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 RT. 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/m2, adriamycin 40 mg/m2, vincristine 1 mg/m2) alternating with VPP (cisplatin 60 mg/m2, etoposide 100 mg/m2) every 3 weeks in 25 (96%) of SDF TRT nd 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 medianand 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-year 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 26.9% 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 grade 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 ccrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.
Appointments and Schedules ; Arm ; Brain ; Chungcheongnam-do ; Cranial Irradiation ; Doxorubicin ; Drug Therapy ; Etoposide ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Neutropenia ; Radiation Oncology ; Radiotherapy ; Retrospective Studies ; Small Cell Lung Carcinoma* ; Vincristine

PURPOSE: This study was performed to analyze the efficacy of induction chemotherapy followed by radiation therapy in locally advanced non-small cell lung cancer. MATERIALS AND METHODS: Eighty patients with locally advanced non-small cell lung cancer treated from 1989 to 1995 at Pusan Paik hospital were analyzed retrospectively. Twenty-one patients were treated with induction chemotherapy followed by radiation therapy and Fifty-nine patients were treated with radiation therapy alone. Chemotherapy regimen consisted of cisplatin-based combination (2 or 3 drugs). All patients were treated by Co-60 or 6 MV linear accelerators. Radiation dose ranged from 50 Gy to 80 Gy (median, 64.8 Gy). We evaluated response rate, survival rate, and pattern of failure in both treatment groups. RESULTS: Overall response rate in induction chemotherapy group and radiotherapy alone group were 48% and 45%, respectively. Of the 80 patients, 46 patients were evaluable for pattern of failure. Initial failure pattern in induction chemotherapy group was as follows: 8 (67%) at locoregional, 4 (33) in distant metastasis. Radiation alone group was 21 (71%) and 5 (29%), respectively. Results showed no difference of distant failure between induction chemotherapy group and radiation alone group. The 1 and 2 year survival rate in induction chemotherapy group were 43% and 14%, respectively and in radiotherapy alone group, 31% and 7%, respectively (p=0.135). CONCLUSION: In stage lll non-small cell lung cancer, induction chemotherapy and radiation therapy showed increased tendency in survival with no statistical significance. Induction chemotherapy seems to have no effect of decreasing distant failure and no survival advantage compared with radiotherapy alone.
Busan ; Carcinoma, Non-Small-Cell Lung* ; Drug Therapy ; Humans ; Induction Chemotherapy* ; Neoplasm Metastasis ; Particle Accelerators ; Radiotherapy ; Retrospective Studies ; Survival Rate

PURPOSE: The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. MATERIALS AND METHODS: We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. RESULTS: The overall survival rate was 53.1% in 1 year, 9.9% in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0% in 1 year, 8.9% in 2 years. Twenty two patients were classified as complete responders to this treatment and their MST was 19.5 months. When this was compared with that of partial responders (MST: 11.7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3%, 2yr 16.8%) than IIIB patients (1yr 43.3%, 2yr 3.6%), which was also statistically signifcant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3%, 2yr 21.4%) than that of squamous cell counterpart (1yr 49.4%, 2yr 7.4%), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. CONCLUSION: Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung* ; Disease-Free Survival ; Fibrosis ; Humans ; Lung Neoplasms ; Pneumonia ; Radiation Oncology ; Radiotherapy* ; Retrospective Studies ; Survival Rate

