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•Baseline 18F-FDG–PET radiomics features can select patients at high risk more accurately than the IPI risk score.•The clinical PET model that was developed in the HOVON-84 data set remained predictive of the outcome in 6 independent studies.

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies.

1. Noradrenaline has paradoxical concentration‐dependent effects on the Purkinje fibre action potential. At concentrations greater than 500 nM, it shortens the action potential whereas at lower concentrations it prolongs the action potential. 2. We determined the dose‐‐response relation for Isi to noradrenaline in Purkinje fibres and found that a noradrenaline concentration of 126 nM produces a half maximal effect. 3. A maintained component of Isi was shown to have a similar response to noradrenaline. 4. The dose‐dependence of noradrenaline‐induced changes in Ix was determined. The half maximal noradrenaline concentration for this relationship was shown to be 133 nM. 5. The dose‐‐response relationships for Ix and Isi were not altered by variation in extracellular Ca2+. 6. Ix appears to be approximately twice as responsive as Isi to saturating doses of noradrenaline. 7. These data were incorporated in a computer‐generated reconstruction of the effects of noradrenaline on the action potential and are sufficient to account for the paradoxical effects of noradrenaline.