CHICAGO, IL— Tumor biology-based therapy offers excellent outcomes among children with intermediate risk (IR) neuroblastoma (NB), according to results from a prospective phase 3 reduction of therapy study from the Children’s Oncology Group, presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Excellent outcomes were maintained with further reduction of therapy for favorable biology IR NB tumors, using a genomic stratification and response-based treatment algorithm,” reported lead author Clare Twist, MD, of Stanford University in Palo Alto, CA, and coauthors.

“To date, there were no deaths due to disease in patients with localized favorable biology tumors,” she reported. There were a total of 20 deaths from all causes among patients with stage 4 neuroblastoma, but 3-year OS for patients with localized NB remained 100%, Dr. Twist reported. Seven of the 20 deaths were due to complications of hepatomegaly in infants. Eight children died because of relapsed metastatic disease, Dr. Twist reported.

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“Young infants with evolving hepatomegaly are at high risk for morbidity and mortality,” she emphasized. “Preemptive therapy is advised” in such cases.

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“The presence of 1p and/or unbalanced 11qLOH was detected in 18% of IR tumors,” she noted.

The researchers enrolled a total of 400 patients with IR neuroblastoma between 2007 and June 2011.

“Risk stratification and therapy assignment was based on patient age, International Neuroblastoma Staging System stage, International Neuroblastoma Pathology Classification, MYCN and tumor ploidy,” explained Dr. Twist.

Therapy included two to eight courses of chemotherapy with or without surgery, she said. The treatment outcome was partial response for localized favorable-biology tumors.

Eligibility requirements included newly diagnosed single-copy MYCN proto-oncogene neuroblastoma age [younger than] 12 years at diagnosis, with stage 2 A/B [less than] 50% resected, or stage 3 with favorable biology; age [younger than] 1 year with stage 3 or 4; and [younger than] 1 year with stage 4S, “including those too ill to undergo biopsy,” the coauthors reported.

Toddlers up to age 1.5 years with favorable biology stage 4 neuroblastoma, and with stage 3 neuroblastoma but unfavorable histology, were administered chemotherapy plus isotretinoin, the researchers reported.

“Among all (n=124) stage 4 patients age [younger than] 1 year, 3-year EFS/OS was 79% ± 4%/91% ± 2%.  for favorable biology was 90 ± 5%/95 ± 4%; for unfavorable biology (diploid and/or UH [unfavorable histology], irrespective of LOH [loss of heterozygosity], n=44) EFS/OS was 64 ± 8%/84 ± 7%,”Dr. Twist reported.

“Real-time tumor genomic testing for 1p and 11qLOH is feasible for risk and treatment group assignment and may identify a biologically distinct subgroup of patients with stage 4 intermediate risk disease,” Dr. Twist noted.

“Infants with stage 4 unfavorable biology tumors remain a therapeutic challenge and may benefit from intensified therapy or novel regimens,” she noted. “Reduction of therapy for stage 4 toddlers warrants further investigation to confirm that IR chemotherapy is appropriate.”


  1. Twist C, London WB, Naranjo A et al. Abstract 10006. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.