Visual decline in pediatric survivors of brain tumors following radiotherapy.

PURPOSE: Radiotherapy-related visual decline is a significant concern in survivors of childhood cancer; however, data establishing the dose-response relationship between dose to the optic apparatus and visual acuity decline in children are sparse. We aimed to determine this relationship in a cohort of children treated with proton therapy. MATERIAL AND METHODS: We identified 458 children with 875 eyes at risk treated with proton therapy for intracranial malignancy between December 2006 and September 2018. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received ≥30 GyRBE to 0.1 cm3. Kaplan-Meier and Normal Tissue Complication Probability modeling was used to establish the relationship between radiotherapy dose and risk of visual decline. RESULTS: Excluding children with tumor progression, no patient experienced complete vision loss. The actuarial 5-year rate of any visual acuity decline was 2.6% (95% confidence interval [CI]: 1.5%-4.6%). The dose to 0.1 cm3 of the ipsilateral optic nerve or optic chiasm resulting in a 1%, 5%, and 10% risk of acuity decline were 52.7 GyRBE, 56.6 GyRBE, and 58.3 GyRBE. Visual decline was only seen in children with primary tumors of the optic pathway or suprasellar region. CONCLUSIONS: Visual acuity decline following radiotherapy for intracranial malignancies in children is rare. A dose of approximately 56 GyRBE to 0.1 cm3 results in an approximately 5% risk of visual acuity decline for children with suprasellar or optic pathway tumors. A dose to 0.1 cm3 of 56 GyRBE appears to be safe for children with tumors elsewhere in the brain.

The impact of proton LET/RBE modeling and robustness analysis on base-of-skull and pediatric craniopharyngioma proton plans relative to VMAT.

Purpose: Pediatric craniopharyngioma, adult base-of-skull sarcoma and chordoma cases are all regarded as priority candidates for proton therapy. In this study, a dosimetric comparison between volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) was first performed. We then investigated the impact of physical and biological uncertainties. We assessed whether IMPT plans remained dosimetrically superior when such uncertainty estimates were considered, especially with regards to sparing organs at risk (OARs).Methodology: We studied 10 cases: four chondrosarcoma, two chordoma and four pediatric craniopharyngioma. VMAT and IMPT plans were created according to modality-specific protocols. For IMPT, we considered (i) variable RBE modeling using the McNamara model for different values of (α/ß)x, and (ii) robustness analysis with ±3 mm set-up and 3.5% range uncertainties.Results: When comparing the VMAT and IMPT plans, the dosimetric advantages of IMPT were clear: IMPT led to reduced integral dose and, typically, improved CTV coverage given our OAR constraints. When physical robustness analysis was performed for IMPT, some uncertainty scenarios worsened the CTV coverage but not usually beyond that achieved by VMAT. Certain scenarios caused OAR constraints to be exceeded, particularly for the brainstem and optical chiasm. However, variable RBE modeling predicted even more substantial hotspots, especially for low values of (α/ß)x. Variable RBE modeling often prompted dose constraints to be exceeded for critical structures.Conclusion: For base-of-skull and pediatric craniopharyngioma cases, both physical and biological robustness analyses should be considered for IMPT: these analyses can substantially affect the sparing of OARs and comparisons against VMAT. All proton RBE modeling is subject to high levels of uncertainty, but the clinical community should remain cognizant possible RBE effects. Careful clinical and imaging follow-up, plus further research on end-of-range RBE mitigation strategies such as LET optimization, should be prioritized for these cohorts of proton patients.

Delineating brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm in head and neck radiotherapy: a CT-based model atlas.

