Green, Olga L

Henke, Lauren E

Michalski, Jeff

Mutic, Sasa

Perkins, Stephanie M

Rodriguez, Vivian L

Schiff, Joshua

English

Digital Commons@Becker

Washington University School of MedicineDigital Commons@BeckerOpen Access Publications2019First reported case of pediatric radiation treatmentwith magnetic resonance image guided radiationtherapyLauren E. HenkeOlga L. GreenJoshua SchiffVivian L. RodriguezSasa MuticSee next page for additional authorsFollow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubsAuthorsLauren E. Henke, Olga L. Green, Joshua Schiff, Vivian L. Rodriguez, Sasa Mutic, Jeff Michalski, and StephanieM. PerkinsTeaching CaseFirst Reported Case of Pediatric RadiationTreatment With Magnetic Resonance ImageGuided Radiation TherapyLauren E. Henke MD, MSCI, Olga L. Green PhD, Joshua Schiff BS,Vivian L. Rodriguez PhD, Sasa Mutic PhD, Jeff Michalski MD, MBA,Stephanie M. Perkins MD*Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MissouriReceived 14 November 2018; accepted 23 January 2019IntroductionMagnetic resonance (MR) image (MRI) guided radia-tion therapy (MRgRT) confers superior daily soft-tissuetarget visualization for many anatomic sites comparedwith traditional computed tomography (CT)ebasedradiation therapy and is increasingly used to manageinter- and intrafraction motion in a variety of cancer di-agnoses.1,2 There is growing evidence that MRgRT maybe used to improve the dosimetric therapeutic index ofradiation treatment through improved daily setup accu-racy, the opportunity for daily online plan adaptation, andreal-time cine MRI tumor motion tracking with beamgating.3 In pediatric patients with cancer, uniqueemphasis is placed on maximization of the therapeuticindex to minimize long-term risks of normal tissueexposure while maximizing durable disease control.Additionally, the young pediatric population is unable toactively participate in respiratory breath-hold treatmenttechniques for motion management, presenting an addi-tional challenge and concern for treatment. Herein, wereport the ﬁrst use of MRgRT to treat a pediatric patient inthe case of a 3-year-old girl with rhabdomyosarcoma. Inaddition, we describe key technical considerations ofMRgRT use for maximization of safety, setup accuracy,and intrafraction motion management for the deﬁnitivetreatment of a primary tumor of the diaphragm in a smallchild.CaseA 3-year-old girl presented with sleep difﬁculty and5 days of abdominal distention with urinary retention. ACT of the chest and abdomen identiﬁed a 17  10 cmmass centered at the diaphragm, with mass effect on theliver and direct extension into the anterior mediastinum,with a mediastinal component measuring 7 cm  2.7 cmwith compression of the right ventricle (Fig. 1). Subse-quent ultrasound guided biopsy revealed a diagnosis ofembryonal rhabdomyosarcoma on histopathologic anal-ysis, with immunohistochemistry staining positive forvimentin and desmin. Fluorescence in situ hybridizationrevealed no evidence for a FOXO1-containing chromo-somal rearrangement. Positron emission tomographyeCTimaging and bilateral bone marrow biopsy indicated noevidence of additional distant metastatic disease. TheseSources of support: This work had no speciﬁc funding.Conﬂicts of interest: Dr Henke reports grants and personal fees fromViewRay, Inc, outside the submitted work and grants from VarianMedical Systems outside the submitted work. Dr Green reports personalfees and other from ViewRay, Inc, outside the submitted work. Dr Muticreports grants and other from ViewRay, Inc; grants and other fromVarian Medical Systems; other from Philips Healthcare; other fromSiemens; other from TreatSafely, LLC; and other from Radialogica,LLC, outside the submitted work.* Corresponding author. Department of Radiation Oncology, Wash-ington University School of Medicine, Campus Box 8224, 4921 Park-view Place, Floor LL, St. Louis, MO 63110.E-mail address: sperkins@wustl.edu (S.M. Perkins).https://doi.org/10.1016/j.adro.2019.01.0082452-1094/ 2019 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article underthe CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Advances in Radiation Oncology (2019) 4, 233-236www.advancesradonc.orgDownloaded for Anonymous User (n/a) at Washington University School of Medicine from ClinicalKey.com by Elsevier on April 24, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.