Brainstem Injury in Pediatric Patients With Posterior Fossa Tumors Treated With Proton Beam Therapy and Associated Dosimetric Factors

Gentile, Michelle S.; Yeap, Beow Y.; Paganetti, Harald; Goebel, Claire P.; Gaudet, D.; Gallotto, Sara L.; Weyman, Elizabeth A.; Morgan, Michael L.; MacDonald, Shannon M.; Giantsoudi, D.; Adams, Judith; Tarbell, Nancy J.; Kooy, Hanne M.; Yock, Torunn I.

doi:10.1016/j.ijrobp.2017.11.026

Cited by 65 publications

(44 citation statements)

References 28 publications

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“…Radiobiological properties unique to proton therapy such as higher relative linear energy transfer, range uncertainty, conversion from Hounsfield units to stopping power, and variable relative biological effectiveness associated with the spread‐out Bragg peak have distinct implications for dose calculation that limit the generalizability of the data in the current study to patients undergoing proton therapy. In addition, these unique physical properties have led to mounting concerns for the risk of brainstem injury . These concerns have motivated the current Children's Oncology Group (COG) ACNS0831 randomized clinical trial to specify more stringent brainstem dose constraints for those treated with proton therapy, which has implications for potential compromises in boost volume dose coverage .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, these unique physical properties have led to mounting concerns for the risk of brainstem injury. [47][48][49][50][51][52] These concerns have motivated the current Children's Oncology Group (COG) ACNS0831 randomized clinical trial to specify more stringent brainstem dose constraints for those treated with proton therapy, which has implications for potential compromises in boost volume dose coverage. 53 In light of these nuances and the infrequent utilization of proton therapy in the current study, additional validation is necessary to quantify the dose-response relationship in children with intracranial ependymoma treated with adjuvant proton therapy.…”

Section: Discussionmentioning

confidence: 99%

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The value of high‐dose radiotherapy in intracranial ependymoma

Ager

Christensen

Burt

et al. 2019

Pediatric Blood & Cancer

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Background We sought to evaluate the impact of adjuvant radiotherapy dose on overall survival (OS) after surgical resection for localized intracranial ependymoma. Procedure The National Cancer Database (NCDB) was queried from 2004 to 2015 for patients of all ages with intracranial WHO grade II to III ependymoma treated with surgery and 4500 to 7000 cGy of adjuvant radiotherapy. Pearson χ2 test and multivariate logistic regression analyses were used to assess clinicodemographic factors and patterns of care. After propensity‐score matching, OS was assessed with Kaplan–Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling. Results Of the 1153 patients meeting criteria, 529 (46%) received ≤ 5400 cGy and 624 (54%) received > 5400 cGy. At a median follow‐up of 54.5 months, an OS benefit was observed for > 5400 cGy in pediatric patients aged 2–18 years (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.28–0.99, P = 0.047). No OS difference was found between ≤ 5400 cGy and > 5400 cGy in pediatric patients aged < 2 years (P = 0.819) or in adults (P = 0.180). Increasing age, WHO grade III, subtotal resection, and receipt of chemotherapy portended worse OS. Age 2 to 18 years, WHO III grade, supratentorial location, and receipt of chemotherapy were associated with receiving > 5400 cGy. Conclusion Adjuvant radiotherapy dose > 5400 cGy was associated with improved OS for children aged 2–18 years with WHO grade II‐III intracranial ependymoma. No OS benefit was found with > 5400 cGy in adults or children less than two years of age.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The value of high‐dose radiotherapy in intracranial ependymoma

Ager

Christensen

Burt

et al. 2019

Pediatric Blood & Cancer

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“…Grade 3-4 RN ranged between 2 and 3.6% at 5 years. [82][83][84][85][86][87][88] PT has demonstrated its ability to better spare uninvolved normal tissues including critical OARs compared to standard photon therapy. It has therefore become a widely accepted radiation modality for several childhood malignancies.…”

