2052 - Dosimetric Tolerances of the Brainstem and Anterior Optic Pathway to Re-Irradiation In Recurrent Gliomas

Purpose/Objective(s): The retreatment of recurrent gliomas is limited by the radiation tolerance of the brainstem and anterior optic pathway (AOP). We hypothesize that, in context of Bevacizumab (BEV), a hypofractionated re-irradiation regimen of 35 Gy in 10 fractions is safe, and that cumulative Equivalent Dose in 2 Gy fractions (EQD2) can exceed historical constraints without inducing severe toxicity.

Materials/Methods: We conducted a single-institution, retrospective review of patients with recurrent gliomas treated with at least one course of hypofractionated re-irradiation (35 Gy in 10 fractions) between 2013 and 2025. Maximum dose (D0.03cc) values received by the brainstem, optic chiasm, and optic nerves were obtained for individual radiation courses, EQD2s (using an alpha/beta ratio of 2 Gy) were calculated for each course and cumulatively for all courses. The primary endpoint was freedom from Grade 3 or more toxicity based on CTCAE v6 criteria. Median cumulative doses, treatment and follow up intervals, and toxicity event rates were analyzed to assess clinical safety thresholds.

Results: Sixty-eight patients were analyzed. Fifty-five were treated with a single course of reirradiation, 12 with a second, and 2 patients with a third. The median interval between the initial radiotherapy and first reirradiation was 16.5 months. For patients who received additional courses of reirradiation, the median interval between the first and second reirradiations was 9 months. Median EQD2 for each structure, calculated after the first reirradiation and (cumulatively after all courses), were - brainstem: 80.6 Gy (cumulative 87.1 Gy), chiasm: 54.8 Gy (cumulative 57.5 Gy), left optic nerve: 34.4 Gy (cumulative 35.0 Gy), and right optic nerve: 24.4 Gy (cumulative 25.1 Gy). The percentages of patients who exceeded the accepted EQD2 values for brainstem (98 Gy) and AOP (55 Gy) after first re-irradiation and (cumulatively after all courses) were - brainstem: 33.8% (cumulative 42.7%), chiasm: 45.6% (cumulative 52.9%), left optic nerve: 29.4% (cumulative 32.4%), and right optic nerve: 17.7% (cumulative 22.1%). Median follow up after the first re-irradiation course was 5.2 months. A single potential event of Grade 3+ visual toxicity was noted in a patient who received a cumulative EQD2 of 76 Gy to the chiasm after a single course of reirradiation; however, no imaging correlate was identified to definitively attribute this event to radiation induced optic neuropathy (RION).

Conclusion: Hypofractionated re-irradiation of 35 Gy in 10 fractions for recurrent gliomas appears safe, even when cumulative EQD2 to the brainstem and AOP routinely exceeds historically suggested constraints. The near absence of severe toxicity in context of BEV suggests that established limits may be overly conservative in the retreatment setting. Characterizing these tolerances has crucial implications by safely expanding eligibility for re-irradiation and guiding future normal tissue complication probability models.