BACKGROUND AND PURPOSE: Sparing of the organs at risk is one of the primary end-points of radiotherapy. The effects of organ-at-risk delineation on the dosimetric parameters can be critical and can influence treatment planning and outcomes. The aim of our study was to provide anatomical boundaries for the identification and delineation of the following critical organs at risk in the head and neck district: brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. PATIENTS AND METHODS: One patient was initially selected to elaborate our atlas. This patient was subjected to a planning computed tomography of the brain and head and neck district; axial images of 3-mm thickness at 3-mm intervals were obtained. In the same set-up a magnetic resonance imaging study was also performed. The obtained images were fused based on anatomical landmarks and used by a radiation oncologist, supported by a neuroradiologist, to provide anatomo-radiological limits for the identification of the brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. These limits were further verified on three consecutive patients. RESULTS: A computed tomography-based atlas was developed with definition of cranial, caudal, medial, lateral, anterior and posterior limits for each organ considered. CONCLUSIONS: This study allows improvement of definitions of anatomic boundaries for the brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. Our multidisciplinary experience led to the production of an institutional reference tool that could represent a useful aid for radiation oncologists in clinical practice.

Development of a modified head and neck quality assurance phantom for use in stereotactic radiosurgery trials.

An anthropomorphic head phantom, constructed from a water-equivalent plastic shell with only a spherical target, was modified to include a nonspherical target (pituitary) and an adjacent organ at risk (OAR) (optic chiasm), within 2 mm, simulating the anatomy encountered when treating acromegaly. The target and OAR spatial proximity provided a more realistic treatment planning and dose delivery exercise. A separate dosimetry insert contained two TLD for absolute dosimetry and radiochromic film, in the sagittal and coronal planes, for relative dosimetry. The prescription was 25 Gy to 90% of the GTV, with ≤ 10% of the OAR volume receiving ≥ 8 Gy for the phantom trial. The modified phantom was used to test the rigor of the treatment planning process and phantom reproducibility using a Gamma Knife, CyberKnife, and linear accelerator (linac)-based radiosurgery system. Delivery reproducibility was tested by repeating each irradiation three times. TLD results from three irradiations on a CyberKnife and Gamma Knife agreed with the calculated target dose to within ± 4% with a maximum coefficient of variation of ± 2.1%. Gamma analysis in the coronal and sagittal film planes showed an average passing rate of 99.4% and 99.5% using ± 5%/3 mm criteria, respectively. Results from the linac irradiation were within ± 6.2% for TLD with a coefficient of variation of ± 0.1%. Distance to agreement was calculated to be 1.2 mm and 1.3mm along the inferior and superior edges of the target in the sagittal film plane, and 1.2 mm for both superior and inferior edges in the coronal film plane. A modified, anatomically realistic SRS phantom was developed that provided a realistic clinical planning and delivery challenge that can be used to credential institutions wanting to participate in NCI-funded clinical trials.

Longitudinal measures of visual function, tumor volume, and prediction of visual outcomes after treatment of optic pathway gliomas.

PURPOSE: To examine longitudinal changes in visual acuity, tumor volume, and visual evoked potentials (VEP) before and after treatment in children with optic pathway gliomas. DESIGN: Retrospective cohort study. PARTICIPANTS: Twenty-one patients (0.7-9 years of age). METHODS: Patients initially were treated either by chemotherapy (n = 18) or radiotherapy (n = 3). Patients were followed up with serial magnetic resonance imaging, age-corrected visual acuity measurements in logarithm of the minimum angle of resolution (logMAR) units, and pattern VEP. Longitudinal visual outcome data were obtained on average for 9 years (range, 4-16 years). Tumor volumes before and after treatment were estimated in 15 patients. Multivariate regression was used to predict visual outcomes. MAIN OUTCOME MEASURES: Visual acuity, relative tumor volumes, and VEP. RESULTS: Before treatment, 81% of patients had reduced visual acuity and 81% had optic nerve pallor, whereas all had a reduced VEP in 1 or both eyes. After initial treatment, tumor volume decreased in 53%, stabilized in 27%, and progressively increased in 20%. Treatment arrested the rapid decline in visual acuity loss and stabilized visual acuity for 4 to 5 years. The rate of visual acuity decline was not correlated with tumor shrinkage. Sixty-two percent of patients required additional treatment with either chemotherapy or radiation because of tumor growth or progressive loss of visual function. Visual acuity at last examination was stable or improved in 33% of patients, but on average declined 0.4 logMAR units. Visual acuity was 20/200 or better in 1 eye of 62% of patients. The rate of visual acuity decline was predicted weakly by tumor volume at presentation (R(2) = 0.19; P<0.009). Visual acuity at last examination was predicted best by visual acuity and tumor volume at presentation (R(2) = 0.66; P<0.001). CONCLUSIONS: Systemic chemotherapy arrested the decline in visual acuity and stabilized vision on average for 5 years. At presentation, VEPs were a more sensitive indicator of optic pathway damage than visual acuity or optic nerve appearance. Although tumor reduction or stabilization was achieved in 80% of patients, pre-existing visual damage, indexed by objective measures of tumor volume and visual function, limited visual outcomes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Incidence of vasculopathy in children with hypothalamic/chiasmatic gliomas treated with brachytherapy.

