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Background: To develop an auxiliary GPU-accelerated proton therapy (PT) dose and LET d engine for the IBA Proteus®ONE PT system. A pediatric low-grade glioma case study is reported using FRoG during clinical practice, highlighting potential treatment planning insights using variable RBE dose (D vRBE ) and LET d as indicators for clinical decision making in PT., Methods: The physics engine for FRoG has been modified for compatibility with Proteus®ONE PT centers. Subsequently, FRoG was installed and commissioned at NPTC. Dosimetric validation was performed against measurements and the clinical TPS, RayStation (RS-MC). A head patient cohort previously treated at NPTC was collected and FRoG forward calculations were compared against RS-MC for evaluation of 3D-Γ analysis and dose volume histogram (DVH) results. Currently, treatment design at NPTC is supported with fast variable RBE and LET d calculation and is reported in a representative case for pediatric low-grade glioma., Results: Simple dosimetric tests against measurements of iso-energy layers and spread-out Bragg Peaks in water verified accuracy of FRoG and RS-MC. Among the patient cohort, average 3D-Γ applying 2%/2 mm, 3%/1.5 mm and 5%/1 mm were > 97%. DVH metrics for targets and OARs between FRoG and RayStation were in good agreement, with ∆D 50,CTV and ∆D 2,OAR both ⪅1%. The pediatric case report demonstrated implications of different beam arrangements on D vRBE  and LET d distributions. From initial planning in RayStation sharing identical optimization constraints, FRoG analysis led to plan selection of the most conservative approach, i.e., minimized D vRBE,max and LET d,max in OARs, to avoid optical system toxicity effects (i.e., vision loss)., Conclusion: An auxiliary dose calculation system was successfully integrated into the clinical workflow at a Proteus®ONE IBA facility, in excellent agreement with measurements and RS-MC. FRoG may lead to further insight on D vRBE and LET d implications to help clinical decision making, better understand unexpected toxicities and establish novel clinical procedures with metrics currently absent from the standard clinical TPS., (© 2021. The Author(s).)

The present study is aimed at determination of accuracy of relocation of Gill-Thomas-Cosman frame during fractionated stereotactic radiotherapy. The study aims to quantitatively determine the magnitudes of error in anteroposterior, mediolateral and craniocaudal directions, and determine the margin between clinical target volume to planning target volume based on systematic and random errors. Daily relocation error was measured using depth helmet and measuring probe. Based on the measurements, translational displacements in anteroposterior (z), mediolateral (x), and craniocaudal (y) directions were calculated. Based on the displacements in x, y and z directions, systematic and random error were calculated and three-dimensional radial displacement vector was determined. Systematic and random errors were used to derive CTV to PTV margin. The errors were within ± 2 mm in 99.2% cases in anteroposterior direction (AP), in 99.6% cases in mediolateral direction (ML), and in 97.6% cases in craniocaudal direction (CC). In AP, ML and CC directions, systematic errors were 0.56, 0.38, 0.42 mm and random errors were 1.86, 1.36 and 0.73 mm, respectively. Mean radial displacement was 1.03 mm ± 0.34. CTV to PTV margins calculated by ICRU formula were 1.86, 1.45 and 0.93 mm; by Stroom's formula they were 2.42, 1.74 and 1.35 mm; by van Herk's formula they were 2.7, 1.93 and 1.56 mm (AP, ML and CC directions). Depth helmet with measuring probe provides a clinically viable way for assessing the relocation accuracy of GTC frame. The errors were within ± 2 mm in all directions. Systematic and random errors were more along the anteroposterior axes. According to the ICRU formula, a margin of 2 mm around the tumor seems to be adequate.

The multimodality management of visual pathway tumors frequently involves radiation. Most commonly, photons are delivered via multiple focused beams aimed at the tumor while sparing adjacent tissues. The dose can be delivered in multiple treatments (radiation therapy) or in a single treatment (radiosurgery). Children with visual pathway gliomas should be treated with chemotherapy alone, delaying the use of radiation therapy until progression. Definitive radiation therapy of optic nerve sheath meningiomas results in stable vision in most patients. Radiation therapy or radiosurgery for pituitary tumors can result in control of both tumor growth and hormone hypersecretion. Postoperative radiation therapy or radiosurgery of craniopharyngiomas significantly improves local control rates compared with surgery alone. Radiation therapy is highly effective for eradicating orbital pseudolymphoma and lymphoma. The risk of complications from radiation treatment is dependent on the organ at risk, the cumulative dose it receives, and the dose delivered per fraction.

Optic pathway glioma associated with neurofibromatosis 1 has a classically indolent course. However, involvement of the optic radiations is relatively rare and is associated with a more aggressive course. A three-year-old girl presented with strabismus and loss of vision in the left eye with relative afferent pupillary defect and optic disc pallor. She had multiple cafiota au lait spots. Visually evoked potential was suggestive of an optic nerve conduction defect and magnetic resonance imaging of the brain was suggestive of an optic pathway glioma involving the optic nerves, the optic chiasma and the optic tracts. The optic radiations and the dendate nuclei had hamartomas. Optic nerve biopsy confirmed pilocytic astrocytoma. Radical radiotherapy under general anesthesia was subsequently given. This case report aims to highlight the involvement of the optic radiations and the unusually aggressive clinical course in this case.

A 35-year-old man with neurofibromatosis type 1 (NF1) had a left ophthalmic artery occlusion that caused no light perception OS 28 years after having been treated with external beam radiation therapy for a presumed glioma of the right optic nerve and chiasm. Clinical and imaging findings were consistent with radiation-induced cerebral vasculopathy. This ophthalmic complication has never been reported, despite the common occurrence of severe carotid-ophthalmic artery junction stenosis after radiation in NF1 patients. Even though modern radiation techniques limit collateral damage, this modality should be used with discretion in NF1 patients, given the vulnerability of their immature cerebral vasculature to radiation.

Standard treatment of optic pathways gliomas consists of radiotherapy and surgery when feasible. Owing to the toxicity of irradiation, chemotherapy has emerged as an interesting therapeutic option, especially in young children. This study describes the neuropsychological profile of 27 children (aged between 1.5 and 15.7 years) with optic pathways gliomas treated with chemotherapy as first-line treatment. Eight of them also received radiotherapy as salvage treatment. Eight had neurofibromatosis type 1 (NF1). Intellectual outcome was preserved in children treated with chemotherapy only (mean=107+/-17) compared to children also receiving radiotherapy (mean IQ=88+/-24) or children having NF1 and treated with chemotherapy (mean IQ=80+/-13). Scores for abstract reasoning, mental arithmetic, chessboard/coding, perception, judgement of line orientation were lower in children irradiated than in those treated only by chemotherapy. Children with Nf1 showed subnormal IQ scores with marked impairment of short- and long-term memory. With respect to long-term neuropsychological outcome, our study shows that a chemotherapy-first strategy can preserve the intellectual outcome of these patients either by avoiding the need of radiotherapy or by delaying its use as much as possible.

A rare case of a ruptured internal carotid artery (ICA) aneurysm, with ICA stenosis and moyamoya vessels, was diagnosed in a young female patient after radiotherapy for optic glioma. Retrospective analysis revealed that an extraordinarily high dose of radiation (110 Gy) had been delivered to the area around the ICA in two therapeutic sessions. Clipping and wrapping of the aneurysm were performed and the patient made a good recovery. A review of the literature suggested that rupture of radiation-induced aneurysms is a rare event, but may be fatal. Considerable care must therefore be taken when delivering high-dose radiation to cerebral arteries. We suggest that the incidence of radiation-induced moyamoya vessels is higher in younger patients.