Purpose <p>Evaluation of interim-[¹⁸F]FDG-PET/CT as a prognostic tool in limited disease small cell lung cancer (SCLC).</p> Methods <p>We included 35 patients with limited disease SCLC from a prospective institutional registry in this retrospective study. Patients received induction chemotherapy (3–4 cycles) followed by concurrent radiochemotherapy. Baseline [¹⁸F]FDG-PET/CT was performed before or shortly after start of induction chemotherapy, interim PET/CT was acquired during late induction or concurrent chemoradiotherapy. Maximum standardized uptake value (SUV_max), metabolic target volume (MTV), and total lesion glycolysis values (TLG) were determined. An exponential decay model with an asymptotic offset was used to describe treatment response over time. Deviations &gt; 2 standard deviations (SD) above model-predicted means after day 30 were considered poor response. Progression-free survival (PFS) was analyzed.</p> Results <p>All patients underwent twice-daily radiotherapy to a base dose of 45&#xa0;Gy. SUV_max showed greater inter-patient variability than MTV. Poor treatment response was observed in 17%, 31%, or 14% at the SUV_max, MTV and TLG endpoints. Deviations &gt; 2 SD from the model in SUV_max and TLG were significantly associated with shorter PFS (<i>p</i> = 0.0003, <i>p</i> = 0.0014); MTV was not prognostic (<i>p</i> = 0.2630). Leave-one-out cross-validation (LOOCV) could confirm the prognostic value of the standardized residual SUV_max larger than 2 standard deviations above model estimate as negative PFS predictor (<i>p =</i> 0.0152, Fishers exact test).</p> Conclusion <p>Our decay model enables the characterization of [¹⁸F]FDG-PET/CT response parameters from scans acquired at variable time points during induction chemotherapy and at start of concurrent radiochemotherapy. Poor SUV_max or TLG response was predictive of PFS. Interim-[¹⁸F]FDG-PET/CT response may guide individualized treatment adaptation.</p>