Multiple primary malignant neoplasms (MPMN) are defined by the presence of multiple primary cancers of multicentric origin and/or different tissues. The incidence of MPMN is less than 1% in Korea and recently seems to be increased due to early detection of cancer and prolonged survival of cancer patients. Previous investigations suggest that non-Hodgkin's lymphoma (NHL) may be associated with chronic liver disease and hepatocellular carcinoma (HCC). The pathogenesis of this association is thought to be due to chronic antigenic stimulation, the presence of HBsAg, and immunosuppressive therapy. We report a case of synchronous NHL and HCC in a 54-year-old man which is thought to be associated with hepatitis B virus infection. Pathological examination and immunohistochemical study of neck lymph node and liver mass biopsies showed diffuse large cell lymphoma and HCC, respectively. He was treated initially with EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide and prednisolone) chemotherapy for NHL and transarterial chemoembolization with doxorubicin, mitomycin-c, lipiodol, and gelfoam for HCC.
Biopsy ; Carcinoma, Hepatocellular* ; Cyclophosphamide ; Doxorubicin ; Drug Therapy ; Early Detection of Cancer ; Ethiodized Oil ; Gelatin Sponge, Absorbable ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Incidence ; Korea ; Liver ; Liver Diseases ; Lymph Nodes ; Lymphoma, Large B-Cell, Diffuse ; Lymphoma, Non-Hodgkin* ; Middle Aged ; Mitomycin ; Neck ; Vincristine

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.
Bone Marrow ; Cyclophosphamide ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination ; Follow-Up Studies ; Hodgkin Disease* ; Humans ; Korea ; Lymphoma, Non-Hodgkin ; Multivariate Analysis ; Prognosis ; Radiotherapy ; Risk Factors ; Survival Rate

Development of diffuse pulmonary infiltrates in patients receiving chemotherapy is a major diagnostic challenge. Diffuse pulmonary infiltrates may be due to infection, pulmonary hemorrhage, pulmonary edema or drug-induced lung injury. Among these, pulmonary toxicity caused by antineoplastic agent is being recognized more frequently. Cyclophosphamide, an alkylating cytotoxic drug, is used widely in the treatment of malignancies including lymphoma. The incidence of pulmonary toxicity is probably less than 1 percent, and its relation with total dosages and schedule of the drug is not yet defined. The typical pictures of cyclophosphamide-induced pulmonary toxicity are non-productive cough, dyspnea, fever, hypoxemia with respiratory alkalosis and interstitial pneumonitis. However, relatively infrequent pulmonary toxicity of cyclophosphamide and frequent development of infectious pulmonary infiltrate in the patients treated with chemotherapy may hamper the early diagnosis of cyclophosphamide toxicity. Interstitial pattern and unresponsiveness to antibiotics of the pneumonitis might be the clues of suspicion. The best ways to treat the patients with cyclophosphamide toxicity are early diagnosis, discontinuation of the drug and early corticosteroid trial, although usefulness of steroid has not been firmly established. Recently, we experienced three cases of interstitial pneumonitis developing during cyclophosphamide-containing chemotherapy for non-Hodgkin's lymphoma in the absence of neutropenia or thrombocytopenia. Early use of corticosteroid in later two cases could resolve the pulmonary complication completely, whereas the pneumonitis failed to improve in spite of the massive use of multiple antibiotics in the first case.
Alkalosis, Respiratory ; Anoxia ; Anti-Bacterial Agents ; Appointments and Schedules ; Cough ; Cyclophosphamide* ; Drug Therapy* ; Dyspnea ; Early Diagnosis ; Fever ; Hemorrhage ; Humans ; Incidence ; Lung Diseases, Interstitial* ; Lung Injury ; Lymphoma ; Lymphoma, Non-Hodgkin ; Neutropenia ; Pneumonia ; Pulmonary Edema ; Thrombocytopenia