• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3403-3408
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• 2012

The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.201-205
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• 2007

Purpose: This retrospective study was conducted to assess outcome and to determine the prognostic factors in patients with a desmoid tumor treated with postoperative radiotherapy. Materials and Methods: Twenty-seven patients with a desmoid tumor who were treated with postoperative radiotherapy between June 1984 and October 2005 were analyzed. There were 13 male and 14 female patients. The age of the patients ranged from 3 to 79 years (median age, 28 years). Tumors were located in an extra-abdominal area (21 cases), and in the abdominal walls (6 cases). The tumor size ranged from 2.5 to 25 cm (median size, 7.5 cm) in the largest linear dimension. Thirteen cases received radiotherapy after initial surgery, and 14 recurrent cases received radiotherapy after additional surgery. The total radiation dose given was $45{\sim}66$ Gy (median dose, 59.4 Gy), and the fraction size was $1.8{\sim}2.0$ Gy. Results: The median follow-up period was 61 months (range, $12{\sim}203$ months). Two patients developed local progression and six patients experienced local recurrence. The 5-year disease-free survival rate and the 5-year progression-free survival rate were 61 % and 70%, respectively. Wide local excision was associated with better disease free survival with statistical significance (p=0.028). Radiotherapy after initial surgery (p=0.046) and a higher radiation dose of more than 60 Gy (p=0.049) were associated with better progression free survival with statistical significance. At the time of the last follow-up, the number of additional surgeries was higher in patients that received radiotherapy after reoperation (p<0.001). Conclusion: Radiotherapy after the initial operation improved local control and decreased the number of subsequent operations. Thus, postoperative radiotherapy after an initial operation is recommended in patients with a high risk of recurrence for a desmoid tumor.

• Journal of Chest Surgery
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• v.43 no.1
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• pp.39-46
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• 2010

Background: Preoperative chemotherapy has been adopted in our hospital as a standard treatment for non-small cell lung cancer patients with N2 disease. However, there have been cases of pathologic N2 disease that have been detected after curative-intent surgical resection. We retrospectively studied the outcomes of initial surgical treatment without neoadjuvant therapy in patients with unexpected N2 non-small cell lung cancer. Material and Method: Between January 1995 and June 2007, 225 patients were diagnosed with pathologic N2 disease after they underwent initial pulmonary resection without neoadjuvant therapy. Among them, 170 patients were preoperatively diagnosed with lymph node stage N0 or N1. We retrospectively reviewed their medical record and analyzed the outcomes. Result: The overall 5-year survival rate was 35.4%. The prognostic factors that were significantly associated with survival were no adjuvant therapy, histologic cell types other than adenocarcinoma or squamous cell carcinoma, a pathologic T stage more than T1, old age (${\geq}$70 years) and no mediastinoscopic biopsy. During the follow-up, 79 patients (46.5%) experienced tumor recurrence, including loco-regional recurrence in 20 patients (25.3%) and distant metastasis in 56 (70.9%). The 5-year recurrence-free survival rate was 33.7%. Conclusion: Based on our findings, the survival was good for patients with unexpected N2 non-small cell lung cancer and who underwent initial pulmonary resection without neoadjuvant therapy. A prospective comparative analysis is needed to obtain more conclusive and persuasive results.

• Tuberculosis and Respiratory Diseases
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• v.39 no.4
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• pp.310-317
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• 1992

Background: Angiotensin converting enzyme is a glycoprotein peptidyldipeptide hydrolase which cleaves the c-terminal dipeptides of several oligopeptides. It is a menbrane-bound protein mainly synthesized by the endothelial cells. Since the lung has the largest capillary bed of any organ in the body, it is here that ACE acts on circulating substrates like angiotensin I and bradykinin. It is well known that ACE correlates with disease activity in sarcoidosis and also there are reports that changes in serum ACE activity are found in many acute and chronic lung diseases. So we planned this study to see if serum ACE activity can act as a prognostic factor in lung cancer. Methods: Forty-one newly diagnosed lung cancer patients were included in the study group. There were 19 patients with squamous cell lung cancer, 13 with adenocarcinoma, and 9 with small cell carcinoma. Patients were excluded from the study if they had high blood pressure, heart disease, liver disease, renal disease, or other lung disease. Serum ACE activity was analyzed according to cell type, staging, mode of treatment, and clinical response to treatment. Results: 1) There was no difference in serum ACE activity between lung cancer patients and the control group. Also no difference in serum ACE activity was found according to cancer cell type or staging. 2) In patients who underwent curative resection of lung cancer, serum ACE activity was decreased significantly after the operation. 3) In patients who were diagnosed as non-small cell lung cancer and were treated with 4 cycles of anti-cancer chemotherapy without clinical improvement, changes in serum ACE activity were not seen after the treatment. 4) In patients diagnosed as small cell lung cancer treated with 4 cycles of anti-cancer chemotherapy with clinical improvement, changes in serum ACE activity were also not observed. Conclusion: Serum ACE activity was decreased after lung resection but had no relation to cell type, staging, or clinical response to treatment in lung cancer patients. Therefore, serum ACE activity is not suitable in predicting clinical outcome of lung cancer patients.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.77-90
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• 2004

Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.157-163
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• 2006

[ $\underline{Purpose}$ ]: To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. $\underline{Materials\;and\;Methods}$: A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil ($500\;mg/m^2/day$) with leucovorin ($20\;mg/m^2/day$), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for $6{\sim}12$ months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by $5.4{\sim}9\;Gy$ boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. $\underline{Results}$: Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients (p=0.012, p=0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively (p=0.006). Multivariate analysis showed that N stage (p=0.012) was significant prognostic factor for OS and that N stage (p=0.001) and location of tumor (p=0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. $\underline{Conclusion}$: Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.11-18
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• 1997