INTRODUCTION: External brain irradiation in children can cause cognitive decline, endocrine dysfunctions and second malignancies. A rare complication is cerebral vasculopathy, which occurs most often in patients with neurofibromatosis type 1. Interstitial radiotherapy using transient Iodine-125 implants is a radiotherapy option, called brachytherapy, offering excellent survival rates, but little is known on treatment-related morbidity, especially long time vascular changes. PATIENTS AND METHODS: Thirteen children with low-grade hypothalamic gliomas, four of them with neurofibromatosis type 1, were diagnosed and treated at the University Hospital Freiburg, Germany. They belong to a larger group of 44 children with suprasellar low-grade gliomas, treated with transient Iodine-125 seeds and include those who attended all routine follow-up examinations in Freiburg. After written informed consent from the parents or caregivers all patients underwent magnetic resonance imaging with angiographic techniques in 2001, 3 to 13 years after treatment. RESULTS AND DISCUSSION: Six out of 13 revealed cerebral vasculopathies, only one of them revealed symptoms of intermittent cerebral ischemia. Neurofibromatosis type 1 was present in one affected patient. The aetiology of the cerebral vascular changes is not fully understood so far. Tumour encasement, surgical damage and brachytherapy may contribute as a single risk factor or in combination. To get more information, we recommend MRA for artery vasculopathy at follow-up in all patients with suprasellar brain tumours irrespectively to their former treatment or presence of cerebrovascular symptoms.

Intracranial Autograft Fat Placement to Separate the Optic Chiasm from Tumor to Improve Stereotactic Radiotherapy Dosimetry.

BACKGROUND: Radiation therapy for intracranial lesions is constrained by dose to neurologic organs at risk. CASE DESCRIPTION: We report 2 cases, a newly diagnosed chondrosarcoma and a previously irradiated meningioma, with tumors that abutted the optic chiasm following subtotal resection. Definitive radiotherapy would have required either undercoverage of the tumor or treatment of the chiasm with doses posing an unacceptable risk of blindness. Therefore, the patients underwent open surgery with placement of an abdominal fat autograft to provide space between the tumor and the optic structures at risk. Patients received definitive fractionated stereotactic radiotherapy. For each patient, we retrospectively compared the treated plan (with fat autograft) to a second plan generated using the pre-autograft imaging, maintaining similar tumor coverage. For the chondrosarcoma, the fat autograft reduced the optic chiasm maximum dose by 21% (70.4 Gy to 55.3 Gy). For the reirradiated peri-optic meningioma, the optic chiasm maximum dose was reduced by 10% (50.8 Gy to 45.9 Gy), the left optic nerve by 17% (48.9 Gy to 40.4 Gy), and the right optic nerve by 30% (32.3 Gy to 22.6 Gy). CONCLUSIONS: We demonstrate the utility of abdominal fat autograft placement to maximize coverage of tumor while minimizing dose to intracranial organs at risk.

Single- and Multi-Fraction Stereotactic Radiosurgery Dose Tolerances of the Optic Pathways.

PURPOSE: Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation. METHODS AND MATERIALS: Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION). RESULTS: Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy. CONCLUSIONS: Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.

Technical considerations for noncoplanar proton-beam therapy of patients with tumors proximal to the optic nerve.

