjuvant therapy. For comparison of patients' satisfaction, the study was performed with an additional 16 patients who had undergone delayed breast reconstruction. Results Regarding complication rates, the group that had undergone adjuvant therapy showed no significant difference compared to the group that did not undergo adjuvant therapy. In evaluating the patients' satisfaction, there was no significant difference. Conclusions Even after adjuvant therapy, immediate breast reconstruction showed good results with respect to flap stability and patients' satisfaction. Immediate breast reconstruction and adjuvant therapy is a safe and useful option for breast cancer patients.

Aim: Adjuvant chemoradiation has become a standard of care in the USA. We evaluated the efficacy and toxicity of adjuvant chemoradiation versus chemotherapy in completely resected locally advanced gastric cancer. Methods: Patients with stage IIIA, IIIB and IV (without metastasis) gastric cancer were treated with chemoradiation and 5-fluorouracil/cisplatin (FP) (arm A) or FP (arm B). Arm A consisted of one cycle of FP followed by 4500 cGY to radiation field with capecitabine. One month after completion of radiotherapy, patients received three additional cycles of FP every 3 weeks. Arm B consisted of six cycles of FP. Results: A total of 61 patients were enrolled, of whom 31 were placed in arm A and 30 in arm B. The median follow-up duration was 77.2 months (range 24–92.8 months). We did not find any difference in 3-year disease-free survival between arm A and B (80.0 vs 75.2%, respectively; P = 0.887). There was no significant difference between the arms in 5-year disease-free survival (76.7 vs 59.1%, respectively; P = 0.222) or overall survival (70.1 vs 70.0%, respectively; P = 0.814). Seven patients (22.6%) relapsed in arm A and 12 patients (40%) relapsed in arm B. Grade 3/4 neutropenia occurred in 48.5% of patients in arm A and 22.9% in arm B. Grade 3 nausea or vomiting occurred in 6% in arm A and 14.6% in arm B. Conclusion: We could not make any conclusion about the benefit of adding radiation to adjuvant chemotherapy.

Nuclear factor-kappaB (NF-kappaB), hypoxia-inducible factor 1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) are involved in cell proliferation, invasion, angiogenesis, and metastases. The principal objective of this study was to assess the prognostic significance of NF-kappaB, HIF-1alpha, and VEGF expression in stage III colorectal cancer. Tumor tissues from 148 patients with stage III colorectal carcinoma, all of whom underwent potentially curative resection, were immunohistochemically evaluated using monoclonal antibodies against NF-kappaB, HIF-1alpha, and VEGF. Positivity rates of NF-kappaB, HIF-1alpha, and VEGF were 47.3%, 42.6%, and 61.5%, respectively. NF-kappaB expression in tumor tissues was correlated significantly with HIF-1alpha expression (P < 0.001), VEGF expression (P = 0.044), and the presence of vascular invasion (P = 0.013). Univariate analysis demonstrated that NF-kappaB expression was associated with poor 5-year overall survival (55.8 months vs 76.9 months, P = 0.012). Multivariate analysis verified that NF-kappaB was independently associated with adverse outcomes (relative risk: 1.92, P = 0.049). However, HIF-1alpha and VEGF did not appear to be related to clinical outcomes. NF-kappaB expression in tumor tissue is associated with angiogenesis and poor 5-year overall survival in stage III colorectal cancer patients.

Background: The principal objective of this study was to assess clinical outcomes by breast cancer subtype in patients with brain metastases. Methods: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status was evaluated via immunohistochemical staining. Four survival time intervals were compared according to the subtype (ER+/HER2–, HER2+, triple negative (TN)). Results: 20 (30.3%) of the 66 patients in this study were ER+/HER2–, 20 (30.3%) were HER2+, and 26 (39.4%) were TN. The disease-free survival rates of ER+/HER2–, HER2+, and TN patients were 30.0, 17.0, and 17.9 months, respectively (p = 0.040). The median time intervals from distant metastasis to brain metastasis were 20.6, 19.5, and 9.0 months, respectively (p = 0.012). The times from initial diagnosis to brain metastasis were 52.9, 33.6, and 25.5 months, respectively (p = 0.026). However, the overall survival rates did not differ significantly (p = 0.276). Conclusions: Patients with TN breast cancer were more likely to develop distant metastasis earlier, and also evidenced poor overall survival. Triple receptor status may be employed as a prognostic marker for breast cancer patients with brain metastases.

