Neuroblastoma 4S: a heterogeneous disease with variable risk factors and treatment strategies

BACKGROUND: Despite the excellent prognosis for neuroblastoma 4S (NBL 4S; with S indicating "special"), 10-25% of these patients nevertheless do not survive. Since the first description of this subgroup of disseminated neuroblastoma with a favorable natural outcome, treatment modalities have become milder. Current treatment strategies range from observation with supportive care to full cycles of chemotherapy, radiation therapy, and/or surgical removal of the primary tumor.

METHODS: A recent case of NBL 4S seen at the Sophia Children's Hospital led the authors to review their patient charts from 1971 onward, as well as the literature, for the treatment modalities used and the outcome in treated versus nontreated patients.

RESULTS: In addition to the presented case and five additional cases from the authors' patient files, the literature contained 113 reported cases. Of a total of 119 cases, 33 patients died, 12 as a result of hepatomegaly with renal impairment and/or respiratory failure. All but 1 of these patients were diagnosed in the first 4 weeks of life. Of the 33 patients who died, 45% progressed to Stage 4 metastatic disease (15 of 33), a finding that appeared to be unrelated to age. N-myc amplification data were available in 30 cases. Seventeen patients had < or = 3 gene copies; 12% of these patients (2 of 17) died. In the N-myc-amplified group of patients with > 3 gene copies, 69% (9 of 13) died and another patient progressed to Stage 4 with short follow-up.

CONCLUSIONS: The data presented here suggest an important role for age as a prognostic factor. The very young NBL 4S patient (age < 4 weeks at diagnosis) was at high risk of dying of (respiratory) complications as a result of massive hepatomegaly. In contrast, disease progression to Stage 4 appears to be unrelated to age, but is strongly related to the presence of biologic markers in the tumor. The authors propose a therapeutic approach for very young patients and for those with unfavorable biology.