The Prevalence and Clinical Characteristics of Hepatitis-delta Infection in Korea / 대한간학회지

BACKGROUND/AIMS: The prevalence of hepatitis delta virus (HDV) infection has been estimated as being approximately 5% among global HBsAg carriers. The anti-delta positive rate in Koreans had been reported as being 0.85% in 1985. While the prevalence of HBV has been decreased from nearly 10% to 5% during the past twenty years, there have been no more studies on the anti-delta prevalence in Koreans. The aim of this study was to estimate the anti-delta prevalence in Koreans and to study the clinical characteristics of anti-delta positive patients in a single center. METHODS: Serum anti-delta was measured in one hundred ninety four HBsAg-positive patients who were admitted to our hospital from February 2003 to August 2003. We checked the genotypes of the HBV in the anti-delta positive patients. The clinical features of the anti-delta positive patients were compared to those clinical features of the anti-delta negative patients from the aspect of age, gender, mode of transmission, the positivity of HBeAg and serum HBV DNA. RESULTS: Serum anti-delta was positive in seven patients among the 194 subjects, giving a 3.6% positive rate. Among these seven patients, six had hepatocellular carcinoma (HCC) and the other one had cholangiocarcinoma. All of the anti-delta positive patients had the C genotype of HBV. The anti-delta positive patients showed significantly suppressed HBV DNA replication compared to the anti-delta negative patients. CONCLUSIONS: In Koreans, anti-delta was positive mainly in HCC patients with an approximate prevalence of 4%, and this rate has not changed much for the past twenty years. HBV DNA replication was suppressed by HDV infection.

Positron Emission Tomography with Fluorine-18-Fluorodeoxyglucose is Useful for Predicting the Prognosis of Patients with Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is heterogenous in terms of its glucose metabolism. Positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) shows various levels of FDG uptake for patients with HCC. This study was designed to assess the usefulness of FDG-PET for predicting the outcome of the patients with HCC. METHODS: FDG-PET was performed for 27 patients with HCC. The standardized uptake value (SUV) and SUV ratio (defined as the tumor-to-nontumor ratio of SUV) was calculated for each patient. The clinical factors of the outcome were analyzed by regression analysis using Cox's multivariate proportional hazard model. The survival rate was calculated by the Kaplan-Meier method. RESULTS: Among the analyzed clinical factors including tumor size, number of tumors, AFP, involvement of major vessels, presence of systemic metastases, Child-Pugh class the SUV and SUV ratio, only the SUV was the only significant independent prognostic factor (p=0.001). On the basis of the SUV, the patients were divided into two groups of roughly equal size: group A, SUV of or=7. The cumulative survival rate was significantly lower for group B than for group A, and the median survival time was significantly different (4 months vs 15 months, respectively) (p=0.003). CONCLUSIONS: These results suggest that FDG-PET is useful to predict the outcome for patients with hepatocellular carcinoma.

A Case of Neurotoxicity Following 5-Fluorouracil-based Chemotherapy

5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent. However, its neurotoxicity is rare and not well recognized. We report a case of 5-FU neurotoxicity with organic brain syndrome and progression to multifocal leukoencephalopathy in a 44-year-old male patient having malignant gast- rointestinal stromal tumor. 5-FU-induced neurotoxicity should, therefore, be considered as an important differential diagnosis in cancer patients with neurological abnormality and history of chemotherapy.

Evaluation of Various Hepatic Lesions with Positron Emission Tomography / 대한간학회지

BACKGROUND/AIMS: [18F]FDG-PET is a functional imaging modality reflecting cellular glucose metabolism. In most malignant cells, accumulation and trapping of [18F]FDG allows the visualization of increased uptake compared with normal cells. The aim of this study was to assess the value of PET in differentiating benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. METHODS: Eighty patients with liver lesions were enrolled (hepatocellular carcinoma 34, cholangiocarcinoma 8, metastatic liver cancer 25, hemangioma 6, liver abscess 7). Liver metastases were 22 adenocarcinoma, 2 lymphoma, 2 squamous cell carcinoma. The PET images of these patients were analyzed. SUV and lesion-to-normal liver background SUV ratio were obtained and compared among the disease groups. RESULTS: All liver metastases and all cholangiocarcinomas had increased uptake value, with SUV ratios greater than 2. Hepatocellular carcinoma had SUV ratios greater than 2 in 20 of 34 patients (59%). All hemangiomas had poor uptake, a SUV ratio of less than 2. All liver abscesses showed definite uptake. CONCLUSIONS: The PET technique using FDG static imaging was useful in differentiating malignant from benign lesions of the liver in limited situations. Limitations included false negative results in some patients with hepatocellular carcinoma. Liver abscesses raised problems in differential diagnosis from malignant liver tumors. The findings of this study suggest that the PET technique might be applied in tumor staging and the detection of recurrence, as well as monitoring responses to therapy for all adenocarcinomas and some hepatocelluar carcinomas.

