• Tuberculosis and Respiratory Diseases
• /
• v.45 no.5
• /
• pp.962-974
• /
• 1998

Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

• Radiation Oncology Journal
• /
• v.25 no.1
• /
• pp.16-25
• /
• 2007

[ $\underline{Purpose}$ ]: Breast conserving surgery (BCS) followed by chemotherapy (CTx.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. $\underline{Materials\;and\;Methods}$: From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, $27{\sim}76$ years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection. BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An aditional dose of $9{\sim}16\;Gy$ was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CTx. with $4{\sim}6$ cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: $17{\sim}93$ months). $\underline{Results}$: The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five patients developed distant metastases as the first sign of recurrence at $6{\sim}33$ months (mean 21 months). Sites of distant metastatic sites were bone in 3 patients, liver in 1 patient and systemic lesions in 1 patient. Among the patients with distant metastatic sites, two patients died at 17 and 25 months during the follow-up period. According to stage, the 5Y-OSR was 95.5%, 100%, 84.6%, and 100% for stage I, IIa, IIb, and III respectively. The 5Y-DFSR was 96.8%, 92.7%, 76.9%, and 100% for stage I, IIa, IIb, and III respectively. Stage was the only risk factor for local recurrence based on univariate analysis. Ten stage III patients included in this analysis had a primary tumor size of less than 3 cm and had more than 4 axillary lymph node metastases. The 10 stage III patients received not only breast RT but also received posterior axillary boost RT to the supraclavicular node. During the median 53.3 months follow-up period, no any local or distant failure was found. Complications were asymptomatic radiation pneumonitis in 10 patients, symptomatic pneumonitis in 1 patient and lymphedema in 8 patients. $\underline{Conclusion}$: Although our follow up period is short, we had excellent local control and survival results and reaffirmed that BCS followed by RT and CTx. appears to be an adequate treatment method. These results also provide evidence that distant failure occurs earlier and more frequent as compared with local failure. Further studies and a longer follow-up period are needed to assess the effectiveness of BCS followed by RT for the patients with less than a 3 cm primary tumor and more than 4 axillary node metastases.

• Radiation Oncology Journal
• /
• v.21 no.2
• /
• pp.112-117
• /
• 2003

Purpose: The effects of hypefractionation radiation therapy, such as the failure pattern and survival, on the treatment results in advanced stage head and neck cancer were studied. Materials and Methods: Between September 1990 and October 1998, 24 patients with advanced stage (III, IV) head and neck cancers, were treated using hyperfractionation radiation therapy in the Department of Radiation Oncology at the Keimyung University Dongsan Medical Center. The male to female ratio was 7 : 1, and the age range from 38 to 71 years with the median of 56 years. With regard to the TNM stage, 11 patients were stage III and 13 were stage IV. The sites of primary cancer were the nasopharynx in six, the hypopharynx in 6, the larynx in five, the oropharynx in three, the maxillary sinus in three, and the oral cavity in one patient. The radiotherapy was delivered by 6 MV X-ray, with a fraction size of 1.2 Gy at two fractions a day, with at least 6 hours inter-fractional interval. The mean total radiation doses was 72 Gy, (ranging from 64.4 to 75.8 Gy). Follow-up periods ranged between 3 and 136 months, with the median of 52 months. Results: The overall survival rates at 3 and 5 years in all patients were 66.7$\%$, and 52.4$\%$. The disease-free survival rates at 3 and S years (3YDFS, 5YDFS) in all patients were 66.7$\%$ and 47.6$\%$. The 3YDFS and 5YDFS in stage III patients were 81.8$\%$ and 63.6$\%$, and those in stage IV patients were 53.8$\%$ and 32.3$\%$. Ten patients were alive with no local nor distant failures at the time of analyses. Six patients (25$\%$) died due to distant metastasis and 12.5$\%$ died due to local failure. Distant metastasis was the major cause of failure, but 2 patients died due to unknown failures and 3 of other diseases. The distant metastasis sites were the lung (3 patients), the bone (1 patient), and the liver (2 patients). One patient died of second esophageal cancer. There were no severe late complications, with the exception of 1 osteo-radionecrosis of the mandible 58 months after treatment. Conclusion: Although this study was peformed on small patients group, we considered hypefractionated radiation therapy for the treatment of advanced stage head and neck cancer might improve the disease free survival and decrease the local failure with no increase in late complications despite of the slight Increase in acute complications.

• Journal of Chest Surgery
• /
• v.39 no.11 s.268
• /
• pp.828-837
• /
• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Radiation Oncology Journal
• /
• v.20 no.3
• /
• pp.221-227
• /
• 2002

Purpose : To evaluate the role of postoperative chemoradiotherapy in locally advanced rectal cancer, we retrospectively analyzed the treatment results of patients treated by curative surgical resection and postoperative chemoradiotherapy. Materials and Methods : From April 1989 through December 1998, 119 patients were treated with curative surgery and postoperative chemoradiotherapy for rectal carcinoma in Gyeongsang National University Hospital. Patient age ranged from 32 to 73 years, with a median age of 56 years. Low anterior resection was peformed in 59 patients, and abdominoperineal resection in 60. Forty-three patients were AJCC stage II and 76 were stage III. Radiation was delivered with 6 MV X rays using either AP-PA two fields, AP-PA both lateral four fields, or PA both lateral three fields. Total radiation dose ranged from 40 Gy to 56 Gy. In 73 patients, bolus infusions of 5-FU $(400\;mg/m^2)$ were given during the first and fourth weeks of radiotherapy. After completion of radiotherapy, an additional four to six cycles of 5-FU were given. Oral 5-FU (Furtulone) was given for nine months in 46 patients. Results : Forty $(33.7\%)$ of the 119 patients showed treatment failure. Local failure occurred in 16 $(13.5\%)$ patients, 1 $(2.3\%)$ of 43 stage II patients and 15 $(19.7\%)$ of 76 stage III patients. Distant failure occurred in 31 $(26.1\%)$ patients, among whom 5 $(11.6\%)$ were stage II and 26 $(34.2\%)$ were stage III. Five-year actuarial survival was $56.2\%$ overall, $71.1\%$ in stage II patients and $49.1\%$ in stage III patients (p=0.0008). Five-year disease free survival was $53.3\%$ overall, $68.1\%$ in stage II and $45.8\%$ in stage III (p=0.0006). Multivariate analysis showed that T stage and N stage were significant prognostic factors for five year survival, and that T stage, N stage, and preoperative CEA value were significant prognostic factors for five year disease free survival. Bowel complication occurred in 22 patients, and was treated surgically in 15 $(12.6\%)$, and conservatively in 7 $(5.9\%)$. Conclusion : Postoperative chemoradiotherapy was confirmed to be an effective modality for local control of rectal cancer, but the distant failure rate remained high. More effective modalities should be investigated to lower the distant failure rate.

• Tuberculosis and Respiratory Diseases
• /
• v.57 no.3
• /
• pp.265-272
• /
• 2004

Background : RASSF1A, which is one of tumor suppressor genes, is frequently inactivated by hypermethylation of the promoter region in a variety of human cancers, including lung cancer. This study was performed to investigate the association between RASSF1A methylation and the clinicopathological factors in patients with squamous cell carcinoma of the lung. Methods : Eighty-one samples from the patients with squamous cell carcinoma of lung were examined. The promoter methyation of RASSF1A was analyzed by methylation specific PCR and sequencing. Statistical analysis was made to examine the association between RASSF1A methylation and the clinicopathological parameters. Results : RASSF1A methylation was observed in 37.0 % (30 of 81) of the patients with squamous cell carcinoma of the lung. RASSF1A methylation was found to be associated with cellular differentiation(p=0.0097) and the overall survival(p=0.0635). However, there was no association between RASSF1A methylation and the other clinicopathological parameters, such as the pathological TNM stage, the recurrence rate, lymph node invasion and the amount of cigarettes smoked. Conclusion : RASSF1A methylation might be associated with a poor prognosis in patients with squamous carcinoma of the lung. A larger scale study is needed.

• Investigative Magnetic Resonance Imaging
• /
• v.9 no.2
• /
• pp.101-108
• /
• 2005

Purpose : Early detection of small brain metastases is important. The purpose of this study was to compare the detectability of brain metastases according to the size between 1.5 T and 3.0 T MRI. Materials and Methods : We reviewed 162 patients with primary lung cancer who were examined for TNM staging. After administration of double dose of Gd-DTPA, MR imaging was performed with SPGR by 3.0 T MRI and then with T1 SE sequence by 1.5 T MRI. In each patient, three readers performed qualitative assessment. Sensitivity, positive predictive value, and diagnostic accuracy were calculated in 3.0 T and 1.5 T MRI according to size. Using the signal intensity (SI) measurements between the metastatic nodules and adjacent tissue, nodule-to-adjacent tissue SI ratio was calculated. Results : Thirty-one of 162 patients had apparent metastatic nodules in the brain at either 1.5 T or 3.0 T MR imaging. 143 nodules were detected in 3.0 T MRI, whereas 137 nodules were detected at 1.5 T MRI. Six nodules, only detected in 3.0 T MRI, were smaller than 3.0 mm in dimension. Sensitivity, positive predictive value, and diagnostic accuracy in 3.0 T MRI were 100 %, 100 %, and 100 % respectively, and in 1.5 T MRI were 95.8%, 88.3%, and 85.1% respectively. SI ratio was significantly higher in the 3.0 T MRI than 1.5 T MRI (p=0.025). Conclusion : True positive rate of 3.0 T MRI with Gd-DTPA was superior to 1.5 T MRI with Gd-DTPA in detection of metastatic nodules smaller than 3.0 mm.

