RESULTS
Patient demographics:
There were 119 children >1 year of age with metastatic neuroblastoma, forming 50.2% of the total non-infant NB patients. Mean age of the patients was 3.5years (range 1-14 years) and male: female ratio was 1.1:1. 89 patients consented for treatment, and are included in the analysis.
Disease characteristics:
The most common site of primary tumour was suprarenal in 66 patients (55.5%), followed by retroperitoneal (n=25,21%), thoracic/mediastinal (n=7, 5.9%), cervical (n=8, 6.7%) and multifocal (n=3, 2.5%). Primary tumour was undetected in 6 patients (5%). Commonest site of metastasis was bone marrow (76.3%patients), followed by bone (15.9%), lymph nodes (6.2%) and liver (1%). 36 patients (40.4%) had multiple metastatic sites. Baseline LDH values were available for 79 patients, with mean value of 3724 U/L (range 303 -16609 U/L). 58 patients (65%) had LDH>750U/L and 21 patients (23.5%) had LDH<750U/L.
Treatment and response:
Thirty-eight patients (42.6%) received Chemo A, out of which 30 patients (78.9%) had good response to chemotherapy and 6 patients (15.7%) had poor response.  51 patients (57.3%) received Chemo B, out of which 23 patients (45.09%) had good response and 24 patients (47.05%) had poor response.  In 6 patients, response assessment could not be done because of early clinical progression or death. Surgery could be attempted in 26 patients (29.2%), with excision in 16 patients, debulking in 6 patients and biopsy alone in 4 patients. Only 3 patients in this cohort received radiotherapy.12 patients received metronomic maintenance chemotherapy after treatment completion (9 patients after Chemo A and 3 patients after Chemo B).
Table 1 shows the Chemotherapy regimen-based response and outcome
Relapse and death:
Overall 74 patients (86%) developed recurrence/progression of disease. Out of the 53 patients who had good initial response to chemotherapy, 43 patients (81%) relapsed. The median time to recurrence/progression was 9 months (range 1-120months). 73 patients (85.9%) died, the median time to death being 10 months (range1-123months). Cause of death was disease progression in 71patients and toxicity-related deaths in 2 patients. 3 relapsed patients are lost for follow-up.
Survival:
At a median follow-up of 72 months (range 15-135months), there were 16 survivors. 5-year disease-free survival (DFS) was 17.6% and overall survival (OS) was 18.4%.
Mean age of survivors was 2.3 years (range 1-9 years) and their mean LDH at presentation was 728 U/L (range 303-1747 U/L). 11 patients out of 38 (28.9%) who received Chemo A and 5 patients out of 51(9.8%) who received Chemo B survived. Out of the 12 patients who received metronomic chemotherapy, 5 patients survived (41.6%). (Table 2)
Prognostic factors:
In univariate analysis, LDH >750 U/L, type of chemotherapy regimen, response to initial chemotherapy, number of chemotherapy cycles received and surgery were found to be statistically significant factors for DFS and OS. Age, primary site and number of metastatic sites were not statistically significant. On multivariate analysis, LDH>750U/L, Chemo B regimen and poor response to chemotherapy were statistically significant poor prognostic factors. (figure 1.)
Details of prognostic factors are given in Table 3.