• Radiation Oncology Journal
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• v.28 no.3
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• pp.125-132
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• 2010

Purpose: To retrospectively assess the advantages and side effects of prophylactic Paraaortic irradiation in cervical cancer patients with common iliac nodal involvement, the results for survival, patterns of failure, and treatment-related toxicity. Materials and Methods: From May 1985 to October 2004, 909 patients with cervical carcinoma received postoperative radiotherapy at the Seoul National University Hospital. Among them, 54 patients with positive common iliac nodes on pathology and negative Paraaortic node were included in the study. In addition, 44 patients received standard pelvic irradiation delivered 50.4 Gy per 28 fractions (standard irradiation group), and chemotherapy was combined in 16 of them. The other 10 patients received pelvic irradiation at a dose of 50.4 Gy per 28 fractions in addition to Paraaortic irradiation at 45 Gy per 25 fractions (extended irradiation group). In addition, all of them received chemotherapy in combination with radiation. Follow-up times for pelvic and Paraaortic irradiation ranged from 6 to 201 months (median follow-up time, 58 months) and 21 to 58 months (median follow-up time, 47 months), respectively. Results: The 4-year overall survival, disease free survival, and distant metastasis free survival in the standard irradiation group and extended irradiation group were 67.2% vs. 90.0% (p=0.291), 59.0% vs. 70.0% (p=0.568) and 67.5% vs. 90.0% (p=0.196), respectively. The most common site of first failure for the standard irradiation group was the paraaortic lymph node, while no paraaortic failure was observed in the extended irradiation group. Relatively, hematologic toxicity grade 3 or greater was common in the extended irradiation group (2/10 extended vs. 2/44 standard), while gastrointestinal toxicity of grade 3 or greater was lower (2/10 extended vs. 6/44 standard), and urologic toxicity of grade 3 or greater was observed in the standard irradition group only (0/10 vs. 3/44). Conclusion: Concurrent chemotherapy and prophylactic Paraaortic irradiation in patients with common iliac nodal involvement showed slightly improved clinical outcomes aside from increased hematologic toxicity, which was statistically insignificant. Considering the relatively small number of patients and short follow-up times, additional studies are needed to obtain more conclusive outcomes.

• Journal of Chest Surgery
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• v.39 no.2 s.259
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• pp.106-110
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• 2006

Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.359-368
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• 1995

Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.17-25
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• 1998

Purpose : Although local recurrence rates of stomach cancer after radiocal surgery have been reported in the range of $30-70\%$, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. Materials and Methods : From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiornyosarcoma. The numbers of patients with stage I B, II, III A, III B, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion Minimum and median follow-up periods were 12 months and 18 months, respectively, Results : Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than $15\%$ of their pretreatment weight. But hematemesis. melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient Peritoneal seeding occurred in 6, liver metastases months and median disease free survival time was 26 months. Stages andradiation dose were not significant prognostic factors for locoregional in 2, and distant nodes in 2 patients. Four year disease specificsurvival rate was $40\%$ and disease free survival was $48\%$. Median survival was 35 failures. Conculsion : Although all patients in this study had positive surgical margins, locoregional failure rate was $28\%$, and 4 year disease specific survival rate was $40\%$. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences. but we could find a Possibility of the role of postoperative radiotherapy in Patients with high risk factors.

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

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.181-189
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• 2001

Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.219-223
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• 1990

This is a retrospective review of 33 patients with large cell lung carcinoma treated at Yonsei University Cancer Center between Jan.1985 and Dec.1989. Of the thirty-three patients, twenty eight were men and five women. Median age was 59 years. Large cell undifferentiated carcinoma was the most common pathologic type, $78.8\%$. Twenty one of thirty three patients had far advanced diseases, stage IIIB-IV at the time of initial diagnosis. Pleural effusion was initially presented in 12 patients, and SVC syndrome appeared in 5 patients. As to location of the primary tumor,19($57.6\%$) appeared in the right lung and 14 ($42.4\%$) in the left. Patients with a centrally located primary tumor mass were nearly the same as those peripherally located (17 vs.16). Fifteen of thirty three patients developed metastasis involving not only bone, brain, the opposite lung, adrenal gland but also soft tissue, skin, pancreas and appendix. Treatment was individualized with 19 treated radically and 14 palliatively. After treatment, only two patients showed a complete response. Long term survival was observed in 4 patients: 1 (24 mo.),2 (41 mo.) and 1 (54 mo.). The overall 2 year survival rate was $14.3\%$ while the median survival time was 6.0 months. Through the analysis of the various factors affecting survival, we observed that pleural effusion-absent group and complete response group had a statistical significant better survival rate (p<0.01).

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.161-171
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• 1999

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-$\alpha$, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-$\alpha$, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-$\alpha$ increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-$\alpha$ may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.