AIM To determine the national practice processes of care and outcomes of radiotherapy for hepatocellular carcinoma (HCC) in Korea. PATIENTS AND METHODS A national survey of 53 institutions nationwide was conducted by requesting data on their experience of radiotherapy for HCC. Among them, 10 institutions were selected for performing more detailed analysis, based on the radiotherapy experience of at least five HCC patients between 2004 and 2005. RESULTS This study covered the treatment of 398 HCC patients for 2 years. Most patients (78%) were in stage III or IV. Radiotherapy was chosen after the failure of other treatments, most frequently transarterial chemoembolization. Radiotherapy was performed predominantly using the three-dimensional conformal technique (3D-CRT, 81.9%) mostly with a total dose of >/=45 Gy. In 9.3% of the patients, radiotherapy was performed using radiosurgery. In a biologically effective dose (BED) with 10 Gy of alpha/beta, 4.2-124.3 Gy(10) was delivered. The median survival time was 12 months, and the 2-year overall survival rate was 27.9%. A tumour size 53.1 Gy(10) were shown by multivariate analysis to be significant factors for a better prognosis. In a subset analysis for the 326 patients treated with 3D-CRT, better liver function with Child-Pugh class A was shown to be an additional factor for a better prognosis. CONCLUSIONS Radiotherapy has been used to treat advanced HCC in various modes, but mostly as a salvage treatment. Although this study was retrospective, it indicates that radiotherapy is a quite effective modality for HCC patients.

The transverse tensile properties of phenolic composites reinforced with spun-type carbon fabrics (spun C/P composites) have been investigated in order to evaluate the adherent failure behavior of composites in the transverse (90°) direction due to tension. The transverse tensile strength of the spun C/P composite is about 3.4 times higher than that of the conventional composite reinforced with filament type carbon fabrics (filament C/P composites). It is found from stress–strain curve of composites that it exhibits above 4 times higher failure strain than the filament C/P composite. However, the transverse tensile modulus of the spun C/P composite is similar to that of the filament C/P composite. The results indicate that the protruded fibers of spun yarns between the interlaminar layers in the spun C/P composite play an important role in improving the transverse tensile properties by the effects of fiber bridging. Consequently, this result suggests that use of spun yarn type carbon fabrics as reinforcem...

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.

OBJECTIVE The interferon-induced, double-stranded RNA-activated, protein kinase (PKR) is a key regulator of translational initiation, and plays an important role in the regulation of cell proliferation, apoptosis and transformation. The aim of this study was to evaluate the prognostic significance of PKR in lymph node negative rectal cancer. METHODS Forty-three patients with stage II rectal carcinoma who underwent potentially curative resection followed by post-operative adjuvant chemoradiation and 5-fluorouracil-based chemotherapy were investigated immunohistochemically using the monoclonal antibody TJ4C4. Overall scores for PKR expression were calculated based on staining intensity and immunoreactive tumor cell fraction. Clinical information, including tumor grade, carcinoembryonic antigen (CEA), disease-free survival (DFS) and overall survival (OS) was evaluated and compared with the degree of PKR expression. RESULTS The median follow-up duration was 53.2 months, and median patient age was 55 years (range 33-73). No relationships were found between PKR score and age, sex, tumor grade or CEA level; however, smaller tumors (< or =5 cm) were associated with high PKR score (P = 0.025). When patients were subdivided into two groups based on the PKR score, the relapse rate was lower for those with a high PKR score (7.4 versus 43.8%, P = 0.008), and a significant difference was found between these two groups in terms of 5 year DFS (92.6 versus 55.6%, P = 0.0072) and 5 year OS (92.6 versus 57.7%, P = 0.0459). Other clinicopathologic variables were not related to clinical outcome. CONCLUSION PKR expression levels were associated with disease recurrence, DFS and OS in lymph node negative rectal cancer patients.

