Dataset Information

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

ABSTRACT: 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 (?/?)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 (?/?)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.

SUBMITTER: Gutierrez A

PROVIDER: S-EPMC6882303 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Gutierrez A A Rompokos V V Li K K Gillies C C D'Souza D D Solda F F Fersht N N Chang Y-C YC Royle G G Amos R A RA Underwood T T

Acta oncologica (Stockholm, Sweden) 20190820 12

<b>Purpose:</b> 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, especia ...[more]

PMID: 31429359

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Project description:Pediatric craniopharyngioma is a rare sellar-region epithelial tumor that, in spite of its typically benign pathology, has the potential to be clinically devastating, and presents a host of formidable management challenges for the skull base surgeon. Strategies in craniopharyngioma care have been the cause of considerable controversy, with respect to both philosophical and technical issues. Key questions remain unresolved, and include optimizing extent-of-resection goals; the ideal radiation modality and its role as an alternative, adjuvant, or salvage treatment; appropriate indications for expanded endoscopic endonasal surgery as an alternative to transcranial microsurgery; risks and benefits of skull base techniques in a pediatric population; benefits of and indications for intracavitary therapies; and the preferred management of common treatment complications. Correspondingly, we sought to review the preceding basic science and clinical outcomes literature on pediatric craniopharyngioma, so as to synthesize overarching recommendations, highlight major points of evidence and their conflicts, and assemble a general algorithm for skull base surgeons to use in tailoring treatment plans to the individual patient, tumor, and clinical course. In general terms, we concluded that safe, maximal, hypothalamic-sparing resection provides very good tumor control while minimizing severe deficits. Endoscopic endonasal, intraventricular, and transcranial skull base technique all have clear roles in the armamentarium, alongside standard craniotomies; these roles frequently overlap, and may be further optimized by using the approaches in adaptive combinations. Where aggressive subtotal resection is achieved, patients should be closely followed, with radiation initiated at the time of progression or recurrence-ideally via proton beam therapy, although three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and stereotactic radiosurgery are very appropriate in a range of circumstances, governed by access, patient age, disease architecture, and character of the recurrence. Perhaps most importantly, outcomes appear to be optimized by consolidated, multidisciplinary care. As such, we recommend treatment in highly experienced centers wherever possible, and emphasize the importance of longitudinal follow-up-particularly given the high incidence of recurrences and complications in a benign disease that effects a young patient population at risk of severe morbidity from hypothalamic or pituitary injury in childhood.

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:Objectives ?To perform a systematic review examining experiences with endoscopic resection of skull base lesions in the pediatric population, with a focus on outcomes, recurrence, and surgical morbidities. Methods ?PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases were evaluated. Studies were assessed for level of evidence. Bias risk was evaluated using the Cochrane Bias tool, Grades of Recommendation, Assessment, Development and Evaluation (GRADE), and Methodological Index for Non-Randomized Studies (MINORS) criteria. Patient characteristics, pathology, site of primary disease, presenting symptoms, stage, procedure specific details, and complications were evaluated. Results were reported using the Preferred Reporting Systems for Systematic Reviews and Meta-Analysis guidelines. Results ?Ninety-three studies met criteria for inclusion, encompassing 574 patients with skull base tumors. The GRADE and MINORS criteria determined the overall evidence to be moderate quality. The most common benign and malignant pathologies included juvenile nasopharyngeal angiofibromas ( n ?=?239) and chondrosarcomas ( n ?=?11) at 41.6 and 1.9%, respectively. Of all juvenile nasopharyngeal angiofibroma tumors, most presented at stage IIIa and IIIb (25.8 and 27.3%, respectively). Nasal obstruction (16.5%) and headache (16.0%) were common symptoms at initial presentation. Surgical approaches included endoscopic endonasal ( n ?=?193, 41.2%) and endoscopic extended transsphenoidal ( n ?=?155, 33.1%). Early (< 6 weeks) and late (>6 weeks) complications included cerebrospinal fluid leak ( n ?=?36, 17.3%) and endocrinopathy ( n ?=?43, 20.7%). Mean follow-up time was 37 months (0.5-180 months), with 86.5% showing no evidence of disease and 2.1% having died from disease at last follow-up. Conclusion ?Endoscopic skull base surgery has been shown to be a safe and effective method of treating a variety of pediatric skull base tumors. If appropriately employed, the minimally invasive approach can provide optimal results in the pediatric population.

