Hyebin Lee

Tumor volume reduction rate measured during adaptive definitive radiation therapy as a potential prognosticator of locoregional control in patients with oropharyngeal cancer.

The purpose of this study was to evaluate the prognostic significance of the tumor volume reduction rate (TVRR) measured during adaptive definitive radiation therapy (RT) in patients with oropharyngeal cancer.

Overexpression of epithelial-mesenchymal transition–related markers according to cell dedifferentiation: clinical implications as an independent predictor of poor prognosis in cholangiocarcinoma ☆

Although increased evidence has suggested that epithelial-mesenchymal transition has been implicated in cancer invasion and is associated with poor prognosis, its significance in cholangiocarcinoma remains unclear. We evaluated the levels of expression of epithelial-mesenchymal transition-related genes and proteins in 2 established human cholangiocarcinoma cell lines with different morphological characteristics and performed transwell cell invasion assays. Furthermore, we investigated the association between altered expression of 6 epithelial-mesenchymal transition-related proteins and clinical outcomes in human cholangiocarcinoma patients (n = 119) by immunohistochemistry using a tissue microarray approach. Comparative analysis of protein and messenger RNA expression revealed that the cell line with less differentiation (JCK) showed increased expression of mesenchymal markers and zinc-finger proteins and decreased expression of epithelial markers. The invasion activity of JCK cells was significantly higher than that of cells from OZ cell lines. Tissue microarray analysis revealed that the combined expression pattern of 6 epithelial-mesenchymal transition-related proteins predicted shortened disease-free survival (13.0 versus 22.0 months, P = .033) and overall survival (23.0 versus 63.0 months, P = .003) and was confirmed as an independent unfavorable prognostic factor for survival in multivariate survival analysis (disease-free survival, P = .028 for the 3 epithelial-mesenchymal transition-related markers; overall survival, P = .010 for the 6 epithelial-mesenchymal transition-related markers). In conclusion, our results suggest that altered expression of a number of epithelial-mesenchymal transition-related genes in tumor cells with poor differentiation may explain their increased invasive ability. Our results also suggest that altered expression of a suite of epithelial-mesenchymal transition-related proteins could be used as a tool to predict poor outcomes in human cholangiocarcinoma patients.

The efficacy of high-dose 3-dimensional conformal radiation therapy in patients with small hepatocellular carcinoma not eligible for other local modalities.

Purpose:To analyze the efficacy and toxicity of high-dose 3-dimensional conformal radiation therapy (3D-CRT) for patients with small hepatocellular carcinoma (HCC) not eligible for other local modalities. Methods:Between 1998 and 2006, 61 patients with small HCC were treated with high-dose 3D-CRT. The eligibility criteria were as follows: (1) HCC <5 cm; (2) HCC without vascular invasion; (3) HCC without extrahepatic metastasis; and (4) not eligible for other local modalities. The median RT dose was 54 Gy (range, 36 to 55 Gy) daily in 2.5 to 5 Gy fractions. We evaluated tumor response, local control, overall survival, pattern of failure, and toxicity. Results:The median follow-up period was 16.7 months. Tumor response was 68.9% (42 of 61 lesions) with a complete response in 27 lesions (44.3%). Local control was 93.8% at 1 year and 86.9% at 3 years. Intrahepatic metastases developed in 40 patients (65.6%). Thirteen patients (22.3%) had extrahepatic metastasis. The median survival was 56 months (range, 2.8 to 68.1 mo), and the overall survival rate was 81.1% at 1 year and 58.4% at 3 years. Three patients developed radiation-induced liver disease, but there were no instances of grade 3 or higher toxicity. Conclusions:High-dose 3D-CRT for small HCC <5 cm showed favorable local control and overall survival without serious complications. RT might be an effective local modality in patients with small HCC not eligible for other local modalities.

