The recurrence patterns of stages I, II and III neuroblastoma: experience with 77 relapsing patients.
BACKGROUND
Recurrences of neuroblastoma Evans' stage I-III are infrequent events and the types of its progression have rarely been reported. Therefore, we investigated the patterns of progression in a large series of patients with long follow-up.


METHODS
The sites of relapse and time to progression and death of 381 consecutive patients in three cooperative trials (NB 79, 82, 85) with follow-up of 5-16 years were analysed. The Southern blot technique was used for N-myc investigation of tumor tissue.


RESULTS
Of the 77 relapsing patients, 41 (53%) had local and 36 (47%) systemic recurrences. The relapses occurred in 9 of 76 stage I patients (6 local/3 systemic), in 4 of 82 stage II (1 local/3 systemic) and 64 of 223 stage III neuroblastoma (34 local/30 systemic) patients. The main sites of distant metastasis were bone marrow (41%), lymph nodes (39%) and bone (37%). The median transition time from localised to metastatic neuroblastoma was 13 months and the outcome as poor (overall survival 9 +/- 5%) as that of the primary metastatic disease (14 +/- 3%). Fifty-three children died of tumor progression and 15 patients of treatment-related complications or other non-tumor conditions. The median age at diagnosis was 43 months for the group with systemic relapse compared to 19 months with only local and 10 months without recurrences (p < 0.001). Elevated serum LDH levels at first diagnosis were seen in 81% with metastatic, in 55% with local and in 33% with no tumor progression (p < 0.001). N-myc amplification was found in 4/14 with local and in 6/12 with metastatic recurrences.


CONCLUSIONS
The high incidence of systemic relapse and the long transition time suggest that transition from localised to metastatic neuroblastoma is not an uncommon pathway.
Berthold
F
F
Children's Hospital of Köln University, Germany.
Hero
B
B
Breu
H
H
Christiansen
H
H
Erttmann
R
R
Gnekow
A
A
Herrmann
F
F
Klingebiel
T
T
Lampert
F
F
Müller-Weihrich
S
S
Weinel
P
P
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis