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Radiation Therapy and Chemotherapy after Breast Conserving Surgery for Invasive Breast Cancer: An Intermediate Result (침윤성 유방암에서 유방보존수술 후 방사선치료 및 항암화학 병용치료의 성적 및 위험인자 분석)

  • Lee, Seok-Ho;Choi, Jin-Ho;Lee, Young-Don;Park, Heoung-Kyu;Kim, Hyun-Young;Park, Se-Hoon;Lee, Kyu-Chan
    • 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.

Concurrent Chemoradiation Therapy in Stage III Non-small Cell Lung Cancer (III 기 비소세포성 폐암에서 Cisplatin-방사선동시병합요법의 효과)

  • Kim In Ah;Choi Ihl Bhong;Kang Ki Mun;Jang Jie Young;Song Jung Sub;Lee Sun Hee;Kuak Mun Sub;Shinn Kyung Sub
    • Radiation Oncology Journal
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    • v.15 no.1
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    • pp.27-36
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    • 1997
  • Purpose : This study was tried to evaluate the Potential benefits of concurrent chemoradiation therapy (low dose daily cisplatin combined with split course radiation therapy) compared with conventional radiation therapy alone in stage III non-small cell lung cancer. The end points of analyses were response rate. overall survival, survival without locoregional failure, survival without distant metastasis, prognostic factors affecting survival and treatment related toxicities. Materials and Methods : Between April 1992 and March 1994, 32 patients who had stage III non-small cell lung cancer were treated with concurrent chemoradiation therapy. Radiation therapy for 2 weeks (300 cGy given 10 times up to 3000 cGy) followed by a 3 weeks rest period and then radiation therapy for 2 more weeks (250 cGy given 10 times up to 2500 cGy) was combined with $6mg/m^2$ of cisplatin. Follow-up period ranged from 13 months to 48 months with median of 24 months. Historical control group consisted of 32 patients who had stage III non-small cell lung cancer were received conventionally fractionated (daily 170-200 cGy) radiation therapy alone. Total radiation dose ranged from 5580 cGy to 7000 cGy with median of 5940 cGy. Follow-up Period ranged from 36 months to 105 months with median of 62 months. Result : Complete reponse rate was higher in chemoradiation therapy (CRT) group than radiation therapy (RT) group (18.8% vs. 6.3%, CRT group showed lower in-field failure rate compared with RT group(25% vs. 47%. The overall survival rate had no significant differences in between CRT group and RT group (17.5% vs. 9.4% at 2 years). The survival without locoregional failure (16.5% vs. 5.3% at 2 years) and survival without distant metastasis (17% vs. 4.6% at 2 years) also had no significant differences. In subgroup analyses for Patients with good performance status (Karnofsky performance scale 80), CRT group showed significantly higher overall survival rate compared with RT group (62.5% vs. 15.6% at 2 years). The prognostic factors affecting survival rate were performance status and pathologic subtype (squamous cell cancer vs. nonsquamous cell cancer) in CRT group. In RT alone group, performance status and stage (IIIa vs IIIb) were identified as a Prognostic factors. RTOG/EORTC grade 2-3 nausea and vomiting(22% vs 6% and bone marrow toxicities (25% vs. 15.6% were significantly higher in CRT group compared with RT alone group. The incidence of RTOG/EORTC grade 3-4 pulmonary toxicity had no significant differences in between CRT group and RT group (16% vs. 6%. The incidence of WHO grade 3-4 pulmonary fibrosis also had no significant differences in both group (38% vs. 25%. In analyses for relationship of field size and Pulmonary toxicity, the Patients who treated with field size beyond 200cm2 had significantly higher rates of pulmonary toxicities. Conclusion : The CRT group showed significantly higher local control rate than RT group. There were no significant differences of survival rate in between two groups. The subgroup of patients who had good performance status showed higher overall survival rate in CRT group than RT group. In spite of higher incidence of acute toxicities with concurrent chemoradiation therapy, the survival gain in subgroup of patients with good performance status were encouraging. CRT group showed higher rate of early death within 1 year, higher 2 year survival rate compared with RT group Therefore, to evaluate the accurate effect on survival of concurrent chemoradiation therapy, systematic follow-up for long term survivors are needed.

