• Journal of Chest Surgery
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• v.31 no.10
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• pp.973-981
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• 1998

Background: About 30% to 40% of the patients with pathologic stage I non-small cell lung cancer (NSCLC) die within 5 years after complete resection. The identification of poor prognostic factors and the application of additional treatment are very important to improve the survival rate in resected stage I NSCLC. Materials and methods: Sixty-eight(68) patients who had been diagnosed postoperatively between Janury 1989 and December 1995 as having stage I non-small cell lung cancer according to the TNM classification were studied. The postoperative 5-year survival rate was calculated with the Kaplan-Meier method, and clinico- histopathologic factors including age, sex, operative method, type of tumor cell, T factor, grade of the differentiation in a squamous cell carcinoma, invasion of blood vessel and expression of the nm23-H1 protein were investigated and analyzed. Results: The median survival of the entire group of patients was 58$\pm$3 months, with a 5-year survival of 58.9%. In univariate analysis, invasion of blood vessel and poor differentiation of the tumor cell in a squamous cell carcinoma significantly worsened the survival. In multivariate analysis, invasion of blood vessel and grade of the differentiation of the tumor cells in a squamous cell carcinoma remained independent prognostic factors. High expression of the nm23-H1 protein was related to a high postoperative 5-year survival in comparision with low expression of the nm23-H1 pretein (73.0% vs 50.7%), but there was no statistical significance. Conclusions: These results highlight the negative prognostic value of poor differentiation of tumor cells in a squamous cell carcinoma and invasion of blood vessel in stage I non-small cell lung cancer. Also, further studies are necessary to be determined prognostic value of the T factor and expression of the nm23 protein in non-small cell lung cancer.

• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.38-43
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• 2005

Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.28-35
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• 2011

Purpose: Recently, the use of radiosurgery as a local therapy in patients with early stage non-small cell lung cancer has become favored over surgical resection. To evaluate the efficacy of radiosurgery, we analyzed the results of stereotactic body radiosurgery in patients with primary or recurrent non-small cell lung cancer. Materials and Methods: We reviewed medical records retrospectively of total 24 patients (28 lesions) with non-small cell lung cancer (NSCLC) who received stereotactic body radiosurgery (SBRT) at Inha University Hospital. Among the 24 patients, 19 had primary NSCLC and five exhibited recurrent disease, with three at previously treated areas. Four patients with primary NSCLC received SBRT after conventional radiation therapy as a boost treatment. The initial stages were IA in 7, IB in 3, IIA in 2, IIB in 2, IIIA in 3, IIIB in 1, and IV in 6. The T stages at SBRT were T1 lesion in 13, T2 lesion in 12, and T3 lesion in 3. 6MV X-ray treatment was used for SBRT, and the prescribed dose was 15~60 Gy (median: 50 Gy) for PTV1 in 3~5 fractions. Median follow up time was 469 days. Results: The median GTV was 22.9 mL (range, 0.7 to 108.7 mL) and median PTV1 was 65.4 mL (range, 5.3 to 184.8 mL). The response rate at 3 months was complete response (CR) in 14 lesions, partial response (PR) in 11 lesions, and stable disease (SD) in 3 lesions, whereas the response rate at the time of the last follow up was CR in 13 lesions, PR in 9 lesions, SD in 2 lesions, and progressive disease (PD) in 4 lesions. Of the 10 patients in stage 1, one patient died due to pneumonia, and local failure was identified in one patient. Of the 10 patients in stages III-IV, three patients died, local and loco-regional failure was identified in one patient, and regional failure in 2 patients. Total local control rate was 85.8% (4/28). Local recurrence was recorded in three out of the eight lesions that received below biologically equivalent dose 100 $Gy_{10}$. Among 20 lesions that received above 100 $Gy_{10}$, only one lesion failed locally. There was a higher recurrence rate in patients with centrally located tumors and T2 or above staged tumors. Conclusion: SBRT using a CyberKnife was proven to be an effective treatment modality for early stage patients with NSCLC based on high local control rate without severe complications. SBRT above total 100 $Gy_{10}$ for peripheral T1 stage patients with NSCLC is recommended.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.257-264
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• 2000

