• 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.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.21-26
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• 2001

Purpose : This study was peformed to evaluate the cosmetic outcome of conservative treatment for early breast cancer and to analyze the factors influencing cosmetic outcome. Materials and Methods : From February 1992 through January 1997, 120 patients with early breast cancer were treated with conservative surgery and postoperative radiotherapy. The types of conservative surgery were quadrantectomy and axillary node dissection for 108 patients $(90\%)$ and lumpectomy or excisional biopsy for 10 patients $(8.3\%)$. Forty six patients $(38\%)$ received adjuvant chemotherapy (CMF or CAF). Cosmetic result evaluation was carried out between 16 and 74 months (median, 33 months) after surgery. The cosmetic results were classified into four categories, i.e., excellent, good, fair, and poor. The appearances of the patients' breasts were also analyzed for symmetry using the differences in distances from the sternal notch to right and left nipples. A logistic regression analysis was performed to identify independent variables influencing the cosmetic outcome. Results : Cosmetic score was excellent or good in $76\%$ (91/120), fair in $19\%$ (23/120) and poor in $5\%$ (6/120) of the patients. Univariate analysis showed that tumor size (T1 versus T2) (p=0.04), axillary node status (N0 versus N1) (p=0.0002), extent of surgery (quadrantectomy versus lumpectomy or excisional biopsy) (p=0.02), axillary node irradiation (p=0.0005) and chemotherapy (p=0.0001) affected cosmetic score. Multivariate analysis revealed that extent of surgery (p=0.04) and chemotherapy (p=0.0002) were significant factors. For breast symmetry, univariate analysis confirmed exactly the same factors as above. Multivariate analysis revealed that tumor size (p=0.003) and lymph node status (p=0.007) affected breast symmetry. Conclusion : Conservative surgery and postoperative radiotherapy resulted in excellent or good cosmetic outcome in a large portion of the patients. Better cosmetic results were achieved generally in the group of patients with smaller tumor size, without axillary node metastasis and treated with less extensive surgery without chemotherapy.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.45-52
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• 2001

Purpose : Granulocyle-colony stimulating factor (G-CSF) has been widely used to treat neutropenia caused by chemotherapy or radiotherapy. The efficacy of recombinant human hematopoietic growth factors in improving oral mucositis after chemotherapy or radiotherapy has been recently demonstrated in some clinical studies. This study was designed to determine whether G-CSF can modify the radiation injury of the intestinal mucosa in mice. Materials and Methods : One hundred and five BALB/c mice weighing 20 grams were divided into nine subgroups including G-CSF alone group $(I:10\;{\mu}g/kg\;or\;II:100\;{\mu}g/kg)$, radiation alone group (7.5 or 12 Gy on the whole body), combination group with G-CSF and radiation (G-CSF I or II plus 7.5 Gy, G-CSF I or II plus 12 Gy), and control group. Radiation was administered with a 6 MV linear accelerator (Mevatron Siemens) with a dose rate of 3 Gy/min on day 0. G-CSF was injected subcutaneously for 3 days, once a day, from day -2 to day 0. Each group was sacrificed on the day 1, day 3, and day 7. The mucosal changes of jejunum were evaluated microscopically by crypt count per circumference, villi length, and histologic damage grading. Results : In both G-CSF I and II groups, crypt counts, villi length, and histologic damage scores were not significantly different from those of the control one (p>0.05). The 7.5 Gy and 12 Gy radiation alone groups showed significantly lower crypt counts and higher histologic damage scores compared with those of control one (p<0.05). The groups exposed to 7.5 Gy radiation plus G-CSF I or II showed significantly higher crypt counts and lower histologic damage scores on the day 3, and lower histologic damage scores on the day 7 compared with those of the 7.5 Gy radiation alone one (p<0.05). The 12 Gy radiation plus G-CSF I or II group did not show significant difference in crypt counts and histologic damage scores compared with those of the 12 Gy radiation alone one (p>0,05). Most of the mice in 12 Gy radiation with or without G-CSF group showed intestinal death within 5 days. Conclusion : These results suggest that G-CSF may protect the jejunal mucosa from the acute radiation damage following within the tolerable ranges of whole body irradiation in mice.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.27-31
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• 2000