Purpose : To evaluate the efficacy of combined treatment of surgery and chemoradiotherapy for supratentorial primitive neuroectodermal tumors (SPNET) and obtain the Prognostic factors and complications Materials and Methods .The a9e of 18 patients ranged from 1 to 27 years (median=5 years). There were 12 males and 6 females The extents of surgery were gross total (n:9), subtotal (n:8), biopsy only (n: 1). Craniospinal radiotherapy was delivered to all the patients except 2 patients who were treated only with the whole brain and primary lesion. Radiation dose were 3120-5800cGy (median=5460) to primary mass, 1500-4200cGy (median=3600cGy) to the whole brain and 1320-3600cGy (median= 2400 cGy) to the spinal axis. Chemotherapy was done in 13 patients. Median follow-up period was 45 months ranged from 1 to 89 months. Results : Patterns of failure were as follows; local recurrence (1), multiple intracranial recurrence (2), spinal seeding (3), craniospinal seeding (2) and multiple bone metastasis (1). Two of two patients who did not received craniospinal radiotherapy failed at spinal area. All the relapsed cases died at 1 to 13 months after diagnosis of progression. The 2- and 5-rear overall survival rates were $61\%\;and\;49\%$, respectively The a9e, sex, tumor location did not influence the survival but aggressive resection with combined chemotherapy showed better outcome. Among 9 survivors, complications were detected as radiation necrosis (n=1), hypopituitarism (n=2), cognitive defect(n=1), memory deficit (n=1), growth retardation (n=1). Conclusion : To improve the results of treatment of SPNET, maximal surgical resection followed by radiation therapy and chemotherapy is necessary. The extended radiation field including craniospinal axis may reduce the recurrence in spinal axis.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.163-171
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• 1995

Purpose: Primary radiation therapy following breast-conserving surgery has been an accepted alternative to mastectomy during the past 2 decades. In this country, however, the practice of conservative therapy for early invasive breast cancer has not been generalized yet. The purpose of this report was to evaluate the results and complications of breast conservation therapy in Korean Cancer Center Hospital(KCCH). Materials and Methods: From January 1987 to December 1989. 45 Patients with early breast cancer treated with conservative treatment in KCCH were studied retrospectively Median follow up was 54 months(range, 4 to 82 months) . All patients received partial mastectomy (biopsy, tumorectomy. or quadrantectomy) and radiation therapy. Twenty eight patients received axillary dissection The breast was treated with two opposing tangential fields (total 50 Gy or 50.4 Gy in 5 weeks with daily target dose of 2 Gy or 1.8 Gy) Thirty patients received chemotherapy before and after radio-therapy Eleven patients received hormonal therapy. Results: Five-year survival rate, 5-rear disease free survival rate and 5-year local control rate were 87.2%, 86.5% and 97.6%,$ respectively. Administration of systemic Therapy (chemotherapy or hormonal therapy) correlated with good prognosis but statistically not significant (0.05 < p < 0.1). The severe late complication rate was 8.9% Conclusion: Primary radiation therapy following breast-conserving surgery for early breast cancer is an alternative treatment comparing to radical treatment. Long term follow-up and more patients collection is needed to evaluate the Prognostic factor and cosmetic outcome.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.25-43
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• 1997

Introduction : The outcome and incidence of acute respiratory distress syndrome (ARDS) could be variable related to the varied definitions used for ARDS by researchers. The purpose of the national survey was to define the risk factors of ARDS and investigate the prognostic indicies related to mortality of ARDS in Korea according to the definition of ARDS determined by the American-European Concensus Conference on 1992 year. Methods : A Multicenter registry of 48 University or University-affliated hospital and 18 general hospital s equipped with more than 400 patient's beds conducted over 13 months of patients with acute respiratory distress syndrome using the same registry protocol. Results : 1. In the 12 months of the registry, 167 patients were enrolled at the 24 hospitals. 2. The mean age was 56.5 years (${\pm}17.2$ years) and there was a 1.9:1 ratio of males to females. 3. Sepsis was the most common risk factors (78.1%), followed by aspiration (16.6%), trauma (11.6%), and shock (8.5%). 4 The overall mortality rate was 71.9%. The mean duration was 11 days (${\pm}13.1$ days) from the diagnosis of ARDS to the death. Respiratory insufficiency appeared to be a major cause in 43.7% of the deaths followed by sepsis (36.1%), heart failure (7.6%) and hepatic failure (6.7%). 5. There were no significant differences in mortality based on sex or age. No significant difference in mortality in infectious versus noninfectious causes of ARDS was found. 6. There were significant differences in the pulse rate, platelet numbers, serum albumin and glucose levels, the amounts of 24 hour urine, arterial pH, $Pa0_2$, $PaCO_2$, $Sa0_2$, alveolar-arterial oxygen differences, $PaO_2/FIO_2$, and PEEP/$FI0_2$ between the survivors and the deaths on study days 1 through 6 of the first week after enrollment. 7. The survivors had significantly less organ failure and lower APACHE III scores at the time of diagnosis of ARDS (P<0.05). 8. The numbers of organ failure (odd ratio 1.95, 95% confidence intervals:1.05-3.61, P=0.03) and the score of APACHE III (odd ratio 1.59, 95% confidence interval:1.01-2.50, P=0.04) appeared to be independent risk factors of the mortality in the patients with ARDS. Conclusions : The mortality was 71.9% of total 167 patients in this investigation using the definition of American-European Consensus Conference on 1992 year, and the respiratory insufficiency was the leading cause of the death. In addition, the numbers of organ failure and the score of APACHE III at the time of diagnosis of ARDS appeared to be independent risk factors of the mortality in the patients with ARDS.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.237-246
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• 2004

Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.