Jong Young Lee

Prognostic value of vascular endothelial growth factor in Stage IB carcinoma of the uterine cervix

PURPOSE To clarify the role of vascular endothelial growth factor (VEGF) expression as an independent prognostic factor in Stage IB cervical cancer. METHODS AND MATERIALS A total of 117 patients with Stage IB cervical cancer who had undergone radical hysterectomy and pelvic lymph node dissection with complete histopathologic examination were included. Eighty-eight (75.2%) patients received postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry. RESULTS Of 117 patients, 35 (29.9%) showed high-intensity VEGF expression and 69 (59%) had a high score for area of VEGF expression. Strong correlations were found between high VEGF intensity and both deep stromal invasion (p = 0.01) and positive pelvic lymph nodes (p = 0.03). The area of VEGF expression was significantly associated with tumor size (p = 0.02). In a multivariate analysis, high VEGF intensity (p = 0.009) and tumor size (p = 0.01) were significant prognostic factors for overall survival and disease-free survival (p = 0.001 and p = 0.003, respectively). However, the area of VEGF expression was not a prognostic factor for overall survival or disease-free survival. CONCLUSION Our findings on the correlation between VEGF expression and prognosis were conflicting. Functional and quantitative tools to assess tumor angiogenesis in addition to the expression of VEGF need to be developed and would be helpful to support the finding that tumor angiogenesis correlates significantly with prognosis in early-stage cervical cancer.

High-dose Versus Standard-dose Radiotherapy with Concurrent Chemotherapy in Stages II–III Esophageal Cancer

OBJECTIVE In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. METHODS A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. RESULTS The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. CONCLUSIONS High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials.

High-dose-rate vs. low-dose-rate intracavitary brachytherapy for carcinoma of the uterine cervix: Systematic review and meta-analysis

PURPOSE We performed a meta-analysis to compare the treatment outcomes between high-dose-rate (HDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for the treatment of cervical cancer. METHODS AND MATERIALS We searched the PubMed database for articles and the related referenced articles that compared HDR-ICBT and LDR-ICBT. A total of 15 published articles, 3 prospective randomized trials, and 12 retrospective studies performed between 1966 and December 2013 were selected using predefined inclusion and exclusion criteria for each study. The effect sizes were obtained from the odds ratios of the 5-year overall survival, 5-year disease-free survival (DFS), pelvic (locoregional) recurrence, and rectal and bladder complication rates in each study. The common effect sizes and 95% confidence intervals (CIs) were calculated using either the fixed or the random-effect model, according to the results of the homogeneity tests. RESULTS We analyzed the outcome data for 18,937 patients, including 10,807 patients in the HDR-ICBT treatment group and 8,130 patients in the LDR-ICBT group. The common effect sizes (95% CI) for the 5-year survival rate, 5-year DFS rate, and pelvic recurrence rate were 1.1350 (0.9231-1.3955), 1.0777 (0.4896-2.3720), and 0.9521 (0.7624-1.1890), respectively. The common effect sizes (95% CI) for moderate-to-severe complication rates of the rectum and the bladder were 0.7645 (0.5099-1.1463) and 0.9051 (0.6140-1.3342), respectively. There were no significant differences between HDR- and LDR-ICBT considering the 5-year survival, 5-year DFS, pelvic recurrence, and the rectal and bladder complication rates. CONCLUSION The treatment outcome after HDR-ICBT seems to be equivalent to that following LDR-ICBT in terms of survival, pelvic recurrence, and major complications.

IMRT with Simultaneous Integrated Boost and Concurrent Chemotherapy for Nasopharyngeal Cancer: Plan Evaluation and Treatment Outcome

OBJECTIVE This study evaluated the outcome of intensity-modulated radiation therapy with simultaneous integrated boost and concurrent chemotherapy for nasopharyngeal cancer. METHODS We analyzed 53 consecutive nasopharyngeal cancer patients who received definitive treatment using intensity-modulated radiation therapy with simultaneous integrated boost and cisplatin-based concurrent chemotherapy. Forty-six patients were treated with concurrent chemoradiation and seven patients with induction chemotherapy plus concurrent chemoradiation. The gross tumor (PTV(70)) received 69.96 Gy (2.12 Gy/fraction), high-risk subclinical disease (PTV(60)) received 59.4 Gy (1.8 Gy/fraction) and low-risk subclinical disease (PTV(56)) received 56.1 Gy (1.7 Gy/fraction) in 33 fractions. Twenty-eight patients were treated with step-and-shoot intensity-modulated radiation therapy and 25 patients with helical tomotherapy. Dosimetric parameters were compared between the two modalities. RESULTS The median treatment duration was 49 days (range: 41-65 days). The complete response rate was 92.5%. Three local, two regional, one locoregional and seven distant failures were observed. With the median follow-up of 41 months (range: 8-89 months), the 3- and 5-year local control, locoregional control, disease-free survival and overall survival rates were 91.8 and 91.8%; 87.6 and 87.6%; 77.5 and 70.5%; and 86.4 and 82.1%, respectively. Grade 3 mucositis, dermatitis, leucopenia and grade 4 leucopenia were observed in 10, 1, 2 and 1 patient, respectively. No grade 3 or higher xerostomia occurred. Helical tomotherapy significantly improved dosimetric parameters including the maximum dose, volume receiving >107% of the prescribed dose and uniformity index (D(5)/D(95)). CONCLUSIONS Intensity-modulated radiation therapy with simultaneous integrated boost with concurrent chemotherapy is a safe and effective treatment modality for nasopharyngeal cancer. Helical tomotherapy has a dosimetric advantage over step-and-shoot intensity-modulated radiation therapy in a clinical setting.

