Daly, Mackenzie

Fischer-Valuck, Benjamin

Green, Olga

Pachynski, Russell

Rudra, Soumon

English

Digital Commons@Becker

Washington University School of Medicine Digital Commons@Becker Open Access Publications 2019 Magnetic resonance image guided stereotactic body radiation therapy to the primary renal mass in metastatic renal cell carcinoma Soumon Rudra Benjamin Fischer-Valuck Russell Pachynski Mackenzie Daly Olga Green Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Teaching CaseMagnetic Resonance Image Guided StereotacticBody Radiation Therapy to the Primary RenalMass in Metastatic Renal Cell CarcinomaSoumon Rudra MD a, Benjamin Fischer-Valuck MD b,Russell Pachynski MD c, Mackenzie Daly MD a, Olga Green PhD a,*aDepartment of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri; bDepartment of RadiationOncology, Emory University, Atlanta, Georgia; and cDivision of Oncology, Washington University in St. Louis, St. Louis,MissouriReceived 20 December 2018; revised 31 March 2019; accepted 8 April 2019Renal cell carcinoma (RCC) has long been termed aradioresistant histology owing to older data demonstratinga lack of benefit with conventional fractionated radia-tion.1,2 More modern series have demonstrated that high-dose regimens delivered using stereotactic body radiationtherapy (SBRT) offer impressive tumor control.3,4 Pres-ervation of normal kidney function is a priority whenusing radiation therapy (RT). Investigators have previ-ously noted decreased renal function after SBRT, espe-cially in patients with pre-existing renal disease.5,6 Theeffectiveness of SBRT correlates with accurate tumordelineation and avoidance of high-dose radiation tonormal tissue. Furthermore, treatment planning mustcompensate for respiratory motion of renal tumors.We report a case illustrating a patient with metastaticRCC who responded on systemic therapy with nivolumaband underwent SBRT to the primary renal mass for acytoreductive effect. This SBRT regimen was deliveredusing a magnetic resonance (MR) imaging (MRI)-guidedRT system that allows for MR-based simulation imaging,real-time tumor tracking, and respiratory gating. Wefurther highlight the implications of this novel system intreatment planning, treatment delivery, and potentialoutcomes.Case ReportAn 83-year-old man presented to the emergencydepartment with acute shortness of breath and history ofprogressive dyspnea over the prior 2 months. A computedtomography (CT) scan of the chest revealed a large right-sided pleural effusion, multiple bilateral pulmonary nod-ules, and a superior left kidney lesion. The patientreceived a thoracentesis with removal of 1.5 L of pleuralfluid and a biopsy of a right-sided pleural based nodulevia CT guidance. Pathology confirmed a diagnosis ofclear cell RCC, and pazopanib was initiated. After2 months of therapy, the patient developed elevatedtransaminases indicative of pazopanib-induced hepato-toxicity. His systemic therapy was subsequently switchedto nivolumab.Approximately 4 months after diagnosis, the patientdeveloped 4 brain metastases, which were treated withstereotactic radiosurgery. After 1 year of nivolumab, thepatient was reimaged and found to have resolution ofintracranial disease, stable pulmonary nodules, responseof the primary left kidney mass, and no radiographicevidence of new sites of disease. Given that the largestburden of disease was in the left kidney, cytoreductiveSources of support: This work had no specific funding.Disclosures: Dr Fischer-Valuck reports grants and personal fees fromViewRay, Inc, outside the submitted work. Dr Green reports grants andpersonal fees from ViewRay, Inc, outside the submitted work.* Corresponding author. Department of Radiation Oncology, Wash-ington University School of Medicine, 660 South Euclid Ave, CampusBox #8224, St. Louis, MO 63110.E-mail address: ogreen@wustl.edu (O. Green).https://doi.org/10.1016/j.adro.2019.04.0022452-1094/ 2019 The Author(s). 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, 566-570www.advancesradonc.orgDownloaded for Anonymous User (n/a) at Washington University in Saint Louis Bernard Becker Medical Library from ClinicalKey.com by Elsevier on October 23, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.nephrectomy was discussed, but the patient declinedsurgery. After 29 cycles of nivolumab, his diseaseremained stable (Fig. 1A and 1B), and he consented tolocal treatment of the left renal primary using SBRT.The patient’s baseline renal function was assessedusing a renal scintigraphy before starting SBRT. The leftkidney contributed 34% of total renal function. In addi-tion, baseline creatinine was 1.20 mg/dL, and estimatedglomerular filtration rate was 55 mL/min/1.73 m2.Stereotactic body radiation therapyThe patient received a 4-dimensional CT simulationlying supine in a body immobilization device with the leftarm up. MRI coils were placed under the immobilizationdevice, and the patient received MR simulation with theMRI-guided RT system (ViewRay MRIdian System,Oakwood Village, OH). CT and MR images were trans-ferred to the RT planning system, where