Comparative analysis of immunohistochemical markers for differential diagnosis of hepatocelluar carcinoma and cholangiocarcinoma

AIMS AND BACKGROUNDnDifferential diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma is sometimes difficult to accurately perform.nnnMETHODSnEight markers including cytokeratin 7 (CK7), cytokeratin 19 (CK19), MOC31, CD10, glypican 3 (GPC3), claudin 4, biglycan and high mobility group A1 (HMGA1) were immunohistochemically stained in samples from 179 surgically resected hepatocellular carcinomas and 127 intrahepatic cholangiocarcinomas, and the rates of marker expression were statistically compared.nnnRESULTSnWith the exception of biglycan, 7 of the 8 markers were found to have significantly different expression patterns when comparing the two types of cancer (P <0.05). In intrahepatic cholangiocarcinomas, the expression rates of CK7, CK19, MOC31, claudin 4 and HMGA1 were 83.4%, 89.0%, 88.2%, 69.2%, and 31.5%, respectively. These rates of expression in intrahepatic cholangiocarcinomas were all higher than in those in hepatocellular carcinomas (CK7, 31.3%; CK19, 10.1%; MOC31, 34.0%; claudin 4, 11.2%; and HMGA1, 19.5%). The expression rates of GPC3, CD10, and biglycan were 72.6%, 39.7% and 10.0%, respectively, in hepatocellular carcinoma. These were higher than the rates found in intrahepatic cholangiocarcinomas (GPC3, 7.0%; CD10, 18.1%; and biglycan, 7.0%). In a multivariate logistic regression analysis, GPC3, CK19, MOC31 and claudin 4 were found to be independent markers for differentially diagnosing intrahepatic cholangiocarcinoma.nnnCONCLUSIONSnBased on our results, GPC3 and CK19 can be used as first-line markers for differential diagnoses of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (accuracy rate, 73.5%), and additional combined screening for claudin 4 and MOC31 markers in GPC3(-) and CK19(-) tumors might increase the accuracy rate for distinguishing hepatocellular carcinoma from intrahepatic cholangiocarcinoma to 88.5%.

Overexpression of HIF1α and CAXI predicts poor outcome in early-stage triple negative breast cancer

Dysregulated energy metabolism is one of the main mechanisms for uncontrolled growth in solid tumors. Hypoxia-inducible factor 1-alpha (HIF1α) is a transcription factor implicated in regulating several genes that are responsible for cell metabolism, including carbonic anhydrase IX (CAIX). The aim of this study is to determine the clinical significance of immunohistochemical metabolic alteration in early-stage triple negative breast cancer (TNBC) patients who received cyclophosphamide-based chemotherapy or radiotherapy and those with basal phenotype. Immunohistochemical staining for HIF1α and CAIX was performed to determine the correlation with clinicopathologic variables and survival outcome on tissue microarrays from 270 early-stage TNBC patients. In vitro experiments with multiple human TNBC cell lines, suppression of HIF1α by small interfering RNA (siRNA) significantly reduced CAIX protein expression in all cell lines. In multivariate analyses for different therapeutic modalities and basal phenotype, combined HIF1α and CAIX protein overexpression was significantly associated with disease-free survival in the total cohort (ORxa0=xa02.583, Pxa0=xa00.002), stratified cohorts expressing basal phenotype (ORxa0=xa02.234, Pxa0=xa00.021), and in those patients who received adjuvant chemotherapy (ORxa0=xa03.078, Pxa0=xa00.023) and adjuvant radiotherapy (ORxa0=xa02.111, Pxa0=xa00.050), respectively. In early TNBC, combined HIF1α and CAIX protein expression may serve as an unfavorable prognostic indicator particularly in patients treated with cyclophosphamide-based chemotherapy or radiotherapy as well as those with basal phenotype of breast cancer.

Clinical outcomes of stereotactic body radiotherapy for spinal metastases from hepatocellular carcinoma

