[show abstract][hide abstract] ABSTRACT: We tried to investigate the outcome and patterns of failure of endometrial cancer patients who were treated with surgery and postoperative radiation therapy (RT).
Eighty-three patients with endometrial cancer who received postoperative RT between May 1979 and August 2000 were included in this retrospective study. Forty-one patients received total abdominal hysterectomy, 41 patients received Wertheim's operation and 1 underwent vaginal hysterectomy. Pelvic lymph node dissection or pelvic lymph node sampling was done in 56 patients and peritoneal cytology was done in 35. All the patients were staged according to 1988 FIGO (International Federation of Gynecology and Obstetrics) staging system; 2 were stage IA, 23 were stage IB, 20 were stage IC, 4 were stage IIA, 5 were stage IIB, 9 were stage IIIA, 2 were stage IIIB and 18 were stage IIIC. The histologic diagnoses were adenocarcinoma in seventy-four patients (89%). The histologic grades were Grade 1, 2 and 3 in 21 (25%), 43 (52%) and 10 (12%) patients, respectively. All the patients received external beam RT (EBRT) with a median dose of 5,040 cGy (range: 4,500 approximately 5,075 cGy) to the whole pelvis. Five patients with pathologically confirmed paraaortic lymph node metastasis received 4500 cGy to the paraaortic lymph nodes. Fifteen patients received low-dose intracavitary brachytherapy after their EBRT. A total dose of 7,500 approximately 9,540 cGy (median dose: 8511) was prescribed to the vaginal surface.
Overall, 11 patients (13%) experienced disease relapse: 4 with initial stage I or II disease and 7 with initial stage III disease. Among the 54 stage I or II patients, 1 (2%) relapsed in the pelvis only, 2 (4%) relapsed in the vagina and distant organs, and 1 (2%) relapsed in the paraaortic lymph nodes (PANs). Among the 29 stage III patients, 1 (3%) relapsed in the vagina. The most common sites of failure for the stage III patients were the peritoneum (3 patients, 10%), PANs (2 patients, 7%), and lung (2 patients, 7%). With a median follow-up period of 86 months, the overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% for both. The five-year DFS rate was 93%, 100% and 74% for the stage I, II and III patients, respectively. Three patients experienced severe radiation-related late complications: RTOG (Radiation Therapy Oncology Group) grade 3 radiation cystitis was seen in one patient, and grade 3 bowel obstruction was seen in two patients.
Postoperative RT was useful for controlling pelvic disease. The major patterns of failure for stage III patients were peritoneal seeding and distant metastasis. Selective use of whole abdominal radiotherapy or adjuvant chemotherapy may improve the therapeutic outcome of these patients.
Cancer Research and Treatment 06/2006; 38(3):133-8. · 1.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line.
Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone.
The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation.
Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.
Cancer Research and Treatment 06/2005; 37(3):191-5. · 1.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the influence of radiation therapy target volume on the treatment outcome of adjuvant chemoradiotherapy for pancreatic cancer after curative resection.
Between February 1987 and July 2001, 70 patients treated with curative resection and adjuvant chemoradiotherapy for pancreatic adenocarcinoma were analyzed. There were 49 males and 21 females, with a median age of 57 years. Whipple's operation was performed in 44 patients, pylorus-preserving pancreaticoduodenectomy in 14, distal pancreatectomy in 9, and subtotal pancreatectomy in 3. Postoperative adjuvant radiotherapy was given up to 40 Gy at 2 Gy per fraction with a two-week planned rest. Intravenous 5-fluorouracil (500 mg/m2/day) was given on days 1 to 3 of each split course of radiotherapy. Until 1991, whole pancreas or preoperative tumor volume and retroperitoneal lymph nodes were irradiated (extended field, n=14). Thereafter, the target volume included the retroperitoneal lymph nodes and the involved pancreatic resection margin (limited field, n=56). The median follow-up period of all the patients was 16 months (range, 2-99).
The overall 2- and 5-year survival rate of all patients was 29.7% and 14.0%, respectively. According to the radiotherapy target volume, the median survival time was 14 months in the extended field group and 16 months in the limited field group (P = 0.65).
From the viewpoint of the target volume of radiotherapy, a limited field did not worsen the treatment outcome, although the survival rate was poor in both groups.
[show abstract][hide abstract] ABSTRACT: We attempted to analyze the effectiveness of whole brain radiotherapy (WBRT) combined with fractionated stereotactic radiotherapy (FSRT) in brain metastases.
Thirty-seven metastatic brain tumors in 29 patients without previous treatment were treated with WBRT plus FSRT, from October 1996 to February 2002. Four of the patients received stereotactic radiosurgery (SRS) prior to WBRT. Non-small cell lung cancer was the most common type of primary tumor (20/29). The total dose to the whole brain ranged from 30 Gy to 40 Gy, and the boost dose from FSRT ranged from 12 Gy to 40 Gy. End points were survival rate and local control rates. Factors influencing survival were evaluated.
Median survival was 13 months, and actuarial survival rates at one and two years were 81% and 39%, respectively. Actuarial one and two year local control rates for all lesions were 78% and 71%, respectively. Survival was significantly associated with age, tumor size, presence of active extracranial tumors, and performance status. No acute or delayed complications were observed.