Purpose: For early stage non-small-cell lung cancer, surgical resection is the treatment of choice. But when the patients are not able to tolerate it because of medical problem and when refuse surgery, radiation therapy is considered an acceptable alternative. We report on the treatment results and the effect of achieving local control of primary tumors on survival end points, and analyze factors that may influence survival and local control. Materials and Method : We reviewed the medical records of 32 patients with medically inoperable non-small cell lung cancer treated at our institution from June, 1987 through June, 1997. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidate for surgical resection because of either patients refusal (4), old age (2), lung problem (21), chest wail invasion (3) and heart problems (3). In 8 patients, there were more than 2 problems. The median age of the patients was 68 years (ranging from 60 to 86 years). Histologic cell type included souamous (24), adenocarcinoma (6) and unclassiried squamous cell (2). The clinical stages of the patients were 71 in 5, 72 in 25, 73 in 2 patients. Initial tumor size was 3.0 cm in 11, between 3.0 cm and 5.0 cm in 13 and more than 5.0 cm in 8 patients. Ail patients had taken chest x-rays, chest CT, abdomen USG and bone scan. Radiotherapy was delivered using 6 MV or 10 MV linear accelerators. The doses of primary tumor were the ranging from 54.0 Gy to 68.8 Gy (median; 61.2 Gy). The duration of treatment was from 37 days through 64 days (median; 0.5 days) and there was no treatment interruption except 1 patient due to poor general status. In 12 patients, concomitant boost technique was used. There were no neoadjuvant or adjuvant treatments such as surgery or chemotherapy. The period of follow-up was ranging from 2 months through 93 months (median; 23 months). Survival was measured from the date radiation therapy was initiated. Results : The overall survival rate was 44.6$\%$ at 2 years and 24.5$\%$ at 5 years, with the median survival time of 23 months. of the 25 deaths, 7 patients died of intercurrent illness, and cause-specific survival rate was 61.0$\%$ at 2 years and 33.5$\%$ at 5 years. The disease-free survival rate was 38.9$\%$ at 2 years and 28.3$\%$ at 5 years. The local-relapse-free survival rate was 35.1$\%$, 28.1$\%$, respectively. On univariate analysis, tumor size was significant variable of overall survival (p=0.0015, 95$\%$ C.1.; 1.4814-5.2815), disease-free survival (P=0.0022, 95$\%$ C.1., 1.4707-5.7780) and local-relapse-free survival (p=0.0015, 95$\%$ C.1., 1.2910- 4.1197). 7 stage was significant variable of overall survival (p=0.0395, 95$\%$ C.1.; 1.1084-55.9112) and had borderline significance on disease-free survival (p=0.0649, 95$\%$ C.1.; 0.8888-50.7123) and local-relapse-free survival (p=0.0582, 95$\%$ C,1.; 0.9342-52.7755). On multivariate analysis, tumor size had borderline significance on overall survival (p=0.6919, 955 C.1., 0.9610-5.1277) and local-relapse-free survival ( p=0.0585, 95$\%$ C.1.; 0.9720-4.9657). Tumor size was also significant variable of disease-free survival (p=0.0317, 95% C.1.; 1.1028-8.4968). Conclusion : Radical radiotherapy is an effective treatment for small (71 or f3 cm) tumors and can be offered as alternative to surgery in elderly or infirmed patients. But when the size of tumor is larger than 5 cm, there were few long-term survivors treated with radiotherapy alone. The use of hypefractionated radiotherapy, endobronchial boost, radisensitizer and conformal or IMRT should be consider to improve the local control rate and disease-specific survival rate.

• Journal of Chest Surgery
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• v.37 no.10
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• pp.845-855
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• 2004

Background: No general consensus has been available regarding the necessity of postoperative radiation therapy (PORT) and its optimal techniques in the patients with chest wall invasion (pT3cw) and node negative (N0) non-small cell lung cancer (NSCLC). We did retrospective analyses on the pT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. And we compared them with the pT3cwN0 NSCLC patients who did not received PORT during the same period. Material and Method: From Aug. of 1994 till June of 2002, 22 pT3cwN0 NSCLC patients received PORT-PORT (＋) group- and 16 pT3cwN0 NSCLC patients had no PORT-PORT (-) group. The radiation target volume for PORT (＋) group was confined to the tumor bed plus the immediate adjacent tissue only, and no regional lymphatics were included. The prognostic factors for all patients were analyzed and survival rates, failure patterns were compared with two groups. Result: Age, tumor size, depth of chest wall invasion, postoperative mobidities were greater in PORT (-) group than PORT (＋) group. In PORT (-) group, four patients who were consulted for PORT did not receive the PORT because of self refusal (3 patients) and delay in the wound repair (1 patient). For all patients, overall survival (OS), disease-free survival (DFS), loco-regional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS) rates at 5 years were 35.3%, 30.3%, 80.9%, 36.3%. In univariate and multivariate analysis, only PORT significantly affect the survival. The 5 year as rates were 43.3% in the PORT (＋) group and 25.0% in PORT (-) group (p=0.03). DFS, LRFS, DMFS rates were 36.9%, 84.9%, 43.1 % in PORT (＋) group and 18.8%, 79.4%, 21.9% in PORT(-) group respectively. Three patients in PORT (-) group died of intercurrent disease without the evidence of recurrence. Few suffered from acute and late radiation side effects, all of which were RTOG grade 2 or lower. Conclusion: The strategy of adding PORT to surgery to improve the probability not only of local control but also of survival could be justified, considering that local control was the most important component in the successful treatment of pT3cw NSCLC patients, especially when the resection margin was not adequate. Authors were successful in the marked reduction of the incidence as well as the severity of the acute and late side effects of PORT, without taking too high risk of the regional failures by eliminating the regional lymphatics from the radiation target volume.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.