PURPOSE: To identify the genes involved in the carcinogenesis and progression of colorectal cancer, we analyzed the gene-expression profiles of colorectal cancer cells from 12 tumors with corresponding noncancerous colonic epithelia using a cDNA microarray representing 4,08 genes. METHODS: We classified both samples and genes by using a twoway clustering analysis and identified genes that were differentially expressed in the cancerous and noncancerous tissues. Genes associated with lymph node metastasis were identified by means of the supervised learning technique. RESULTS: Differentially expressed genes (77 up-regulated and 45 down-regulated genes) were identified in more than 75 percent of the tumors. The functional categories of these genes belonged to signal transduction (19 percent), metabolism (17 percent), cell structure/motility (14 percent), cell cycle (13 percent), and gene protein expression (13 percent). The gene expression pattern of reverse transcriptase polymerase chain reaction (RT-PCR) results from randomly selected genes shows a pattern similar to that of cDNA microarray. Moreover, the gene expression patterns observed were similar to those reported previously, suggesting rare racial differences. Sixty genes possibly associated with lymph node metastasis in colorectal cancer were selected on the basis of clinicopathological data obtained by performing signal-to-noise calculations. “Leave-one-out” cross-validation testing correctly classified 10 of 12 patients (83.3 percent) as having colorectal cancer with lymph node metastasis vs. those without metastasis. CONCLUSIONS: These results provide not only a new molecular basis for understanding the biologic properties of colorectal cancer, including lymph node metastasis, but also provide a resource for future development of therapeutic targets and diagnostic markers for colorectal cancer.

Purpose To assess the feasibility and therapeutic benefits of a combination of external beam radiotherapy (EBRT) and high-dose-rate intraluminal brachytherapy (ILBT) for treating patients with inoperable carcinoma of the extrahepatic bile ducts. Methods and materials Of 31 patients who received RT at the Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Korea between 1986 and 1995, 17 patients underwent EBRT alone (Group 1) and 14 patients were treated with EBRT in combination with high-dose-rate ILBT (Group 2). After external drainage, EBRT was delivered with a total dose ranging from 36 to 55 Gy (median 50.4) in both groups. High-dose-rate ILBT for the patients in Group 2 was performed using a high-intensity 192 Ir source (Gamma-med remote afterloading system) within the expandable intrabiliary prosthesis (Gianturco stent), inserted transhepatically at the site of the obstruction. The radiation dose of the high-dose-rate ILBT was prescribed at 1.5 cm from the center of the source with a single daily dose of 5 Gy to a total of 15 Gy given in three fractions. The response rate, patterns of treatment failure, treatment morbidity, and survival data in the two groups were compared. Results Although locoregional recurrence was the most common pattern of failure in both groups, no statistically significant difference was found in the recurrence rates between those who did and did not receive ILBT (53% for Group 1 vs. 36% for Group 2; p > 0.05). However, a prolongation of the median time to tumor recurrence was observed in the Group 2 patients (5 months for Group 1 vs. 9 months for Group 2; p = 0.06). When the EBRT dose delivered was >50 Gy, most patients experienced various degrees of GI symptoms, but the frequency of radiation-induced complications in the two groups was similar. No enhancement in treatment morbidity was attributed to the addition of high-dose-rate ILBT to EBRT. With a median follow-up of 12 months, the overall actuarial 2-year survival rate for Group 2 patients was significantly better than that for Group 1 patients (0% for Group 1 vs. 21% for Group 2; p = 0.015). Conclusion Given these observations, we believe that the combined use of EBRT and high-dose-rate ILBT is a beneficial, relatively safe, and effective method of improving the treatment outcome in selected patients with inoperable carcinoma of the extrahepatic bile ducts.

Park, H. J., Lee, S. H., Chung, H., Rhee, Y. H., Lim, B. U., Ha, S. W., Griffin, R. J., Lee, H. S., Song, C. W. and Choi, E.;thK. Influence of Environmental pH on G2-Phase Arrest Caused by Ionizing Radiation. Radiat. Res. 159, 86–93 (2003). We investigated the effects of an acidic environment on the G2/M-phase arrest, apoptosis, clonogenic death, and changes in cyclin B1-CDC2 kinase activity caused by a 4-Gy irradiation in RKO.C human colorectal cancer cells in vitro. The time to reach peak G2/M-phase arrest after irradiation was delayed in pH 6.6 medium compared to that in pH 7.5 medium. Furthermore, the radiation-induced G2/M-phase arrest decayed more slowly in pH 6.6 medium than in pH 7.5 medium. Finally, there was less radiation-induced apoptosis and clonogenic cell death in pH 6.6 medium than in pH 7.5 medium. It appeared that the prolongation of G2-phase arrest after irradiation in the acidic environment allowed for greater repair of radiation-induced DNA damage, thereby decreasing the radi...

