Suk Won Park

Immunohistochemical study identifying prognostic biomolecular markers in nasopharyngeal carcinoma treated by radiotherapy

We evaluated the predictive significance of 14 reported markers using immunohistochemical study in nasopharyngeal carcinoma.

Clinical outcomes of chemoradiotherapy for locally recurrent rectal cancer.

BackgroundTo assess the clinical outcome of chemoradiotherapy with or without surgery for locally recurrent rectal cancer (LRRC) and to find useful and significant prognostic factors for a clinical situation.MethodsBetween January 2001 and February 2009, 67 LRRC patients, who entered into concurrent chemoradiotherapy with or without surgery, were reviewed retrospectively. Of the 67 patients, 45 were treated with chemoradiotherapy plus surgery, and the remaining 22 were treated with chemoradiotherapy alone. The mean radiation doses (biologically equivalent dose in 2-Gy fractions) were 54.6 Gy and 66.5 Gy for the chemoradiotherapy with and without surgery groups, respectively.ResultsThe median survival duration of all patients was 59 months. Five-year overall (OS), relapse-free (RFS), locoregional relapse-free (LRFS), and distant metastasis-free survival (DMFS) were 48.9%, 31.6%, 66.4%, and 40.6%, respectively. A multivariate analysis demonstrated that the presence of symptoms was an independent prognostic factor influencing OS, RFS, LRFS, and DMFS. No statistically significant difference was found in OS (p = 0.181), RFS (p = 0.113), LRFS (p = 0.379), or DMFS (p = 0.335) when comparing clinical outcomes between the chemoradiotherapy with and without surgery groups.ConclusionsChemoradiotherapy with or without surgery could be a potential option for an LRRC cure, and the symptoms related to LRRC were a significant prognostic factor predicting poor clinical outcome. The chemoradiotherapy scheme for LRRC patients should be adjusted to the possibility of resectability and risk of local failure to focus on local control.

Identifying genes related to radiation resistance in oral squamous cell carcinoma cell lines

Radioresistance is one of the main determinants of treatment outcome in oral cancer, but the prediction of radioresistance is difficult. The authors aimed to establish radioresistant oral squamous cell carcinoma (OSCC) cell lines to identify genes with altered expression in response to radioresistance. To induce radioresistant cell lines, the authors treated OSCC cell lines with an accumulated dosage of 60Gy over 30 cycles of radiotherapy. They compared the results from cDNA arrays and proteomics between non-radiated and radioresistant cell lines in order to identify changes in gene expression. Western blot analysis was used to validate the results. The cDNA array revealed 265 commonly up-regulated genes and 268 commonly down-regulated genes in radioresistant cell lines, 30 of which were cancer-related genes. Proteomics identified 51 proteins with commonly altered expression in radioresistant cell lines, 18 of which were cancer-related proteins. Both the cDNA array and proteomics indicated that NM23-H1 and PA2G4 were over-expressed. Western blot analysis showed increased expression of NM23-H1, but not PA2G4, in radioresistant cell lines. The authors concluded that NM23-H1 may be a radioresistance-related gene and over-expression of NM23-H1 could serve as a biomarker to predict radioresistance in OSCC.

