Precis. Oncol., Volume 1, Issue 1 (December 2025) – 2 articles

Background/Objectives: Radioactive iodine (RAI) therapy is widely used to treat metastatic differentiated thyroid cancer. To investigate physiological determinants of treatment response, a mechanistic model was developed, formulated as a system of coupled ordinary differential equations. Methods: The model captures the interactions between tumor burden, thyroglobulin (T_g) production and clearance, and radioactive iodine activity within a pharmacokinetic–pharmacodynamic framework. Model parameters were estimated using the Monte Carlo Stochastic Approximation Expectation–Maximization (MCMCSAEM) algorithm, based on clinical data from a cohort of 50 patients. Results: Tumor radiosensitivity (ρ) and initial tumor burden (N₀) consistently emerged as the most influential factors in both responder and non-responder groups classified by disease doubling time under RAI (T_d). A reduced model using only these two parameters preserved the principal response patterns of the full model. Other parameters influenced transient dynamics but had limited effect on overall T_g variance. Conclusions: These results support the use of a reduced calibration approach focused on ρ, N₀, and the effective doubling time T_d. The findings establish a theoretical foundation for developing tractable dynamic surrogates that reproduce the main treatment kinetics and support model-based clinical decision-making in RAI therapy. Full article

Background and Clinical Significance: Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms with low metastatic potential but a high recurrence rate. Approximately 60–80% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors (ALKis) a key therapeutic option. However, resistance to ALKis remains a significant clinical challenge, necessitating alternative treatment strategies. Case Presentation: We report the case of a 23-year-old woman diagnosed with a metastatic TPM3::ALK fusion-positive IMT, initially managed with crizotinib and ceritinib. Disease progression prompted a switch to alectinib, followed by lorlatinib in combination with immune checkpoint inhibitors (nivolumab + ipilimumab). The patient tolerated this regimen well, with manageable side effects, and has remained progression-free for over three years, demonstrating the potential efficacy of ALK-ICI combination therapy. Conclusions: This case highlights the rapid development of resistance to first- and second-generation ALKis and the emerging role of immune checkpoint inhibitors (ICIs) in IMT treatment. PD-L1 expression in ALK-positive IMTs suggests an immune escape mechanism, supporting combination ALK-ICI therapy as a viable approach. The successful long-term disease control achieved in this case underscores the importance of molecular profiling in guiding personalized treatment strategies for IMT. This report contributes to the growing body of evidence supporting precision medicine and immunotherapy in rare sarcomas. Full article