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.