PURPOSE: This prospective study has been conducted to assess the value of three dimensional conformal radiation therapy (3DCRT) for lung cancer and to determine its potential advantage over current treatment approaches. Specific aim of this study were to 1) find the most ideal 3DCRT technique 2) establish the maximum tolerance dose that can be delivered with 3DCRT and 3) identify patients at risk for development of radiation pneumonitis. MATERIALS AND METHODS: Beginning in Nov. 1994, 95 patients with inoperable non-small cell lung cancer (stage I; 4, stage II; 1, stage IIIa; 14, stage IIIb; 76) were entered onto this 3D conformal trial. Areas of known disease and elective nodal areas were initially treated to 45 Gy and then using 3DCRT technique 65 to 70 Gy of total dose were delivered to the gross disease. Sixty nine patients received 65 Gy of total dose and 26 received 70 Gy. Seventy eight patients (82.1%) also received concurrent MVP chemotherapy. 3DCRT plans were compared with 2D plans to assess the adequacy of dose delivery to target volume, dose volume histograms for normal tissue, and normal tissue complication probabilities (NTCP). RESULTS: Most of plans (78/95) were composed of non-coplanar multiple (4-8) fields. Coplanar segmented conformal therapy was used in 17 pateints, choosing the proper gantry angle which minimize normal lung exposure in each segment. 3DCRT gave the full dose to nearly 100% of the gross disease target volume in all patients. The mean NTCP for ipsilateral lung with 3DCRT (range ; 0.17-0.43) was 68% of the mean NTCP with 2D treatment planning (range ; 0.27-0.66). DVH analysis for heart showed that irradiated volume of heart could be significantly reduced by non-coplanar 3D approach especially in the case of left lower lobe lesion. Of 95 patients evaluable for response, 75 (79%), showed major response including 25 (26%) with complete responses and 50 (53%) with partial responses. One and two year overall survivals of stage lll patients were 62.6% and 35.2% respectively. Twenty percent (19/95) of patients had pneumonitis ; Eight patients had grade 1 pneumonitis and 11 other patients had grade 2. Comparison of the average of NTCP for lung showed a significant difference between patients with and without radiation pneumonitis. Average NTCP for patients without complication was 62% of those with complications. CONCLUSIONS: This study showed that non-coplanar multiple fields (4-8) may be one of the ideal plans for 3DCRT for lung cancer. It also suggested that 3DCRT may provide superior delivery of high dose radiation with reduced risk to normal tissue and that NTCP can be used as a guideline for the dose escalation.
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy ; Heart ; Humans ; Lung ; Lung Neoplasms ; Pneumonia ; Prospective Studies ; Radiation Pneumonitis

PURPOSE: This study was to evaluate the effectiveness of preoperative radiotherapy in maxillary sinus cancer. MATERIALS AND METHODS: A retrospective analysis was done for 42 patients with maxillary sinus cancer who were treated with radiation with or without surgery from April 1986 to September 1996. There were 27 male and 15 female patients. Patients' age ranged from 24 to 75 years (median 56 years). Stage distribution showed 2 in T2, 19 in T3, and 21 in T4 lesions. The histologic type was squamous cell carcinoma in 38, undifferentiated carcinoma in 1, transitional cell carcinoma in 1, and adenoid cystic carcinoma in 2 patients. All patients were treated with radiation initially with a dosage range of 50.4-70.2 Gy (median 70.2 Gy) before further evaluation of remnant disease. Eleven patients were given induction chemotherapy (2 cycles of 5-fluorouracil and cisplatin) concurrently with radiotherapy. Six to eight weeks after radiotherapy with or without chemotherapy, computerized tomography (CT) of paranasal sinus was taken to evaluate remnant disease. If the CT finding showed remnant disease, a Caldwell-Luc procedure was done to get the specimen of suspicious lesions. A radical maxillectomy was done if the specimen was proven to contain malignancy. In contrast periodic follow-up examination was done without any radical surgery if the tissue showed only granulation tissue. Follow-up period ranged from 3 to 92 months with a median 16 months. RESULTS: Nine (21.4%) patients showed complete response (CR) and 33 patients (78.6%) showed persistent disease (PER) to initial radiotherapy. Among the 9 CR patients, 7 patients had no evidence of disease (NED), 1 patient had local failure, and 1 patient had regional failure. Among 33 PER patients, salvage total maxillectomy was done in 10 patients, and the surgery was not feasible or refused in 23 patients. Following the salvage radical surgery, 2 patients were NED and 8 patients were PER status. Overall and disease- free survival rate at 5 years was 23.1% and 16.7%, respectively. The only factors associated with the overall survival rate was the response to radiotherapy (p<0.01). CONCLUSION: The only factors associated with the overall survival rate was the response to radiotherapy. We could omit a radical mutilating surgery by preoperative irradiation in 7 of 42 patients (21.4%) so as to preserve their facial integrity.
Carcinoma ; Carcinoma, Adenoid Cystic ; Carcinoma, Squamous Cell ; Carcinoma, Transitional Cell ; Drug Therapy ; Female ; Fluorouracil ; Follow-Up Studies ; Granulation Tissue ; Humans ; Induction Chemotherapy ; Male ; Maxillary Sinus Neoplasms* ; Maxillary Sinus* ; Radiotherapy* ; Retrospective Studies ; Survival Rate

