ABSTRACT
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.
Method - Retrospective study of children 1-14years of age treated for metastatic neuroblastoma in our center from January 2008 to December 2017
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>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.
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.
INTRODUCTION
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.
MATERIALS AND METHOD S
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.
Chemotherapy:
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.
Response to chemotherapy:
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.
Surgery and radiotherapy:
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.
Maintenance Chemotherapy:
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.