Dataset Information

Pre- and Posttherapy Risk Factors for Vasculopathy in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Radiation Therapy.

ABSTRACT:

Purpose

Vasculopathy (VAS) is a significant complication associated with radiation therapy in patients treated for brain tumors. We studied the type, location, severity, timing, and resolution of VAS in children with craniopharyngioma treated with proton radiation therapy (PRT) and evaluated predictors of stenosis (STN) using a novel patient and imaging-based modeling approach.

Methods and materials

Children with craniopharyngioma (n = 94) were treated with 54 Gy relative biological effectiveness PRT in a clinical trial, NCT01419067. We evaluated VAS type, location, severity, and resolution. VAS events were segmented and related to their location, operative corridor, PRT dose, and vascular territory to facilitate mixed effect logistic regression modeling of spatial predictors of STN events.

Results

Forty-five (47.9%) patients had 111 instances of confirmed VAS (pre-PRT n = 37, 33.3%). The median time to post-PRT VAS was 3.41 years (95% confidence interval, 1.86-6.11). STN events were observed post-PRT in 23.4% (n = 22) of patients. Post-PRT VAS was detected by cerebral angiogram in 9.6% (n = 9), severe in 4.3% (n = 4), and compensated on perfusion in 2.1% (n = 2). Revascularization was required for 5 (5.3%) patients. Postsurgical, pre-PRT VAS, and PRT dose to unperturbed vessels were predictive of STN. The effect of PRT on STN was negligible within the surgical corridor.

Conclusions

VAS often precedes PRT and was the strongest predictor of post-PRT STN. The adverse effect of PRT on STN was only apparent in unperturbed vasculature beyond the operative corridor.

SUBMITTER: Lucas JT

PROVIDER: S-EPMC9018579 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Pre- and Posttherapy Risk Factors for Vasculopathy in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Radiation Therapy.

Lucas John T JT Faught Austin M AM Hsu Chih Yang CY Wilson Lydia J LJ Guo Yian Y Li Yimei Y Khan Raja R Becksfort Jared B JB LeVine David A DA Ismael Yousef Y Darrow Kaleb K Moskvin Vadim P VP Pirlepesov Fakhriddin F Klimo Paul P Elijovich Lucas L Indelicato Daniel J DJ Boop Fredrick A FA Merchant Thomas E TE

International journal of radiation oncology, biology, physics 20220103 1

<h4>Purpose</h4>Vasculopathy (VAS) is a significant complication associated with radiation therapy in patients treated for brain tumors. We studied the type, location, severity, timing, and resolution of VAS in children with craniopharyngioma treated with proton radiation therapy (PRT) and evaluated predictors of stenosis (STN) using a novel patient and imaging-based modeling approach.<h4>Methods and materials</h4>Children with craniopharyngioma (n = 94) were treated with 54 Gy relative biologic ...[more]

PMID: 34990778

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Project description:Background and purposeProton radiotherapy has been increasingly utilized to treat pediatric brain tumors, however, limited information exists regarding radiation necrosis among these patients. Our aim was to evaluate the incidence, timing, clinical significance, risk factors, and imaging patterns of radiation necrosis in pediatric patients with brain tumors treated with proton radiation therapy.Materials and methodsA retrospective study was performed on 60 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation necrosis was assessed by examining serial MRIs and clinical records to determine the incidence, timing, risk factors, imaging patterns, and clinical significance associated with the development of radiation necrosis in these patients. Radiation necrosis was defined as areas of new enhancement within an anatomic region with previous exposure to proton beam therapy with subsequent decrease on follow-up imaging without changes in chemotherapy.ResultsThirty-one percent of patients developed radiation necrosis with a median time to development of 5.0 months (range, 3-11 months). Risk factors included multiple chemotherapy agents (>3 cytotoxic agents) and atypical teratoid rhabdoid tumor pathology (P = .03 and P = .03, respectively). The most common imaging patterns were small (median, 0.9 cm) and multifocal (63% of patients) areas of parenchymal enhancement remote from the surgical site. The median time to complete resolution on imaging was 5.3 months (range, 3-12 months). Among patients with imaging findings of radiation necrosis, 25% demonstrated severe symptoms with medical intervention indicated.ConclusionsPediatric patients with brain tumors treated with proton radiation therapy demonstrate a high incidence of radiation necrosis and a short time to development of necrosis. Multiple small areas of necrosis are frequently identified on imaging. Exposure to multiple chemotherapy agents was a significant risk factor associated with radiation necrosis in these patients.

Project description:OBJECT The aim of the study was to document postoperative cerebral glucose distribution before proton therapy using F-18 fluorodeoxyglucose positron emission tomography (FDG PET) in children with craniopharyngioma. METHODS Between August 2011 and April 2014, 50 patients (20 males, 30 females) enrolled in a prospective trial for craniopharyngioma underwent FDG PET imaging before proton therapy. Proton therapy was delivered using doublescattered beams with a total prescribed dose of 54 cobalt gray equivalent. Tracer uptake in each of 63 anatomical regions was computed after warping PET images to a 3D reference template in Talairach coordinates. Regional uptake was deemed significantly low or high if it exceeded age-corresponding 95% prediction intervals of the normal population. The reference group included 132 children with non-CNS-related diseases and normal-appearing cerebral FDG PET scans. RESULTS Median patient age at diagnosis was 8.5 years (range 2-18 years). Forty-eight patients underwent 1-4 tumor-related surgeries before proton therapy, including placement of an Ommaya reservoir in 14 patients. Sixteen patients had symptomatic hydrocephalus that was treated with temporary (external ventricular drain, n = 16) or permanent CSF shunting (ventriculoperitoneal shunt, n = 1). The most commonly seen PET abnormalities in patients before proton therapy were significantly reduced uptake in subregions of the frontal lobe (often involving more than 1 gyrus), medial and ventral portions of the temporal lobe, cingulate gyrus, and caudate nucleus. A significantly high uptake was frequently observed on the contralateral side, including the superior, medial, and inferior temporal gyri and a large portion of the parietal lobe. Statistically significant predictor variables identified in the multivariate analysis for the extent of hypometabolism were sex (p = 0.005), hydrocephalus (p = 0.026), and the number of tumor-related surgeries (p = 0.017). CONCLUSIONS Postoperative FDG PET of patients with craniopharyngioma revealed metabolic abnormalities in specific regions of the brain. The ability to identify anatomical metabolic defects in individual patients facilitates the investigation of brain injury in children with craniopharyngioma.

Project description:PurposeThe purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy.Methods and materialsFifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51 atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect.ResultsSurgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non-surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect.ConclusionsDTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.

Project description: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/β)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/β)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.

Dataset Information

Pre- and Posttherapy Risk Factors for Vasculopathy in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Radiation Therapy.

Purpose

Methods and materials

Results

Conclusions

Publications

Pre- and Posttherapy Risk Factors for Vasculopathy in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Radiation Therapy.

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