PURPOSE: This study was performed to analyze the factors affecting local control in malignant tumors of the parotid gland treated with surgery and postoperative radiation. MATERIALS AND METHODS: Twenty-six patients were treated for malignant tumors of the parotid gland from 1986 to 1995 at Department of Therapeutic Radiology, Chonnam University Hospital. Age of the patients ranged from 14 to 72 years (median : 55 years). Histologically 10 patients of mucoepidermoid carcinoma, 7 of squamous cell carcinoma, 4 of acinic cell carcinoma, 4 of adenoid cystic carcinoma and 1 of adenocarcinoma were treated. Total parotidectomy was performd in 15 of 26 patients, superficial in 7, subtotal in 4. Facial nerve was sacrificed in 5 patients. Postoperatively 4 patients had residual disease, 4 had positive resection margin. Radiation was delivered through an ipsilateral wedged pair of photon in 11 patients. High energy electron beam was mixed with photon in 15 patients. Electron beam dose ranged from 900 cGy to 3800 cGy (median : 1760 cGy). Total radiation dose ranged from 5000 cGy to 7560 cGy (median : 6020 cGy). Minimum follow-up period was 2 years. Local control and survival rate were calculated using Kaplan-Meier method. Generalized Wilcoxon test and Cox proportional hazard model were used to test factors affecting local control. RESULTS: Five (19%) of 26 patients had local recurrence. Five year local control rate was 77%. Overall five year survival rate was 70%. Sex, age, tumor size, surgical involvement of cervical lymph node, involvement of resection margin, surgical invasion of nerve, and total dose were analyzed as suggested factors affecting local control rate. Among them patients with tumor size less than 4 cm (p=0.002) and negative resection margin (p= 0.011) were associated with better local control rates in univariate analysis.Multivariate analysis showed only tumor size factor is associated with local control rate (p=0.022). CONCLUSION: This study suggested that tumor size is important in local control of malignant tumors of parotid gland.
Adenocarcinoma ; Carcinoma, Acinar Cell ; Carcinoma, Adenoid Cystic ; Carcinoma, Mucoepidermoid ; Carcinoma, Squamous Cell ; Facial Nerve ; Fibrinogen ; Follow-Up Studies ; Humans ; Jeollanam-do ; Lymph Nodes ; Parotid Gland* ; Proportional Hazards Models ; Radiation Oncology ; Radiotherapy* ; Recurrence ; Survival Rate

PURPOSE: This study was to evaluate survival, failure patterns, and prognostic factors of stage I squamous cell carcinoma of the glottic larynx after curative radiation therapy. MATERIALS AND METHODS: A retrospective analysis was done for 57 patients with glottic cancer who were treated with curative radiation therapy from June 1985 to November 1992. There were 55 male and two female patients. Patients' age ranged from 17 to 71 years (median 39 years). Radiation therapy was delivered five times a week, 2 Gy daily, total 66 Gy using 6 MV X- ray. RESULTS: Complete response (CR) was noted in 51 out of 57 patients (89.5%) and persistent disease (PER) in six out of 57 patients (10.5%). The disease-free survival rates at 3 and 5 years were 72.9% and 63.8%, respectively. Seven failures were observed among 51 CR patients during follow-up. Salvage total laryngectomy for six recurred patients and partial laryngectomy for one recurred patient were done with successful results, i.e., all of them were actually salvaged. Among six PER patients, salvage total laryngectomy for two patients and partial laryngectomy for two patients were done and two patients refused operation. Following salvage surgery for the four PER patients, three were salvaged and one failed locoregionally. Among the 13 failures 10 (76.9%) were salvaged with surgery. The ultimate local control rate at 5 years was 92.3% and overall 47 out of 57 (82.5%) patients were able to preserve their larynx. The 5-year disease-free survival rates were 85.5% for posterior lesions, and 61.6% for anterior lesions (p<0.05). Cord mobility, involvement of anterior commissure, field size, and T stage did not impact on disease-free survival. CONCLUSION: Considering the high percentage of voice preservation with initial radiotherapy, radiotherapy should be the first choice in the treatment of stage I glottic carcinoma.
Carcinoma, Squamous Cell ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Laryngectomy ; Larynx ; Male ; Radiotherapy* ; Retrospective Studies ; Voice

