DISCUSSION
Spontaneous tumour regression is well recognised in Infants with
low-risk neuroblastoma and favourable biology (i.e. no SCAs and
hyperdiploidy).2 The concept of a ‘wait-and-see’
approach has been described previously and avoids the morbidity and
mortality associated with chemotherapy and potentially extensive
surgery.3,5–11,16 However, there is currently no
international consensus about which cases this observational approach is
appropriate for, and what criteria should be used to define progression
requiring active intervention.
Yamamoto et al. defined criteria for using an observation-only
approach for small lesions detected in a Japanese population screening
programme in 1998.12 Subsequent publications have
cited these same criteria or adapted versions which have generally only
included tumours < 5 cm in diameter at diagnosis.
In 2007, the German Society of Paediatric Oncology and Haematology
published data showing that spontaneous regression in non-MYCNamplified, localised neuroblastoma may start after 1 year of age, and
occur in patients with larger tumours, suggesting that a ‘wait-and-see’
strategy may be more widely appropriate.3
A 2012 Children’s Oncology Group (COG) study demonstrated the safe and
effective use of ‘expectant-observation’ in Stage 1 and 2 adrenal
tumours in patients less than 6 months old.7 However,
this study used conservative tumour diameter cut offs of 3.1 cm or 5 cm
for solid and cystic tumours respectively. Additionally,
‘expectant-observation’ was terminated if tumour volume increased by
50% or if catecholamine levels increased above 50% and did not return
to baseline within 12 weeks. A phase III COG trial is currently
investigating an observational approach using response and biology-based
risk factor-guided therapy in infants < 18 months with L2
tumours and favourable biology. In this trial, a 25% increase in tumour
volume prompts use of adjuvant therapy.17
In the current case, the initial tumour size and the observed growth
(100% increase in anteroposterior diameter, 57% in transverse diameter
and 67% in craniocaudal diameter), resulting in a > 3 fold
increase in tumour volume, along with 9-10 fold increase in HMMA and
HVA, would have precluded a ‘wait-and-see’ strategy based on previous
study criteria.6,7,12 Persevering with an
observational approach, with parental agreement, in the absence of life-
or organ-threatening features, avoided the risks of active treatment
while still achieving a positive clinical outcome. However, it is
critical to consider patient tumour biology and clinical features before
embarking on an observation-only strategy. Utilising pan-genomic
techniques such as SNP (single nucleotide polymorphism) arrays and more
recently whole genome sequencing (WGS) allows SCAs conferring a higher
risk of progression and relapse to be excluded.18 Age
at diagnosis is also important as some groups e.g. infants < 2
months of age with MS disease, have the potential for rapid
deterioration and may benefit from early treatment regardless of
biology.19
This case demonstrates that a ‘wait-and-see’ approach may be more widely
applicable than previously used, including tumours > 5 cm
in diameter at diagnosis. This case also illustrates that in patients
with favourable biology without life- or organ-threatening features,
tumour growth and rising catecholamines, do not by themselves preclude
safe continuation of an observation-only approach.3
Further work is required to establish international evidence-based
criteria to identify subgroups of patients where embarking on an
observational approach is appropriate and to review criteria for active
treatment when using this initial management strategy.