Purpose : The aim of this study was to investigate treatment results, toxicity and efficacy of hypefractionated radiation therapy combined with paclitaxel for paraaortic node recurrence in cervix cancer. Materials and Methods: Between September 1997 to March 1999, 12 patients with paraaortic node recurrence in cervix cancer who previously received radical or postoperative radiotherapy were treated with hypefractionated radiation therapy combined with paclitaxel. Of these, 2 patients who irradiated less than 30 Gy were excluded, 10 patients were eligible for this study. Median age was 51 years. Initial FIGO stage was 1 stage IBI, 2 stage IIA, 7 stage IIB. For initial treatment, 7 patients received radical radiotherapy and 3 received postoperative radiotherapy. The paraaortic field encompassed the gross recurrent disease with superior margin at T12, and inferior margin was between L5 and S1 with gap for previously pelvic radiation field. The radiation field was initially anterior and posterior opposed field followed by both lateral field. The daily dose was 1.2 Gy, twice daily fractions, and total radiotherapy dose was between 50.4 and 60 Gy(median, 58.8 Gy). Concurrent chemotherapy was done with paclitaxel as a radiosensitizer. Dose range was from 20 mg/m$^{3}$ to 30 mg/m$^{3}$ (median, 25 mg/m$^{3}$), and cycle of chemotherapy was from 3 to 6 (median, 4.5 cycle). Follow-up period ranged from 3 to 21 months. Results : Interval between initial diagnosis and paraaortic node recurrence was range from 2 to 63 months (median, 8 months). The 1 year overall survival rate and median survival were 75$\%$ and 9.5 months, respectively. The 1 year disease free survival rate and median disease free survival were 30$\%$ and 7 months, respectively. At 1 month after treatment, 4 (40$\%$) achieved a complete response and 6 (60$\%$) experienced a partial response and all patients showed response above the partial response. There was distant metastasis in 6 patients and pelvic node recurrence In 2 patients after paraaortic node irradiation. There was 2 patients with grade 3 to 4 leukopenla and 8 patients with grade 1 to 2 nausea/ vomiting which was usually tolerable with antlemetic drug. There was no chronic complication in abdomen and pelvis during follow up period. Conclusion : hypefractionated radiation therapy combined with paclitaxel chemotherapy diosensitizer showed high response rate and few complication rate in paraaortic node recurrence in cervix cancer Therefore, present results suggest that hypefractionated radiation therapy combined with paclitaxel chemotherapy can be used as optimal treatment modality in this patients.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.242-248
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• 2007

Purpose: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. Materials and Methods: Twenty-four ICR mice were divided into three groups-the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days $1{\sim}5$. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. Results: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of. the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. Conclusion: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.343-352
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• 2002

Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.349-356
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• 1997