Implications of Serum Levels of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor in Chronic Liver Diseases and Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Angiogenesis occurs in response to tissue damage, and is of vital importance for tumor growth and metastasis. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are potent angiogenic factors, and have been suggested to be useful diagnostic markers in certain hypervascular tumors. However, little is known of serum bFGF and VEGF in patients with hepatocellular carcinoma (HCC). We attempted to measure serum bFGF and VEGF in patients with chronic liver diseases (CLD) and HCC to assess their pathogenetic role and usability as tumor markers. METHODS: Serum bFGF and VEGF were measured in 8 patients with chronic hepatitis (CH), 15 patients with liver cirrhosis (LC), and 49 patients with HCC. bFGF was measured in 33, and VEGF was measured in 50, healthy blood donors. RESULTS: Serum bFGF was 3.8+/-1.9, 2.0+/-1.4, 4.2+/-6.0, 17.4+/-30.0 pg/mL in normal control, CH, LC, HCC, respectively. The serum bFGF level was significantly increased in patients with HCC when compared with normal control or patients with CLD. No difference, however, was observed in serum VEGF levels among the four groups. The serum levels of bFGF and VEGF were not significantly different in patients with HCC according to tumor type, size and stage. Serum bFGF showed good sensitivity (90%), specificity (87%), and positive predictive value (94%) in differentiating patients with HCC from those with CLD at the cut-off value of 4.6 pg/mL. CONCLUSIONS: bFGF might play a role in the growth of HCC and its serum level might be used as a tumor marker. On the other hand, serum VEGF does not seem to be an adequate tumor marker.

Clinical Characteristics of Non-B, Non-C Hepatocellular Carcinoma and Detection of HBV, HCV and TTV Viremia / 대한간학회지

BACKGROUND/AIMS: About 15% of Korean hepatocellular carcinoma (HCC) are negative both of Hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (anti-HCV) in their sera. They can be classified as a non-B, non-C hepatocellular carcinoma group (NBNC group). The aims of our study were, firstly, to describe the clinical characteristics of Korean NBNC HCC and compare them with those of HBsAg-positive HCC (HBV group) and anti-HCV-positive HCC (HCV group). Secondly we wanted to assess the frequency of viremia of HBV, HCV and transfusion-transmitted virus (TTV) in NBNC HCC patients. METHODS: We prospectively collected clinical data and sera from 113 NBNC HCC patients and performed PCR for HBV DNA, HCV RNA and TTV DNA. We also collected clinical data from 125 HBsAg-positive HCC patients and 61 anti-HCV-positive HCC patients during a similar period. RESULTS: The mean age of the NBNC HCC group was 59 years, in-between that of the HBV and the HCV groups. A History of heavy alcohol drinking was found in 48% of the NBNC HCC group. This was significantly higher than that of the HBV group, but similar to that of the HCV group. Serum alphaFP level in the NBNC HCC group was more frequently in the normal range compared to that in the HBV and HCV groups. The detection rates of HBV DNA, HCV RNA and TTV DNA in the NBNC HCC group were 17%, 13%, and 67% respectively. CONCLUSIONS: The NBNC HCC patients seemed to comprise a heterogeneous group of various etiologies and clinical presentations. About one third of these patients displayed evidence of viremia of HBV or HCV.

