Neuroblastoma detected by mass screening: the Tumor Board?s role in its treatment

Abstract

Japan has a nationwide mass-screening program for neuroblastoma in 6-month-old infants. Neuroblastoma can regress spontaneously, and some institutions observe selected cases. We evaluated the management of screened neuroblastoma at our hospital since 1997 when an observation program was introduced. Criteria for the observation program were stage-I, stage-II, or stage-IVs tumors, urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels <40 microg/mg creatinine, tumor <5 cm in diameter, no invasion to the intraspinal canal or great vessels, and parental consent to participate. Patients who did not meet observation criteria underwent surgery or mild chemotherapy according to the location of the tumor. If patients met observation criteria after chemotherapy, surgical intervention was no longer performed. Thirty-six patients attended our hospital for screened neuroblastoma from 1997 to 2002. Thirty-three patients who were managed at our hospital participated in this study. Ten subjects met observation criteria. Tumors regressed in 7 patients (mean follow-up period 36.3 months) with corresponding decreases in VMA and HVA levels (group A). Three underwent surgery (group B) because of increasing VMA and HVA levels, increase in tumor size, or guardian's request. Twenty-three subjects did not meet observation criteria. Four patients underwent primary surgery (group C), and 19 patients had chemotherapy initially. Fourteen patients met observation criteria after chemotherapy and two are still having chemotherapy (group D). Three patients required surgery due to insufficient regression of their tumors (group E). Fourteen subjects in group D had marked decreases in VMA and HVA levels and tumor size (mean follow-up period 29.1 months), and tumors were not detected using imaging techniques in 8 patients. Histological examination of all resected specimens during the study period showed favorable histology and no N-myc amplification. There was no evidence of unfavorable prognosis in any of the 33 subjects, although 1 patient who underwent primary surgery had a vanishing kidney 1 year later and 1 patient had multiple bony metastases after complete resection of tumor, which was treated by chemotherapy. Until the real significance of mass screening for neuroblastoma as a public health measure is confirmed, observation with careful follow-up should be adopted more extensively because it has a favorable outcome in many cases, and is associated with minimal therapeutic complications.

Neuroblastoma

“…Multiple prospective studies have shown that tumours <5 cm in diameter are likely to regress spontaneously. [35][36][37][38] Surgery is the initial treatment of choice for patients with localised disease who are able to have more than 50% of their tumour safely removed as determined by image-defined risk • Stage 3: Unresectable unilateral tumour infiltrating across the midline (beyond the opposite side of the vertebral column) with or without regional lymph node involvement, or localised unilateral tumour with contralateral regional lymph node involvement, or midline tumour with bilateral extension via infiltration (unresectable) or lymph node involvement • Stage 4: Any primary tumour with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs (except as defined for stage 4S disease)…”

“…Although a portion of these patients will have disease progression after surgery, they can be salvaged with surgery or chemotherapy, or both, and achieve overall survival rates comparable to those of similar patients whose disease did not progress. [30][31][32][33][34][35][36][37][38][39][40] Observation, with serial ultrasound scans every three to six weeks, is a reasonable alternative in the following patient groups:…”

“…The timing of surgery varies, but usually follows a few cycles of chemotherapy. [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] If chemotherapy and surgery are not effective, radiotherapy may be used.…”

Neuroblastoma in childhood: review and radiological findings

“…antenatal ultrasound, chest radiograph for pneumonia or screening protocols [4]. Screening with measurements of urine VMA and HVA levels in 6-month-old infants began in Japan in 1973 [10]. Unfortunately, epidemiologic analyses showed that this did not alter the incidence of tumours in older children nor did it improve cure rates; the incidence of stage 1 disease dramatically increased, and the tumours discovered at screening were of low stage and favourable histological characteristics.…”

A Prospective Study of Expectant Observation as Primary Therapy for Neuroblastoma in Young Infants

“…Previous observation trials suggest that tumor size and characteristics, as well as certain patterns of urine catecholamine metabolite (vanillylmandelic acid (VMA) and homovanillic acid (HVA)) secretion, are associated with a benign pattern of behavior and increased probability of spontaneous regression 13,15,16,24–26 . We conducted a prospective trial of expectant observation of infants with small adrenal tumors identified either prenatally or within the first six months of life.…”