Background: Patients with high-risk neuroblastoma (HRNB) treated on the HR-NBL-1/SIOPEN trial typically undergo surgical resection of the primary tumour after induction chemotherapy and before high-dose chemotherapy (HDC) with busulfan/melphalan (BuMel). Occasionally surgery may be delayed until after HDC because the tumour is unresectable or has unacceptable surgical risk. Whether treatment with BuMel can lead to further shrinkage of the primary tumour and improvement of surgical risk following induction chemotherapy is currently unknown.
Methods: This was a retrospective review of all patients treated at Great Ormond Street Hospital and enrolled on HR-NBL-1/SIOPEN trial between 2002-2015. In patients in whom primary tumour (whole or part) was in situ during HDC response by International Neuroblastoma Response Criteria (INRC) and Response Evaluation Criteria in Solid Tumour (RECIST), and surgical risk and resectability, was assessed by comparison of pre- and post-HDC CT/MR imaging. Tumour volume was calculated as the product of three dimensions x0.52.
Results: Of 84 patients enrolled on HR-NBL-1/SIOPEN, 16 (19%) had primary tumour in situ during HDC. Surgery had been attempted but abandoned in 5 cases; 3 had bilateral or two-compartment disease with partial resection only; the remaining 8 had surgery deferred until post-HDC. BuMel was given in all but one case, who received treosulfan/melphalan due to an underlying cardiomyopathy. Tumour measurements could be made in 13 of 16 cases (no imaging was available in one case and 2 had ultrasounds only): 8 had stable disease; 4 (31%) had partial responses (by INRC and RECIST criteria) and 1 was stable by RECIST, but progressed by INRC criteria. Mean tumour volume before HDC was 61.4cm3 versus 43.1cm3 after (p=0.0044, paired t-test), with a median overall volume reduction of 37%. 9 of 16 (56%) patients ultimately underwent complete/partial resection.
Conclusion: These preliminary data suggest that HDC can lead to useful further shrinkage of primary tumours in patients with HRNB and that delaying surgery until after HDC may make complete surgical resection easier to achieve.