PURPOSE: To investigate technical feasibilities of noncoplanar proton-beam therapy (PBT) on dose reduction to critical organs. MATERIAL AND METHODS: The degree of mechanical precision, rotational limitations of the gantry and the treatment couch were evaluated, and dose-volume histograms were compared for noncoplanar and coplanar PBT. Following these studies, three patients with tumors proximal to the optic nerve underwent noncoplanar PBT. RESULTS: Noncoplanar PBT offered advantage in dose reduction to the optic nerve when compared to coplanar therapy. This advantage was more significant if the tumor reduced in size during treatment. None experienced radiation injury to the optic nerve during a short follow-up time of 7-12 months. CONCLUSION: Noncoplanar PBT appears to reduce doses to organs at risk.

Comparison of three-dimensional vs. conventional radiotherapy in saving optic tract in paranasal sinus tumors.

PURPOSE: To assess the possibility of delivering a homogeneous irradiation with respect to maximal tolerated dose to the optic pathway for paranasal sinus (PNS) tumors. METHODS: Treatment planning with conformal three-dimensional (3D) and conventional two-dimensional (2D) was done on CT scans of 20 patients who had early or advanced PNS tumors. Four cases had been previously irradiated. Dose-volume histograms (DVH) for the planning target volume (PTV) and the visual pathway including globes, chiasma and optic nerves were compared between the 2 treatment plannings. RESULTS: The area under curve (AUC) in the DVH of the globes on the same side and contralateral side of tumor involvement was significantly higher in 2D planning (p <0.05), which caused higher integral dose to both globes. Also, the AUC in the DVH of chiasma was higher in 2D treatment planning (p=0.002). The integral dose to the contralateral optic nerve was significantly lower with 3D planning (p=0.007), but there was no significant difference for the optic nerve which was on the same side of tumor involvement (p >0.05). The AUC in the DVH of PTV was not significant (201.1 + or - 16.23 mm(3) in 2D planning vs. 201.15 + or - 15.09 mm(3) in 3D planning). The volume of PTV which received 90% of the prescribed dose was 96.9 + or - 4.41 cm(3) in 2D planning and 97.2 + or - 2.61 cm(3) in 3D planning (p >0.05). CONCLUSION: 3D conformal radiotherapy (RT) for PNS tumors enables the delivery of radiation to the tumor with respect to critical organs with a lower toxicity to the optic pathway.

Radiation-induced optic neuropathy after pencil beam scanning proton therapy for skull-base and head and neck tumours.

OBJECTIVE: To assess the radiation-induced optic neuropathy (RION) prevalence, following high dose pencil beam scanning proton therapy (PBSPT) to skull base and head and neck (H&N) tumours. METHODS: Between 1999 and 2014, 216 adult patients, median age 47 years (range, 18-77), were treated with PBS PT for skull base or H&N malignancies, delivering ≥45 GyRBE to the optic nerve(s) (ON) and/or optic chiasma (OC). The median administered dose to the planning target volume was 74.0 GyRBE (range, 54.0-77.4). The median follow-up was 5.3 years (range, 0.8-15.9). RESULTS: RION was observed in 14 (6.5%) patients at a median time of 13.2 months (range, 4.8-42.6) following PBSPT. Most (92.9%) of RION were symptomatic. Most affected patients (11/14; 79%) developed unilateral toxicity. Grade 4, 3, 2 and 1 toxicity was observed in 10, 2, 1 and 1 patients, respectively. On univariate analyses, age (<70 vs ≥70 years; p < 0.0001), hypertension (p = 0.0007) and tumour abutting the optic apparatus (p = 0.012) were associated with RION. OC's V60 GyRBE was of border line significance (p = 0.06). None of the other evaluated OC-ON dose/volume metrics (Dmax, Dmean, V40-60) were significantly associated with this complication. CONCLUSION: These data suggest that high-dose PBS PT for skull base and H&N tumours is associated with a low prevalence of RION. Caution should be however exercised when treating elderly/hypertensive patients with tumours abutting the optic apparatus. ADVANCES IN KNOWLEDGE: This is the first study reporting the risk of developing RION following proton therapy with PBS technique, demonstrating the safety of this treatment.

Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

Development of a contouring guide for three different types of optic chiasm: A practical approach.

INTRODUCTION: Sparing of the organs at risk (OARs) is a crucial task in daily radiotherapy practice. Irradiation of the optic chiasm (OC) results in radiation-induced optic neuropathy (RION). The structure of the OC is complex, and OC morphology can vary in axial images. Therefore, a standard atlas can result in inaccurate descriptions of OC morphology in different patients. The aim of our study was to provide a guide based on computed tomography (CT) for the delineation of different types of OC. METHODS: Thirty-six patients were selected to participate in our study. These patients underwent CT analysis of the brain, head and neck regions in a supine position. Axial images 3 mm in thickness were obtained at 3-mm intervals. A magnetic resonance imaging (MRI) study was also performed using the same set-up. The OC was then delineated. The contours were revised by three neuroradiologists and nine radiation oncologists with > 5 years of expertise. RESULTS: Three types of OC were distinguished by magnetic resonance (MR). The location and boundaries of normal, prefixed and postfixed chiasms were developed with a CT-based atlas. Discrepancies were observed in the delineation of the prefixed and postfixed OC. CONCLUSIONS: Our guide allows improved definitions of the anatomical boundaries for different types of OC. Our experience could provide useful information for radiation oncologists in daily practice.

Physiological motion of the optic chiasm and its impact on stereotactic radiosurgery dose.

OBJECTIVE: Avoidance of radiation-induced optic neuropathy (RION) from stereotactic radiosurgery (SRS) requires precise anatomical localization; however, no prior studies have characterized the physiologic motion of the optic chiasm. We measured the extent of chiasm motion and its impact on SRS dose. METHODS: In this cross-sectional study, serial MRI was performed in multiple planes in 11 human subjects without optic pathway abnormalities to determine chiasm motion across time. Subsequently, the measured displacement was applied to the hypothetical chiasm dose received in 11 patients treated with SRS to a perichiasmatic lesion. RESULTS: On sagittal images, the average anteroposterior chiasm displacement was 0.51 mm [95% confidence interval (CI) 0.27 - 0.75 mm], and the average superior-inferior displacement was 0.48 mm (95% CI 0.22 - 0.74 mm). On coronal images, the average superior-inferior displacement was 0.42 mm (95% CI 0.13 - 0.71 mm), and the average lateral displacement was 0.75 mm (95% CI 0.42 - 1.08 mm). In 11 patients who underwent SRS to a perichiasmatic lesion, the average displacements increased the maximum chiasm dose (Dmax) by a mean of 14 % (range 6-23 %; p < 0.001). CONCLUSION: Average motion of the optic chiasm was approximately 0.50-0.75 mm, which increased chiasm Dmax by a mean of 14%. In the occasional patient with higher-than-average chiasm motion in a region of steep dose gradient, the increase in chiasm Dmax and risk of RION could be even larger. Similarly, previously reported chiasm dose constraints may underestimate the true dose received during radiosurgery. ADVANCES IN KNOWLEDGE: To limit the risk of RION, clinicians may consider adding a 0.50-0.75 mm expansion to the chiasm avoidance structure.

Normofractionated stereotactic radiotherapy versus CyberKnife-based hypofractionation in skull base meningioma: a German and Italian pooled cohort analysis.