Expression of P-glycoprotein and p53 Protein in Stage IV Hepatocellular Carcinoma Treated with Systemic Chemotherapy / 대한간학회지

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a drug-resistant tumor. The expression of a multidrug resistant gene, P-glycoprotein (P-gp) is a major mechanism of drug resistance. The aims of our study were, firstly, to observe the expression rate of P-gp in HCC tissue obtained by percutaneous fine needle aspiration (PCNA) from stage IV HCC patients; secondly to examine the association between P-gp and chemotherapeutic response; and finally to investigate the correlation between p53 protein expression and P-gp expression. Subjects and METHODS: We studied 29 cases of stage IV HCC treated by systemic chemotherapy. Expression of P-gp and p53 were evaluated by immunohistochemical staining of HCC tissue with human monoclonal antibody, JSB-1 (Anti P-gp) and DO-7 (Anti p53), respectively. We analyzed the results of immunohistochemical staining of HCC tissues of the patients in relation to chemotherapeutic response and other clinical characteristics. RESULTS: The expression rate of P-gp was 27.6%. Partial response to anti-cancer chemotherapy was observed in 16.7% of the patients. Although we could not see a statistically significant association between P-gp expression and chemotherapeutic response, none of the responsive patients showed P-gp expression. p53 protein expression was found in 45% of the patients. There was no significant correlation between p53 protein expression and P-gp expression. CONCLUSIONS: Although the number of our study subjects was small, chemotherapy- responsive patients didn't show P-gp expression. P-gp expression might be used as a predictor of response to potentially toxic anti-cancer chemotherapy in HCC patients. Further study is warranted to confirm our results.

Supraumbilical Skin Rash as a Rare Complication of Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma / 대한간학회지

Transcatheter arterial chemoembolization (TACE) is a therapeutic option for unresectable hepatocellular carcinoma. Supraumbilical skin rash is a rare complication of TACE caused by patent hepatic falciform artery. We report herein two cases of supraumbilical skin rash developed after TACE for hepatocellular carcinoma, with discussion on the pathogenesis, prophylaxis, and treatment.

Clinical Characteristics of Female Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: The incidence of hepatocellular carcinoma has been universally lower in female than in male. The aims of our study are to define whether there are any difference between female and male patients with hepatocellular carcinoma in terms of clinical characteristics and results of treatment. METHODS: Retrospective analyses of medical history, physical findings, laboratory results, etiological factors, characteristics of tumor, and therapeutic results were performed in 80 female patients with hepatocellular carcinoma compared to 160 male patients. RESULTS: Asymptomatic presentation and family history of liver disease were found more frequently in female patients than in male patients. A history of smoking and alcohol drinking were found less frequently in female patients than in male patients. The detection rate of spider angioma was significantly lower in female patients than in male patients. There was no difference in laboratory results, characteristics of tumor, and therapeutic results between female and male patients. CONCLUSIONS: Environmental factors such as smoking and alcohol drinking could contribute the sexual difference of hepatocarcinogenesis. However, clinical characteristics at the time of diagnosis and therapeutic results were not significantly different between female and male patients with hepatocellular carcinoma.

Necessity and Safety of Fine-needle Aspiration Cytology for Diagnosis of Hepatocellular Carcinoma / 대한간학회지

BACKGROUNDS/AIMS: The fine-needle aspiration (FNA) is a useful method for diagnosis of hepatocellular carcinoma (HCC). The aims of our study are to assess diagnostic accuracy of FNA, to define proper indications of FNA for diagnosis of HCC, and to evaluate the complications of FNA. SUBJECTS AND METHODS: To assess diagnostic accuracy we compared the results of preoperative FNA with postoperative pathology in 38 resected cases with primary liver cancer. To define proper indications and complications of FNA, we prospectively followed 138 patients received FNA for their liver tumors which were suspicious of primary liver tumor. RESULTS: The sensitivity, specificity, positive and negative predictive values of FNA were 100%, 97%, 100% and 66% respectively. All patients with serum alpha-fetoprotein (AFP) level over 1000 ng/ml were having HCC on FNA result. Among 36 patients with AFP level ranged 15-1000 ng/ml and hypervascular mass on angiography, 96% were having HCC. Among 50 patients with normal AFP level and hypervascular mass on angiography, 92% were having HCC. The major complications after FNA such as hemoperitoneum, pneumothorax, and iatrogenic arterioportal shunt developed in 2%, 2%, and 7% of subjects, respectively. We did not find any case of needle-tract seeding of cancer during a mean 4.7 months of follow-up. CONCLUSIONS: Although the FNA is an accurate method for diagnosis of HCC, FNA was usually not indicated for patients with serum AFP level over 1000 ng/ml or patients with hypervascular mass on angiography when they were suspected of having primary liver cancer. Major complications were hemoperitoneum, pneumothorax and iatrogenic arterioportal shunt. Iatrogenic arterioportal shunt may influence the efficacy of subsequent transcatheter arterial embolization.

