• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Journal of Life Science
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• v.14 no.6 s.67
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• pp.913-919
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• 2004

Mitochondrial DNA mutations have been reported in recent years in association with sensorineural hering loss. The purpose of this study is to identify the association between the noise-induced sensorineural hearing loss and the A to G mutation at nucleotide 3243, 1555, 7445 of mitochondrial DNA. Study subjects were established by history and chart review, and audiological and clinical data were obtained. Blood was sampled from 214 normal controls, 102 noise-induced hearing loss, and 28 sensorineural hearing loss. The DNA of these individuals were extracted, and mitochondrial DNA fragments were analyzed by polymerase chain reaction. Subsequently, the coding sequence of mitochondrial DNA 3243, 1555, 7445 were sequenced, and compared to the normal sequence, and all sequence variations were analyzed by restriction enzymes. Mitochondrial DNA mutations $(3243A{\rightarrow}G,\;1555A{\rightarrow}4G,\;7445A{\rightarrow}G)$ were not detected by polymerase chain reactions in any patients with noise-induced hearing loss, sensorineural hearing loss, and normal controls. The DNA sequencing of PCR products did not revealed an A to G substitution at nucleotide 3243, 1555, 7445 of mitochondrial DNA. The noise-induced sensorineural hearing loss was not associated with mitochondrial DNA mutation $(3243A{\rightarrow}G,\;1555A{\rightarrow}4G,\;7445A{\rightarrow}G)$.

• The Korean Journal of Nuclear Medicine
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• v.39 no.5
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• pp.269-277
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• 2005

Purpose: This study evaluated the diagnostic value of $^{18}F-FDG$ PET/CT in detecting cervical lymph node metastases in head and neck cancer patients. Materials & Methods: The patients were divided into two groups, 46 patients underwent PET/CT scan for initial staging before surgery, and 20 patients for restaging of recurrence after primary treatment. Increased FDG uptakes in cervical lymph nodes were evaluated retrospectively and correlated with the histopathologic results. Results: In the initial staging group, 21 lymph nodes were detected by PET/CT in 15 patients. 20 lymph nodes were confirmed as metastases with a mean peak SUV of 5.84, and the remaining one lymph node was an inflammatory lesion, with a peak SUV of 2.75. Seven metastatic lymph nodes were reported only by histopatholoay. The sensitivity, specificity, positive predictive value and negative predictive value were 74.0%, 99.6%, 95.2% and 97.3%, respectively. In the recurrence group, 11 lymph nodes were detected in 9 patients, and 8 nodes were true positive, with a mean peak SUV of 5.65. The other three were inflammatous lymph nodes, and the peak SUVs were 2.16, 2.94 and 3.53. One false negative lymph node was reported. The sensitivity, specificity, positive predictive value and negative predictive value were 88.8%, 97.7%, 72.7% and 92.9%, respectively. Conclusions: FDG-PET/CT shows higher positive predictive value in the initial staging group, and better sensitivity in the recurrence group. Therefore PET/CT could be useful for both initial staging and restaging of recurrent cervical lymph node metastases.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.349-359
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• 1994

Purpose: The primary gastrointestinal non-Hodgkin's lymphoma(GI-NHL) is the most common extranodal NHL. Surgery with postoperative radiotherapy or chemotherapy was tried with some success, but proper management guidelines have not been estabilished in localized GI-NHL due to its rarity and the lack of randomized trials. So we designed this study to evaluate treatment results and the lack of randomized trials. So we designed this study to evaluate treatment results and prognostic factors in localized GI-NHL, and to assess proper treatment mdality after surgical resection accordig to risk factors by survival analysis. Method: Seventy three patients who received surgical resection due to localized GI-NHL from Jan. 1916 to Apr. 1991 were reviewed in this study. Prognostic factors were analyzed by multivariate analysis program including postoperative treatment methods, and treatment results were compared according to prognostic factors and treatment modalities. Results: Overall 5-year survival rate was 62.3%, for all patients. The 5-year survival rate was 80.0% for patients with stage I GI-NHL and 45.7% for those with stage II. Chemotherapy or not, stage and residuum or not after surgical resection were significant independent prognositic factors. Postoperative adjuvant treatments showed significant survival benefit. In patients with high risk factors such as stage II or residuum after surgical resection, postoperative combined chemotherapy and radiotherapy showed better survival than those treated with single modality. Conclusions: Chemothrapy or not, stage, and residuum or not were important prognostic factors of patients with localized GI-NHL after surgical resection. Either chemotherapy or radiation therapy alone after surgical resection is recommanded for patients without high risk factors(stage II or residuum after surgical resection) but the postoperative combined chemotherapy and radiotherapy seems to be beneficial for patients with high risk factors.

• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.668-675
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• 2001

Background : Non-smalll lung cancer(NSCLC) develops as a result of the accumulation of multiple genetic abnormalities. Loss of heterozygosity(LOH) is one of the most frequent genetic alterations that is found in NSCLC, and the chromosomal regions that display a high rate of LOH are thought to harbor tumor suppressor genes(TSGs). This study was done to determine the frequency of LOH in 21q with the aim of identifying potential TSG loci. Method : Thirty-nine surgically resected NSCLCs were analysed. Patients peripheral lymphocytes were used as the source of the normal DNA. Five microsatellite Inarkers of 21q were used to study LOH : 21q21.1(D21S1432, and D21S1994); 21q21.2-21.3(D21S1442) ; 21q22.1(21S1445) ; and 21q22.2-22.3(D21S266). The fractional allelic loss(FAL) in a tumor was calculated as the ratio of the number of markers showing LOH to the number of informative markers. Result : LOH for at least one locus was detected in 21 of 39 tumors(53.8%). Among the 21 tumors with LOH, 5(21.8%) showed LOH at almost all informative loci. Although statistically not significant, LOH was found more frequently in squamous cell carcinomas(15 of 23, 65.2%) than in adenocarcinomas(6 of 16, 37.5%). In the squamous cell carcinomas the frequency of LOH was higher in stage II-III (80.0%) than in stage I (53.8%). The FAL value in squamous cell carcinomas($0.431{\pm}0.375$) was significantly higher than that found in adenocarcinomas($0.l92{\pm}0.276$). Conclusion : These results suggest that LOH on 21q may be involved in the development of NSCLC, and that TSG(s) that contribute to the pathogenesis of NSCLC may exist on 21q.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.40-47
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• 2009

Purpose: Differentiated thyroid cancer (DTC) has variable degree of F-18 FDG avidity. The purpose of this study was to evaluate the relationship between F-18 FDG uptake and pathological or immunohistochemical features of DTC. Materials and Methods: DTC patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included in the study. Maximum standardized uptake values (SUVmax) of primary tumor were calculated. If the primary tumor showed no perceptibly increased F-18 FDG uptake, region of interest was drawn based on finding of a portion of the PET/CT images. Pathological and immunohistochemical markers such as presence of lymph node (LN) metastasis and underlying thyroiditis, tumor size, Ki-67 labeling index, expressions of EGFR, COX-2, and Galectin-3 were evaluated. Results: Total of 106 patients was included (102 papillary carcinomas, 4 follicular carcinomas). The mean SUVmax of the large tumors (above 1 cm) was significantly higher than the mean SUVmax of small (equal to or less than 1 cm) ones ($7.8{\pm}8.5$ vs. $3.6{\pm}3.1$, p=0.004). No significant difference in F-18 FDG uptake was found according to the presence or absence of LN metastasis and underlying thyroiditis, or the degree of Ki-67 labeling index, expression of EGFR, COX- 2 and Galectin-3. Conclusion: In conclusion, the degree of F-18 FDG uptake in DTC was associated with the size of primary tumor. But there seem to be no relationship between F-18 FDG uptake of DTC and expression of Ki-67, EGFR, COX-2 and Galectin-3.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.255-262
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• 1997

Purpose : This is retrospective study to compare the results of radiation therapy alone and neoadjuvant chemotherapy and radiation in advanced stage of uterine cervical cancer. Materials and Methods : Seventy-six Patients who were treated with definitive radiation therapy for locally advanced cervical cacinoma between June 1988 and December 1993 at the department of radiation oncology, Keimyung University Dong-san Hospital. Thirty six patients were treated with radiation therapy alone and forty patients were treated with cisplatin based neoadjuvant chemotherapy and radiation therapy. According to FIGO staging system. there were 48 patients in stage IIb, 3 patients in stage IIIa, 23 patients in stage lIIb and two patients in stage IVa with median age of 53 years old. Follow-up periods ranged from 7 to 95 months with median 58 months. Results : Complete response (CR) rate were $86.1\%$ in radiation alone group and $80\%$ in chemoradiation group. There was no statistical difference in CR rate between the two groups. Overall five-year survival rate was $67.3\%$. According to stage, overall five-rear survival rates were $74\%$ in stage IIb, $66.7\%$ in stage IIIa, $49.8\%$ in stage IIb, $50\%$ in stage IVa. According to treatment modality overall five year survival rates were $74.1\%$ in radiation alone and $61.4\%$ in chemoradiation group (P=0.4) Five rear local failure free survival rates were $71.5\%$ in radiation alone group and $60\%$ in chemoradiation group (P=0.17). Five year distant metastasis free survival rates were $80.7\%$ in radiation aione group and $89.9\%$ in chemoradiation group (P=0.42). Bone marrow suppression (more than noted in 3 cases of radiaion alone group and 1 case of chemoradiation group. Grade II retal complication was noted in 5 patients of radiation group and 4 patients In chemoradiation group. Bowel obstruction treated with conservative treatment (1 patient) and bowel perforation treated with surgery (1 patient) were noted in radiation alone group. There was no statistical difference in complication between two groups. Conclusion : There was no statistical difference in survival, failure and complication between neoadjuvant chemotherapy and radiation versus radiation alone in locally advanced uterine cervical carcinoma.

• Radiation Oncology Journal
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• v.28 no.3
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• pp.133-140
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• 2010

Purpose: We retrospectively investigated the effect of irradiation using helical tomotherapy in recurrent pelvic tumors that underwent prior irradiation. Materials and Methods: Fourteen patients with recurrent pelvic tumors consisting of rectal cancer (57.1%), cervical cancer (35.7%) and cancer with an unknown origin (7.1%) were treated with tomotherapy. At the time of irradiation, median tumor size was 3.5 cm and 7 patients complained of pain originating from a recurrent tumor. The median radiation dose delivered to the gross tumor volume, clinical target volume, and planning target volume was 50 Gy, 47.8 Gy and 45 Gy, respectively and delivered at 5 fractions per week over the course of 4 to 5 weeks. Treatment response and duration of local disease control were evaluated using the Response Evaluation Criteria in Solid Tumors (ver. 1.0) and the Kaplan-Meyer method. Treatment-related toxicities were assessed through Common Terminology Criteria for Adverse Events (ver. 3.0). Results: The median follow-up time was 17.3 months, while the response rate was 64.3%. Symptomatic improvement appeared in 6 patients (85.7%). The median duration time of local disease control was 25.8 months. The rates of local failure, distant failure, and synchronous local and distant failure were 57.1%, 21.4%, and 7.1%, respectively. Acute toxicities were limited in grade I or II toxicities, except for one patient. No treatment related death or late toxicity was observed. Conclusion: Helical tomotherapy could be suggested as a feasible palliative option in recurrent pelvic tumors with prior radiotherapy. However, to increase treatment effect and overcome the limitation of this outcome, a large clinical study should be performed.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.285-292
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• 2008

Background: A diagnosis of malignant pleural effusion is clinically important, as the prognosis of lung cancer patients with malignant pleural effusion is poor. The diagnosis will be difficult if a cytological test is negative. This study was performed to investigate whether the detection of hypermethylation of the p16 (CDKN2A) and retinoic acid receptor b2 (RARB2) genes in pleural fluid is useful for a diagnosis of malignant pleural effusion. Methods: Pleural effusion was collected from 43 patients and was investigated for the aberrant promoter methylation of the RARB2 and CDKN2A genes by use of methylation-specific PCR. Results were compared with findings from a pleural biopsy and from pleural fluid cytology. Results: Of 43 cases, 17 cases of pleural effusion were due to benign diseases, and 26 cases were from lung cancer patients with malignant pleural effusion. Hypermethylation of the RARB2 and CDKN2A genes was not detected in the case of benign diseases, independent of whether or not the patients had ever smoked. In 26 cases of malignant pleural effusion, hypermethylation of RARB2, CDKN2A or either of these genes was detected in 14, 5 and 15 cases, respectively. The sensitivities of a pleural biopsy, pleural fluid cytology, hypermethylation of RARB2, hypermethylation of CDKN2A, or hypermethylation of either of the genes were 73.1%, 53.8%, 53.8%, 19.2%, and 57.7%, respectively; negative predictive values were 70.8%, 58.6%, 58.6%, 44.7%, and 60.7%, respectively. If both genes are considered together, the sensitivity and negative predictive value was lower than that for a pleural biopsy, but higher than that for pleural fluid cytology. The sensitivity of hypermethylation of the RARB2 gene for malignant pleural effusion was lower in small cell lung cancers than in non-small cell lung cancers. Conclusion: These results demonstrate that detection of hypermethylation of the RARB2 and CDKN2A genes showed a high specificity, and sensitivity was higher than for pleural fluid cytology. With a better understanding of the pathogenesis of lung cancer according to histological types at the molecular level, and if appropriate genes are selected for hypermethylation testing, more precise results may be obtained.