Response, survival, and toxicity after iodine‐131–metaiodobenzylguanidine therapy for neuroblastoma in preadolescents, adolescents, and adults

Cancer (Impact Factor: 4.89). 09/2011; 117(18):4286 - 4293. DOI: 10.1002/cncr.25987


Adolescent and adult patients with neuroblastoma appear to have a more indolent disease course but a lower survival rate compared with their younger counterparts. The majority of neuroblastoma tumors specifically accumulate the radiolabeled norepinephrine analogue iodine-131–metaiodobenzylguanidine (131I-MIBG). Therefore, 131I-MIBG has become increasingly used as targeted radiotherapy for patients with recurrent or refractory neuroblastoma. The objective of the current study was to characterize the toxicity and activity of this therapy in older patients.
The authors performed a retrospective analysis of 39 consecutive patients aged ≥10 years with recurrent or refractory neuroblastoma who were treated with 131I-MIBG monotherapy at the University of California at San Francisco under phase 1, phase 2, and compassionate access protocols.
Sixteen patients were aged ≥18 years at the time of MIBG treatment initiation, whereas 23 patients were ages 10 to 17 years. The median cumulative administered dose of 131I-MIBG was 17.8 millicuries (mCi)/kg. The majority of treatments led to grade 3 or 4 hematologic toxicities (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3]) that were similar in frequency among age strata. Three patients subsequently developed a hematologic malignancy or myelodysplasia. The overall rate of complete plus partial response was 46%. Patients aged ≥18 years at the time of first MIBG treatment had a significantly higher response rate compared with patients ages 10 to 17 years (56% vs 39%; P = .023). The median overall survival was 23 months with a trend toward longer overall survival for the subgroup of patients aged ≥18 years (P = .12).
The findings of the current study suggest that 131I-MIBG is a highly effective salvage agent for adolescents and adults with neuroblastoma. Cancer 2011;.

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    • "This variation in clinical behavior is also highly age dependent: children who are diagnosed after two years of age suffer predominantly from aggressive forms. Neuroblastomas that are diagnosed during adolescence and young adulthood are rare, but they are of particular concern because they almost invariably progress, although with an indolent course [4,5]. In sharp contrast, tumors that are diagnosed before 18 months of age are generally associated with a favorable prognosis. "
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    ABSTRACT: Background Aggressive neuroblastoma remains a significant cause of childhood cancer death despite current intensive multimodal treatment protocols. The purpose of the present work was to characterize the genetic and clinical diversity of such tumors by high resolution arrayCGH profiling. Methods Based on a 32K BAC whole-genome tiling path array and using 50-250K Affymetrix SNP array platforms for verification, DNA copy number profiles were generated for 34 consecutive high-risk or lethal outcome neuroblastomas. In addition, age and MYCN amplification (MNA) status were retrieved for 112 unfavorable neuroblastomas of the Swedish Childhood Cancer Registry, representing a 25-year neuroblastoma cohort of Sweden, here used for validation of the findings. Statistical tests used were: Fisher’s exact test, Bayes moderated t-test, independent samples t-test, and correlation analysis. Results MNA or segmental 11q loss (11q-) was found in 28/34 tumors. With two exceptions, these aberrations were mutually exclusive. Children with MNA tumors were diagnosed at significantly younger ages than those with 11q- tumors (mean: 27.4 vs. 69.5 months; p=0.008; n=14/12), and MNA tumors had significantly fewer segmental chromosomal aberrations (mean: 5.5 vs. 12.0; p<0.001). Furthermore, in the 11q- tumor group a positive correlation was seen between the number of segmental aberrations and the age at diagnosis (Pearson Correlation 0.606; p=0.037). Among nonMNA/non11q- tumors (n=6), one tumor displayed amplicons on 11q and 12q and three others bore evidence of progression from low-risk tumors due to retrospective evidence of disease six years before diagnosis, or due to tumor profiles with high proportions of numerical chromosomal aberrations. An early age at diagnosis of MNA neuroblastomas was verified by registry data, with an average of 29.2 months for 43 cases that were not included in the present study. Conclusion MNA and segmental 11q loss define two major genetic variants of unfavorable neuroblastoma with apparent differences in their pace of tumor evolution and in genomic integrity. Other possible, but less common, routes in the development of aggressive tumors are progression of low-risk infant-type lesions, and gene amplifications other than MYCN. Knowledge on such nosological diversity of aggressive neuroblastoma might influence future strategies for therapy.
    BMC Cancer 05/2013; 13(1):231. DOI:10.1186/1471-2407-13-231 · 3.36 Impact Factor
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    ABSTRACT: Neuroblastoma is a heterogeneous disease; tumors can spontaneously regress or mature, or display an aggressive, therapy-resistant phenotype. Increasing evidence indicates that the biological and molecular features of neuroblastoma significantly influence and are highly predictive of clinical behavior. Because of this, neuroblastoma has served as a paradigm for biological risk assessment and treatment assignment. Most current clinical studies of neuroblastoma base therapy and its intensity on a risk stratification that takes into account both clinical and biological variables predictive of relapse. For example, surgery alone offers definitive therapy with excellent outcome for patients with low-risk disease, whereas patients at high risk for disease relapse are treated with intensive multimodality therapy. In this review recent advances in the understanding of the molecular genetic events involved in neuroblastoma pathogenesis are discussed, and how they are impacting the current risk stratification and providing potential targets for new therapeutic approaches for children with neuroblastoma. In addition, the results of significant recent clinical trials for the treatment of neuroblastoma are reviewed.
    Seminars in Pediatric Surgery 02/2012; 21(1):2-14. DOI:10.1053/j.sempedsurg.2011.10.009 · 2.22 Impact Factor
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    ABSTRACT: Neuroblastoma is a complex disease with many contradictions and challenges. It is, by and large, a cancer of babies and preschool children, but it does occur, albeit increasingly rarely, in older children, adolescents and young adults. The prognosis is very variable, with outcome related to age, stage and molecular pathology. Neuroblastoma may behave in an almost benign way, with spontaneous regression in some infants, but the majority of older patients have high-risk disease, which is usually fatal, despite best current treatments. As a rare disease, international collaboration is essential to run clinical trials of adequate statistical power to answer important questions in a reasonable time frame. High-risk disease requires multimodality therapy including chemotherapy, surgery and radiotherapy as well as biological and immunological treatments for optimal outcomes. Innovative treatment approaches, sometimes associated with appreciable toxicity, offer hope for the future but, despite parental wishes, cannot be generally implemented without adequate assessment in clinical trials.
    Future Oncology 07/2012; 8(7):839-58. DOI:10.2217/fon.12.70 · 2.48 Impact Factor
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