A Phase 2 Trial of Verapamil for Reversal of Drug Resistance in Refractory Non - Hodgkin's Lymphoma / 대한암학회지

PURPOSE: Drug resistance is one of the major obstacles to treatment of cancer. Multidrug resistance (MDR) caused by overexpression of p-glycoprotein (Pgp) in cancer cell membrane is a well-known mechanism of drug resistance in in vitro system and was reported to be a significant mechanism of resistance in non-Hodgkins lymphoma (NHL). Verapamil, a calcium channel blocker, is proven in vitro to overcome the MDR caused by Pgp. We performed a phase II trial of verapamil in patients with NHL refractory to EPOCH regimen (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) to overcome the MDR caused by Pgp. MATERIALS AND METHODS: Verapamil was administered via intravenous route from 1 hour before to 12 hour after the 96-hour infusion of etoposide, doxorubicin, and vincristine which were known to be substrates of Pgp in EPOCH regimen. The dose of verapamil was 0.15 mg/Kg in bolus and 0.2 mg/Kg/hr in infusion at the beginning and escalated by 0.05 mg/Kg/hr every 24 hours if there was no dose-limiting toxicities such as 2nd or 3rd degree AV block, hypotension, or congestive heart failure. Plasma verapamil concentrations were measured every 24 hour by gas chromatography. Mdrl expression level in tumor tissues was measured by RT-PCR. RESULTS: From Feb. to Nov. 1994, 14 patients were treated with this protocoL However, poor tolerability and no response in these patients led to early closure of the study at this 1st stage of patient accrual according to Gehans method. Among 14 patients, 12 experienced 2nd or 3rd degree AV block and/or hypotension and required temporary cessation of infusion and reduction of verapamil dose. However, there was no congestive heart failure or treatment-related death. The peak concentrations of verapamil were 0.29-1.94 pM (mean 0.93 pM) and mean concentrations during the 4-day infusion were 0.22-1.21 pM (mean 0.6 pM). Mdrl expression levels measured in 6 patients were 0.99-14.43 U (median 4.39). CONCLUSION: These results suggest that verapamil in this dose and schedule was neither tolerable nor effective for the reversal of drug resistance in NHL patients.

A Phase 2 Trial of EPOCH (Etoposide, Vincristine, Doxorubicin, Cyclophophamide and Prednisolone) Chemotherapy for Previously Treated Non - Hodgkin's Lymphoma / 대한암학회지

PURPOSE: As a new strategy to modulate drug resistance in the treatment of relapsed or refractory non-Hodgkin's lymphoma(NHL), continuos infusion of drugs has been incorporated into the chemotherapy. We conducted a phase II study to determine the activity and safety of EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisolone) chemotherapy, in which the natursl products are administered as a continuous infusion, for previously treated NHL's of intermediate grade. MATERIALS AND METHODS: EPOCH chemotherapy (etoposide 50 mg/m2/day 24 hour- continuous infusion, days 1~4, vincristine 0.4 mg/m2/day 24 hour-continuous infusion, days 1~4, doxorubicin 10 mg/m2/day 24 hour-continuous infusion, days 1~4, cyclophosphamide 750 mg/m2 i.v., day 5, prednisolone 60 mg/m2/day p.o. days 1-5) was given to eligible patients every 3 weeks and we assessed response and toxicity of the regimen. RESULTS: Between June 1993 and December 1995, total 56 patients entered this trial and 49 were evaluable. The complete response rate was 41%(95% C.I.: 27-55%). After follow up of 9~50(median 38) months, progression free survival was 0~39+(median 7) months and the overall survival was 1~44+(median 14) months. The prognostic factor analyses showed that B symtoms and serum LDH level before treatment and response to previous treatment affected complete response rate, and patients' performance status and response to previous treatment affected progression free survival and overall survival. Toxicities of EPOCH regimen were leukopenia, stomatitis, nausea/vomiting and neurotoxicity, but they were tolerable. There was 1 case of treatment-related death due to sepsis. CONDUSION: EPOCH chemotherapy was safe and effective for the patients with relapsed NHL. However, the results of patients with NHL refractory to previous treatment were so poor that more intensive, novel treatment would be needed for this category of patients.