Purpose To investigate the outcomes of patients with spinal metastases from hepatocellular carcinoma (HCC), who were treated by stereotactic body radiotherapy (SBRT). Materials and Methods This retrospective study evaluated 23 patients who underwent SBRT from October 2008 to August 2012 for 36 spinal metastases from HCC. SBRT consisted of approximately 2 fractionation schedules, which were 18 to 40 Gy in 1 to 4 fractions for group A lesions (n = 15) and 50 Gy in 10 fractions for group B lesions (n = 21). Results The median follow-up period was 7 months (range, 2 to 16 months). Seven patients developed grade 1 or 2 gastrointestinal toxicity, and one developed grade 2 leucopenia. Compression fractures occurred in association with 25% of the lesions, with a median time to fracture of 2 months. Pain relief occurred in 92.3% and 68.4% of group A and B lesions, respectively. Radiologic response (complete and partial response) occurred in 80.0% and 61.9% of group A and B lesions, respectively. The estimated 1-year spinal-tumor progression-free survival rate was 78.5%. The median overall survival period and 1-year overall survival rate were 9 months (range, 2 to 16 months) and 25.7%, respectively. Conclusion SBRT for spinal metastases from HCC is well tolerated and effective at providing pain relief and radiologic response. Because compression fractures develop at a high rate following SBRT for spinal metastases from primary HCC, careful follow up of the patient is required.

Negative impact of pretreatment anemia on local control after neoadjuvant chemoradiotherapy and surgery for rectal cancer

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.

Prognostic significance of survivin in rectal cancer patients treated with surgery and postoperative concurrent chemo-radiation therapy

Background & Aims This study is designed to investigate the expression of survivin and p53 in human rectal cancer tissues and analyze associations between expression and clinical outcomes in terms of disease recurrence and survival duration. Results During follow-up (median 119.0, range 6.6 to 161.3 months), tumor recurrence was detected in 50 patients (43.1%), and local recurrence developed as a first failure site in 13 patients (11.2%). Positive immunostaining of nuclear and cytoplasmic survivin was observed in about one quarter of patients, and about half of all patients had positive staining for p53. Both survivin and p53 were significant prognostic factors of disease-free survival in the univariate analyses, but only survivin remained a significant prognostic factor in the multivariate analysis. Methods We performed a retrospective study with 116 locally advanced rectal cancer patients who underwent total mesorectal excision (TME) followed by postoperative concurrent chemo-radiation therapy (CCRT). Immunohistochemical staining was conducted using antibodies for survivin or p53, and their expression was analyzed using an individual score that combined the percentage of positive cells and staining intensity. Conclusions Overexpression of nuclear and cytoplasmic survivin in locally advanced rectal cancer patients was associated with a higher recurrence rate in rectal cancer patients treated with TME followed by postoperative CCRT.

Radiation sigmoiditis mimicking sigmoid colon cancer after radiation therapy for cervical cancer: the implications of three-dimensional image-based brachytherapy planning.

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

SU‐GG‐T‐549: Development of Respiration Verification Program and Procedure for 4‐Dimensional Stereotactic Body Radiation Therapy

Purpose: In order to verify the behavior of tumor motion caused by breathing, respiration & tumor motion verification procedure was designed and its feasibility was tested. Method and Materials: Visual software was developed using LabView 7.0 to analyzerespiration by detecting peak/valley points from RPM signals. The software displays the number of detected peaks/valleys, peak/valley locations, amplitude of signals, and 2nd order differential coefficients at each data points. It calculates mean, standard deviation, variance, maximum and minimum of all detected peak/valley points. It can analyze data for user defined intervals and exports the results in excel file. The program performance was tested using known RPM signals which were sine waves with period of 3 and 6 sec with amplitude of 1 and 2 cm. Also irregular signals obtained from patients breathing were used to generate irregular respiratory signals by moving a phantom and the software performance was tested. In clinical application, the analyzed respiratory data were converted into tumor motion by applying scaling factor defined by tumor‐motion amplitude to respiration amplitude. To determine the scaling factor, gated On‐Board‐Image (OBI)s were acquired at 0% and 50% of respiratory phases and the imaging times were recorded. From the RPM file, the respiratory signal values at imaging times were read and displacement of tumor was measured from the OBI images. The scaling factor was, then, determined as the ratio of tumor displacement between 0% and 50% phases to difference of two respiratory signals values at corresponding phases. Results: The computed results by the software were extremely consistent with true values within 0.1% difference for regular and irregular motions. Conclusion: Developed software was proven to have sufficient accuracy for clinical application. The proposed method has advantages of non‐invasive, fine temporal resolution without extra radiation, thereby providing a useful tool for 4‐dimensional body stereotactic radiotherapy.