We believe that WBRT plus FSRT should be included in the treatment options for metastatic brain tumors, and we consider the effect of this non-invasive method to be quite good in patients with good prognostic factors, although other invasive modalities could also be effective in them.
[show abstract][hide abstract] ABSTRACT: To evaluate the efficacy and toxicity of chemotherapy with ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3-nitrosourea) plus cisplatin followed by cranial irradiation in patients with newly diagnosed glioblastoma multiforme.
Between August 1999 and July 2001, previously untreated 30 patients with histologically confirmed glioblastoma multiforme were treated. Chemotherapy consisting of up to 2 cycles of 72 h of continuous intravenous infusion of ACNU (40 mg/m2/day) and cisplatin (40 mg/m2/d) was given over a 6-week period. Radiation was begun 6 weeks after the second cycle of chemotherapy.
Median age was 48 years (range 18-66 years) and 22 patients with residual measurable disease after surgery were eligible for response analysis. One (5%) had a complete response (CR), 36% partial response (PR), 14% stable disease (SD), and 45% progressive disease (PD) after chemotherapy. After additional radiation, 22% had CR, 22% PR, 16% SD, and 42% PD. Grades III and IV leukopenia and thrombocytopenia occurred in 18 cycles (36%) and 15 cycles (30%), respectively. No fatal complications occurred. Median time to progression was 5.9 months (95% CI 5.1-6.8 months) and median overall survival was 14.9 months (95% CI 9.1-20.7 months).
Preradiation chemotherapy with ACNU plus cisplatin is effective and feasible in patients with gliobiastoma multiforme.
Journal of Neuro-Oncology 12/2002; 60(2):171-6. · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: To analyze the outcome of postoperative radiotherapy (RT) or chemoradiation for patients with extrahepatic bile duct cancer who had undergone either curative or palliative surgery, and to identify the prognostic factors for these patients.
Between March 1982 and December 1994, 91 patients with extrahepatic bile duct cancer underwent RT at the Department of Therapeutic Radiology, Seoul National University Hospital. Of these patients, 84 were included in this retrospective study. The male/female ratio was 3.7:1 (66 men and 18 women). The median age of the patients was 58 years (range 33-76). Gross total surgical resection was performed in 72 patients, with pathologically negative margins in 47 and microscopically positive margins in 25. Twelve patients underwent surgical exploration and biopsy or subtotal resection with palliative bypass procedures. All the patients received >40 Gy of external beam RT after surgery. Concurrent 5-fluorouracil was administered during external beam RT in 71 patients, and maintenance chemotherapy was performed in 61 patients after RT completion. The minimal follow-up of the survivors was 14 months, and the median follow-up period for all the patients was 23 months (range 2-75).
The overall 2- and 5-year survival rate was 52% and 31%, respectively. The 2- and 5-year disease-free survival rate was 48% and 26%, respectively. On univariate analysis using the Kaplan-Meier product limit method, the use of chemotherapy, performance status, N stage, size of residual tumor, stage, and tumor location were significant prognostic factors. However, on multivariate analysis using Cox's proportional hazard model, N stage (N0 vs. N1 and N2, p = 0.02) was the only significant prognostic factor.
Long-term survival can be expected in patients with extrahepatic bile duct cancer who undergo radical surgery and postoperative chemoradiation. Regional lymph node metastasis is a poor prognostic factor for these patients.
International Journal of Radiation OncologyBiologyPhysics 11/2002; 54(2):414-9. · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate whether doses or dose rates at International Commission on Radiation Units (ICRU) reference points are of value for predicting risks of late rectal and bladder morbidity in patients with uterine cervical cancer who have undergone external beam radiotherapy and intracavitary irradiation.
Late rectal complications and late bladder complications were evaluated in 54 patients who were treated by external beam radiotherapy followed by intracavitary irradiation between January 1996 and December 1999. External beam radiotherapy was delivered in 1.8 Gy daily fractions to a whole pelvis dose of 50.4 Gy followed by intracavitary irradiation at total point A doses ranging from 75 Gy to 85 Gy. Intracavitary irradiation was performed with dose rates of 0.5-0.7 Gy/h to point A in most patients, but 8 patients were treated at a higher dose rate (0.83-1.15 Gy/h) to shorten the hospitalization period. Biologically effective doses for the reference points were calculated using a linear quadratic model.
Grade 3 rectal and bladder morbidity by Radiation Therapy Oncology Group (RTOG) criteria developed in 4 patients (7.4%) and 1 (1.9%), respectively. An age of >60 years (P = 0.01) and a total dose to the rectal reference point of > or =80 Gy (P = 0.03) were found to be correlated with a higher rate of rectal morbidity. Total dose (> or =80 Gy), dose rate (> or = 0.75 Gy/h), and biologically effective doses (> or =135 Gy3) at the bladder reference point were found to be significant factors for the development of late bladder morbidity. By multivariate analysis, age was identified as the only significant factor of late rectal complications, and biologically effective doses at the bladder reference point was the only significant factor of late bladder complications.
RTOG grade 3 late rectal and bladder morbidity developed in respectively 7.4% and 1.9% of the patients. The significant risk factors for late rectal and bladder morbidity were old age and biologically effective doses at the bladder reference point, respectively.