Multi-institutional analysis of T3 subtypes and adjuvant radiotherapy effects in resected T3N0 non-small cell lung cancer patients.

Purpose We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). Materials and Methods T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. Results The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). Conclusion The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC.

Influence of different boost techniques on radiation dose to the left anterior descending coronary artery.

Purpose The purpose of this study is to compare the dosimetry of electron beam (EB) plans and three-dimensional helical tomotherapy (3DHT) plans for the patients with left-sided breast cancer, who underwent breast conserving surgery. Materials and Methods We selected total of 15 patients based on the location of tumor, as following subsite: subareolar, upper outer, upper inner, lower lateral, and lower medial quadrants. The clinical target volume (CTV) was defined as the area of architectural distortion surrounded by surgical clip plus 1 cm margin. The conformity index (CI), homogeneity index (HI), quality of coverage (QC) and dose-volume parameters for the CTV, and organ at risk (OAR) were calculated. The following treatment techniques were assessed: single conformal EB plans; 3DHT plans with directional block of left anterior descending artery (LAD); and 3DHT plans with complete block of LAD. Results 3DHT plans, regardless of type of LAD block, showed significantly better CI, HI, and QC for the CTVs, compared with the EB plans. However, 3DHT plans showed increase in the V1Gy at skin, left lung, and left breast. In terms of LAD, 3DHT plans with complete block of LAD showed extremely low dose, while dose increase in other OARs were observed, when compared with other plans. EB plans showed the worst conformity at upper outer quadrants of tumor bed site. Conclusion 3DHT plans offer more favorable dose distributions to LAD, as well as improved target coverage in comparison with EB plans.

A case of radiation bronchitis induced massive hemoptysis after high-dose-rate endobronchial brachytherapy.

High-dose-rate endobronchial brachytherapy (HDREB) have been used as the treatment of early endobronchial cancer, as well as for palliation of advanced cancer. However, fatal hemoptysis can occur after HDREB at the rate of 7~32%. We report a case of massive hemoptysis due to radiation bronchitis developed after HDREB. A 67-year-old man was treated with HDREB for early endobronchial cancer on the left upper lobe bronchus. He complained of persistent cough from 4 weeks after completion of HDREB. Radiation bronchitis was observed on the bronchoscopy at 34 weeks, and it was progressed from mucosal swelling and exudate formation to necrosis and ulceration without local relapse. In addition, he died of massive hemoptysis after 15 months. The patient had no sign or radiologic evidences to predict the hemoptysis. This case implies that HDREB directly contributes to an occurrence of a fatal hemoptysis, and follow-up bronchoscopy is important to predict a progression of radiation bronchitis and fatal hemoptysis.

Atomically precise graphene etch stops for three dimensional integrated systems from two dimensional material heterostructures

Atomically precise fabrication methods are critical for the development of next-generation technologies. For example, in nanoelectronics based on van der Waals heterostructures, where two-dimensional materials are stacked to form devices with nanometer thicknesses, a major challenge is patterning with atomic precision and individually addressing each molecular layer. Here we demonstrate an atomically thin graphene etch stop for patterning van der Waals heterostructures through the selective etch of two-dimensional materials with xenon difluoride gas. Graphene etch stops enable one-step patterning of sophisticated devices from heterostructures by accessing buried layers and forming one-dimensional contacts. Graphene transistors with fluorinated graphene contacts show a room temperature mobility of 40,000 cm2 V−1 s−1 at carrier density of 4 × 1012 cm−2 and contact resistivity of 80 Ω·μm. We demonstrate the versatility of graphene etch stops with three-dimensionally integrated nanoelectronics with multiple active layers and nanoelectromechanical devices with performance comparable to the state-of-the-art.Fabrication methods to pattern thin materials are a critical tool to build molecular scale devices. Here the authors report a selective etching method using XeF2 gas to pattern graphene based heterostructures with multiple active layers and achieve 1D contacts with low contact resistivity of 80 Ω·µm