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Once vs. Twice Daily Thoracic Irradiation in Limited Stage Small Cell Lung Cancer (국한성 병기 소세포폐암의 방사선치료시 분할 조사방식에 따른 치료성적)

  • Kim, Jun-Sang;Kim, Jae-Sung;Kim, Ju-Ock;Kim, Sun-Young;Cho, Moon-June
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.291-301
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    • 1998
  • Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

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A Study on Urinary Cadmium Concentration and Renal Indices of Inhabitant in an Abandoned Mine Area (폐광지성(廢鑛地城) 주민(住民)의 요중(尿中) 카드뮴 농도(濃度)와 현기능평가(賢機能評價))

  • Park, Jung-Duck;Park, Chan-Byung;Choi, Byung-Sun;Kang, Eun-Yong;Hong, Yeon-Pyo;Chang, Im-Won;Chun, Byung-Yeol;Yeh, Min-Hae
    • Journal of Preventive Medicine and Public Health
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    • v.31 no.3 s.62
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    • pp.424-439
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    • 1998
  • Urinary cadmium is used as a sensitive indicator for internal Cd dose, and increased excretion of $N-acetyl-\beta-D-glucosaminidase(NAG)$, $\beta_2-microglobulin(MG)$ and total protein are useful indices for renal dysfunction by chronic exposure to Cd. The target group was 184 inhabitant(82 men and 102 women) in an abandoned mine area known as exposure to low level Cd. The control group was took 160 individuals(64 men and 96 women) in Cd not-exposed area. Urinary Cd concentration was significantly higher in the target group than the control. The geometric mean of urinary Cd for male was $2.56{\mu}g/\ell,\;2.80{\mu}g/g$ creatinine and $2.50{\mu}g/S.G.$ in the target group and $1.19{\mu}g/\ell,\;1.36{\mu}g/g$ creatinine and $1.17{\mu}g/S.G.$ in the control. For female $2.69{\mu}g/\ell,\;3.94{\mu}g/g$ creatinine and $2.63{\mu}g/S.G.$ in the target group and $1.27{\mu}g/\ell,\;1.97{\mu}g/g$ creatinine and $1.25{\mu}g/S.G.$ in the control, respectively. In addition, urinary Cd of the target group had affected by the period of residence and dietary habit for the rice and the vegetables from the target area. These findings suggest the chronic exposure to Cd of the target population. Mean excretion of urinary NAG, $\beta_2-MG$ and total protein were not significant between two groups. In the target group, urinary NAG activity and total protein were significantly correlated with urinary Cd, but $\beta_2-MG$ was not related. Urinary excretion of NAG, $\beta_2-MG$ and total protein were significantly increased in $10\leqq$ than in <2 of urinary Cd level. In $2\sim10$ group of urinary Cd level, the excretion of NAG significantly increased while not showed for $\beta_2-MG$. In present study, urinary excretion of NAG was relatively sensitive than $\beta_2-MG$ in chronic exposure population to low level Cd.

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The 1998, 1999 Patterns of Care Study for Breast Irradiation after Mastectomy in Korea (1998, 1999년도 우리나라에서 시행된 근치적 유방 전절제술 후 방사선치료 현황 조사)

  • Keum,, Ki-Chang;Shim, Su-Jung;Lee, Ik-Jae;Park, Won;Lee, Sang-Wook;Shin, Hyun-Soo;Chung, Eun-Ji;Chie, Eui-Kyu;Kim, Il-Han;Oh, Do-Hoon;Ha, Sung-Whan;Lee, Hyung-Sik;Ahn, Sung-Ja
    • Radiation Oncology Journal
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    • v.25 no.1
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    • pp.7-15
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    • 2007
  • [ $\underline{Purpose}$ ]: To determine the patterns of evaluation and treatment in patients with breast cancer after mastectomy and treated with radiotherapy. A nationwide study was performed with the goal of improving radiotherapy treatment. $\underline{Materials\;and\;Methods}$: A web- based database system for the Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Randomly selected records of 286 eligible patients treated between 1998 and 1999 from 17 hospitals were reviewed. $\underline{Results}$: The ages of the study patients ranged from 20 to 80 years (median age 44 years). The pathologic T stage by the AJCC was T1 in 9.7% of the cases, T2 in 59.2% of the cases, T3 in 25.6% of the cases, and T4 in 5.3% of the cases. For analysis of nodal involvement, N0 was 7.3%, N1 was 14%, N2 was 38.8%, and N3 was 38.5% of the cases. The AJCC stage was stage I in 0.7% of the cases, stage IIa in 3.8% of the cases, stage IIb in 9.8% of the cases, stage IIIa in 43% of the cases, stage IIIb in 2.8% of the cases, and IIIc in 38.5% of the cases. There were various sequences of chemotherapy and radiotherapy after mastectomy. Mastectomy and chemotherapy followed by radiotherapy was the most commonly performed sequence in 47% of the cases. Mastectomy, chemotherapy, and radiotherapy followed by additional chemotherapy was performed in 35% of the cases, and neoadjuvant chemoradiotherapy was performed in 12.5% of the cases. The radiotherapy volume was chest wall only in 5.6% of the cases. The volume was chest wall and supraclavicular fossa (SCL) in 20.3% of the cases; chest wall, SCL and internal mammary lymph node (IMN) in 27.6% of the cases; chest wall, SCL and posterior axillary lymph node in 25.9% of the cases; chest wall, SCL, IMN, and posterior axillary lymph node in 19.9% of the cases. Two patients received IMN only. The method of chest wall irradiation was tangential field in 57.3% of the cases and electron beam in 42% of the cases. A bolus for the chest wall was used in 54.8% of the tangential field cases and 52.5% of the electron beam cases. The radiation dose to the chest wall was $45{\sim}59.4\;Gy$ (median 50.4 Gy), to the SCL was $45{\sim}59.4\;Gy$ (median 50.4 Gy), and to the PAB was $4.8{\sim}38.8\;Gy$, (median 9 Gy) $\underline{Conclusion}$: Different and various treatment methods were used for radiotherapy of the breast cancer patients after mastectomy in each hospital. Most of treatment methods varied in the irradiation of the chest wall. A separate analysis for the details of radiotherapy planning also needs to be followed and the outcome of treatment is needed in order to evaluate the different processes.