BACKGROUND: This retrospective German and Italian multicenter analysis aimed to compare the role of normofractionated stereotactic radiotherapy (nFSRT) to CyberKnife-based hypofractionated stereotactic radiotherapy (CK-hFSRT) for skull base meningiomas. METHODS: Overall, 341 patients across three centers were treated with either nFSRT or CK-hFSRT for skull base meningioma. Treatment planning was based on computed tomography (CT) and magnetic resonance imaging (MRI) following institutional guidelines. Most nFSRT patients received 33 × 1.8 Gy, and most CK-hFSRT patients received 5 × 5 Gy. The median follow-up time was 36 months (range: 1-232 months). RESULTS: In the CK-hFSRT group, the 1-, 3-, and 10-year local control (LC) rates were 99.4, 96.8, and 80.3%, respectively. In the nFSRT group, the 1-, 3-, and 10-year LC rates were 100, 99, and 79.1%, respectively. There were no significant differences in LC rates between the nFSRT and CK-hFSRT groups (p = 0.56, hazard ratio = 0.76, 95% confidence interval, 0.3-1.9). In the CK-hFSRT group, only one case (0.49%) of severe toxicity (CTCAE 4.0 ≥ 3) was observed. In the nFSRT group, three cases (2.1%) of grade III toxicity were observed. CONCLUSION: This analysis of pooled data from three centers showed excellent LC and low side effect rates for patients treated with CK-hFSRT or nFSRT. The efficacy, safety, and convenience of a shortened treatment period provide a compelling case for the use of CK-hFSRT in patients with moderate size skull base meningioma and provided that OAR constraints are met.

A case of neurofibromatosis 1 presenting with optic pathway glioma with an early onset and an aggressive course.

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.

Evaluation of Hybrid Arc and Volumetric-Modulated Arc Therapy Treatment Plans for Fractionated Stereotactic Intracranial Radiotherapy.

PURPOSE: The study was aimed to compare hybrid arc and volumetric-modulated arc therapy treatment plans for fractionated stereotactic radiotherapy of brain tumors. METHODS: Treatment plans of 22 patients were studied. Hybrid arc and volumetric-modulated arc therapy plans were generated using Brainlab iPlanDose and Varian Eclipse treatment planning systems, respectively, with 6 MV photon beams on a Varian TrueBeam STx linear accelerator (Palo Alto, CA). Prescription dose was 54 Gy. The fractionation was 1.8 Gy per fraction and 30 fractions in total, or 2 Gy per fraction and 27 fractions in total. Planning target volume ranged from 2.4 to 28.6 cm3. Dose conformity index, gradient index, homogeneity index, and maximum doses in organs at risk were compared. Wilcoxon signed rank test was used to determine statistical significance in paired comparison. RESULTS: Conformity indexes of hybrid arc and volumetric-modulated arc therapy plans are 1.10 ± 0.10 and 1.14 ± 0.07, respectively ( P = .4); gradient indexes are 5.02 ± 1.20 and 5.64 ± 1.28, respectively ( P = .0001); homogeneity indexes are 1.02 ± 0.01 and 1.05 ± 0.01, respectively ( P = .0001); brainstem maximum doses are 53.87 ± 1.63 Gy and 54.06 ± 3.17 Gy, respectively ( P = .1); and optic chiasm maximum doses are 53.86 ± 1.28 Gy and 53.95 ± 1.81, respectively ( P = .4). The monitor unit efficiencies of hybrid arc and volumetric-modulated arc therapy plans are 2.57 ± 0.25 MU/cGy and 2.68 ± 0.24 MU/cGy, respectively ( P = .2). The differences of conformity index, gradient index, and homogeneity index between hybrid arc and volumetric-modulated arc therapy plans are small: 0.08 ± 0.05, 0.65 ± 0.46, and 0.02 ± 0.01, respectively. The maximum doses in organs at risks are similar between hybrid arc and volumetric-modulated arc therapy plans. Hybrid arc and volumetric-modulated arc therapy plans, which have similar monitor unit efficiencies, present similar dosimetric results in the fractionated intracranial radiotherapy.

Risk of Radiation Vasculopathy and Stroke in Pediatric Patients Treated With Proton Therapy for Brain and Skull Base Tumors.

