• Radiation Oncology Journal
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• v.11 no.2
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• pp.355-361
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• 1993

Since May 1991, authors have conducted a pilot study to determine the feasibility and evaluate the effect of concurrent radiation therapy and chemotherapy with 5-FU and Cis-platinum for locally advanced cervical cancer (stage IIB-IVA). Radiation therapy consisted of external irradiation to whole pelvis (4140 cGy/23 fx) in 4.5 weeks followed by high dose rate intracavitary radiation therapy (HDR ICRT) to deliver a dose of 30 to 35 Gy to A point in 6 to 7 fractions. After the intracavitary radiation therapy, parametrial boost was delivered for B point dose of 60 Gy in Stage IIB and 65 Gy in stage IIIB. 5-FU (1000 $mg/m^2/24hr$ for 96 hour iv infusion) and Cis-platinum (20 $mg/m^2/day$ IV bolus for 3 days) were given during the second week of external RT and the second course chemotherapy administered at the first HDR ICRT with the same method as the first chemotherapy. Sixteen patients (10 stage IIB,4 stage IIIB,2 stage IVA) were registered to this protocol. Among these 16 patients, two refused treatment after 2 fractions of external irradiation, and one could not continue intracavitary irradiation because of treatment related genitourinary toxicity. So 14 patients were evaluated for toxicity and 13 patients were evaluated for response analysis. Five of 14 patients developed grade 3 gastrointestinal toxicity but 4 of them recovered at the completion of treatment. One stage IIIB patient with inguinal lymph node metastasis who received higher dose of radiation in spite of initial poor performance status did not recover from gastrointestinal toxicity at the completion of treatment. And she died of distant metastasis at one month after the completion of treatment. Two of 14 evaluable patients showed weight loss, more than $10\%$ of initial weight. One patient developed grade 3 leukopenia. In this study, the average total treatment period of completely treated patients was 75 days and three of them took more than 80 days (84, 84, 89 days). Toxicities were generally acceptable and there were no treatment related death. At the last follow-up, complete response was achieved in $62\%(8/13)$ and especially of nine patients with stage IIB, eight patients showed complete response. This study suggests that concurrent radiation therapy and chemotherapy (5-FU and Cis-platinum) is tolerable and effective. Further follow-up is needed to determine whether this protocol will have a favorable impact on survival and to evaluate the late effect on normal tissues. In future, prospective randomized trials are needed to compare the standard radiation therapy alone with concurrent chemotherapy and radiation therapy for locally advanced cervical carcinoma.

• 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.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.230-236
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• 2001

Purpose : To evaluate treatment results in terms of local control, complications and survival after reirraidiation in recurrent cervical cancer following definite radiation therapy. Material and methods : From November 1987 through March 1998, eighteen patients with recurrent cervical cancer following definite radiation therapy were subsequently treated with reirradiation at Keimyung University Dongsan Medical Center. In regard to the initial FIGO stage, one patient was stage la, five were stage IIa, three were IIb, two were IIb and two were IVa. The age range was 37 to 79 years old with median age of 57. The time interval from initial definite radiation therapy to recurrence ranged from 6 to 122 months with a median of 58 months. The recurrent sites were the uterine cervix in seven patients, vagina in ten and pelvic lymph node in one. Reirradiation was peformed with external radiation and intracavitary radiation in twelve patients, external radiation and implantation in four and external radiation alone in two. The range of external radiation dose was $2,100\~5,400\;cGy$ and the range of the total radiation dose was $3,780\~8,550\;cGy$. The follow-up periods ranged from 8 to 20 months with median of 25 following reirradiation. Results : Fourteen of eighteen patients $(78\%)$ had local control just after reirradiation. The two year disease free survival (2YDFS) rate was $53.6\%$. There were statistically significant differences in the 2YDFS according to both recurrent site (2YDFS $28.5\%$ in uterine cervix, $71.4\%$ in vagina, (p=0.03)) and the total dose (2YDFS $71.8\%$ in >6,000 cGy , $25\%$ in $\leq6,000$ cGy, p=0.007). Seven of ten patients who were followed for more than 20 months remain alive and disease free (7/18, $39\%$). Patients treated with external radiation and intracavitary radiation had a higher rate of 2YDFS. Seven patients including 4 patients with no local control experienced local failure in the uterus or vagina and two patients died with distant metastasis. Complications included rectal bleeding in 3 patients, bowel obstruction treated with surgery in two, hematuria in one, radiation cystitis in two, soft tissue swelling in two and vaginal necrosis spontaneously healed in one. There was no statistical difference in complications according to the total dose or the time to recurrence from initial radiation. Conclusion : In patients with recurrence following definite radiation therapy in the uterine cervical cancer, reirradiation may be effective but requires an effort to reduce radiation induced severe complications.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.259-266
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• 1995

