The phenomenon of non-FDG-avid tumor volumes - A prognostic factor in Pediatric Hodgkin Lymphoma?

Objectives In the EuroNet-PHL-C1 trial (EudraCT 2006-000995-33), staging and response assessment PET images of ~ 1600 children and adolescents with HL have been centrally reviewed at the Department of Nuclear Medicine in Leipzig, Germany. Some PHL patients showed demarcated areas of missing tracer uptake within a clearly F-18-FDG-PET positive tumor. Our aim was to further characterize this phenomenon and explore its prognostic relevance.

Methods PET/CT images of 1422 EuroNet-PHL-C1-trial patients were retrospectively reviewed for the occurrence of non-uptake areas (NUA). NUA volumes were measured (a[asterisk]b[asterisk]c/2) on initial staging and following 2 courses of OEPA chemotherapy. Presence of NUA was correlated to patient characteristics, PET response and prognosis.

Results 102 of 1422 PHL patients (7.2%) displayed NUA, mostly within a mediastinal tumor bulk (93%). Patients with NUA had a larger mediastinal tumor volume (467ml vs 122ml in geometric mean), more B-symptoms (59% vs 39%, p<0,001), but were similar in stage distribution. After 2 OEPA a higher PET positivity rate according to International Harmonization Project Criteria (81% vs 53%, p<0,001) was seen. The maximum FDG uptake was frequently (in 66%) located on the edge of the former NUA. 81% of the NUA either disappeared or shrunk markedly. The average NUA volume decreased from 48 ml (range 0.24-525ml) to 19.5ml (range 0-361ml). NUA patients had a higher risk of relapse (36 months PFS, p<0.001) despite more extensive treatment.

Conclusions NUAs in FDG-PET/CT are present in a non-negligible subgroup of PHL patients. Response to chemotherapy appears to be compromised particularly in these volumes and relapse risk is increased. NUAs may point out anaerobic conditions which lead to the formation of hypoxia resistant cells that pose a particular therapeutic challenge.