PURPOSE: To estimate the rate of and identify risk factors for vasculopathy after proton therapy in pediatric patients with central nervous system and skull base tumors. METHODS AND MATERIALS: Between 2006 and 2015, 644 pediatric patients with central nervous system and skull base tumors were treated with proton therapy at a single institution. The 3 most common histologies were craniopharyngioma (n = 135), ependymoma (n = 135), and low-grade glioma (n = 131). The median age was 7.6 years (range, 0.7-21.8 years), and the median prescribed dose was 54 cobalt gray equivalent (CGE) (range, 25.2-75.6 CGE). For this analysis, vasculopathy included asymptomatic vessel narrowing identified on imaging, transient ischemic attacks, and cerebrovascular accidents. Serious vasculopathy was defined as events resulting in permanent neurologic complications or requiring revascularization surgery. Multivariate logistic regression (MVA) was used to assess predictors of toxicity. Variables examined included age, neurofibromatosis, extent of surgical resection, chemotherapy, postoperative stroke, total prescribed dose, and dose delivered to the optic nerves, chiasm, and hypothalamus. RESULTS: With a median follow-up of 3.0 years (range, 0.1-9.6 years), the 3-year cumulative rates of any vasculopathy and serious vasculopathy were 6.4% and 2.6%, respectively. Seven children (1.2%) experienced a stroke with permanent neurologic deficits; 4 required revascularization surgery. On MVA, maximum dose to the optic chiasm ≥ 54 CGE was significantly associated with the development of any vasculopathy (13.1% vs 2.2%; P < .001); age < 5 years was also significant (8.4% vs 5.4%; P < .01). On MVA, maximum dose to the optic chiasm ≥ 54 CGE also predicted serious vasculopathy (3.8% vs 1.7%; P < .05). CONCLUSIONS: Childhood cancer survivors are at risk of vasculopathy after cranial radiation therapy. Young children and those receiving ≥54 CGE to the chiasm are at an increased risk of this toxicity. These findings suggest appropriate follow-up and screening are important in this population.

A treatment planning comparison of combined photon-proton beams versus proton beams-only for the treatment of skull base tumors.

PURPOSE: To compare treatment planning between combined photon-proton planning (CP) and proton planning (PP) for skull base tumors, so as to assess the potential limitations of CP for these tumors. METHODS AND MATERIALS: Plans for 10 patients were computed for both CP and PP. Prescribed dose was 67 cobalt Gray equivalent (CGE) for PP; 45 Gy (photons) and 22 CGE (protons) for CP. Dose-volume histograms (DVHs) were calculated for gross target volume (GTV), clinical target volume (CTV), normal tissues (NT), and organs at risk (OARs) for each plan. Results were analyzed using DVH parameters, inhomogeneity coefficient (IC), and conformity index (CI). RESULTS: Mean doses delivered to the GTVs and CTVs with CP (65.0 and 61.7 CGE) and PP (65.3 and 62.2 Gy CGE) were not significantly different (p > 0.1 and p = 0.72). However, the dose inhomogeneity was drastically increased with CP, with a mean significant incremental IC value of 10.5% and CP of 6.8%, for both the GTV (p = 0.01) and CTV (p = 0.04), respectively. The CI(80%) values for the GTV and CTV were significantly higher with PP compared with CP. Compared with CP, the use of protons only led to a significant reduction of NT and OAR irradiation, in the intermediate-to-low dose (< or =80% isodose line) range. CONCLUSIONS: These results suggest that the use of CP results in levels of target dose conformation similar to those with PP. Use of PP significantly reduced the tumor dose inhomogeneity and the delivered intermediate-to-low dose to NT and OARs, leading us to conclude that this treatment is mainly appropriate for tumors in children.

A complication probability planning study to predict the safety of a new protocol for intracranial tumour radiotherapy in dogs.

Technical advances make it possible to deliver radiation therapy for canine intracranial tumours in fewer fractions, under the assumption of equivalent tumour control. With the aim of estimating the late toxicity risk profile for various tumour sizes and locations, the present paper evaluates the normal tissue complication probability (NTCP) values for the intracranial organs at risk. By making isoeffect calculations, a new 10-fraction radiation protocol was developed with the same tumour control probability (TCP) as a currently used 20-fraction standard protocol, and complication risk profiles for brain, brainstem and optic chiasm were modelled using a representative population of 64 dogs with brain tumours. For >59% of cases, the new 10-fraction protocol yielded an acceptable, low risk estimate of late toxicity (<10%). Our calculations suggest that it may be safe to treat small to intermediate-sized tumours that are neither located near the optic chiasm nor at the brainstem with 10 daily fractions of 4.35 Gy.