High-Dose Chemotherapy with Vandervilt Regimen and CSF Support for High-Risk Aggressive Non-Hodgkin's Lymphoma / 대한암학회지

PURPOSE: To detennine the therapeutic effect and toxicities of high-dose chemotherapy with Vanderbilt regimen and colany-stimulating factors(CSF) support for high-risk aggressive non-Hodgkin's lymphoma(NHL). MATERIALS AND METHODS: Between Aug. 1995 and Mar. 1997, 40 patients with high-risk aggressive NHLs were treated with high-dose chemotherapy with Vandebilt regimen and CSF support. If the complete response(CR) was induced, four cycles of CHOP were administered for the maintenance of response. In cases of lymphoblastic lymphomas, CNS prophyiaxis with cranial irradiation and intrathecal methotrexate was done after CR. RESULTS: CR was achieved after Vanderbilt regimen in 62.5%(25/40) of the total patients. CR rste in refractory group(12.5%: 1/8) was significantly lower than in other groups (75%: 24/32)(p=0.001). With a median follow-up of 14 months, the failure free survival (FFS) was 0~18+ months(median 6.1 months). The overall FFS rate at one year was 31.7%. The 1-year FFS rate in refractory group(0%) was significantly lower than in other patients groups(41%)(p=0.001). The range of survival time was 0.5~18+ months, and median survival time was 6.2 months. Grade 4 leukopenia was observed in 100% of chemotherapy cycles and its median duration was 7 days. However, only one patient died due to treatment-relate sepsis. Non-hematological toxicities were tolerable and all reversible. CONCLUSION: High-dose chemotherapy with Vanderbilt regimen was effcctive for induction of CR in high-risk aggressive NHL patients and safe with the CSF support. However, poor CR rate in reftactory group and poor FFS in other groups indicate that a new, more intensive approach is needed for the induction of CR in refractory group and for the maintenance of CR in other high-risk patient groups.

Transarterial Chemoembolization ( TACE ) for Hepatocellular carcinoma: Comparison of Adriamycin alone vs . Cisplatin alone vs . Adriamycin + Cisplatin / 대한암학회지

PURPOSE: Although transarterial chemoembolization (TACE) has been widely used for the treatment of unresectable hepatocellular carcinoma, it has not been determined yet which chemotherapeutic agents were best for TACE. To determine the best chemotherapeutic regimen for TACE, we performed a prospective randomized study comparing 3 chemo- therapeutic regimen (adriamycin alone vs. cisplatin alone vs. adriamycin + cisplatin). MATERIALS AND METHODS: The patients with unresectable hepatocellular carcinoma were eligible for this study and were randomly assigned to three treatment groups (A: adriamycin 30 mg/m(2), B: cisplatin 60 mg/m(2), C: adriamycin 30 mg/m(2) + cisplatin 60 mg/m(2)). The TACE were performed by administering the mixture of lipiodol and the assigned chemotherapeutic drugs through the hepatic artery, followed by embolization with gelfoam powder. The treatment was planned to be repeated every 4 weeks. RESULTS: After 40 patients (14 in group A, 16 in group B, 10 in group C) entered, the study was stopped prematurely because of serious treatment-related complications including 15% of local complications, 18% of hepatic encephalopathy, and 8% of deaths. Because TACE could result in necrosis without reduction of mass size, the response could not be evaluated by the change of mass size, but by the change of serum alpha-fetoprotein level. Of 25 patients who had elevated serum alpha-fetoprotein and were assessable for response, there were one complete response (CR) and 5 partial responses (PR) out of 10 in group A, 5 PRs out of 10 in group B, and 2 PRs out of 5 in group C. There was no difference in response rates among the 3 treatment groups (p > 0.05). The response rate in patients treated with gelform embolization was higher than patients without embolization (63% (12/19) vs 19% (1/6): p<0.05). The median survival (OS) was 23 weeks for all 40 patients, 15 weeks for group A, 42 weeks for group B and 24 weeks for group C. The difference of OS between group A and B was statistically significant (p=0.02). However, the OS was not associated with any prognostic factors including treatment group in multivariate analysis. CONCLUSION: Although cisplatin seemed to be more effective in TACE than adriamycin, no firm conclusion could be drawn from this prematurely ended study. However, we could conclude that the TACE with gelform powder is so toxic that it could not be given safely to the patients with unresectable hepatocellular carcinoma

