Myocardial Metabolic Response Predicts Chemotherapy Curative Potential on Hodgkin Lymphoma: A Proof-of-Concept Study

Abstract

Genome sharing between cancer and normal tissues might imply a similar susceptibility to chemotherapy toxicity. The present study aimed to investigate whether curative potential of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is predicted by the metabolic response of normal tissues in patients with Hodgkin lymphoma (HL). METHODS: According to current guidelines, 86 patients with advanced-stage (IIB-IVB) HL, prospectively enrolled in the HD0607 trial (NCT00795613), underwent 18 F-fluorodeoyglucose PET/CT imaging at diagnosis and, at interim, after two ABVD courses, to decide regimen maintenance or its escalation. In both scans, myocardial FDG uptake was binarized according to its median value. Death and disease relapse were recorded to estimate progression-free survival (PFS) during a follow-up with median duration of 43.8 months (range 6.97–60). RESULTS: Four patients (4.6%) died, while six experienced disease relapse (7%). Complete switch-off of cancer lesions and cardiac lighting predicted a favorable outcome at Kaplan–Mayer analyses. The independent nature and additive predictive value of their risk prediction were confirmed by the multivariate Cox regression analysis. CONCLUSION: Susceptibility of HL lesions to chemotherapy is at least partially determined by factors featuring the host who developed it.

Divergent Oxidative Stress in Normal Tissues and Inflammatory Cells in Hodgkin and Non-Hodgkin Lymphoma

“…This finding can hardly be attributed to the presence of a high number of circulating neoplastic cells and, thus, indicates that the oxidative damage extends to tissues and cells not affected by the disease even before the occurrence of treatment-related toxicity. This observation might possibly predict the risk for the oxidative damage induced in HL patients by several chemotherapeutic drugs, particularly to the myocardium, in agreement with the previous evidence about a significant predictive power of increased myocardial uptake of FDG after the first two cycles of doxorubicin therapy [25].…”

“…The extension of this response to the myocardium implies the presence of signals released either by HL itself or by the inflammatory reaction it activated. This generalized shift in systemic metabolic pattern has been already found to retain a potential role in predicting anthracycline effectiveness [ 25 ]. Understanding the underlying mechanisms might open new windows to monitor cancer response to chemotherapy.…”