Project description:Currently, the relative biological effectiveness (RBE) is assumed to be constant with a value of 1.1 in proton therapy. Although trends of RBE variations are well known, absolute values in patients are associated with considerable uncertainties. This study aims to evaluate the impact of a variable proton RBE in proton therapy liver trials using different fractionation schemes. Sixteen liver cancer cases were evaluated assuming two clinical schedules of 40 Gy/5 fractions and 58.05 Gy/15 fractions. The linear energy transfer (LET) and physical dose distribution in patients were simulated using Monte Carlo. The variable RBE distribution was calculated using a phenomenological model, considering the influence of the LET, fraction size and ?/? value. Further, models to predict normal tissue complication probability (NTCP) and tumor control probability (TCP) were used to investigate potential RBE effects on outcome predictions. Applying the variable RBE model to the 5 and 15 fractions schedules results in an increase in mean fraction-size equivalent dose (FED) to the normal liver of 5.0% and 9.6% respectively. For patients with a mean FED to the normal liver larger than 29.8 Gy, this results in a non-negligible increase in the predicted NTCP of the normal liver averaging 11.6%, ranging from 2.7% to 25.6%. On the other hand, decrease in TCP was less than 5% for both fractionation regimens for all patients when assuming a variable RBE instead of constant. Consequently, the difference in TCP between the two fractionation schedules did not change significantly assuming a variable RBE while the impact on the NTCP difference was highly case specific. In addition, both the NTCP and TCP decrease with increasing ?/? value for both fractionation schemes, with the decreases being more pronounced when using a variable RBE compared to using RBE??=??1.1. Assuming a constant RBE of 1.1 most likely overestimates the therapeutic ratio in proton therapy for liver cancer, predominantly due to underestimation of the RBE-weighted dose to the normal liver. The impact of applying a variable RBE (as compared to RBE??=??1.1) on the NTCP difference of the two fractionation regimens is case dependent. A variable RBE results in a slight increase in TCP difference. Variations in patient radiosensitivity increase when using a variable RBE.

Project description:BackgroundSkull base chordoma and chondrosarcoma are exceptionally rare bone tumors with high propensity for local recurrence. Different postoperative radiation modalities are often used to improve the clinical efficacy. Proton therapy (PT) might be among the most promising ones because of the unique ballistic characteristics of high-energy particles. However, previous meta-analysis often included studies with combined radiation techniques. No systematic review to date has directly analyzed the survival and toxicity of pure PT for these two types of malignancies.MethodsBy following the PRISMA guidelines, a systematic search of three databases was conducted. Articles were screened and data were extracted according to a prespecified scheme. R 4.2.0 software was used to conduct the meta-analysis. Normal distribution test was used for the incidence rate of each subgroup.ResultsA total of seven studies involving 478 patients were included in this analysis. The quality of included articles ranged from moderate to high quality. All patients were histopathologically diagnosed with chordoma or chondrosarcoma, and the follow-up time of the cohort ranged from 21 to 61.7 months. For PT planning, the median target volume ranged from 15 cc to 40 cc, and the administered median dose varied from 63 to 78.4 GyRBE at 1.8-2.0 GyRBE per fraction. The 1-, 2-, 3-, 5-, and 7-year local control and overall survival rates were 100%, 93%, 87%, 78%, and 68%, and 100%, 99%, 89%, 85%, and 68%, respectively. The late grade 3 or higher toxicities were reported in only two involved articles.ConclusionsUntil now, medical centers worldwide have exerted PT to improve outcomes of skull base chordomas and chondrosarcomas. PT not combined with other radiation modalities showed favorable local control and survival with a low incidence of severe radiation-induced toxicities, which manifests promising clinical benefits. However, high-quality evidence is still limited, requiring future clinical trials and prospective studies in selected patients.

Dataset Information

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

Publications

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

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