Purpose : The aim of this study is to analyze the survival rate, treatment failure and complication of radiation therapy alone in stage III uterine cervical cancer. Materials and Methods : From January 1980 through December 1985, 227 patients with stage III uterine cervical cancer treated with radiation therapy at Kosin Medical Center were retrospectively studied. Among 227 patients, 72 patients($317{\%}$) were stage IIIa, and 155 patients($68.3{\%}$) were stage IIIb according to FIGO classification. Age distribution was 32-71 years (median: 62 years). Sixty nine patients($95.8{\%}$) in stage IIIa and 150 patient ($96.8{\%}$) in stage IIIb were squamous cell carcinoma. pelvic lymph node metastasis at initial diagnosis was 8 patients($11.1{\%}$) in stage IIIa and 29 patients($18.7{\%}$) in stage IIIb, Among 72 patients with stage IIIa, 36 patients ($50{\%}$) were treated with external radiation therapy alone by conventional technique (180-200 cGy/fr.) and 36 patients($50{\%}$) were treated with external radiation therapy with intracavitary radiotherapy(ICR) with $Cs^{137}$ sources, and among 155 patients with stage IIIb, 80 patients ($51.6{\%}$) were treated with external radiation therapy alone and 75 patients ($48.4{\%}$) were treated with external radiation therapy with ICR. Total radiation doses of stage IIIa and IIIb were 65-105 Gy(median: 78.5 Gy) and 65-125.5 Gy (median 83.5 Gy). Survival rate was calculated by life-table method. Results : Complete response rates were $58.3{\%}$(42 patients) in stage IIIa and $56.1{\%}$(87 patients) in stage IIIb. Overall 5 year survival rates were $57{\%}$ in stage IIIa and $40{\%}$ in stage IIIb. Five year survival rates by radiation technique in stage IIIa and IIIb were $64{\%},\;40{\%}$ in the group treated in combination of external radiation and ICR, and $50\%,\;40\%$ in the group of external radiation therapy alone(P=NS). Five year survival rates by response of radiation therapy in stage IIIa and IIIb were $90\%,\;66\%$ in responder group and $10\%,\;7\%$ in non-responder group (P<0.001) There were statistically no significant differences of 5 year survival rate by total radiation doses and external radiation doses(40 Gy vs 50 Gy) of whole or true pelvis in stage IIIa and IIIb(P=NS). Treatment failures rates were $40.3\%$(29 patients) in stage IIla and $57.4\%$(89 patients) in stage IIIb. 17 patients ($23.6\%$) in stage IIIa and 46 patients ($29.7\%$) in stage IIIb experienced complications. Total radiation doses more than 85 Gy produced serious complication in both stage IIIa($50\%$) and IIIb($50\%$). Serious complication rates were higher in group received external radiation doses of 50 Gy than 40 Gy to whole or true pelvis in stage IIIa and IIIb. Serious rectal complication developed in rectal doses more than 65 Gy, and serious bladder complication developed in bladder doses more than 75 Gy. Major cause of death was cachexia due to locoregional failure in both stage IIIa($34.7\%$) and IIIb($43.9\%$). Conclusion : From this study, we found that external radiation therapy with ICR was found to have a tendency to be superior to external radiation therapy alone in survival rate, local control rate and complication rate but not different in statistics, and external radiation doses of 50 Gy than 40 Gy to whole or true pelvis produced serious rectal and bladder complications in stage III uterine cervical cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.3
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• pp.263-268
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• 1998

Many myocutaneous flaps have been used for the reconstruction of intraoral defects caused by the excision of oral cancer. Among these myocutaneous flaps, cervical island flap has been introduced by Farr et al. Although different in detail, this flap was designed as the platysma myocutaneous flap by Futrell et al in the supraclavicular site. Since many authors applied this flap to cover intraoral defect, they discussed deeply the blood supply of this flap. To improve further flap survival, it was modified by Tashiro et al. This flap makes its vascularity highly reliable. The amount of tissue needed for reconstruction can be accurately planned. The surgical and reconstruction procedure can be performed simply, rapidly, and effectively. Oral functions including deglutition, speech, and denture fitting are not compromised. With it's minimal deformity, new donor fields is not necessory. Of course, we keep in mind that this flap has limitations in patients where much bulk of tissue defects is needed and more than 3000 rad radiation due to the metastasis of neck lymph node is exposed. In three patients with intraoral squamous cell carcinoma($T_{1-3}N_0M_0$), we performed induction chemotherapy with FP regimen including pepleomycin. Thereafter, we ablated oral cancer and peformed reconstruction of intraoral defects with cervical island flap designed by Tashiro et al. Due to these significant benefits and minimal limitations, we have found that this flap is adequate for reconstruction of most intraoral defects following cancer ablation.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.11-17
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• 2002

