Efficacy of Transarterial Chemolipiodolization with or without 3-Dimensional Conformal Radiotherapy for Huge HCC with Portal Vein Tumor Thrombosis / 대한간학회지

BACKGROUND/AIMS: The treatment efficacy for advanced hepatocellular carcinoma is poor. This study examined the efficacy and toxicity of 3-dimensional conformal radiotherapy (3D-CRT) in combination with transarterial chemolipiodolization (TACL) for a huge hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS: From March 2001 to November 2004, 49 patients with advanced HCC with PVTT (size>8 cm, modified UICC stage IVa) were enrolled in this retrospective study. Twenty two patients underwent more than 2 cycles of TACL (adriamycin 50 mg/m2, cisplatin 60 mg/m2, 5-fluorouracil 200 mg/m2 every 4-6 weeks) without 3D-CRT, while 27 patients underwent consecutive TACL with 3D-CRT (40-45 Gy for 4-5 weeks) that was started one week after the 1st TACL. The response was assessed by a computed tomography (CT) and the serum alpha-fetoprotein (AFP) level at 1-2 month intervals. RESULTS: The objective response rates in the TACL group and TACL with 3D-CRT group were 18% and 48% at 3 months (P=0.051), and 10.5% and 42% at 6 months (P=0.024) respectively. The median survival time was 13 months and 13.5 months in TACL and TACL with 3D-CRT groups, respectively (P=0.502). The treatment response was better in the TACL with 3D-CRT group but there was no significant difference in survival between the two groups. Most toxicities in the two groups were mild, not exceeding grade 1 according to the WHO criteria. CONCLUSIONS: For patients with a huge HCC with PVTT, TACL with 3D-CRT achieved some meaningful clinical benefit. Prospective controlled trials will be needed to confirm the real benefit of TACL combined with 3D-CRT.

Effects of Fractionated Stereotactic Radiotherapy for Primary Hepatocellular Carcinoma / 대한방사선종양학회지

PURPOSE: Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. In this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. MATERIALS AND METHODS: A retrospective analysis was performed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was 2~6.5 cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was 5 or 10 Gy; each dose was prescribed based on the planning target volume and normalized to 85~99% isocenter dose. Patients were treated 3~5 times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was 3~55 months (the median follow up period: 23 months). RESULTS: The response rate was 60% (12 patients), with 4 patients showing complete response (20%), 8 patients showing partial response (40%), and 8 patients showing stable disease (40%). The 1-year and 2-year survival rates were 70.0% and 43.1%, respectively, and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were 65% and 32.5%, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients (60%), nausea/emesis in 8 patients (40%), and transient liver function impairment in 6 patients (30%). However, there was no treatment related death. CONCLUSION: The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC.

Allogeneic Bone Marrow Transplantation for Myelodysplastic Syndromes / 대한혈액학회지

BACKGROUND: The myelodysplastic syndromes (MDS) can be categorized as a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Although the natural history of MDS varies, traditional treatments are not curative and allogeneic marrow transplantation offers potentially curative treatment for MDS. METHODS: In our center, 10 patients underwent allogeneic bone marrow transplantation (BMT) between December 1989 and May 1997. The minimum follow-up of 3 months was possible in 10 patients, for whom treatment-related complications and clinical outcomes were assessed. RESULTS: The median age of the 10 patients was 33 (range 20~40) years. The median time from diagnosis to BMT was 34 (3~116) months. By morphology, 5 patients had advanced MDS (i.e., RAEB, RAEB-t, CMML) and 5 patients had less advanced MDS (RA). By Bournemouth score, 8 patients had a score 2~3 and two patients had a score 4. By IPSS, 5 patients were in intermediate-1 group, 3 patients in intermediate-2 group and 2 patients in high risk group. Patients were prepared for transplant with either a total body irradiation (TBI)+cyclophosphamide (n=7), busulfan+TBI (n=2) and busulfan+cyclophophamide (n=1). All patients received CsA+short course MTX for GVHD prophylaxis. Successful engraftment was confirmed in all patients. The overall incidence of acute GVHD was noted in 70% (7/10 patients) and grade IV acute GVHD developed in 2 patients (20%). Five patients were evaluable for the development of chronic GVHD and 2 patients (40%) developed limited chronic GVHD. The duration of median follow-up was 8.1 months. At present five patients are alive and disease-free 3 to 21 months (median survival duration : 8.2 months) post-transplantation resulting in a 2-year disease-free survival of 44%. 2-year disease free survival was 63% in less advanced MDS and 25% in advanced MDS. CONCLUSION: Allogeneic BMT should be considered when any clinical evidence of disease progression to a more advanced stage becomes apparent. International prognostic scoring system (IPSS) and Bournemouth score can also be used to gauge timing for BMT. For patients were in intermediate-1 or intermediate-2 group by IPSS, BMT can be justified if the patient is young and has an HLA matched sibling donor.