ﬁndings were consistent with intergroup rhabdomyosar-coma study group T2bN0M0 stage III disease of favor-able histologic characteristics and unfavorable site.The patient initiated a chemotherapy regimenincluding cycles of vincristine, ifosfamide, etoposide,dactinomycin, cyclophosphamide, irinotecan, and doxo-rubicin with ﬁlgrastim support. Interval CT imagingindicated a partial response to chemotherapy, and thepatient subsequently underwent gross total surgicalresection of her diaphragmatic and mediastinal disease.Histopathologic examination revealed a 5.8  5.3-cmprimary diaphragmatic tumor with evidence of treatmentresponse and negative margins, containing a small resid-ual focus of viable embryonal rhabdomyosarcoma and noevidence of residual mediastinal disease. PostoperativeCT indicated no evidence of residual or metastatic dis-ease. The patient reinitiated chemotherapy and wasreferred to radiation oncology to consider adjuvant radi-ation therapy with concurrent chemotherapy.Considering the pathology ﬁndings from surgery, arecommendation was made that the primary tumor siteinvolving the diaphragm be treated with radiation therapyto a total dose of 36 Gy in 20 daily fractions of 1.8 Gyusing intensity modulated radiation therapy. MR guidancewas selected for maximal setup accuracy and intrafractionmotion management without the additional imagingdose inherent to CT-guided treatment paradigms withkilovoltage-based on-board imaging. Given the young ageof the patient, daily anesthesia was required for all treat-ment fractions.Treatment Planning and DeliveryDetailed descriptions of the initial planning process,simulation, and MRgRT treatment device, including itsimaging characteristics and dedicated treatment planningsystem (TPS), have been previously published.4-7 For thispediatric patient, simulation comprised both CT and MRI,with use of CT as the primary data set. The gross tumorvolume (GTV) was deﬁned as the preoperative visibletumor volume with modiﬁcations accounting for return oforgans to their normal anatomic position after surgery.The clinical target volume (CTV) comprised a 1 cmvolumetric expansion on the GTV, with modiﬁcation forextension into normal organs (eg, heart). The planningtarget volume (PTV) was created using a 0.5 cm volu-metric expansion on the CTV. Treatment target volumesare shown in Figure 1.Motion of the target volume was evaluated with use of4-dimensional CT at the time of simulation. Imagingindicated movement of the target with breathing. Giventhe patient’s age, there was no ability to employ a breath-hold technique for treatment; the decision was made toproceed with real-time cine MR beam gating, which hasbeen previously described in the literature,8 and noFig. 1 (A-C) Diaphragmatic rhabdomyosarcoma tumor burden at time of diagnosis. (D and E) Gross target volume (yellow contour),clinical target volume (green contour), and planning target volume (red contour). (F) 1-, 2-, and 3-Gy isodose lines from the deliveredtreatment plan indicate curvature of low-dose isodose lines away from the body under the inﬂuence of the magnetic ﬁeld, without dosereturn to the skin, to show lack of clinically signiﬁcant electron return effect or magnetic ﬁeldeinduced dose distortions. Abbreviations:CTV Z clinical target volume; GTV Z gross tumor volume; PTV Z planning target volume.234 L.E. Henke et al Advances in Radiation Oncology: AprileJune 2019Downloaded for Anonymous User (n/a) at Washington University School of Medicine from ClinicalKey.com by Elsevier on April 24, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.additional PTV motion margin was required. Prescribeddose to the PTV was 36 Gy in 20 fractions of 1.80 Gyeach. Step-and-shoot intensity modulated radiation ther-apy planning was completed using the dedicated TPS ofthe MRgRT system.Brieﬂy, the hybrid MRgRT system used for this patientconsists of a split-solenoid 0.35-T superconducting mag-net, with 3 co-rotating cobalt-60 sources equally distrib-uted, mounted on a gantry sandwiched by the magnet.Multileaf collimators positioned under each source pro-vide beam shaping and full shielding. The system candeliver from all 3 sources simultaneously while imagingin the sagittal plane at a rate of 4 frames per second. Thepresence of the magnetic ﬁeld is taken into account duringtreatment planning by the Monte Carloebased TPS inte-grated in the MRgRT device. For this pediatric patient,the presence of the magnetic ﬁeld during treatment pre-sented 2 