• Radiation Oncology Journal
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• v.7 no.2
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• pp.149-156
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• 1989

Multicellular tumor spheroids of HeLa cells have been grown in a static culture system. Samples of spheroids were exposed for 2 h to graded concentration of cis-platinum and its analogue, carboplatin, and then response assayed by survival of clonogenic cells. The purpose of present experiment is to clarify the effectiveness of these platinum compounds and to evaluate intrinsic radiosensitivity of cells using spheroids of HeLa cells as an experimental in vitro model. Variations of the drug sensitivity of monolayers as well as spheroids were also evaluated in cell-survival curves. In cis-platinum concentration-survival curve, there was a large shoulder extending as far as $Cq=3.4{\mu}M$, after which there was exponential decrease in survival curve having a Co Value of $1.2{\mu}M$ in spheroids. While the Co for the spheroids was essentially no significant change, but Cq value was larger than that of monolayers. This suggest that the effect of cis-platinum is greater En the monolayer with actively proliferaing cells than hypoxic one. In the carboplatin concentration-survival curves, the Co value of spheroids was $15.0{\mu}M$ and the ratio with the Co from monolayer cell $(32.5{\mu}M)$ was 0.40, thus indicating that the spheroids had a greater sensitivity to carboplatin than monolayers. Therefore, the effect of carboplatin is mainly on the deeper layers of spheroids acting as hypoxic cell sensitizer. The enhanced effect was obtained for monolayer cells using combined X-ray and carboplatin treatment 2 hours before irradiation. The result shown in isobologram analysis for the level of surviving fraction at 0.01 indicated that the effect of two agents was trusty supra-additive. From this experimental data, carboplatin has excited much recent interest as one of the most promising, since it is almost without nephrotoxicity and causes less gastrointestinal toxicity than cis-platinum. Interaction between carboplatin and radiation might play an important role for more effective local tumor control.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.241-253
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• 1990

331 patients of stage IIb uterine cervix cancer trated by radiation alone at Kosin Medical Center between June 1980 and Dec. 1985 were analysed to determine parameters of radiotherapy associated to disease states. Survival rate was highest among the reported ($82.8{\%}$ for crude and $82.4{\%}$ for disease free survival). Pelvic control rate in 6 weeks after the end of radiotherapy was $93.6{\%}$ in the patients treated with ICR following total pelvic radiation and $71.6{\%}$ with small field additional external irradiation. 5 year survival rate in those who achieved pelvic control was $98.9{\%}$ and $12.9{\%}$ in those who had pelvic failure and/or metastasis after radiation. The survival rate figured maximal $88.5{\%}$ with dosage of $7500{\~}8500$ cGy to point A with acceptable incidence of complications ($4.9{\%}$) but without increasing survival above it and minimal $74.1{\%}$ with dosage of less than 6500 cGy. The treatment failure was counted $18.7{\%}$ (62 of 331 patients): Local failure $72.6{\%}$ (45 of 62 patients), locoregional failure $3.2{\%}$ (2 of 62 patients) and distant failure $24{\%}$ (15 of 62 patients). Late complications were found in 50 patients ($15.1{\%}$) and $42{\%}$ of them was rectal bleeding and stenosis. The dose of 8500 cGy to point A was found to be critical for complication and $70{\%}$ of complications occurred above it and was more serious one such as fistula. Rectal complications were developed above rectal dose 6500 cGy and bladder complication above bladder dose 7500 cGy. Major cause of death was cachexia due to locoregional failure ($73.7{\%}$ of death), next was due to metastasis to lung, liver and bone, and only 3 patients died of complication of intestinal perforations and obstruction. In conclusion higher external radiation dose for a bulky uterine cervix and barrel shaped uterus was essential for local control.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.2
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• pp.190-199
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• 2003