Purpose The purpose of this study was to investigate the efficacy and toxicity of radiation therapy (RT) following incomplete transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC). Methods and Materials The study was designed as a prospective phase 2 multicenter trial. Patients with unresectable HCC, who had viable tumor after TACE of no more than 3 courses, were eligible. Three-dimensional conformal RT (3D-CRT) was added for HCC treatment with incomplete uptake of iodized oil, and the interval from TACE to RT was 4 to 6 weeks. The primary endpoint of this study was the tumor response after RT following incomplete TACE in unresectable HCC. Secondary endpoints were patterns of failure, progression-free survival (PFS), time to tumor progression (TTP), overall survival (OS) rates at 2 years, and treatment-associated toxicity. Survival was calculated from the start of RT. Results Between August 2008 and December 2010, 31 patients were enrolled. RT was delivered at a median dose of 54 Gy (range, 46-59.4 Gy) at 1.8 to 2 Gy per fraction. A best objective in-field response rate was achieved in 83.9% of patients, with complete response (CR) in 22.6% of patients and partial response in 61.3% of patients within 12 weeks post-RT. A best objective overall response rate was achieved in 64.5% of patients with CR in 19.4% of patients and PR in 45.1% of patients. The 2-year in-field PFS, PFS, TTP, and OS rates were 45.2%, 29.0%, 36.6%, and 61.3%, respectively. The Barcelona Clinic liver cancer stage was a significant independent prognostic factor for PFS ( P =.023). Classic radiation-induced liver disease was not observed. There were no treatment-related deaths or hepatic failure. Conclusions Early 3D-CRT following incomplete TACE is a safe and practical treatment option for patients with unresectable HCC.

We studied the modulating effect of protein tyrosine kinase inhibitors on the response of cells of the human chronic myelogenous leukemia cell line K562 to radiation. The radiosensitivity of the cells was increased by treatment with herbimycin A and decreased by treatment with genistein. This modulating effect of protein tyrosine kinase inhibitors on radiation sensitivity was associated with the alteration of the mode of radiation-induced cell death. After X irradiation, the cells arrested in the G(2) phase of the cell cycle, but these TP53(-/-) cells were unable to sustain cell cycle arrest. This G(2)-phase checkpoint deficit caused cell death. The morphological pattern of cell death was characterized by swelling of the cytoplasmic compartments, cytosolic vacuolation, disruption of the plasma membrane, less evident nuclear condensation, and faint DNA fragmentation, all of which were consistent with oncosis or cytoplasmic apoptosis. The nonreceptor protein tyrosine kinase inhibitor herbimycin A accelerated the induction of typical apoptosis by X irradiation, which was demonstrated by morphological assessments using nuclear staining and electron microscopy as well as oligonucleosomal fragmentation and caspase 3 activity. Herbimycin A is known to be a selective antagonist of the BCR/ABL kinase of Philadelphia chromosome-positive K562 cells; this kinase blocks the induction of apoptosis after X irradiation. Our results showed that the inhibition of protein tyrosine kinase by herbimycin A enhanced radiation-induced apoptosis in K562 cells. This effect was associated with the activation of caspase 3 and rapid abrogation of the G(2)-phase checkpoint with progression out of G(2) into G(1) phase. In contrast, the receptor-type protein tyrosine kinase inhibitor genistein protected K562 cells from all types of radiation-induced cell death through the inhibition of caspase 3 activity and prolonged maintenance of G(2)-phase arrest. Further investigations using this model may give valuable information about the mechanisms of radiation-induced apoptosis and about the radiosensitivity and radioresistance of chronic myelogenous leukemia cells having the Philadelphia chromosome.

Agency for Deefnse Development P., O. Box 35-5, Yuseong Dae, eoj n 305-600, KoreaReceived August 1, 2005Key Words : Polyisoprene Vu, lcanizate without eeml enat slulfur, Thermal aging Cro, sslink denstiyRubber materials have good physical properties bycrosslinking. Crosslink density of a rubber vulcanizatedetermines the physical properties.