A Phase 2 Trial of PEF ( Cispatin , Etoposide , 5-Fluorouracil ) Chemotherapy for Metastatic Stomach Cancer / 대한암학회지

PURPOSE: To determine the activity and toxicities of PEF (Cisplatin, Etoposide, 5-Fluorouracil) chemotherapy for stomach cancer. MATERIALS AND METHODS: Patients with previously untreated metastatic stomach cancer were treated with PEF regimen which consisted of cisplatin (20 mg/m2 i.v. days 1~5), etoposide (100 mg/m2 i.v. days 1, 3, 5), and 5-fluorouracil (5-FU)(800 mg/m2 i.v. infusion for 12 hours days 1~5). Chemotherapy was repeated every 3 weeks until disease progressed or toxicities were intolerable. RESULTS: Between May 1989 and July 1990, 40 patients were enrolled in this protocol. Twelve patients were lost to follow up after one cycle of chemotherapy and inevaluable. After 2~8 cycles (median 3) of chemotherapy, 20 out of 28 evaluable patients showed objective responses without any complete response, making the response rate 71% (95% confidence interval: 54~89%). The responses lasted from 4+ to 39 weeks (median: 38 weeks). The overall survival of total evaluable patients was 4+ ~50+ weeks (median 38 weeks). Among total 109 cycles of chemotherapy, cycles were delayed or doses were reduced in 48 cycles (44%) because of leukopenia (in 61 cycles: 56%) and/or thrombocytopenia (in 14 cycles: 13%). However, there was no treatment-related death. Nausea/vomiting and alopecia were experienced in most of patients. The stomatitis was experienced in 7 patients (25%) but completely reversible. In contrast, the peripheral neuropathy which developed in 4 patients (14%) after 5 cycles of chemotherapy was not reversible. CONCLUSION: The PEF regimen was active and tolerable in stomach cancer.

Primary CHOP Chemotherapy Followed by Involved Field Radiation Therapy in Clinical Stage I or II Aggressive Non-Hodgkin's Lymphomas / 대한암학회지

PURPOSE: Although radiation therapy had been the treatment of choice for localized non-Hodgkin's lymphoma(NHL), recent studies have revealed that treatment result after radiation therapy alone is not successful for localized aggressive NHL, if it is not pathologically but clinically staged. A prospective phase II trial was conducted to evaluate the therapeutic results of 4 cycles of CHOP chemotherapy followed by involved field radiation therapy in clinically staged localized aggressive NHL. MATERIALS AND METHODS: Patients with a diagnosis of aggressive NHL(all intermediate grade and immunoblastic histology in NCI working formulation), Ann Arbor stage I or II without poor prognostic factors(presence of B symptoms, bulky diseases, or 2 or more extranodal involvement) were treated with 4 cycles of CHOP(cyclophosphamide, doxorubicin, vincristine, prednisolone) followed by involved field radiation therapy of 3,000~6,000(median: 4,500) cGy. RESULTS: Between April 1990 and March 1995, 62 consecutive patients entered this trial. Forty six patients with measurable diseases were evaluable for response. Complete response was achieved in 41(89.1%) patients after CHOP chemotherapy and 4 more patients after subsequent radiation therapy, making total CR rate of 98%. Progression free survival(PFS) of all 62 patients were 2.2+~73+ months and 5 year PFS rate was 64.6%. Overall survival(OS) were 2.4+~75+ months and 5 year OS rate was 75.2%. Old age (> 60) was the only significant prognostic factor, which-affected overall survival negatively. Treatment was relatively well tolerated, but 3 patients died associated with treatment. CONCLUSIONS: Four cycles of CHOP chemotherapy followed by involved field radiation therapy is highly curative and safe treatment for clinically staged, localized aggressive NHLs.