Purpose : To evaluate the efficacy of hyperfractionated radiation therapy in carcinoma of the cervix, especially on huge exophytic and endophytic stage Ib, IIa and IIb Materials and Materials : Fourty one patients with carcinoma of the cervix treated with hyperfractionated radiation therapy at the Department of Therapeutic Radiology, Dongsan Hospital, Keimyung University. School of Medicine from Jul, 1991 to Apr, 1994. According to FIGO s1aging system, therewere stage Ib (3 patients) IIa (6 patients) with exophytic ($\geq$5cm in dinmeter) and huge endophytic mass. and IIb (32 patients) with median age of 55 yeavs old. Radiation therapy consisted of hyperfractionated external irradition to the whole pelvis (120cGy/fraction, 2 fraction/day (minimum interval of 6 hours), 3600-5520cGy) and boost parametrial doses (for a total of 4480-6480cGy) with midline shield $(4\times10cm)$, and combined with intracavitary irradiation (up to 7480-8520cGy in Ib, IIa and 8480-9980cGy in IIb to point A). The maximum and mean follow up durations were 70 and 47 months respectively . Results : Five year local control rate was $78\%$ and the actuarial overall five year survival rate was $66.1\%$ for all patients, $44.4\%$ for stage Ib, IIa and $71.4\%$ for stage IIb. In bulky IIb (above 5cm in tumor size, 11 patients) five year local control rate and five rear survival rate was $88.9\%,\;73\%$ respectively Pelvic lymph node status (negative : $74\%,\;positive:25\%$, p=0.0015) was significant Prognostic factor affecting to five rear survival rate. There was marginally significant survival difference by total dose to A point ($>84Gy\;:\;70\%,\;>84Gy\;:\;42.8\%$, p=0.1). We consider that the difference of total dose to A point by stage (mean Ib,IIa : 79Gy. IIb 89Gy P=0.001) is one of the causes in worse local control and survival of Ib,IIa than IIb The overall recurrence rate was $39\%$ (16/41). The rates of local failure alone. distant failure alone. and combined local and distant failure were $9.7\%,\;19.5\%,\;and\;9.7\%$, respectively. Two Patients developed leukopenia ($\geq$ grade 3) and Three patients develoued grade 3 gastrointestinal complication. Above grade 3 complication was not noted. There was no treatment related death noted. Conclusion : We thought that it may be necessary to increase A point dose to more than 85Gy in hyperfractionated radiotherapy of huge exophytic and endophvtic stage Ib,IIa. We considered that hyperfractionated radiation therapy may be tolerable in huge exophytic and endophytic stage IIb cervical carcinoma with acceptable morbidity and possible survival gain but this was results in small patient group and will be confirmed by long term follow up in many patients.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.147-157
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• 1998

Purpose : The aim of this retrospective study is to assess the necessity of s1aging laparotomy in the management of supradiaphragmatic CS I-II Hodgkin's disease. Prognostic factors and the usefulness of prognostic factor groups were also analyzed. Materials and Methods : From 1985 to 1995, fifty one Patients who were diagnosed as supradiaphragmatic CS I-II Hodgkin's disease at Yonsei Cancer Center in Seoul, Korea were enrolled in this study Age range was 4 to 67 with median age of 30. The number of patients with each CS IA, II A, and IIB were 16, 25, and 10, respectively. Radiotherapy(RT) was delivered using 4 or 6 MV photon beam to a total dose of 19.5 to 55.6Gy (median dose : 45Gy) with a 1.5 to 1.BGy per fraction. Chemotherapy(CT) was given in 2-12 cycles(median : 6 cycles). Thirty one Patients were treated with RT alone, 4 patients with CT alone and 16 patients with combined chemoradiotherapy. RT volumes varied from involved fields(3), subtotal nodal fields(18) or mantle fields(26). Results : Five-year disease-free survival rate(DFS) was $78.0\%$ and overall survival rate(05) was $87.6\%$. Fifty Patients achieved a complete remission after initial treatment and 8 patients were relapsed. Salvage therapy was given to 7 patients, 1 with RT alone, 4 with CT alone, 2 with RT+CT. Only two patients were successfully salvaged. Feminine gender and large media-stinal adenopathy were significant adverse prognostic factors in the univariate analysis for DFS. The significant adverse prognostic factors of OS were B symptom and clinical stage. When patients were analyzed according to European Organization for Research and Treatment of Cancer(EORTC) prognostic factor groups, the DFS in Patients with very favorable, favorable and unfavorable group was 100, 100 and $55.8\%$(p<0.05), and the 05 in each patients' group was 100, 100 and $75.1\%$(p<0.05), respectively. In very favorable and favorable groups, the DFS and 05 were all $100\%$ by RT alone, but in unfavorable group, RT with CT had a lesser relapse rate than RT alone. The subtotal nodal irradiation had better OFS than mantle RT in patients treated with RT. Conclusion : In present study, the DFS and OS in patients who did not undergo s1aging laparotomy were similar with the results in the literatures of which patients were surgically staged. Therefore, we may suggest that staging laparotomy would not influence the outcome of treatments. In univariate analysis, gender, large mediastinal adenopathy. B symptoms and clinical stage were significant prognostic factors for the survival rate. We confirm the usefulness of EORTC prognostic factor groups which may be a good.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.200-207
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• 2004

Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.