PURPOSE: The aim of this nonrandomized study was to assess effects against radiation-induced enteropathy by constructing an omental pedicle hammock, thus isolating the small bowel outside the pelvis. METHODS: Since 1991, 32 patients received the omental pedicle hammock procedure as an adjunct to definitive cancer surgery, and the perioperative experiences and toxic effects of radiation therapy were evaluated and compared with 25 patients who received pelvic floor reperitonealization only. RESULTS: There were no surgical complications related to the omental hammock procedure. Contrary to control cases that showed the bowel to adhere deeply in the pelvis, exclusion of the small bowel from the pelvic cavity demonstrated by contrast study was successful in all except four cases of a segment of bowel loop descent within the radiation portals. According to acute and late radiation morbidity scoring criteria, 26 patients (81 percent) scored Grade 0 in the treatment group, whereas only 3 patients (12 percent) scored Grade 0 in the control group (P

PURPOSE There are conflicting results surrounding the prognostic significance of epidermal growth factor receptor (EGFR) status in glioblastoma (GBM) patients. Accordingly, we attempted to assess the influence of EGFR expression on the survival of GBM patients receiving postoperative radiotherapy. MATERIALS AND METHODS Thirty three GBM patients who had received surgery and postoperative radiotherapy at our institute, between March 1997 and February 2006, were included. The evaluation of EGFR expression with immunohistochemistry was available for 30 patients. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. RESULTS EGFR was expressed in 23 patients (76.7%), and not expressed in seven (23.3%). Survival in EGFR expressing GBM patients was significantly less than that in non-expressing patients (median survival: 12.5 versus 17.5 months, p=0.013). Patients who received more than 60 Gy showed improved survival over those who received up to 60 Gy (median survival: 17.0 versus 9.0 months, p=0.000). Negative EGFR expression and a higher radiation dose were significantly correlated with improved survival on multivariate analysis. Survival rates showed no differences according to age, sex, and surgical extent. CONCLUSION The expression of EGFR demonstrated a significantly deleterious effect on the survival of GBM patients. Therefore, approaches targeting EGFR should be considered in potential treatment methods for GBM patients, in addition to current management strategies.

To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver.Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d.Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC.The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis.

Adjuvant chemoradiation has become a standard of care in the USA. We evaluated the efficacy and toxicity of adjuvant chemoradiation versus chemotherapy in completely resected locally advanced gastric cancer.Patients with stage IIIA, IIIB and IV (without metastasis) gastric cancer were treated with chemoradiation and 5-fluorouracil/cisplatin (FP) (arm A) or FP (arm B). Arm A consisted of one cycle of FP followed by 4500 cGY to radiation field with capecitabine. One month after completion of radiotherapy, patients received three additional cycles of FP every 3 weeks. Arm B consisted of six cycles of FP.A total of 61 patients were enrolled, of whom 31 were placed in arm A and 30 in arm B. The median follow-up duration was 77.2 months (range 24-92.8 months). We did not find any difference in 3-year disease-free survival between arm A and B (80.0 vs 75.2%, respectively; P = 0.887). There was no significant difference between the arms in 5-year disease-free survival (76.7 vs 59.1%, respectively; P = 0.222) or overall survival (70.1 vs 70.0%, respectively; P = 0.814). Seven patients (22.6%) relapsed in arm A and 12 patients (40%) relapsed in arm B. Grade 3/4 neutropenia occurred in 48.5% of patients in arm A and 22.9% in arm B. Grade 3 nausea or vomiting occurred in 6% in arm A and 14.6% in arm B. We could not make any conclusion about the benefit of adding radiation to adjuvant chemotherapy.

To control pitch and yaw motion of a TVC(Thrust Vector Control) nozzle with 3-DOF(Degree Of Freedom), additional apparatuses are usually required to prevent induced rolling motion. However, the supplemental devices bring hardware designers many difficulties related to the spatial arrangement of TVC nozzle and actuators. In this paper, in order to solve the problem, the type of two joints linked between the nozzle and two actuators are proposed. And, by using the proposed type of two joints, new kinematic model to restrict the rolling motion is established. Moreover, a novel control algorithm based on the analytic solution for the kinematic model is suggested. The usefulness of this algorithm is verified through simulation study.

