Oral Presentation Advances in Neuroblastoma Research Congress 2016

High-dose 131I-MIBG treatment incorporated into tandem HDCT/auto-SCT for high-risk neuroblastoma: Results of SMC NB-2009 study (#121)

Ji Won Lee 1 , Eun Sang Lee 1 , Young Bae Choi 1 , Keon Hee Yoo 1 , Ki Woong Sung 1 , Hong Hoe Koo 1 , Ju Youn Kim 1 , Eun Joo Cho 1
  1. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Background: The strategy using tandem HDCT/auto-SCT for high-risk neuroblastoma in which TBI was incorporated into the second HDCT/auto-SCT (SMC NB-2004 study) demonstrated a very encouraging survival rate. However, most survivors experienced significant short- and long-term toxicities associated with tandem HDCT/auto-SCT, particularly TBI. Therefore, we incorporated high-dose 131I-MIBG treatment into the second HDCT/auto-SCT instead of TBI from 2009 (SMC NB-2009 study).

Methods: From 2009 to 2013, 54 patients were assigned to receive tandem HDCT/auto-SCT after 9 cycles of induction chemotherapy. CEC (carboplatin + etoposide + cyclophosphamide) and TM (thiotepa + melphalan) with (for stage 4) or without (for stage 3) high-dose 131I-MIBG treatment were used as the first and second HDCT regimen, respectively. High-dose 131I-MIBG was infused on day -21 of the second HDCT/auto-SCT. Local radiotherapy, 13-cis-retinoid acid, and IL-2 were given after tandem HDCT/auto-SCT. Acute toxicities during the second HDCT/auto-SCT, late effects, and survival rates were compared between NB-2004 and NB-2009 studies.

Results: All but 2 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. Five patients died from toxicities during the first HDCT/auto-SCT. There was no significant immediate toxicity during 131I-MIBG infusion and no toxic death during the second HDCT/auto-SCT. The duration of high fever was shorter (P<0.001) and frequencies of grade 3/4 stomatitis, diarrhea, and liver enzyme elevation during the second HDCT/auto-SCT were lower in NB-2009 study than in NB-2004 study (P=0.005, 0.054, and 0.028, respectively). Late effects evaluated at 3 years after the second HDCT/auto-SCT were less significant in 2009 study than in 2004 study (less GH deficiency, SNHL, cataract, and glomerulopathy). There was no difference in 5-yr EFS (67.4 ± 6.7% vs. 64.9 ± 6.8%, P=0.833).

Conclusions: High-dose 131I-MIBG treatment incorporated into tandem HDCT/auto-SCT was feasible and could reduce acute and chronic toxicities without jeopardizing survival rate.