Screening for neuroblastoma in North America. Preliminary results of a pathology review from the Quebec Project.

BACKGROUND

The Quebec Neuroblastoma Screening Project was initiated to assess clinical and biologic aspects of neuroblastomas detected by screening infants born in the province of Quebec from May 1, 1989, to April 30, 1994.

METHODS

Infants were screened for preclinical detection of neuroblastoma by determination of catecholamine metabolites, vanillylmandelic acid (VMA), and homovanillic acid (HVA). Patients with tumors discovered through this screening as well as patients in the same birth cohort with clinically detected tumors were referred to Quebec Oncology Centers for further investigation, diagnosis, and treatment. Pathology specimens were submitted to Childrens Hospital Los Angeles for central review. Tumors were histopathologically classified according to the Shimada system.

RESULTS

As of August, 1993, 340,000 infants were screened at 3 weeks and 245,000 of them were retested at 6 months of age. Thirty-one tumors were detected through this screening and removed. Histologic material was available for 27 cases: 14 were detected at 3 weeks of age and 13 at 6 months of age. Twenty-six patients had tumors with favorable histology (FH), and one patient had a Stage I tumor with unfavorable histology (UH). At the time of this writing, all mass screening patients are alive, including one child with relapsed disease. During this period, 48 tumors were detected clinically in the same birth cohort, 40 of which were evaluated histologically. Of these 40 cases, 28 of 29 tumors diagnosed in patients up to age 12 months indicated an FH, whereas 9 of 11 tumors diagnosed in patients older than age 12 months indicated a UH. All patients with FH tumors are alive including a child with relapsed disease. The single patient with UH diagnosed before age 12 months died of disease. Of the nine patients with UH diagnosed after age 12 months, four died of disease, one relapsed, and four are alive (including one treated with bone marrow transplantation) after variable follow-up periods.

CONCLUSIONS

The tumors detected by mass screening, similar to those tumors detected through clinical examination before age 12 months, were predominantly FH with good prognosis. However, those tumors that were missed by screening and were detected clinically after the patient was 12 months of age were predominantly UH, with serious clinical problems. This subgroup of patients not detectable by the current screening system presents an immediate and important clinical challenge that should be addressed in future studies.