Purpose The aim of this study is to present the incidence of radiation pneumonitis (RP) reported within 6 months after treatment for breast cancer with or without internal mammary node irradiation (IMNI). Methods In the Korean Radiation Oncology Group (KROG) 08-06 phase III randomized trial, patients who were node-positive after surgery were randomly assigned to receive radiotherapy either with or without IMNI. A total of 747 patients were enrolled, and three-dimensional treatment planning with computed tomography simulation was performed for all patients. Of the 747 patients, 722 underwent chest X-rays before and within 6 months after radiotherapy. These 722 patients underwent evaluation, and RP was diagnosed on the basis of chest radiography findings and clinical symptoms. The relationship between the incidence of RP and clinical/dosimetric parameters was analyzed. Results RP developed in 35 patients (4.8%), including grade 1 RP in 26 patients (3.6%), grade 2 RP in nine patients (1.2%); there was no incidence of grade 3 or higher RP. Grade 2 RP cases were observed in only the IMNI group. The risk of developing RP was influenced by IMNI treatment; pneumonitis occurred in 6.5% of patients (n=23/356) who underwent IMNI and in 3.3% of patients (n=12/366) who did not (p=0.047). The differences in lung dosimetric parameters (mean lung dose, V10-40) were statistically significant between the two groups. Conclusion IMNI treatment resulted in increased radiation exposure to the lung and a higher rate of RP, but the incidence and severity of RP was minimal and acceptable. This minor impact on morbidity should be balanced with the impact on survival outcome in future analyses.

HS-1200, a synthetic chenodeoxycholic acid derivative, has cytotoxic activity in various human cancer cells. The present study was undertaken to examine whether HS-1200 sensitizes radiation-induced apoptosis in MCF-7 human breast carcinoma cells. Clonogenic assay elucidated that the combination treatment with HS-1200 and radiation induced more cytotoxic effects than the radiation treatment alone. Nuclear staining, DNA electrophoresis and Western blot analysis for poly(ADP-ribose) polymerase revealed that the increased cytotoxic effect by the combination treatment resulted from the augmentation of apoptosis. There was an increase in the expression level of Bax and its translocation onto the mitochondria, a reduction in the mitochondrial membrane potential in the earlier time-points, and the release of cytochrome c into the cytosol increased in the MCF-7 cells treated with radiation and HS-1200 compared to the cells treated only with radiation. Therefore, the synthetic bile acid derivative, HS-1200, could have the therapeutic potential as a radiosensitizer in MCF-7 cells.

Tumor budding along the invasive margin is known to be associated with biological behavior in colorectal carcinoma. The aims of this study were to explore if the semiquantitative assessment of tumor budding in rectal cancers correlates with oncological behavior and to appraise if the tumor budding is valid as a pathological parameter in distinguishing tumors with higher malignancy potential from those with lower one for prognostic stratification. Surgical specimens from 244 patients with well- or moderately differentiated rectal carcinoma were retrieved to assess the intensity of tumor budding at the invasive margin. Intensities were divided semiquantitatively into four groups based on quartiles, and the 5-year disease-free survivals (DFS) were analyzed to search for a cutoff point of prognostic stratification. The cutoff of the intensity considered to be the best indicator for dividing patients into subgroups with different DFS was between quartiles 3 and 4, but this survival difference in subgroups in either side of the cutoff was significant only in stage-III disease [5-year DFS, 62.1 vs 35.1%; p = 0.0023; 95% confidence interval (CI), 0.1824–0.6919]. Based on multivariate analysis, the intensity of budding proved to be an independent variable associated with DFS (hazard ratio, 2.005; p = 0.0086; 95% CI, 1.021–3.934). When scores were given to grade of budding (lower, 0; higher, 1) and N stage (N1, 0; N2, 1) in stage III, a better prognostic stratification in terms of the 5-year DFS was obtained than the American Joint Committee on Cancer nodal staging only (0 vs 1 vs 2, 66.5 vs 42.6 vs 29.2%; p = 0.0101). Quantitative assessment of tumor budding is a reliable biological prognostic variable to identify higher malignancy potential. Scoring system using tumor budding and N stage showed better prognostic stratification in stage-III rectal carcinoma. A prospective evaluation would confirm the clinical significance of tumor budding for prognostic stratification.

