Incidence and risk factors for secondary malignancy in patients with neuroblastoma after treatment with 131I-metaiodobenzylguanidine

Abstract

Several reports of second malignant neoplasm (SMN) in patients with relapsed neuroblastoma after treatment with (131)I-MIBG suggest the possibility of increased risk. Incidence of and risk factors for SMN after (131)I-MIBG have not been defined. This is a multi-institutional retrospective review of patients with neuroblastoma treated with (131)I-MIBG therapy. A competing risk approach was used to calculate the cumulative incidence of SMN from time of first exposure to (131)I-MIBG. A competing risk regression was used to identify potential risk factors for SMN. The analytical cohort included 644 patients treated with (131)I-MIBG. The cumulative incidence of SMN was 7.6% (95% confidence interval [CI], 4.4-13.0%) and 14.3% (95% CI, 8.3-23.9%) at 5 and 10 years from first (131)I-MIBG, respectively. No increase in SMN risk was found with increased number of (131)I-MIBG treatments or higher cumulative activity per kilogram of (131)I-MIBG received (p = 0.72 and p = 0.84, respectively). Thirteen of the 19 reported SMN were haematologic. In a multivariate analysis controlling for variables with p< 0.1 (stage, age at first (131)I-MIBG, bone disease, disease status at time of first (131)I-MIBG), patients with relapsed/progressive disease had significantly lower risk of SMN (subdistribution hazard ratio 0.3, 95% CI, 0.1-0.8, p = 0.023) compared to patients with persistent/refractory neuroblastoma. The cumulative risk of SMN after (131)I-MIBG therapy for patients with relapsed or refractory neuroblastoma is similar to the greatest published incidence for high-risk neuroblastoma after myeloablative therapy, with no dose-dependent increase. As the number of patients treated and length of follow-up time increase, it will be important to reassess this risk.

Metachronous Medulloblastoma in a Child With Successfully Treated Neuroblastoma: Case Report and Novel Findings of DNA Sequencing

“…Analyses of 9,432 long-term neuroblastoma survivors in 3 major studies indicated that 96 patients developed second cancers, including carcinomas, soft tissue sarcomas, glioblastomas, meningioma, melanomas, and hematologic malignancies, but none developed medulloblastoma (Table 3). [5][6][7] Neuroblastoma and, less commonly, medulloblastoma, have been reported in patients with cancer predisposition syn- [22][23][24] Our patient did not have clinical stigmata of these conditions and her genetic testing was negative for these syndromes.…”

“…Agda Karina Eterovic, PhD a ; Ossama M. Maher, MD b ; Joya Chandra, PhD c ; Ken Chen, PhD d ; Jason Huse, MD, PhD e ; and Wafik Zaky, MD c cers have mostly occurred many years after long-term surveillance. [5][6][7] This report presents a case of medulloblastoma in a child 5 months after successful treatment of stage IV neuroblastoma, and discusses the findings in the DNA sequencing results of both the resected posterior fossa tumor and the germline mutations.…”

Norepinephrine Transporter as a Target for Imaging and Therapy

“…Other commonly observed toxicities are transient thyroid dysfunction, sialoadenitis (100), hepatic transaminitis (101), and mild acute hypertension (102). The incidence of secondary malignancy is similar to that observed in children treated with chemotherapy with a cumulative incidence of 7.6% and 14.3% at 5 and 10 y after therapy, respectively (103). Secondary malignancies including acute nonlymphoblastic leukemia, chronic myelomonocytic leukemia, angiomatoid malignant fibrous histiocytoma, malignant schwannoma, and rhabdomyosarcoma have been reported to occur at a median of 3 y (1-15 y) (104).…”

Strategies to Improve Chimeric Antigen Receptor Therapies for Neuroblastoma

“…It ranges from an adrenal mass tumor that regresses without treatment to a metastatic tumor that causes critical illness [ 6 ]. At present, while intensive therapies can be beneficial for patients with localized disease, these therapies have frequently not been useful against patients with high-risk disease (approximately 40% of cases associated with the extent of metastases and genetic factors) nor patients with relapse [ 7 , 8 ]. Hence, novel therapies based on immunotherapy were subsequently developed to improve survival for high-risk patients.…”