• Radiation Oncology Journal
• /
• v.27 no.3
• /
• pp.153-162
• /
• 2009

Purpose: To evaluate the long-term results after breast-conserving surgery and radiation therapy in early breast cancer in terms of failure, survival, and cosmesis. Materials and Methods: One hundred fifty-four patients with stage I and II breast cancer were treated with conservative surgery plus radiotherapy between January 1992 and December 2002 at the Keimyung University Dongsan Medical Center. According to TNM stage, 93 patients were stage I, 50 were IIa, and 11 were IIb. The affected breasts were irradiated with 6 MV photons to 50.4 Gy in 28 fractions over 5.5 weeks with a boost irradiation dose of 10~16 Gy to the excision site. Chemotherapy was administered in 75 patients and hormonal therapy in 92 patients with tamoxifen. Follow-up periods were 13~179 months, with a median of 92.5 months. Results: The 5- and 10-year overall survival rates were 97.3% and 94.5%, respectively. The 5- and 10-year disease-free survival (5YDFS and 10YDFS, respectively) rates were 92.5% and 88.9%, respectively; the ultimate 5YDFS and 10YDFS rates after salvage treatment were 93.9% and 90.2%, respectively. Based on multivariate analysis, only the interval between surgery and radiation therapy ($\leq$6 weeks vs. >6 weeks, p=0.017) was a statistically significant prognostic factor for DFS. The major type of treatment failure was distant failure (78.5%) and the most common distant metastatic site was the lungs. The cosmetic results were good-to-excellent in 96 patients (80.7%). Conclusion: Conservative surgery and radiation for early stage invasive breast cancer yielded excellent survival and cosmetic results. Radiation therapy should be started as soon as possible after breast-conserving surgery in patients with early breast cancer, ideally within 6 weeks.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.4
• /
• pp.542-547
• /
• 1999

Background: Decision in mediastinal lymph node involvement of lung cancer by CT scan is very important and valuable for the treatment planning and prognosis prediction. In general, long diameter of mediastinal lymph node more than 15mm is used as criterion of lung cancer involvement. Adenocarci-noma has a tendency of early distant metastasis and micrometastasis, so adenocarcinoma may involve lymph node earlier and cannot be detected before lymph nodes are enlarged enough. The authors tried to determine the difference between two size criteria(15mm, 10mm) in adenocarcinoma for the detection of cancer involvement. Methods: Numbers of sample are 60 cases(male 46, female 14, median age: 61.5 years). According to pathology, squamous cancer 41, large cell cancer 2, adenocarcinoma 17. According to TNM stage, I 23, III 24, IIIA 13. Results : Mean long diameter of lymph node involvement is 16.0($\pm8.0$) mm in non-adenocarcinoma group, and that of adenocarcinoma group is 12.0($\pm3.2$) mm(p<0.05). If long diameter of lymph node larger than 15mm as involvement criterion is applied, sensitivity, specificity, positive predictive index, negative predictive index, accuracy of nonadenocarcinoma group are 54%, 100%, 100%, 83%, 86%, and those of adenocarcinoma group are 43%, 90%, 75%, 69%, 71%. If long diameter of lymph node larger than 10mm as involvement criterion is applied, sensitivity, specificity, positive predictive index. negative predictive index. accuracy of nonadenocarcinoma group are 65%, 77%, 61%, 92%, 79%, and those of adenocarcinoma group are 100%, 80%, 78%, 100%, 88%. Conclusion: Long diameter of lymph node larger than 10mm is more valuable criterion as lymph node involvement in adenocarcinoma of lungs.

• Journal of Gastric Cancer
• /
• v.6 no.4
• /
• pp.257-262
• /
• 2006

Purpose: We analyzed the clinicopathologic features, including treatment and outcome, and the survival rates between young and elderly patients with gastric cancer. Materials and Methods: Clinical information was reviewed for 1086 patients who had undergone a gastrectomy for gastric cancer during a 10-year period from 1990 to 1999, and the patients were assigned to one of two groups: the A group (<40 years of age, 91 patients) and the B group (${\geq}70\;years\;of\;age,\;85\;patients)$). Results: Compared to the B group, the A group had more females (47.3% vs 32.9%), a greater frequency of family history of cancer (15.4% vs 3.5%), and greater proportions of histologically poorly differentiated tumors (84.5% vs 40.2%) and Lauren diffuse-type tumors (69.1% vs 35.1%)(P<0.05). There was no difference in TNM stage. Cardiopulmonary co-morbidities were more in the B group, respectively, 1.1% (A group) and 11.8% (B group)(P<0.01), but the morbidity and the mortality were similar. Although there was no difference in curability, the B group underwent less aggressive operations in lymph-node dissection above D3 and had a shorter operation time, a smaller number of retrieved lymph nodes, and less adjuvant chemotherapy (P<0.001). However, there were no differences in the disease-specific 5-year survival rates, 67.6% and 67.0% respectively. Conclusion: Young and elderly patients with gastric cancer had different clinicopathological features. Especially, elderly patients underwent relatively less aggressive treatment. In spite of these facts, the outcome of treatment and the disease-specific survival rates were not different.