VACOP-B (Etoposide/Doxorubicin/Cyclophosphamide/Vincristine/Prednisolone/Bleomycin) Combination Chemotherapy for the Treatment of Intermediate and High Grade Non-Hodgkin's Lymphoma / 대한암학회지

PURPOSE: To determine the antitumor activity of VACOP-B regimen for advanced non- Hodgkin's lymphoma (NHL) in terms of complete response rate, disease free survival, and overall survival, to assess the toxicities of this regimen, and to analyze the prognostic factors influencing the treatment results.Patients and methods: Between Apr. 1991 and Aug. 1993, thirty-six previously untreated patients with the intermediate or high grade NHL were treated with VACOP-B (etoposide/doxorubicin/cyclophosphamide/vincristine/prednisolone/bleomycin) combination chemotherapy. In case of initial bulky disease or residual disease after chemotherapy, radiation therapy of involved field was added. RESULTS: Complete response (CR) was achieved in 69% (25/36) of the eligible patients after VACOP-B chemotherapy, and 5 of 11 patients who remained in partial response (PR) after chemotherapy achieved CR after additional radiation therapy of involved field, resulting in 83% (30/36) of CR rate. With a median follow-up of 47.2 months, the disease free survival was 1~42.1+ months, and its median was 24 months. The range of survival time was 7~49.1+ months, and the median survival time was not reached at this time. The projected 3-year survival rate was 70%. Leukopenia was observed in 43% of chemotherapy cycles and thrombocytopenia in 2.3%. However, no treatment-related death was observed. For non-hematologic toxicities, nausea and vomiting were observed in 58% of patients, stomatitis in 58%, peripheral neuropathy in 58%, pulmonary toxicity in 3% and congestive heart failure in 3%. These toxicities were tolerable and all reversible. The prognostic factors influencing the complete response rate were performance status of patient (p=0.026) and relative dose intensity of cyclophosphamide (p=0.013). CONCLUSION: VACOP-B regimen is an effective and tolerable regimen for the intermediate and high grade NHL. And long term follow-up and phase III study will be needed for evaluation of these results compared to previous other treatment modality.

Analysis of Prognostic Factors and Application of International Prognostic Index Model to Determine the High Risk Group for the Treatment of Aggressive Non - Hodgkin's Lymphoma / 대한내과학회지

OBJECTIVE: Although the therapeutic outcome of aggressive non-Hodgkin's lymphoma (NHL) has been considerably improved by the introduction of combination chemotherapy, many patients still fail to achieve complete response(CR) and/or long-term survival. Because the outcome appears to depend on certain prognostic factors, long term prognosis can be predicted by identification of risk group. And also, the patients in high risk group may benefit from new therapeutic modality. In 1993, the international prognostic index model for aggressive NHL as developed far the purpose of predicting outcome and designing of therapeutic trial. Thus, analysis of prognostic factors was performed to identify independent factors for the end points of CR, overall survival, and disease-free survival. METHODS: From 1989 to 1994, total 340 patients were treated with combination chemotherapy and/or radiotherapy for NHL in Korea Cancer Center Hospital. Among 340, informations on eleven prognostic factors(sex, age, performance status, Ann Arbor stage, serum LDH level, tumor size, number of extranodal disease sites, bone marrow involvement, presence of B symptom, sex, time to CR, and histologic grade) were avaliable for 273 patients. Among these, 221 patients with aggressive NHL(NCI clinical schema) were eligible for the prognostic factor analysis for the response and survival. Also, 186 patients were eligible to determine whether International Prognostic Index Model could be applicable for Korean NHL. RESULTS: One hundred fifty patients(68%, 95% CI 62-74%) achieved a complete remission, 43 patients (20%) a partial remission. With a median follow-up of 3,5 years, overall 3 year survival rate was 6396, and 3 year DFS for the 150 CRs was 72%. In a univariate analysis for the CR and survival, Ann Arbor stage, number of extranadal disease, performance status, presence of B symptoms, presence of BM involvement, serum LDH level and histologic grade were found to be statistically significant prognostic factors. Among them, by multivariate analysis, number of extranodal disease(RR 0.2, 95% CI 0.1-0.7), B Symptoms (RR 0.4, 95% CI 0.2-0.9), and histologic grade(RR 0.2, 95% CI 0.08-0.7) showed to be independent adverse prognostic factors for CR. For disease-free survival, Ann Arbor stage(RR 2.6, 95% CI 1.1-6.4) was independent risk factor. For overall survival, number of extranodal involvement(RR 2, 95% CI 1.3-4) and histologic grade(RR 2, 95% CI 1.2-3.7) were independently significant prognostic factors. With these 2 independent prognostic factors for survival, we could establish a prognastic index model which could separate the high risk patients. However, the usefulness of this model should be confirmed in a larger patient population. The dose intensity of cyclophosphamide, during initial 3 months of treatment, was significantly associated with CR rate and overall survival(p=0.01 and 0.03, respectively). When International Prognostic Index Model was applied to our patients, patients in the lower risk groups had significantly better outcome than patients in the higher risk groups(3 year survival and RR: 77% and 1 for low risk group, 61% and 1.9 for low-intermediate risk group, 50% and 2.2 for high-intermediate risk group, and 25% and 6 for high risk group). CONCLUSION: In this study, we confirmed that features other than the Ann Arbor stage were independently associated with CR and survival, and the International Prognostic Index Model would be an useful tool for the selection of high-risk patients who could be benefited from more aggressive chemotherapy.