concerns. The ﬁrst was the effect of the magneticﬁeld on the dose distribution both inside and outside thepatient. The second was the need for anesthesia moni-toring equipment, for which the vault housing theMRgRT system was not initially designed.Regarding the ﬁrst of these concerns, previous publi-cations have reported that the 0.35-T magnetic ﬁeld haslittle effect on dose deposition in soft tissue, where themean free path of secondary electrons is too short to becurved by the Lorentz force.9 However, as the beam exitsthe patient, secondary electrons created at the exit surfaceinto air are indeed curved toward a path along the body,potentially impinging on other parts of the body such as,in this case, the chin.10 In vivo dosimetry measurementswere performed during the ﬁrst 2 fractions of therapy toevaluate the peripheral doses in 3 areas: the chin, thepelvis, and breast (site of particular exposure concern nearthe treatment area). Optically stimulated luminescencedosimeters (Microstar-II, Landauer, Inc, Glenwood, IL)were placed on the patient’s body and read out immedi-ately after delivery. Based on these measurements, thechin and pelvis were estimated to receive about 1% and0.5% of the total prescription dose, respectively, compa-rable to peripheral surface doses from standard linearaccelerators (Fig. 1). Comparison with TPS predictionwas made for the optically stimulated luminescence do-simeters placed near the breast; however, the chin andpelvis were outside the planning image data set andtherefore outside the calculation grid. The 2 maximumpoints measured for the breast were within 3% of the TPSprediction. Detailed results are presented in Table 1.Special considerations were also required in this casefor MR-compatible treatment monitoring. The hospital’sanesthesia team was present for every fraction, andalthough their monitoring equipment was MR compatible,it was not possible to see it inside the room with theexisting patient camera system. A standalone camera witha tripod was acquired and connected to a laptop computerplaced in the radiofrequency insulated equipment closetinside the treatment vault. An ethernet cable from thislaptop was fed via a ﬁlter panel in the equipment closet toanother laptop outside the treatment area, thus eliminatingthe concern of reduced MR image quality from moni-toring equipmenteproduced radiofrequency noise. Pre-liminary testing was performed with this equipment set upand a homogenous, liquid spherical phantom to evaluatethe signal-to-noise ratio compared with baseline; nochange in signal-to-noise ratio was detected.All treatment fractions were delivered with a customimmobilization device and real-time MR guidance,including cine MR gating on the target volume, based onthe exhale phase during free breathing, using thedescribed monitoring for daily sedation. At time of clin-ical setup for each treatment fraction, the patientunderwent high-resolution volumetric MRI at exhale-breath-hold in the treatment position and was thenaligned to the GTV to maximize plan/tumor overlap.Gating window targets and settings were selected by thetreating physician and evaluated on each treatment day.Table 1 In vivo peripheral dose measurements with optically stimulated luminescence dosimeters for chin, pelvis, and breast areasMeasurement point Measured dose perfraction (cGy)Total dose for 20fractions (cGy)TPS predicted totaldose (cGy)Difference between TPS andmeasurement (%)Chin 1 2.04 40.8 - -Chin 2 2.03 40.6 - -Chin 3 2.05 41 - -Pelvis 1 0.81 16.2 - -Pelvis 2 0.85 17 - -Pelvis 3 0.86 17.2 - -Breast(average of2 highestmeasurements)109.13 2182.6 2242.5 2.70%Abbreviation: TPS Z treatment planning system.Comparisons with the treatment planning system predictions are shown where available.Advances in Radiation Oncology: AprileJune 2019 Pediatric MRgRT 235Downloaded for Anonymous User (n/a) at Washington University School of Medicine from ClinicalKey.com by Elsevier on April 24, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.Details of MR guidance with cine MR gating, as imple-mented at our institution for standard clinical practice,have been previously published.8The decision to proceed with MRgRT resulted inimproved sparing of normal tissues. As described earlier,a 0.5-cm CTV to PTV expansion was used in this case tobetter account for intrafraction motion via real-time cineMRI beam gating on the target. Had the patient beentreated without