P53 Overexpression and Outcome of Radiation Therapy in Head & Neck Cancers / 대한방사선종양학회지

PURPOSE: Experimental studies have implicated the wild type p53 in cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancers. METHODS: Immunohistochemical analysis with a mouse monoclonal antibody (D0-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at St. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multivariate analysis was performed that included all clinical variables and status of p53 expression. RESULTS: Thirty-seven (67.2%) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 76% of laryngeal, 66.7% of oropharyngeal, 66.7% of hypopharyngeal cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease (P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. CONCLUSIONS: The p53 overexpression as detected by immunohistochemical staining had significant correaltion with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

Autologous or Allogeneic Bone Marrow Transplantation Compared with Consolidation Chemotherapy in Acute promyelocytic Leukemia / 대한암학회지

PURPOSE: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia characterized by the morphology of blast cells (M3 in FAB classification), the t (15;17) translocation, and a coagulopathy combining disseminated intravascular coagulation and fibrinolysis. It has been considered to have better response to combination chemo- therapy of an anthracycline and cytosine arabinoside and a higher cure rate than other subtypes because of recent approach of differentiating leukemic blasts by all-transretinoic acid (ATRA). The role of stem cell transplantation in APL has to be determined in comparison with that of consolidation chemotherapy. MATERIALS AND METHODS: We compared the leukemia-free survival and overall survival between APL patients receiving the consolidation chemotherapy and those undergoing the allogeneic or autologous stem cell transplantation following the high-dose anticancer therapy. Of the 65 patients achieving the first complete remission from 1992 to 1997, 33 patients were treated with 3 courses of consolidation chemotherapies and 32 with the stem cell transplantation. RESULTS: With a median follow-up of 22 months (8-60), the actuarial leukemia-free survival at 3 years was significantly higher in transplantation group than in chematherapy group (73.8% versus 33.5%; P=0.0087), and the probability of leukemic relapse was considerably lower in transplantation group than in chemotherapy group (6.3% versus 57.5%; P=0.001). The treatment-related mortalities of the groups were 0% in chemotherapy group and 14.3% in transplantation group. The main cause of deaths was relapse in the consolidation chemotherapy group. CONCLUSION: These data demonstrate that the stem cell transplantation results in better leukemia-free survival than the consolidation chemotherapy for patients with APL in the first complete remission because of lower risk of relapse.

Prenatal Deaths and External Malformations Caused by X-Irradiation during the Preimplantation Period of ddy Mice / 대한방사선종양학회지

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.

Concurrent Chemoradiation Therapy in Stage III Non-small Cell Lung Cancer / 대한치료방사선과학회지

PURPOSE: This study was tried to evaluate the potential benefits of concurrent chemoradiation therapy (low dose daily cisplatin combined with split course radiation therapy) compared with conventional radiation therapy alone in stage III non-small cell lung cancer. The end points of analyses were response rate, overall survival, survival without locoregional failure, survival without distant metastasis, prognostic factors affecting survival and treatment related toxicities. MATERIAL AND METHODS: Between April 1992 and March 1994, 32 patients who had stage III non-small cell lung cancer were treated with concurrent chemoradiation therapy. Radiation therapy for 2 weeks (300cGy given 10 times up to 3000cGy) followed by a 3 weeks rest period and then radiation therapy for 2 more weeks (250cGy given 10 times up to 2500cGy) was combined with 6mg/M2 of cisplatin. Follow-up period ranged from 13 months to 48 months with median of 24 months. Historical control group consisted of 32 patients who had stage III non-small cell lung cancer were received conventionally fractionated (daily 170-200cGy) radiation therapy alone. Total radiation dose ranged from 5580cGy to 7000cGy with median of 5940 cGy. Follow-up period ranged from 36 months to 105 months with median of 62 months. RESULTS: Complete reponse rate was higher in chemoradiation therapy (CRT) group than radiation therapy (RT) group (18.8% vs. 6.3%). CRT group showed lower in-field failure rate compared with RT group (25% vs. 47%). The overall survival rate had no significant differences in between CRT group and RT group (17.5% vs. 9.4% at 2 years). The survival without locoregional failure (16.5% vs. 5.3% at 2 years) and survival without distant metastasis (17% vs. 4.6% at 2 years) also had no significant differences. In subgroup analyses for patients with good performance status (Karnofsky performance scale 80), CRT group showed significantly higher overall survival rate compared with RT group (62.5% vs. 15.6% at 2 years). The prognostic factors affecting survival rate were performance status and pathologic subtype (squamous cell cancer vs. nonsquamous cell cancer) in CRT group. In RT alone group, performance status and stage (IIIa vs IIIb) were identified as a prognostic factors. RTOG/EORTC grade 2-3 nausea and vomiting (22% vs. 6%) and bone marrow toxicities (25% vs. 15.6%) were significantly higher in CRT group compared with RT alone group. The incidence of RTOG/EORTC grade 3-4 pulmonary toxicity had no significant differences in between CRT group and RT group (16% vs. 6%). The incidence of WHO grade 3-4 pulmonary fibrosis also had no significant differences in both group (38% vs. 25%). In analyses for relationship of field size and pulmonary toxicity, the patients who treated with field size beyond 200cm2 had significantly higher rates of pulmonary toxicities. CONCLUSION: The CRT group showed significantly higher local control rate than RT group. There were no significant differences of survival rate in between two groups. The subgroup of patients who had good performance status showed higher overall survival rate in CRT group than RT group. In spite of higher incidence of acute toxicities with concurrent chemoradiation therapy, the survival gain in subgroup of patients with good performance status were encouraging. CRT group showed higher rate of early death within 1 year, higher 2 year survival rate compared with RT group. Therefore, to evaluate the accurate effect on survival of concurrent chemoradiation therapy, systematic follow-up for long term survivors are needed.