Objectives: Expression of HMGI(Y), a nucleoprotein that binds to A/T rich sequences in the minor groove of the DNA helix, is observed in neoplastically transformed cells but not in normal cells. We have analyzed HMGI(Y), p53 expression and Ki-67 labelling index in squamous cell carcinomas of the head and neck, and evaluated its clinicopathologic significance. Materials and Methods: 40 cases of squamous cell carcinoma of the head and neck were entered on the study of immunohistochemical stains for HMGI(Y), p53 and Ki-67. We analyzed the relationship between HMGI(Y), p53, Ki-67 expression and age, sex, primary tumor site, stage, survival rate, recurrence. Results: HMGI(Y) expression evidenced by immunohistochemical staining was observed in 35 of 40 (87.5%) squamous cell carcinoma of the head and neck. But no significant correlation was observed between HMGI(Y) expression and other clinical factors such as primary site, tumor stage, differenciation, cervical lymph node, metastasis, recurrence and immunohistochemical status of p53. The Ki-67 labelling index was significantly correlated with recurrence and HMGI(Y) expression (p<0.05). Conclusion: This results suggest the Ki-67 is a good prognostic factor and the HMGI(Y) expression plays some roles in carcinogenesis and cellular proliferation of squamous cell carcinoma of the head and neck. HMGI(Y) gene can be used as a cancer marker, the correlation between the gene expression and the prognosis of the cancer patient should be proved in the future studies.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.54-60
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• 1998

Objectives: We'd like to give help in diagnosis and treatment of children's thyoid tumor through our clinical experiences and reference consideration. Materials and Methods: The authors report their experiences with 33 cases of thyroid tumor in patients younger than 16 years of age who were treated at Presbyterian Medical Center from 1979 to 1995. Results: 1) Girls were more predominant than boys by a ratio of 5.6:1. The peak incidence was in the 15 years old of age. 2) The final diagnosis in the 33 patients were thyroid carcinoma in 12 cases, nodular goiter in 6 cases, adenoma in 6 cases, Graves disease in 4 cases, Hasimoto's disease in 4 cases and cyst in 1 case. 3) All of 12 patients with thyroid cancer had nodular tumor. 4) In 5 of 6 patients with palpable cervical lymphadenopathy, the final diagnosis was thyroid carcinoma. 5) Delayed diagnosis arose in 6 of 12 thyroid carcinomas which were treated for long periods as benign disease. 6) The surgical procedures were total thyroidectomy in 3 cases, subtotal thyroidectomy in 13 cases and thyroid lobectomy in 17 cases. 7) 11 of 12 patients with thyroid carcinoma had subtotal or total thyroidectomy with lymphnode dissection and only one had lobectomy. 8) The overall rate of postoperative complication was 3%(1 of 33 patient). 9) Postoperative $^{131}I$ therapy was done in 7 case because of recurrence and distant metastasis in six and severe local invasion in one. 10) In thyroid cancer, the metastatic rate of lymph node at initial surgery was 81%(9/11) and rate of recurrence was 50%(6/12). 11) Patients with thyroid carcinoma were followed up for a mean of 12 years but only one died as a result of thyroid carcinoma 3.5 years later. Conclusion: The authors suggest that thyroid tumors in childhood should receive the benifit of joint management by endocrine pediatrician and experianced surgeons with an agreed protocol of diagnosis and management. We, also, recommend aggressive surgical and $^{131}I$ treatment as the most effective regimen for children with thyroid carcinoma.