Section: Pediatric Brain Tumoursmentioning

confidence: 99%

Proton therapy for brain tumours in the area of evidence-based medicine

Weber

Lim

Tran

et al. 2019

The British Journal of Radiology

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Proton therapy (PT) has been administered for many years to a number of cancers, including brain tumours. Due to their remarkable physical properties, delivering their radiation to a very precise brain volume with no exit dose, protons are particularly appropriate for these tumours. The decrease of the brain integral dose may translate with a diminution of neuro-cognitive toxicity and increase of quality of life, particularly so in children. The brain tumour patient’s access to PT will be substantially increased in the future, with many new facilities being planned or currently constructed in Europe, Asia and the United States. Although approximately 150’000 patients have been treated with PT, no level I evidence has been demonstrated for this treatment. As such, it is this necessary to generate high-quality data and some new prospective trials will include protons or will be activated to compare photons to protons in a randomized design. PT comes however with an additional cost factor that may contribute to the ever-growing health’s expenditure allocated to cancer management. These additional costs and financial toxicity will have to be analysed in the light of a more conformal radiation delivery, non-target brain irradiation and lack of potential for dose escalation when compared to photons. The latter is due to the radiosensitivity of organs at risk in vicinity of the brain tumour, that photons cannot spare optimally. Consequentially, radiation-induced toxicities and tumour recurrences, which are cost-intensive, may decrease with PT resulting in an optimized photon/proton financial ratio in the end. Advances in knowledge: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.

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“…While RBE~1.1 when LET d~1 keV/lm, RBE may be significantly higher (around 1.5) when LET d is high (around 10 keV/lm) near the end of the proton beam range and in the corresponding lateral penumbra regions due to multiple Coulomb scattering. 6 Recently, Michelle et al 16 reported a clear increasing trend of brainstem injury with the increasing RBE dose in brainstem for pediatric patients with posterior fossa tumors. And similar evidence was also reported in chest wall and pediatric cancer patients for lung injury 17 and brain necrosis, 18 respectively, which suggested that proton RBE can exceed 1.1 in vivo.…”

Section: Introductionmentioning

confidence: 99%

Hybrid 3D analytical linear energy transfer calculation algorithm based on precalculated data from Monte Carlo simulations

et al. 2019

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Purpose The dose‐averaged linear energy transfer (LETd) for intensity‐modulated proton therapy (IMPT) calculated by one‐dimensional (1D) analytical models deviates from more accurate but time‐consuming Monte Carlo (MC) simulations. We developed a fast hybrid three‐dimensional (3D) analytical LETd calculation that is more accurate than 1D analytical model. Methods We used the Geant4 MC code to generate 3D LETd distributions of monoenergetic proton beams in water for all energies and used a customized error function to fit the LETd lateral profiles at various depths to the MC simulation. The 3D LETd calculation kernel was a lookup table of these fitted coefficients, and LETd was determined directly from spot energies and voxel coordinates during analytical dose calculations. We validated our new method by comparing the calculated LETd distributions to MC results using 3D Gamma index analysis with 3%/2 mm criteria in 12 patient geometries. The significance of the improvement in Gamma index analysis passing rates over the 1D analytical model was determined using the Wilcoxon rank‐sum test. Results The passing rate of 3D Gamma analysis comparing LETd distributions from the hybrid 3D method and the 1D method to MC simulations was significantly improved from 94.0% ± 2.5% to 98.0% ± 1.0% (P = 0.0003). The typical time to calculate dose and LETd simultaneously using an Intel Xeon E5‐2680 2.50 GHz workstation was approximately 2.5 min. Conclusions Our new method significantly improved the LETd calculation accuracy compared to the 1D method while maintaining significantly shorter calculation time even comparing with the GPU‐based fast MC code.

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Brainstem Injury in Pediatric Patients With Posterior Fossa Tumors Treated With Proton Beam Therapy and Associated Dosimetric Factors

Cited by 65 publications

References 28 publications

The value of high‐dose radiotherapy in intracranial ependymoma

The value of high‐dose radiotherapy in intracranial ependymoma

Proton therapy for brain tumours in the area of evidence-based medicine

Hybrid 3D analytical linear energy transfer calculation algorithm based on precalculated data from Monte Carlo simulations

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