Reversal of Multidrug Resistance with KR-30035: Evaluated with Biodistribution of Tc-99m MIBI in Nude Mice Bearing Human Tumor Xenografts (이종이식된 인체종양에서 KR-30035가 Tc-99m MIBI체내 분포에 미치는 영향으로 평가한 다약제내성 역전가능성)

  • Kim, Jung-Kyun;Lee, Byung-Ho;Choi, Sang-Woon;Yoo, Sung-Eun;Lee, Sang-Woo;Chun, Kyung-Ah;Ahn, Byeong-Cheol;Park, Jae-Young;Suh, Jang-Soo;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.3
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    • pp.168-184
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    • 2001
  • Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

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Postoperative Radiation Therapy in the Soft-tissue Sarcoma (연부 조직 육종의 수술 후 방사선 치료 결과)

  • Kim Yeon Shil;Jang Hong Seok;Yoon Sei Chul;Ryu Mi Ryeong;Kay Chul Seung;Chung Su Mi;Kim Hoon Kyo;Kang Yong Koo
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.485-495
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    • 1998
  • Purpose : The major goal of the therapy in the soft tissue sarcoma is to control both local and distant tumor. However, the technique of obtaining local control has changed significantly over the past few decades from more aggressive surgery to combined therapy including conservative surgery and radiation and/or chemotherapy. We retrospectively analyzed the treatment results of the postoperative radiation therapy of soft tissue sarcoma and its prognostic factor. Materials and Methods : Between March 1983 and June 1994, 50 patients with soft tissue sarcoma were treated with surgery and postoperative radiation therapy at Kang-Nam St. Mary's hospital. Complete follow up was possible for all patients with median follow up duration 50 months (range 6-162 months). There were 28 male and 32 female patients. Their age ranged from 6 to 83 with a median of 44 years. Extremity (58$\%$) was the most frequent site of occurrence followed by trunk (20$\%$) and head and neck (12$\%$). Histologically malignant fibrous histiocytoma (23$\%$), liposarcoma (17$\%$), malignant schwannoma (12$\%$) constitute 52$\%$ of the patients. Daily radiation therapy designed to treat all areas at a risk for tumor spread upto dose of 4500-5000 cGy. A shrinking field technique was then used and total 55-65 Gy was delivered to tumor bed. Twenty-five patients (42$\%$) received chemotherapy with various regimen in the postoperative period. Results : Total 41 patients failed either with local recurrence or with distant metastasis. There were 29 patients (48$\%$) of local recurrence. Four patients (7$\%$) developed simultaneous local recurrence and distant metastasis and 8 patients (13$\%$) developed only distant metastasis. Local recurrence rate was rather higher than of other reported series. This study included patients of gross residual, recurrent cases after previous operation, trunk and head and neck Primary This feature is likely explanation for the decreased local control rate. Five of 29 Patients who failed only locally were salvaged by re-excision and/or re-irradiation and remained free of disease. Factors affecting local control include histologic type, grade, stage, extent of operation and surgical margin involvement, lymph node metastasis (p<0.05). All 21 patients who failed distantly are dead with progressive disease at the time of this report. Our overall survival results are similar to those of larger series. Actuarial 5 year overall survival and disease free survival were 60.4 $\%$, 30.6$\%$ respectively. Grade, stage (being close association with grade), residual disease (negative margin, microscopic, gross) were significant as a predictor of survival in our series (p<0.05). Conclusion : Combined surgery and postoperative radiation therapy obtained 5 year survival rate comparable to that of radical surgery.

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