Purpose: The aim of this study was to find out a clinically appliable method to insert a biodegradable solid material containing holmium-166-chitosan complex into the surgical field, and to evaluate the histological changes in the normal tissues after ${\beta}$ -ray irradiation from holmium-166 according to the dose, period and type of tissues. Materials and Methods: 3.0 mCi, 50 ${\mu}l$ of the liquid state $^{166}$Ho-chitosan complex was attached to the absorbable gelatin sponge. The radiation activity measured by dose caliberator was 1.5 mCi. These $^{166}$Ho-chitosan complex containing absorbable gelatin sponges were inserted into the thigh muscles and over the femur bones of the Wistar rats. The cases were evaluated at 2 weeks after insertion, and 4, 6 weeks with respect to the histological changes of the soft tissues and bone, the depth of the tissue necrosis, and the changes of the $^{166}$Ho-chitosan complex containing absorbable gelatin sponges. Results: At 2 weeks, the muscles showed coagulation necrosis, degenerating myocytes, regenerating myocytes, intermuscular edema, and inflammatory cells. The necrosis depth was 3.3 mm. In the bones, there was no osteocyte in the lacuna of cortex (empty lacuna), marrow fibrosis, inflammation. The necrosis depth was 2.9 mm. At 4 weeks, in the muscle, calcification and increased fibrosis with necrosis depth by 3.3 mm were the additional findings. In the bone, marrow fibrosis with necrosis depth by 3.3 mm were detected. At 6 weeks, soft tissue shrinkage, increased fibrosis and granulation tissue formation, and nearly resolving inflammatory reaction were the findings. Conclusion: The local application of the $^{166}$Ho-chitosan complex attached to biodegradable gelatin material with surgery in the laboratory animals resulted in no mortality and morbidity, and satisfactory tissue necrosis. Holmium-166 can be applied to the treatment of the malignant tumor patients.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1982.05a
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• pp.6.1-6
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• 1982

Papilloma is the common benign tumor of the larynx and the incidence of its malignant change was variable. The authors recently experienced 2 cases of squamous cell carcinoma of the larynx which were considered to be transformed from laryngeal papilloma. Case 1. A 58 year old male patient visited O.P.D. of Department of Otolaryngology of Busan National University Hospital, because of hoarseness for 3 years on May 13th, 1980. At that time, local finding of indirect laryngoscopy revealed whitish hypertrophic papillomatous mass on both vocal cords and anterior commissure, and dirty gray white pseudomembrane on left aryepiglottic fold, and the result of biopsy was squamous cell papilloma. So the laryngeal papilloma was removed under suspension laryngoscopy and then he had no specific treatment in spite of being recommended 5-FU topical spray. On March 5th, 1981, he visited O.P.D. again because of progressive exacerbation of hoarseness with mild dyspnea and histopathological finding was revealed squamous cell carcinoma of the larynx. Seven days later from that day, he visited emergency room due to severe dyspnea, and emergency tracheostomy was performed on sitting position. On April 7th 1981, total laryngectomy was performed successfully and postoperative irradiation therapy was recommended. Case 2. A 47 year old male patient visited our O.P.D. because of hoarseness for 5 years on Sep. 27, 1978. At that time, local finding of indirect laryngoscopy revealed papillomatous mass on left vocal cord and left ventricle and result of biopsy was squamous cell papilloma. So he had been treated with 11 times removal of papilloma, topical spray of 5-Fu and estrogen for 3 years, but the papilloma had been recurred. On Sep. 9th, 1981, he visited O.P.D. because of severe dyspnea and emergency tracheostomy and biopsy was performed. The result of biopsy was squamous cell carcinoma of larynx and total laryngectomy was performed successfully.

• Radiation Oncology Journal
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• v.4 no.1
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• pp.35-43
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• 1986

Study patients with head and neck carcinoma were studied retrospectively to assess the impact of treatment on survival and local control rate by stage in the Dept of Radiation Therapy, Korea University Hae Wha Hospital between March 1981 and March 1986. Prior to definite radiotherapy, patients were evaluated by physical examination and radiologic studies including chest, laryngogram and CT scan and then these patients were grouped according to the American Joint Committee (AJC) staging system. They were treated with RT alone or postoperative irradiation to the dose of 7,200 cGy/8 weeks and 6,000 cGy/7 weeks respectively. The results were obtained and as follows; 1. Overall male to female sex ratio was 3.6:1. The peak age of patients with head and neck cancer was 6th decade. 2. In all patients treated by RT, the ratio of squamous cell 1 carcinoma to non-squamous cell carcinoma was 3.5:1 (60/77 patients). 3. The incidence according to the anatomic site of primary tumor was 22 cases in the larynx, 12 cases in PNS, 7 cases in nasopharynx, 6 cases in oropharynx, and 3 cases in hypopharynx. 4. According to AJC staging system,4 cases were Stage 1,7 in Stage II, 19 in Stage III and 27 in Stage IV. 5. The overall incidence of cervical lymph node metastases was $43\%$ and subdigatric and submaxillary triangle lymph nodes were the most frequent site of metastases. 6. Local control was achieved in $48\%$ of patients treated by radio-therapy. 7. The lung was the most common site for distant metastases, comprising 4 cases among 7 cases in which distant metastases occured. 8. The overall estimated 5-year survival rate was $43\%$ in the head and neck cancer treated with radiotherapy by life-table analysis.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.40-44
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• 2001