PURPOSE: To evaluate the effects of X-irradiation on prenatal deaths, i.e., preimplantation deaths, embryonic deaths, and fetal deaths, and on external malformations in precompacted preimplantation ddy mice. MATERIALS AND METHODS: Pregnant mice (n=85), obtained by limiting the mating time to from 6 to 9 A.M., were segregated into 11 groups. The first five groups (n=26) were irradiated with X-ray doses of 0.1, 0.5, 0.75, 1.5, and 3 Gy, respectively, at 24 h post conception (p.c.) of the preimplantation period. The second five (n=27) groups were irradiated at the same X-ray doses, respectively, but at 48 h p.c. of the preimplantation period. The last group (n=32) was the control group. The uterine contents were examined on the 18th day of gestation for prenatal deaths and external malformations. RESULTS: 1) A statistically significant increase in preimplantation deaths with increasing dose was observed in the experimental groups irradiated at 24 h p.c. and in the groups irradiated at 48 h p.c., as compared to the control group. The threshold dose was close to 0.05 Gy and 0.075 Gy for the irradiations at 24 h p.c. and 48 h p.c. respectively.2) A statistically significant increase in embryonic deaths with increasing dose was observed in all irradiation groups, except the group irradiated with a dose of 0.1 Gy at 48 h p.c..3) No fetal deaths were found in any experimental group.4) In the experimental groups irradiated at 24 h p.c., anomalies increased with statistical significance, as compared with the control group: 2 exencephalies, 2 open eyelids, 3 anophthalmias, 2 cleft palates, 2 gastroschisis, 1abdominal wall defect, 1 leg defect, and 2 short tail anomalies; the threshold dose for external malformations was close to 0.2 Gy at 24 h p.c.. In the groups irradiated at 48 h p.c., 1 open eyelid and 2 short tail anomalies were observed, but there was no statistical significance in those malformations. CONCLUSION: The results of this study reveal that X-irradiation of precompacted preimplantation ddy mice causes not only preimplantation deaths and embryonic deaths but also external malformations. In addition, external malformations were observed in our experiments at diagnostic doses, including 0.1 and 0.5 Gy. For this reason, we recommend that irradiation should be avoided during the preimplantation period by applying Rugh's 10-day rule.
Animals ; Anophthalmos ; Cleft Palate ; Eyelids ; Fertilization ; Fetal Death ; Gastroschisis ; Leg ; Mice* ; Neural Tube Defects ; Pregnancy ; Tail

PURPOSE: To determine whether TNF-alpha increases the antitumor effect of radiotherapy in murine syngeneic tumor system. MATERIALS AND METHODS: Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I (hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter, mice were treated with TNF-alpha, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-alpha mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 microgram per mouse for 7 days. In combination of radiation and TNF-alpha, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. RESULTS: Among 4 tested tumors, TNF-alpha alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-alpha showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-alpha alone and radiation, i.e., 6.5 days and 26.9 days, respectively (p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-alpha did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-alpha alone and radiation. CONCLUSIONS: TNF-alpha alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-alpha acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-alpha and radiation has different therapeutic potential depending on tumor model and further study is advocated.
Animals ; Korea ; Leg ; Mice ; Radiotherapy* ; Tumor Necrosis Factor-alpha*

BACKGROUND: Early hepatocellular carcinoma (HCC) is an early stage HCC, and it is sometimes difficult to identify the margins of the cancer nodules in the resected specimens. METHODS: We studied 22 cases of early HCC to investigate the clinicopathologic features of early stage HCC. RESULTS: Seven of 22 cases were single HCC, and 15 were multicentric HCC. The average tumor size was 1.34 cm (0.4-2.7 cm). Early HCCs didn't destroy the basic architecture of the liver lobules or pseudolobules and the lesions had an indistinct margin. Most tumors were uniformly composed of well-differentiated cancer tissue that was characterized by an increased cell density and an irregular thin-trabecular pattern. The tumor retained a varying number of portal tracts. There was a replacing growth pattern at the tumor-nontumor boundary without tumor capsule. Three of 22 cases had a "nodule-in-nodule" lesion, and the inner nodules consisted of moderately differentiated HCC without portal tracts. All 22 cases showed no vascular invasion. All 7 patients with single early HCC have survived for the past 11-54 months without any local recurrence. But in one patient with single early HCC, multicentric HCC developed 20 months after surgery. CONCLUSION: The clinicopathologic features of early HCCs are quite different from those of advanced HCCs. The increased recognition of early HCC during routine clinical practice will contribute to improved patient survival.
Carcinoma, Hepatocellular* ; Cell Count ; Humans ; Liver ; Recurrence