2099 - First Clinical Experience of Adaptive MRI-Guided Radiotherapy for Midline Glioma: CTV Dynamics in H3K27M-Altered Tumors

Purpose/Objective(s): Midline gliomas, particularly those harboring H3K27M alterations, are aggressive tumors arising in eloquent central nervous system structures such as the brainstem and thalamus. Radiotherapy remains the standard treatment; however, these tumors often exhibit infiltrative growth and dynamic changes during treatment, which may compromise target coverage and increase the risk to adjacent critical organs. MRI-guided radiotherapy (MRgRT) provides excellent soft tissue visualization and enables online adaptive radiotherapy (ART), allowing response to inter-fractional anatomical changes. This study evaluates the feasibility of MR-guided ART (MRgART) for midline gliomas and characterizes clinical target volume (CTV) dynamics, focusing on differences between H3K27M-altered and wild-type tumors.

Materials/Methods: Seven patients with midline glioma were treated using a 1.5T MR-Linac. Four patients had H3K27M-altered tumors and three had wild-type tumors. All patients received 54 Gy in 27 fractions. The CTV was defined as the FLAIR hyperintense region with a 10–15 mm margin. Daily MRI was utilized for image guidance and online adaptation. Changes in FLAIR hyperintense volume were evaluated daily, with inter-fractional variability assessed via standard deviation (SD). The frequency of adaptive strategies—specifically adapt-to-shape (ATS) versus adapt-to-position (ATP)—was compared between molecular subgroups using a Fisher's exact test.

Results: All patients successfully completed MRgART. Inter-fractional variability in FLAIR hyperintense volume was markedly greater in H3K27M-altered tumors (SD range: 0.68–2.91), whereas wild-type tumors demonstrated relatively stable changes (SD range: 0.23–0.48). In certain H3K27M-altered cases, FLAIR hyperintensity volumes increased by over 200% during treatment, compared to minimal variation in wild-type tumors. Consequently, ATS was required significantly more frequently in the H3K27M-altered group (45 of 108 fractions, 41.6%) than in the wild-type group (15 of 81 fractions, 18.5%) (p < 0.01). Adaptive replanning was primarily driven by anatomical shifts in the FLAIR-defined CTV along midline structures. MRgART successfully maintained target coverage and respected critical organ dose constraints across all fractions. No grade =3 acute toxicities occurred.

Conclusion: MRgART for midline glioma is clinically feasible and highlights significant CTV dynamics during a standard treatment course. H3K27M-altered tumors show significantly greater volumetric variability and require more frequent ATS replanning than wild-type tumors. These findings indicate that daily adaptive strategies are essential to account for the rapid biological and anatomical changes in H3K27M-altered tumors, warranting further investigation in larger prospective cohorts.