Prognostic Factor Analysis of Small Cell Lung Cancer: Appropriateness of Two Staging System / 대한암학회지

PURPOSE: The two staging system, which divides the tumors into limited disease (LD) and extensive disease (ED) has been widely accepted as a major prognostic determinant in small cell lung cancer (SCLC). However this system has provoked several controversial issues in defining stage categories, for instance, ipsilateral pleural effusion as LD or ED. Furthermore, identification of favorable subgroups in the same stage has been recognized as an important factor to determine appropriate treatment strategies. In this study, we performed a retrospective analysis in an attempt to resolve the controversial issues about staging and identify the patient group with favorable prognosis based on this two staging system. MATERIALS AND METHODS: The clinical data of 233 patients with SCLC treated from 1990 to 1996 at Korea Cancer Center Hospital were retrospectively analyzed for this study. All patients were treated with chemotherapy containing cisplatin and/or radiotherapy. The independent prognostic factors for survival were identified by multivariate analysis using Cox's proportional hazards model. RESULTS: Performance status (relative risk of death [RR]:2.89), number of metastasis (RR:2.2), response to treatment (RR:2.2) as well as stage (RR:1.77) were identified as independent prognostic factors for survival in patient with SCLC. The median survival of patients with ipsilateral pleural effusion (13 months) which was categorized as ED was similar to that of patients with contralateral mediastinal or supraclavicular lymph nodes (13.8 months) or other LD patients (13.7 months). This result suggests that ipsilateral pleural effusion should be categorized as LD. In LD, response to treatment was the only independent prognostic factor (RR:2.34) and thoracic radiotherapy moderately improved survival as compared with combination chemotherapy alone (17.7 months vs. 10.4 months, p=0.06). In ED, the patient group with a good performance status (ECOG 0-1), normal range of serum alkaline phophatase, and metastasis less than 2 sites showed significantly prolonged survival, comparing with other ED patients (11.2 months vs. 7.2 months, p=0.0001). CONCLUSION: As a result of survival analysis, we confirmed independent prognostic factors such as stage and performance status in SCLC. We could recommend that LD category include patients with ipsilateral pleural effusion as well as those with contralateral lymphadenopathy. In ED, the survival in patients with favorable prognostic factors was comparable to LD, suggesting this patient group may be a candidate for aggressive therapy.

Phase II Study of Concurrent Chemotherapy with Etoposide and Cisplatin (EP) and Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer / 결핵

BACKGROUND: Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC), however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, arid survival of concurrent chemotherapy with etoposide and cisplatin(EP) arid radiation therapy for unresectable stage III NSCLC. METHODS: Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without, malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide arid cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. RESULTS: Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient The median survival was l2.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia(> or = grade 3,46%) Thrombocytopenia over grade 3 was found in 1%. Radiation pneumonitis occurred in 13 patients(46%). CONCLUSION: Concurrent chemotherapy(EP) pins radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.