Long-term outcome of treatment for Hodgkin's disease: the University Hospital Sofia experience.

BACKGROUND: To establish the efficacy of the combined modality treatment (CMT) including curative extended field radiotherapy (EFRT) and chemotherapy (CHT) by examining the long-term outcome in Hodgkin's disease (HD) patients at the Sofia University Hospital "Queen Giovanna-ISUL", with particular focus on second primary malignancy (SPM), and to establish independent factors correlated with treatment outcome. METHODS AND MATERIALS: Between 1982 and 2007, 170 patients with HD with median age of 12 years (range 3-40), (68 females, 102 males), were included in this retrospective study. The clinical stage (CS) distribution was CS I in 1 patient (0.6%), CS II in 86 (50.5%), CS III in 77 (45.3%) and CS IV in 6 (3.5%) patients. Histologic subtypes included lymphocyte predominance 7.6%, mixed cellularity 47.1%, nodular sclerosis 42.9% and lymphocyte depletion 0.6%. B symptoms were observed in 57.6% of the patients, hepatosplenomegaly--in 30.6%, anemia--in 27.1% and elevated serum lactat dehydrogenase (LDH)--in 41.2%. The overall treatment consisted of both EFRT and CHT. In 115 patients (67%) supradiaphragmatic irradiation of lymphatic nodes was carried out, in 3 (2%) patients subdiaphragmatic irradiation was performed and in 52 (31%)--irradiation of the supra- and infra-diaphragmatic lymph nodes basically by subtotal 35 (20.6%), and total lymphoid irradiation--in 4 (2.4%) patients. The daily dose was 1.5-2 Gy, the total dose for EFRT was 20-40 Gy. From the analyzed 170 patients 150 were assessable for long-term outcome and 120 for SPM analyses.
RESULTS: Follow-up extended from a minimum of 0,3 years to maximum 25,7 years, with a median observation time 12 years.The 5-, 10-, 15-, and 25-year overall survival (OS) in the whole group was 93% : 86% : 82% : 82%, respectively. A tendency for better survival was found for patients with age < or = 15 than for those with > 15 years, with 5-, 10-, and 15- year OS of 95% : 87% : 84% vs 84% : 84% : 56%, p = 0.09. There was a trend for better survival in males compared with females with 5-, 10- and 15-year OS of 96%: 93%: 91% vs 88% : 73% : 65%, p = 0.001. The OS difference between CS IIB and IIIA turned out to be significant in favor of the patients in CS IIIA with 5- and 10-year OS of 89%: 76% vs 95%: 90%, respectively, p = 0.03. The following factors were analyzed for their prognostic influence: age, gender, stage, histologic subtype at first diagnosis, sites of involvement, number of involved lymph node areas, B symptoms, hepatosplenomegaly, anemia, elevated serum LDH, daily dose, total dose, boost and technique used in EFRT. In univariate analysis, independent risk factors were gender (p < 0.001), stage (IIB: IIIA) (p = 0.03), mediastinal involvement (p = 0.03), daily dose (p = 0.01) and total dose (p = 0.02). In multivariate analysis, independent risk factors age < or = 15 years (p < 0.001), male gender (p = 0.005), daily dose < or = 1.5 Gy (p = 0.009), and total dose 26-30 Gy (p = 0.048) were found to positively affect OS. We investigated a prognostic model, identifying groups of HD patients with particularly responsive disease, combining prognostic factors as age < or = 15 years (p = 0.001), male gender (p = 0.011), and total dose 26-30 Gy (p = 0.012). In the observed 25-year period SPM development was not established in any of the 120 patients subjected to follow-up.
CONCLUSION: The performed first Bulgarian study on CMT including EFRT and CHT exhibited a certain therapeutic potential in the treatment of HD patients, expressed in the achievement of high long term outcome and low SPM frequency.