• Korean Journal of Head & Neck Oncology
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• v.21 no.1
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• pp.3-9
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• 2005

Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.335-344
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• 2001

Purpose : The aim of this study was to clarify the role of VEGF expression as an independent prognostic factor and to identify the patients at high risk for poor prognosis in stage IB cervical cancer. Materials and methods : A total of 118 patients with stage IB cervical cancer who had radical hysterectomy and pelvic lymph node dissection were included in the study. All known high risk factors of the patients were pathologically confirmed from the surgical specimen. Of the 118 patients, n patients were treated with postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded specimens of post-hysterectomy surgical materials. A semiquantitative analysis was made using a scoring system of 0, +, ++, and +++ for increasing intensity of stain. We classified the patients with scores from 0 to ++ as low VEGF expression and the patients with a score of +++ as high VEGF expression. Results : Of the 118 patients, 35 patients $(29.7\%)$ showed high VEGF expression. Strong correlations were found between the high VEGF expression and both deep stromal invasion (p=0.01) and the positive pelvic node (p=0.03). The 5-year overall and disease-free survival rates for all 118 patients were $95.5\%\;and\;93.8\%$. The 5-year overall (p=0.03) and disease-free survival (p<0.001) rates were $98.5\%\;and\;100%$ for low VEGF expression (0, +, and ++) and $85.5\%\;and\;79.7\%$ for high VEGF expression, respectively. Pelvic and distant failures for low versus high VEGF expression were $1.2\%$ versus $17.1\%$, (p=0.001) and $0\%$ versus $14.3\%$ (p<0.001), respectively. In a Cox multivariate analysis of survival, the high VEGF expression (p=0.02) and the bulky mass (p=0.02) were significant prognostic factors for overall survival. The high VEGF expression (p=0.002), and bulky mass (p=0.01) demonstrated as significant prognostic indicators for disease free survival. Conclusion : These results showed that VEGF expression was a highly significant predictor for pelvic and distant failure and the most significant prognostic factor of overall and disease free survival for the patients with stage IB cervix cancer treated with radical surgery. We strongly suggest that the immune-histochemistry for VEGF expression be performed in a routine clinical setting in order to identify the patients at high risk for poor prognosis in early stage cervical cancer. Furthermore, postoperative and/or chemotherapy did not reduce the pelvic failure and distant metastasis. To improve the cure rate for the patients with high VEGF expression in stage IB cervical cancer, antiangiogenic therapy including anti-VEGF Ab may be new treatment option.

• The Journal of Korean Society for Radiation Therapy
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• v.21 no.1
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• pp.17-23
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• 2009

Purpose: In treating head and neck cancer, it is very important to irradiate uniform dose on the junction of the bilateral irradiation field of the upper head and neck and the anterior irradiation field of the lower neck. In order to improve dose distribution on the junction, this study attempted to correct non uniform dose resulting from under dose and over dose using the field-in-field technique in treating the anterior irradiation field of the lower neck and to apply the technique to the treatment of head and neck cancer through comparison with conventional treatment. Materials and Methods: In order to examine dose difference between the entry point and the exit point where beam diffusion happens in bilateral irradiation on the upper head and neck, we used an anthropomorphic phantom. Computer Tomography was applied to the anthropomorphic phantom, the dose of interest points was compared in radiation treatment planning, and it was corrected by calculating the dose ratio at the junction of the lower neck. Dose distribution on the junction of the irradiated field was determined by placing low-sensitivity film on the junction of the lower neck and measuring dose distribution on the conventional bilateral irradiation of the upper head and neck and on the anterior irradiation of the lower neck. In addition, using the field-in-field technique, which takes into account beam diffusion resulting from the bilateral irradiation of the upper head and neck, we measured difference in dose distribution on the junction in the anterior irradiation of the lower neck. In order to examine the dose at interest points on the junction, we compared and analyzed the change of dose at the interest points on the anthropomorphic phantom using a thermoluminescence dosimeter. Results: In case of dose sum with the bilateral irradiation of the upper head and neck when the field-in-field technique is applied to the junction of the lower neck in radiation treatment planning, The dose of under dose areas increased by 4.7~8.65%. The dose of over dose areas also decreased by 2.75~10.45%. Moreover, in the measurement using low-sensitivity film, the dose of under dose areas increased by 11.3%, and that of over dose areas decreased by 5.3%. In the measurement of interest point dose using a thermoluminescence dosimeter, the application of the field-in-field technique corrected under dose by minimum 7.5% and maximum 17.6%. Thus, with the technique, we could improve non.uniform dose distribution. Conclusion: By applying the field-in-field technique, which takes into account beam divergence in radiation treatment planning, we could reduce cold spots and hot spots through the correction of dose on the junction and, in particular, we could correct under dose at the entry point resulting from beam divergence. This study suggests that the clinical application of the field-in-field technique may reduce the risk of lymph node metastasis caused by under dose on the cervical lymph node.