A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer

OBJECTIVES More than half of cases of gastric cancer (GC) are diagnosed in elderly patients (≥70years). While doublet combination with fluoropyrimidines and platinum is currently considered standard first-line chemotherapy in advanced GC, the main goal of chemotherapy remains palliation. MATERIALS AND METHODS In a multi-center phase III trial, patients with chemotherapy-naïve, metastatic GC, aged 70years or older were randomized 1:1 to receive X monotherapy (capecitabine 1000mg/m2 bid po on days one to fourteen) or XELOX (X plus oxaliplatin 110mg/m2 iv on D1). Treatment was repeated every 21days until disease progression, unacceptable toxicity, or withdrawal. Primary endpoint was overall survival (OS). RESULTS In total, 50 patients with a median age of 77 (range, 70 to 84) were enrolled (X, n=26; XELOX, n=24). No treatment-related serious adverse events or unexpected toxicities were observed. The most frequently observed toxicities were nausea and hand-foot syndrome, with fatigue and peripheral neuropathy more common in XELOX than in X patients. Median OS was 11.1months for XELOX arm and 6.3months for X arm (HR 0.58, 95% CI 0.30-1.12, P=0.108). Although the difference was not significant, on the basis of evidence of superiority of XELOX seen in the first interim analysis, an independent data monitoring committee recommended early stopping of the trial. PFS was significantly longer (HR 0.32, 95% CI 0.17-0.61, P<0.001) with XELOX (7.1months) than with X (2.6months). CONCLUSION Platinum-based combination chemotherapy was associated with survival benefit, as compared with X monotherapy in elderly patients with GC.

Multi-institutional Comparison of Intensity Modulated Radiation Therapy (IMRT) Planning Strategies and Planning Results for Nasopharyngeal Cancer

The intensity-modulated radiation therapy (IMRT) planning strategies for nasopharyngeal cancer among Korean radiation oncology facilities were investigated. Five institutions with IMRT planning capacity using the same planning system were invited to participate in this study. The institutions were requested to produce the best plan possible for 2 cases that would deliver 70 Gy to the planning target volume of gross tumor (PTV1), 59.4 Gy to the PTV2, and 51.5 Gy to the PTV3 in which elective irradiation was required. The advised fractionation number was 33. The planning parameters, resultant dose distributions, and biological indices were compared. We found 2-3-fold variations in the volume of treatment targets. Similar degree of variation was found in the delineation of normal tissue. The physician-related factors in IMRT planning had more influence on the plan quality. The inhomogeneity index of PTV dose ranged from 4 to 49% in Case 1, and from 5 to 46% in Case 2. Variation in tumor control probabilities for the primary lesion and involved LNs was less marked. Normal tissue complication probabilities for parotid glands and skin showed marked variation. Results from this study suggest that greater efforts in providing training and continuing education in terms of IMRT planning parameters usually set by physician are necessary for the successful implementation of IMRT.

Role of cancer stem cell in radioresistant head and neck cancer

OBJECTIVE Radioresistance is the main determinant of treatment outcome in head and neck cancer. The aim of this study was to establish radioresistant head and neck cancer cell lines and isolate cancer stem cells from them to investigate the role of cancer stem cells in radioresistant head and neck cancer. METHODS To induce radioresistant cell lines, radiation was delivered to SCC15, SCC25, and QLL1 cells with an accumulated dosage of 60Gy over 30 cycles of irradiation. After a total of 60Gy of irradiation, the radioresistance of irradiated cancer cells was verified by MTT assay. The radioresistant cells were cultured in serum-free medium in ultra-low-attachment culture flasks to induce sphere-forming cells. Then, sphere-forming cells were analyzed using Western blotting to identify the expression of stem cell markers, such as Nanog and Sox-2. RESULTS The MTT assay of cell viability showed more radioresistance in the irradiated cancer cell lines than in the non-irradiated cancer cell lines. Sphere-forming cells were identified in all three cancer cell lines 3-5 days after serum deprivation. All sphere-forming cells from the three cancer cell lines expressed stem cell markers. Sphere-forming cells showed more radioresistance than monolayer cells after irradiation by colony forming assay. CONCLUSION Cancer stem cells seem to play an important role in the radioresistance of head and neck cancer. Further research is required to find a precise mechanism of radioresistance related to cancer stem cells.

Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery

Objective We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM) in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model. Methods A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25) and saline as the control group (group CO; n = 25). In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery. Results In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001). Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002) and fibrosis score (P = .018) than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant. Conclusions In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required.

