Abstract
To evaluate the long-term outcomes of childhood stage 4 neuroblastoma (NB) and its correlative prognostic factors. Comprehensive protocols including tumor resection, intensive chemotherapy, radiotherapy, autologous bone marrow transplantation and 13-cis-retinoid were designed and implemented. A total of 112 newly diagnosed NB stage 4 patients at Shanghai Children's Medical Center collected from June 1998 to December 2010 were treated. Their clinical features, therapeutic efficacies, long-term outcomes and prognostic factors were analyzed. There were 69 males and 43 females with an age range of 4 months to 15 years. Among them, 12 improving patients didn't complete treatment because of parental decisions. Among those completing the comprehensive protocols, 62 cases (62.0%) achieved very good partial remission (VGPR), 20 (20.0%) achieved partial remission (PR) while another 18 (18.0%) progressed during treatment. The efficiency rate (including VGPR+PR) of treatment was 82.0 % (n = 82). The median follow-up period was 78 (56, 120) months. And 13 cases were lost after a median follow-up of 16 months. The 2, 3, 5-year event-free survival (EFS) was 56.2% (59/105) , 40.8% (40/98) and 21.1% (19/90) respectively. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated level of lactate dehydrogenase (LDH) (> 5 times normal value), bone marrow involvement and brain metastasis were poor prognostic factors (χ(2) = 12.01, 13.66, 6.29, 5.44, 16.18, all P < 0.05) . According to the multivariate estimates of hazards, age, high levels of LDH, poor curative effect and brain metastasis were associated with a worse survival (OR = 3.54, 1.89, 3.08, 3.45, all P < 0.05) . Brain metastasis predicted a worse outcome with 100% mortality rate (n = 6). Compared to traditional chemotherapy, topotecan-based chemotherapy could not improved the efficiency (52.6% (10/19) vs 63.2% (36/57) , P > 0.05) and long-term outcome (2 ys-EFS 42.1% (8/19) vs 56.4% (31/55) , P > 0.05). The prognosis remains poor for neuroblastoma of stage 4. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated LDH level (>5 times normal value) and bone marrow infiltration are associated with worse prognosis. Brain metastasis predicts the worst with 100% death rate. Topotecan included chemotherapy can not be proved more effective in this study.
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