Hepatopathy in patients with stage 4S neuroblastoma

Abstract

The survival probability is 79% for patients with neuroblastoma stage 4S treated according to the German Society for Pediatric Oncology and Hematology (GPOH) treatment studies. Most of these patients (80%) have liver metastases. Patients are grouped according to their condition at diagnosis and tumour resectability to different risk groups (A, B, C). Chemotherapy is provided for patients who are initially diagnosed as critically ill, caused for example by excessive hepatomegaly due to liver metastases. The aim of this study is to clarify whether liver infiltration is associated with liver dysfunction and whether chemotherapy plays a role in this process. Hepatopathy was diagnosed when clinical signs were present and/or liver function tests revealed pathologic results. The charts of 48 patients (22 boys, 26 girls) diagnosed between 1990 and 1994 from the ongoing NB-90 treatment study were evaluated retrospectively. Median age at diagnosis was 52 days (range: 1-328). 41 patients (85%) had liver infiltration, 26 patients (54%) had bone marrow involvement and in nine patients (19%) skin metastases were found. 12 patients were in poor general condition at diagnosis (risk group C). 36 of 48 patients (75%) received chemotherapy, three children were treated with radiotherapy additionally, due to massive liver enlargement. 15 patients (31%) had signs of hepatic dysfunction at diagnosis or during their illness, 14 of these had liver metastases. All these 15 patients were treated with chemotherapy. 12 of 15 patients with hepatopathy were younger than two months at diagnosis. Five patients with liver dysfunction were not critically ill at diagnosis. Hepatomegaly > or = 6 cm was present in 10 of 15 patients with liver dysfunction. Hepatopathy was transient in eight patients, four patients died soon of multiorgan failure during progression of disease. Three children developed liver fibrosis with conversion to cirrhosis. Hepatopathy was correlated with distribution to risk groups (A and B (5/36) vs. C (10/12), p < 0.001). The appearance of hepatic dysfunction in patients with neuroblastoma stage 4S remains a serious problem especially for young children with excessive hepatic infiltration. Liver dysfunction was of short duration and reversible in most patients, however, even with age-adapted dosages of chemotherapy long-standing cases of hepatopathy were observed. A general recommendation for treatment strategy in this heterogeneous patient group is difficult. Attention should be given to for this complication.