Purpose : To evaluate effect and tolerance of external beam radiotherapy for carcinoma of the prostate and define the optimal radiotherapeutic regimen. Materials and methods : We retrospectively analyzed the records of 60 patients with prostate cancer who were treated with external beam radiotherapy with curative intent in our institution between September, 1987 and March, 2000. Histologic diagnosis was established by transurethral resection or ultrasonography guided biopsy. The major presenting symptoms were a nodule at routine prostatic examination and frequency and urgency of urination, along with dysuria. The median age was 63 years with range of 51 to 87 years. There were 6 patients in Stage A, 20 in Stage 8, 26 in Stage C, and 8 in Stage Dl. All patients were treated with megavoltage equipment producing 10 MV photons. The 4 field pelvic brick technique was used to a dose of 45 Gy or 50.4 Gy at 1.8 Gy per day in 5 to 6 weeks, after which a small boost field was delivered 2.0 Gy per day to a total dose of 66 to 70 Gy. The follow-up period ranged from 1 to 8 years. Results : Actuarial 5-year and 7-year survival rates for Stage A, B, C, and D1 were $100\%\;and\;84\%$, $83\%\;and\;72\%$, $67\%\;and\;54\%$, and $v$, respectively. The corresponding 5-year and 7-year relapse free survival rates were $84\%\;and\;84\%$, $77\%\;and\;67\%$, $48\%\;and\;40\%$, and $33\%\;and\;25\%$, respectively. Relapse free 5-year survival rates for Stage B were $80\%,\;80\%,\;and\;50\%$ for well, moderately, and poorly differentiated tumors, respectively. These were $64\%,\;44\%,\;and\;33\%$ for Stage C, respectively. The local control rates at 5 years were $84\%,\;85\%,\;78\%,\;and\;60\%$ for Stage A, B, C, and D1, respectively. Mild to moderate complications were observed in $22\%$ of patients. Severe complications requiring surgical procedures were documented in only $3\%$ of patients. Conclusion : This study confirms that external beam irradiation is an effective and safe treatment for prostatic cancer, providing long-term local control and good survival with acceptable complications.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.143-148
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• 2003

Purpose: The purpose of this study was to evaluate treatment results in terms of the survival and failure patterns subsequent to radiation therapy in recurrent cervical cancer, fellowing primary surgery. Material and Methods: Between January 1990 and December 1999, 27 patients, with recurrent cervical cancer following primary surgery, were subsequently treated with radiation in the Department of Radiation Oncology, at the Keimyung University Dongsan Medical Center. Their median age was 48, ranging from 31 to 70 years old. With regard to the Initial FIGO stage on presentation, 20 and 7 patients were stages I and II, respectively. Twenty three patients had squamous cell carcinomas and 4 had adenocarcinomas. The time interval from the primary surgery to the recurrence ranged from 2 to 90 months with a median of 29 months. The recurrent sites were the vaginal cuff alone, the pelvic cavity and combined recurrence in 14, 9 and 4 patients, respectively. Radiation was peformed, with external and vaginal intracavitary radiation in 13 patients, external radiation alone in 13 and vaginal intracavitary radiation alone in another one. The median follow-up period was 55 months, ranging from 6 to 128 months. Results: The five year disease free survival (5y DFS) and five year overall survival (5y OS) rates were 68.2 and 71.9$\%$, respectively. There was a marginal statistically significant difference in the 5y DFS in relation to the recurrent site (5y DFS, 85.7$\%$ in vaginal cuff recurrence alone, 53.3$\%$ in pelvic cavity recurrence, p=0.09). There was no difference in the survival according to the time interval between the primary surgery and a recurrence. There was only a 7$\%$ local failure rate in the patients with a vaginal cuff recurrence. The major failure patterns were local failure in the patients with pelvic cavity recurrence, and distant failure in the patients with a combined recurrence. There were no complications above grade 3 after the radiation therapy. Conclusion: Radiation therapy was safe and effective treatment for a recurrent carcinoma of the uterine cervix following primary surgery, especially the external beam radiation and vaginal intracavitary irradiation achieved the best results in the patients with a vaginal cuff recurrence following primary surgery.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.253-260
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• 2003