To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection.Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m(2) on d 1 to 5 and cisplatin 60 mg/m(2) on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m(2) daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo.The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed.These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival.

To evaluate the effect of an intravenous contrast agent (CA) on dose calculations and its clinical significance in intensity modulated radiation therapy (IMRT) plans for head and neck cancer.Fifteen patients with head and neck cancer and involved neck nodes were enrolled. Each patient took two sets of computerized tomography (CT) in the same position before and after intravenous CA injections. Target volumes and organs at risk (OAR) were contoured on the enhanced CT, and then an IMRT plan of nine equiangular beams with a 6 MV X-ray was created. After the fusion of non-enhanced and enhanced CTs, the contours and the IMRT plan created from the enhanced CT were copied and placed to the non-enhanced CT. Doses were calculated again from the non-enhanced CT by the same IMRT plan. The radiation doses calculated from the two sets of CTs were compared with regard to planning target volumes (PTV) and the three OARs, both parotid glands and the spinal cord, by Wilcoxon's signed rank test.The doses (maximum, mean, and the dose of 95% of PTV received (D95%)) of PTV70 and PTV59.4 calculated from the enhanced CTs were lower than those from the non-enhanced CTs (p0.05), but the dose differences were less than 1% compared to the doses calculated from the enhanced CTs. The doses of PTV50.4, parotid glands, and spinal cord were not significantly different between the non-enhanced and enhanced CTs.The difference between the doses calculated from the CTs with and without CA enhancement was tolerably small, therefore using intravenous CA could be recommended for the planning CT of head and neck IMRT.

Doxorubicin is known to be the most effective single cytotoxic drug against anaplastic thyroid carcinoma (ATC). Although doxorubicin has been shown to cause cell death, at least partly, by inducing apoptosis in ATC cells, the mechanism underlying its pharmacological efficacy has not been fully delineated. We, in this study, revealed that doxorubicin induced apoptosis in ATC cells by altering the acetylation state of histone. Doxorubicin reduced histone deacetylase activity and induced hyperacetylation of histone 3. Noticeably, ladder-like DNA fragments from their genomic DNA on agarose gel were not detected irrespective of several lines of evidence supporting the induction of apoptosis. Pulse field electrophoresis showed disintegration of nuclear DNA into giant fragments of 1-2 Mbp and high molecular-weight fragments of 100-1000 kbp. We next examined whether a histone deacetylase inhibitor trichostatin A (TsA) augmented doxorubicin-induced apoptosis in ATC cells. TSA potentiated doxorubicin-induced stage I apoptosis in ATC cells. Our study sheds light on the development of a new combination therapy strategy for more effective responses for ATC treatment.

Purpose: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes. MMPs are known to be involved in tumor invasion, and several have been implicated in tumor prognosis. The aim of this study was to evaluate the prognostic significances of the expressions of MMP-7 and -9 in rectal cancer. Materials and Methods: The tumor tissues of 87 patients with stage II or III rectal carcinoma that underwent potentially curative resection followed by postoperative adjuvant chemoradiation and 5-fluorouracil based chemotherapy, were investigated immunohistochemically using monoclonal antibodies against MMP-7 and MMP-9. Clinical information, including tumor grades, carcinoembryonic antigen (CEA) levels, and disease-free survival and overall survival were evaluated with respect to the expressions of MMP-7 and -9. Results: Median follow-up duration was 53.2 months, and median patient age was 5511 years (range 32-75). MMP-7 expression in tumor tissue was found to be significantly correlated with the presence of nodal metastasis (p=0.029), whilst MMP-9 expression correlated with depth of tumor invasion (p=0.019). No relationships were found between the expressions of MMP-7 or -9 and age, sex, tumor size, tumor grade, or CEA level. Univariate analysis showed that MMP-7 expression was associated with poor 5-year overall survival (12.8 months vs. 65.3 months, p=0.0405). Multivariate analysis confirmed that MMP-7 was independently associated with an adverse outcome (Relative risk: 1.415, p=0.027). However, MMP-9 expression was not found to be related to clinical outcome. Conclusion: MMP-7 expression in tumor tissue is associated with lymph node metastasis and a poor 5-year overall survival in rectal cancer patients.