Prophylactic Cranial Irradiation for Acute Lymphoblastic Leukemia in Childhood / 대한치료방사선과학회지

PURPOSE: This report is the result of retrospective analysis for children who received prophyactic cranial irradiation combined with intrathecal chemotherapy. METHODS AND MATERIALS: Ninety children with ALL who had got bone marrow remission after induction chemotherapy received PCI. All but 3 children were treated with a dose of 1800 cGy as a standard regimen. While the PCI was given, all patients received intrathecal chemotherapy. RESULTS: Nine of 90 patients experienced CNS relapse during the duration of follow-up ranged from 36 to 96 months (median 60 months). Three children experienced BM relapse prior to CNS relapse. Therefore, CNS relapse rate as the first adverse event was 6.7%. Median time interval of CNS relapse was 16 months from the first day of hematologic complete remission. Eighty-nine percent of patients who had CNS relapse occurred during maintenance chemotherapy (on-therapy relapse). The CNS RFS at 2 and 5 years are 68 % and 42 %, respectively with median of 43 months. The prognostic factors affecting CNS RFS are initial WBC count (cut-off point of 50,000/mul), FAB subtype and CALGB risk WBC count (cut-off point of 50,000/mul), FAB subtype, POG and CALGB risk criteria. CONCLUSION: In our study, 6.7% of CNS relapse rate as a first adverse event was comparable with other studies. Various risk criteria was based on age at diagnosis and initial WBC count such as POG and CALGB criteria, had prognostic significance for CNS RFS and DFS. Prospective randomized trial according to prognostic subgroup based on risk criteria and systematic study about neuropsychologic function for long term survivors, are essential to determine the most effective and least toxic form of CNS prophylaxis.

Intraluminal High-Dose-Rate Brachytherapy for the Tumors of Gastrointestinal Tract / 대한치료방사선과학회지

PURPOSE: Intraluminal High dose rate brachytherapy is an accepted treatment for the tumors of GI tract. However, there is only some limited clinical data for intraluminal high dose rate brachytherapy for the tumors of GI tract. MATERIALS AND METHODS: Between February 1991 and July 1993, 18 patients who have the tumors of GI tract (esophageal cancer-8 cases, rectal cancer-10 cases) were treated with gigh dose rae iridium-192 afterloading system )Microselectron-HDR, Nucletron CO, Netherland) at the department of therapeutic radiology, St. Mary's hospital, Catholic university medical college. Age rage was 47-87 years with a mean age 71 years. All patients were treated with intraluminal high dose rate brachytherapy within two weeks after conventional external radiation therapy and received 3-5 Gy/fraction 3-4 times per week to a total dose 12-20 Gy (mean 17 Gy). Standard fractionation and conventional dose were delivered for external radiation therapy. Total dose of external radiation therapy ranged 41.4-59.4 Gy (mean 49.6 Gy). Median follow up was 19 months. RESULTS: The analysis was based on 18 patients. The complete response and partial response in esophageal cancer was similar (38%). Two year rates for survival and median survival were 13% and 10 months, respectively. Among 10 patients of rectal cancers, partial response was obtained in 6 patients (60%). There was no complete response in the patients with rectal cancer, but good palliative results were achieved in all patients. CONCLUSION: Although the number of patients was not large and the follow up period was relatively short, these findings suggested that intraluminal high dose rate brachytherapy could be useful in the treatment of the patients with advanced tumors of GI tract.

The Effect of Intermittent Craniospinal Irradiation and Intrathecal Chemotherapy for Overt Meningeal Leukemia / 대한치료방사선과학회지

Between 1988 and 1992, seven patients with overt meningeal leukemia who had received adequate central nervous system (CNS) prophylaxis were treated with intermittent craniospinal irradiation and intrathecal methotrexate(IIIC). Follow-up time ranged from 8 months to 41 months with median of 20 months. Three of 7 patients developed subsequent CNS relapse. CNS remission durations were 8, 9, 13, 20, 28, 34, 36 months from diagnosis of CNS leukemia for which IIIC was given. Disease free survival after CNS relapse ranged from 2 to 36 months with median of 11 months. Overall survival after CNS relapse ranged from 8 to 41 months with median of 28 months. Five patients died of sepsis and bleeding secondary to bone marrow relapse. Two patients are alive at present. But they developed recurrent CNS disease 10 to 11 months after completion of IIIC. To improve the outcome, modification of IIIC by reduction of rest period and prolonged administration of intrathecal chemotherapy after completion of IIIC are required.