MR guidance for motion management(using standard cone beam CTebased image guidanceinstead), the comparison-planned PTV expansion wouldhave been 1.0 cm because of the need to account for bothrespiratory motion of the diaphragmatic target and setupuncertainty. This would have resulted in a 59% largerPTV volume (357.8 cm3 vs the 224.8 cm3 PTV volumetreated here). Thus, 133 cm3 more normal tissue,including the adjacent diaphragm, lungs, liver, and heart,would have been treated in the absence of MRgRTtechnology, given that any additional PTV expansionwould comprise a hollow sphere of additional normaltissue around the target (357.8 cm3 e 224.8 cm3Z 133 cm3).Regarding treatment outcome, the patient tolerated alltreatment fractions without identiﬁed acute toxicity.Speciﬁcally, she had no nausea, vomiting, or diarrheaduring or immediately after radiation treatment; her par-ents noted only mild fatigue. At 28 months after radiation,the patient remained without evidence of local or distantdisease recurrence and without identiﬁed late toxicityattributable to radiation treatment.ConclusionsThis is the ﬁrst described clinical use of MRgRT for apediatric patient. In this reported case, MRgRT was usedto maximize soft-tissue visualization and daily setup ac-curacy while optimizing the management of motion in ahighly mobile (diaphragmatic) disease site to minimizetreatment volumes. Delivery of MRgRT to a pediatricpatient requires several unique technical considerations,including the use of MR-compatible anestheticmonitoring, but has been successfully and safely accom-plished in a routine clinical setting. As MRgRT enterswidespread clinical use, indications in the pediatric pop-ulation for applications such as online adaptive radiationtherapy and motion management to better spare normaltissues while maintaining target coverage are likely toexpand.References1. Noel CE, Parikh PJ, Spencer CR, et al. Comparison of onboard low-ﬁeld magnetic resonance imaging versus onboard computed to-mography for anatomy visualization in radiation therapy. ActaOncol. 2015;54:1474-1482.2. Fischer-Valuck BW, Henke LE, Green O, et al. Two-and-a-half-yearclinical experience with the world’s ﬁrst magnetic resonance imageguided radiation therapy system. Adv Radiat Oncol. 2017;2:485-493.3. Henke L, Kashani R, Robinson CG, et al. Phase I trial of stereotacticMR-guided online adaptive radiation therapy (SMART) for thetreatment of oligometastatic or unresectable primary malignancies ofthe abdomen. Radiother Oncol. 2018;126:519-526.4. Hu Y, Rankine L, Green OL, et al. Characterization of the onboardimaging unit for the ﬁrst clinical magnetic resonance image guidedradiation therapy system. Med Phys. 2015;42:5828-5837.5. Mutic S, Dempsey JF. The ViewRay system: Magnetic resonance-guided and controlled radiation therapy. Semin Radiat Oncol.2014;24:196-199.6. Yang D, Wooten HO, Green O, et al. A software tool to auto-matically assure and report daily treatment deliveries by a cobalt-60 radiation therapy device. J Appl Clin Med Phys. 2016;17:492-501.7. Acharya S, Fischer-Valuck BW, Kashani R, et al. Online magneticresonance image guided adaptive radiation therapy: First clinicalapplications. Int J Radiat Oncol Biol Phys. 2016;94:394-403.8. Green OL, Rankine LJ, Cai B, et al. First clinical implementation ofreal-time, real anatomy tracking and radiation beam control. MedPhys. 2018 May 28. https://doi.org/10.1002/mp.13002. [Epub aheadof print].9. Raaijmakers AJE, Raaymakers BW, Lagendijk JJW. Magnetic-ﬁeld-induced dose effects in MR-guided radiotherapy systems: Depen-dence on the magnetic ﬁeld strength. Phys Med Biol. 2008;53:909-923.10. Hackett SL, van Asselen B, Wolthaus JWH, et al. Spiralingcontaminant electrons increase doses to surfaces outside the photonbeam of an MRI-linac with a perpendicular magnetic ﬁeld. PhysMed Biol. 2018;63:095001-095011.236 L.E. Henke et al Advances in Radiation Oncology: AprileJune 2019Downloaded for Anonymous User (n/a) at Washington University School of Medicine from ClinicalKey.com by Elsevier on April 24, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

First reported case of pediatric radiation treatment with magnetic resonance image guided radiation therapy

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First reported case of pediatric radiation treatment with magnetic resonance image guided radiation therapy

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