<div>ABSTRACT</div><div>Background: Children with metastatic neuroblastoma have inferior
survival despite therapeutic advances. Myeloablative chemotherapy
followed by stem cell transplantation, accepted as the current standard
of care, is not accessible to patients in many developing countries due
to resource constraints. We share our experience of treating metastatic
neuroblastoma in a non-transplant facility with conventional
chemotherapy, surgery, and radiotherapy.</div><div>Method - Retrospective study of children 1-14years of age treated for
metastatic neuroblastoma in our center from January 2008 to December
2017</div><div>Results – Eighty-nine patients with metastatic neuroblastoma received
treatment. Mean age was 3.5years and male:female ratio was 1.1:1. The
commonest primary site was suprarenal(55%) and commonest site of
metastasis was bone marrow(76%). 40% patients had multiple metastatic
sites. Mean baseline LDH was 3724 U/L(range303-16609 U/L) and most(65%)
patients had LDH&gt;750U/L.53 patients(59.6%)had good
response to chemotherapy as evidenced by clearance of metastatic
disease, but out of them, 43 patients (81%) progressed subsequently. 26
patients underwent surgery and 12 patients received maintenance therapy.
74 patients(86%) developed recurrence and all but one died. Median time
to recurrence and death were 9months(range 0-120months) and
10months(range 1-123months) respectively. At a median follow-up of
72months(range15-135months), 16 patients are alive, with 5-year
disease-free survival and overall survival of 17.6% and 18.4%
respectively. Age, baseline LDH, chemotherapy regimen and response to
treatment affected survival.</div><div>Conclusion: Outcome of non-infant metastatic neuroblastoma remains
dismal in a non-transplant setting. Younger age, lower baseline LDH and
good response to chemotherapy appear to confer survival advantage, and
may be used for risk-stratification in developing
countries<i>.</i></div><div><b>INTRODUCTION</b> –</div><div>Neuroblastoma (NB), the most common pediatric extracranial solid tumour,
is one of the most challenging childhood cancers to treat. Children with
metastatic NB have inferior survival despite therapeutic advances like
myeloablative chemotherapy and autologous stem cell transplantation
(ASCT). These modern facilities are cost-prohibitive, and are not
available in most of the public healthcare institutions in developing
countries. In the non-transplant setting, metastatic NB is treated with
conventional chemotherapy combined with local control modalities like
surgery and/or radiotherapy. We determined treatment outcome and factors
affecting survival of children over one year of age with metastatic NB
treated at our centre with chemotherapy, surgery and radiotherapy.</div><div><b>MATERIALS AND METHOD</b> S</div><div>Children 1-14years of age with Stage 4 NB treated at our centre over a
10-year period (1st January 2008 to 31st December 2017) were studied.
Approval from Institutional review Board was obtained for the study.
Clinical assessment for palpable disease, blood investigations including
lactate dehydrogenase (LDH) and imaging of the primary site with
ultrasound or computed tomography (CT) scan were done for disease
evaluation. Metastatic workup included skeletal X-rays and bone marrow
biopsy.  The diagnosis of NB was established by histopathology and
immunohistochemistry of bone marrow or primary tumour tissue.</div><div>Chemotherapy:</div><div>Based on the general condition, number of metastases, logistic and
social factors and parental decision, patients received either of the
two chemotherapy schemes derived from the St.Jude Neuroblastoma
protocols. Chemo A was a moderately aggressive regimen consisting of
vincristine 1.5mg/m2, adriamycin 40mg/m2 and cyclophosphamide 1500mg/m2
alternating with cisplatin 100mg/m2 and etoposide 450mg/m2 every 3weekly
for one year (maximum cumulative dose of adriamycin 360mg/m2). Chemo B
was the less intensive regimen consisting of six 3-weekly cycles of
vincristine 1.5mg/m2, adriamycin 30mg/m2 and cyclophosphamide 750mg/m2.</div><div>Response to chemotherapy:</div><div>Response assessment was done after 4 cycles of chemotherapy with bone
marrow examination, skeletal x-rays and imaging of the primary site.
Disappearance of disease from metastatic sites was considered as good
response.</div><div>Surgery and radiotherapy:</div><div>For patients who cleared the disease from metastatic sites, surgery was
done if feasible, followed by further chemotherapy according to the
assigned regimen. Radiotherapy was given for unresectable/residual
disease after completion of intravenous chemotherapy regimen.</div><div>Maintenance Chemotherapy:</div><div>In patients with stable disease after completion of chemotherapy, 6-8
months of oral metronomic chemotherapy was given with  cyclophosphamide
50mg/m2 and etoposide 50mg/m2 daily for 20 days per month.</div>