Objective
To study the impact of presentation features and treatment modalities on the outcome in a large cohort of patients
Methods
Patients were included in this retrospective analysis with (i) stage 4 neuroblastoma at initial diagnosis ≥18 months and <21years, (ii) enrolment in first line trials between 01.01.1990 and 31.12.2010, and (iii) first recurrence or progression. Excluded were patients with continuous progression from initial diagnosis, with refusal of curative front-line therapy, with second malignancy, or insufficient medical information.
Results
517 patients met the inclusion and exclusion criteria. 15% had recurrence at primary only, 57% at metastatic sites only and 28% at primary and metastatic sites. Involved sites were osteomedullary (66%), primary site (43%), CNS (14%), lymph nodes (9%), and liver (9%). 36% of patients received palliative or no treatment for recurrence, 46% chemotherapy (± other modalities except myeloablative therapy), and 18% chemo- and myeloablative therapy. The median time from 1st to 2nd recurrence was 3.8 months (secEFS) and from 1st recurrence to death 7.0 months (secOS). Children under palliative care had a median secEFS time of 1.9 months, under chemotherapy (± others) of 5.4 months and under chemo- and myeloablative therapy of 15.0 months (p<0.001). The 5 year secEFS for all patients including the palliative care group was 6.1±1.1%, the 5 year secOS 9.8±1.4%. By multivariate analysis most significant diagnostic factors for secEFS were time to 1st recurrence <18 months (HR 2.204), MYCN amplification (HR 1.424), liver metastases at inital diagnosis (HR 1.830), lung/pleural metastasis at recurrence (HR 1.830) and >1 recurrent site (HR 1.435). In non-palliatively treated patients, the most significant therapeutic impact had myeloablative therapy (HR 0.544) and radiotherapy (HR 0.611).
Conclusion
This study describes risk factors which may help to tailor recurrence treatment in high risk neuroblastoma patient groups.