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. 2024 Nov 4;14(1):26685.
doi: 10.1038/s41598-024-78370-x.

Initial feasibility cohort of temporally modulated pulsed proton re-irradiation (TMPPR) for recurrent high-grade intracranial malignancies

Alonso La Rosa  1 , Zachary Fellows  1 , Andrew J Wroe  1   2 , Len Coutinho  1 , Eduardo Pons  1 , Nicole C McAllister  1 , Ranjini Tolakanahalli  1   2 , Tugce Kutuk  1 , Matthew D Hall  1   2 , Robert H Press  1   2 , Michael W McDermott  2   3 , Yazmin Odia  2   4 , Manmeet S Ahluwalia  2   5 , Minesh P Mehta  1   2 , Alonso N Gutierrez  1   2 , Rupesh Kotecha  6   7
Affiliations

Initial feasibility cohort of temporally modulated pulsed proton re-irradiation (TMPPR) for recurrent high-grade intracranial malignancies

Alonso La Rosa et al. Sci Rep. .

Abstract

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32-72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14-40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting.

Keywords: CNS malignancies; Pulsed-reduced dose rate; Recurrence/progression; Temporally modulated proton re-irradiation.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Case number 1. Proton isodose distribution in axial, sagital and coronal views for the first (initial) course of proton radiation therapy and re-irradiation with the novel TMPPR technique in a multiprogressive high-grade glioma. As seen, reirradiation volumes completely overlap with prior radiation fields but with limited dose to the surrounding normal brain.
Fig. 2
Fig. 2
Diagram describing the temporal distribution sequence of each field delivery during a 3-field TMPPR treatment fraction.
Fig. 3
Fig. 3
Case number 5. Axial slices in three anatomic sequences (T2, T2/FLAIR, and T1-post contrast), and one functional (perfusion, cerebral blood flow [CBV]) demonstrating retraction of the surgical cavity and significant reduction of the heterogenoeus enhacement. Perfusion imaging continued to demonstrate lack of elevated CBV, consistent with radiation necrosis vs. tumor progression.
Fig. 4
Fig. 4
Example of a patient with leptomeningeal disease development after prior TMPPR, with development of numerous enhancing nodules in periventricular and parafalcine locations, three of three are highlighted by green arrows.
See this image and copyright information in PMC

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