PURPOSE The combination of chemoradiation and fluorouracil based chemotherapy has been the standard adjuvant treatment for colorectal cancer patients. The aim of this study was to evaluate treatment outcome of patients classified by the new AJCC staging system and to compare treatment outcome of oral doxifluridine and the standard Mayo Clinic regimen after chemoradiation in advanced rectal cancer patients. MATERIALS AND METHODS One hundred nine patients underwent curative surgical resection and chemoradiation followed by chemotherapy. 45 Gy pelvic irradiation was given to the entire pelvis and the boost radiation with 50.4 to 54 Gy, and simultaneously 5-fluorouracil (5-FU) 375 mg/m(2)/day was given on day 1 approximately 3 and 26 approximately 28. After the completion of chemoradiation, patients were given either 6 cycles of the Mayo Clinic regimen (5-FU 425 mg/m(2) plus leucovorin 20 mg/m(2) intravenous bolus infusion on day 1~5, every 4 weeks) or oral doxifluridine (600 mg/m(2)/day) for 1 year. RESULTS The median follow-up duration was 30 months. Among 102 evaluable patients, 38 patients (37.3%) relapsed: the locoregional recurrence in 10 patients (9.8%) and systemic relapse in 28 patients (27.5%). The systemic relapse rate was 15.6% in the stage IIA, 25.0% in the stage IIIB , and 59.1% in the stage IIIC (p=0.048). The 5-year disease-free survival (DFS) rate was significantly higher in the IIA and IIIA patients than the IIIB and IIIC patients (72% and 100% vs 48.1% and 11.2%, respectively. p

We assessed whether the urokinase could increase the yield of progenitor cells during processing in elapsed, anticoagulated cord blood (CB) after collection, and we also determined the optimal dose of urokinase. The total nucleated cell (TNC) counts after red cell depletion in 48-hr-elapsed CB were significantly higher in samples treated with 10,000 and 50,000 IU of urokinase/mL than in untreated samples or treated with 5,000 IU of urokinase/mL. The CD34+ cell counts were significantly higher in samples treated with 10,000 IU of urokinase/mL than in untreated samples and in samples treated with 5,000 or 50,000 IU of urokinase/mL. In 6-, 12-, and 24-hr-elapsed CB, however, there were no significant differences of TNC, CD34+ cells, or CFU-GM counts between untreated samples and samples treated with 10,000 IU of urokinase/mL. These findings suggest that the addition of 10,000 IU of urokinase/mL before red cell depletion in 48-hr-elapsed, anticoagulated CB could increase the yield of progenitor cells. However, there are no advantages in using urokinase for processing CB prior to 24 hr after collection. Am. J. Hematol. 71:336–339, 2002. © 2002 Wiley-Liss, Inc.

Purpose: To assess the effect of a rectal enema on interfraction prostate movement in bone alignment (BA) for prostate radiotherapy (RT), we analyzed the spatial difference in prostates in a bone-matched setup. Materials and Methods: We performed BA retrospectively with data from prostate cancer patients who underwent image-guided RT (IGRT). The prostate was identified with implanted fiducial markers. The setup for the IGRT was conducted with the matching of three fiducial markers on RT planning computed tomography images and those on two oblique kV x-ray images. Offline BA was performed at the same position. The coordinates of a virtual prostate in BA and a real prostate were obtained by use of the ExaxTrac/NovalisBody system, and the distance between them was calculated as the spatial difference. Interfraction prostate displacement was drawn from the comparison of the spatial differences. Results: A total of 15 patients with localized prostate cancer treated with curative hypofractionated IGRT were enrolled. A total of 420 fractions were analyzed. The mean of the interfraction prostate displacements after BA was 3.12±2.00 mm (range, 0.20–10.53 mm). The directional difference was profound in the anterior-posterior and supero-inferior directions (2.14±1.73 mm and 1.97±1.44 mm, respectively) compared with the right-left direction (0.26±0.22 mm, p＜0.05). The required margin around the clinical target volume was 4.97 mm with the formula of van Herk et al. Conclusions: The interfraction prostate displacement was less frequent when a rectal enema was performed before the procedure. A rectal enema can be used to reduce interfraction prostate displacement and resulting clinical target volume-to-planning target volume margin.