Modified dose difference method for comparing dose distributions

The quantitative comparison of two‐dimensional dose distributions (e.g., calculated versus measured) has become a key issue in intensity‐modulated radiotherapy (IMRT) QA. We proposed a new evaluation method referred to as modified dose difference (MDdiff) evaluation. Hereinafter, features and effectiveness of the MDdiff evaluation method will be described. In this work, the formalism of MDdiff was defined by introducing a dimensionless parameter βDG(r)(r→r). A new formalism is compared to a gamma method, and the MDdiff and the gamma method are respectively applied to patient‐specific IMRT QA. The calculation of the evaluation of dose distributions was performed using a C++ program. Evaluations were performed by counting the number of data points satisfying MDdiff≥(1/2)δD(0),γ≥1. The evaluation result of dose distributions using the MDdiff method had the same tendency as the evaluation result using the gamma evaluation method. The modified dose difference tool also provides a quantitative method for comparing two dose distributions like the gamma evaluation. Furthermore, many problems of gamma evaluation are resolved. PACS numbers: 87.55.km, 87.55.Qr

Expression of cyclooxygenase (COX)-2 as a prognostic factor in nasopharyngeal cancer.

PURPOSE To evaluate the relationship between treatment failure and COX-2 expression in nasopharyngeal cancer patients treated with chemotherapy and radiotherapy. MATERIALS AND METHODS The subjects of this study were 22 nasopharyngeal cancer patients. The patients were treated with neoadjuvant chemotherapy, followed by radiotherapy, or with radiotherapy alone. The formalin-fixed, paraffin-embedded tissues of 11 patients who developed a locoregional recurrence (n=7) or distant metastasis (n=4) were compared with those of 11 disease free patients. Prognostic factors, including histological type, stage, radiation dose and chemotherapy, were well balanced between the two groups. The COX-2 expression was determined immunohistochemically. RESULTS COX-2 expression was stronger in the patients with a locoregional recurrence or distant metastasis than in those free of disease. The COX-2 distribution scores of the control group were as follows: 0 in 7, 1 in 2 and 2 in 2 patients. In the recurrence group, the scores were as follows; 0 in 3, 1 in 1, 2 in 2 and 3 in 5 patients. COX-2 expression was shown to have a statistically significant influence on the treatment failure by the Mann-Whitney U test (p=0.024) and Mantel-Haenszel Chi-Square test (p=0.018). It also significantly influenced the treatment failure when an analysis was performed within patients with a undifferentiated histology (p=0.039 by the Mann-Whitney U test, p=0.037 by the Mantel-Haenszel Chi-Square test). CONCLUSION COX-2 expression is believed to be one of the important factors associated with a locoregional recurrence or distant metastasis.

Determination of small-field correction factors for cylindrical ionization chambers using a semiempirical method.

A semiempirical method based on the averaging effect of the sensitive volumes of different air-filled ionization chambers (ICs) was employed to approximate the correction factors for beam quality produced from the difference in the sizes of the reference field and small fields.We measured the output factors using several cylindrical ICs and calculated the correction factors using a mathematical method similar to deconvolution; in the method, we modeled the variable and inhomogeneous energy fluence function within the chamber cavity. The parameters of the modeled function and the correction factors were determined by solving a developed system of equations as well as on the basis of the measurement data and the geometry of the chambers. Further, Monte Carlo (MC) computations were performed using the Monaco® treatment planning system to validate the proposed method.The determined correction factors () were comparable to the values derived from the MC computations performed using Monaco®. For example, for a 6 MV photon beam and a field size of 1  ×  1 cm2, was calculated to be for a PTW 31010 chamber and for a PTW 31016 chamber. On the other hand, the values determined from the MC computations were 1.121 and 1.031, respectively; the difference between the proposed method and the MC computation is less than 2%. In addition, we determined the values for PTW 30013, PTW 31010, PTW 31016, IBA FC23-C, and IBA CC13 chambers as well.We devised a method for determining from both the measurement of the output factors and model-based mathematical computation. The proposed method can be useful in case the MC simulation would not be applicable for the clinical settings.