Purpose: No general consensus has been reached regarding the necessity of postoperative radiation therapy (PORT) and the optimal techniques of its application for patients with chest wall invasion (pT3cw) and node negative (NO) non-small cell lung cancer (NSCLC). We retrospectively analyzed the PT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. Materials and Methods: From Aug. 1994 till June 2000, 21 pT3cwN0 NSCLC patients received PORT at Samsung Medical Center; all of whom underwent curative on-bloc resection of the primary tumor plus the chest wall and regional lymph node dissection. PORT was typically stalled 3 to 4 weeks after operation using 6 or 10 MV X-rays from a linear accelerator. The radiation target volume was confined to the tumor bed plus the immediate adjacent tissue, and no regional lymphatics were included. The planned radiation dose was 54 Gy by conventional fractionation schedule. The survival rates were calculated and the failure patterns analyzed. Results: Overall survival, disease-free survival, loco-regional recurrence-free survival, and distant metastases-free survival rates at 5 years were 38.8$\%$, 45.5$\%$, 90.2$\%$, and 48.1$\%$, respectively. Eleven patients experienced treatment failure: six with distant metastases, three with intra-thoracic failures, and two with combined distant and intra-thoracic failures. Among the five patients with intra-thoracic failures, two had pleural seeding, two had in-field local failures, and only one had regional lymphatic failure in the mediastinum. No patients suffered from acute and late radiation side effects of RTOG grade 3 or higher. Conclusion: The strategy of adding PORT to surgery to improve the probability, not only of local control but also of survival, was 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. The incidence and the severity of the acute and late side effects of PORT were markedly reduced, which contributed to improving the patients' qualify of life both during and after PORT, without increasing the risk of regional failures by eliminating the regional lymphatics from the radiation target volume.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.709-719
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• 1996

Background: Surgical resection is the only way to cure non-small cell lung cancer(NSCLC) and the prognosis of NSCLC in patients who undergo a complete resection is largely influenced by the pathologic stage. After surgical resection, recurrences in distant sites is more common than local recurrences. An effective postoperative adjuvant therapy which can prevent recurrences is necessary to improve long tenn survival Although chemotherapy and radiotherapy are still the mainstay in adjuvant therapy, the benefits of such therapies are still controversial. We initiated this retrospective study to evaluate the effects of adjuvant therapies and analyze the prognostic factors for survival after curative resection. Method: From 1990 to 1995, curative resection was perfomled in 282 NSCLC patients with stage I, II, IIIa, Survival analysis of 282 patients was perfonned by Kaplan-Meier method. The prognostic factors, affecting survival of patients were analyzed by Cox regression model. Results: Squamous cell carcinoma was present in 166 patients(59%) ; adenocarcinoma in 86 pmients(30%) ; adenosquamous carcinoma in II parients(3.9%); and large cell undifferentiated carcinoma in 19 patients(7.1%). By TNM staging system, 93 patients were in stage I; 58 patients in stage II ; and 131 patients in stage rna. There were 139 postoperative recurrences which include 28 local and 111 distant failures(20.1% vs 79.9%). The five year survival rate was 50.1% in stage I ; 31.3% in stage II ; and 24.1% in stage IIIa(p <0.0001). The median survival duration was 55 months in stage I ; 27 months in stage II ; and 16 months in stage rna. Among 131 patients with stage rna, the median survival duration was 19 months for 81 patients who received postoperative adjuvant chemotherapy only or cherne-radiotherapy and 14 months for the other 50 patients who received surgery only or surgery with adjuvant radiotherapy(p=0.2982). Among 131 patients with stage IIIa, the median disease free survival duration was 16 months for 21 patients who received postop. adjuvant chemotherapy only and 4 months for 11 patients who received surgery only(p=0.0494). In 131 patients with stage IIIa, 92 cases were in N2 stage. The five year survival rate of the 92 patients with N2 was 25% and their median survival duration was 15 months. The median survival duration in patients with N2 stage was 18 months for those 62 patients who received adjuvant chemotherapy and 14 months for the other 30 patients who did not(p=0.3988). The median survival duration was 16 months for those 66 patients who received irradiation and 14 months for the other 26 patients who did not(p=0.6588). We performed multivariate analysis to identify the factors affecting prognosis after complete surgical resection, using the Cox multiple regression model. Only age(p=0.0093) and the pathologic stage(p<0.0001) were significam prognostic indicators. Conclusion: The age and pathologic stage of the NSCLC parients are the significant prognostic factors in our study. Disease free survival duration was prolonged with statistical significance in patients who received postoperative adjuvant chemotherapy but overall survival duration was not affected according to adjuvant therapy after surgical resection.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.