images wereregistered and contouring was performed. The primarycontouring dataset was the MRI data obtained using a fastgradient echo sequence (TrueFISP) as set by the manu-facturer of the MRI-guided RT system. The treating ra-diation oncologist contoured the gross tumor volume(GTV), defined as the left kidney mass visible on the MRIset. Planning tumor volume (PTV) was created using amargin of 5 mm (Fig. 2A and 2B). Organs at risk (OARs)were also delineated and included stomach, small bowel,large bowel, kidneys, liver, and spinal cord.An SBRT treatment plan was developed to deliver4000 cGy in 5 daily fractions (Fig. 2C and 2D). Doseconstraints were used during planning for the followingOARs: stomach (V36 Gy [OAR volume receiving 36 Gy]<0.5 mL, V18 Gy < 10 mL), small bowel(V20 Gy < 5 mL, Dmax [maximum dose to volume]<35 Gy), large bowel (V36 Gy < 0.5 mL,V25 Gy < 20 mL), kidneys (V16 Gy < 60%), liver (meandose <18 Gy, V21 Gy < 700 mL), and spinal cord(V25 Gy < 0.5 mL). The treatment was prescribed withpurposeful hotspots within the GTV. PTV coverage wasnot compromised due to OARs. The treatment plandelivered 95% prescription dose to 99% of the PTV. OARdoses were as follows: stomach (V36 Gy Z 0 mL,V18 GyZ 6 mL), small bowel (V20 GyZ 0 mL), largebowel (V36 Gy Z 0 mL, V25 Gy Z 0 mL), kidneys(V16 Gy Z 10%), liver (mean dose Z 2 Gy,V21 Gy Z 0 cmL), and spinal cord (V25 Gy Z 0 mL).All treatments were performed on the MRI-guided RTmachine using a 0.35T magnet, Co-60 delivery, and real-time MRI acquisition. During daily set-up for treatment, avolumetric MRI was obtained to visualize the left kidneyFigure 1 (A) Axial computed tomography (CT) scan of an abdomen demonstrating a 4.3  5.6 cm exophytic mass in the upper poleof the left kidney with internal calcifications before radiation. (B) Coronal view of the CT scan of the abdomen before radiation.(C) Axial CT scan of the abdomen after radiation demonstrating stable size of primary renal mass. (D) Coronal view of CT scan of theabdomen after radiation.Advances in Radiation Oncology: OctobereDecember 2019 MRI-guided SBRT in renal cell carcinoma 567Downloaded for Anonymous User (n/a) at Washington University in Saint Louis Bernard Becker Medical Library from ClinicalKey.com by Elsevier on October 23, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.and OARs. RT was delivered using the end-expirationgating technique. The treatment target was the GTV with a5-mm expansion acting as the gating boundary (same asPTV). Typical gating margins are 3 to 5 mm. The treatingphysician selected a larger gating margin so that beam-offtime could be minimized. This was an important consid-eration for an elderly patient who had difficulty maintain-ing arm-up position for substantial treatment durations.Figure 3A demonstrates the GTV within the gatingboundary resulting in radiation delivery, and Figure 3Bdemonstrates the GTV moving outside the boundaryresulting in the beams turning off and temporarily stoppingdelivery. The average delivery time for each fraction was14.8 minutes, and the average on-table time for the patientwas 33 minutes. The average duty cycle was 75%.During treatment, the patient experienced some mildfatigue but did not report any nausea, vomiting, diarrhea,or skin irritation. He presented for follow-up at 5 weeksafter completion of therapy and continued to reportfatigue without any new symptoms. CT of the chest,abdomen, and pelvis was performed at 6 weeks, demon-strating stable size of the primary renal mass and stablemetastatic disease. At 8 weeks after RT, the patientdecided to stop nivolumab because of continued fatigueon therapy and proceeded with close observation. Imag-ing was repeated at 6 months after RT and demonstratedstable disease at the primary (Fig. 1C and 1D) and met-astatic sites. In addition, the patient received a repeatevaluation of his kidney function after SBRT. At6 months after treatment, the patient’s kidney functionremained stable with creatinine of 1.20 mg/dL and esti-mated glomerular filtration rate of 54 mL/min/1.73 m2.DiscussionCytoreductive nephrectomy in certain subgroups ofpatients with metastatic RCC may improve overallFigure 2 (A) Axial simulation magnetic resonance imaging (MRI) scan of the abdomen demonstrating gross tumor volume (GTV)shaded in light green and planning target volume (PTV) in light blue. (B) Coronal view of MRI scan of the abdomen with treatmentvolumes. (C) Axial MRI scan of the abdomen with treatment volumes and isodose lines: blue, 120%; orange, 100%; magenta, 80%.(D) Coronal view of MRI scan of the abdomen with treatment volumes and isodose lines.568 S. Rudra et al Advances in Radiation Oncology: OctobereDecember 2019Downloaded for Anonymous User (n/a) at Washington University in Saint Louis Bernard Becker Medical Library from ClinicalKey.com by Elsevier on October 23, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.survival. Flanigan et al performed a randomized trialdemonstrating that surgery followed by interferon therapyimproved survival over interferon therapy alone.7 Mick-isch et al demonstrated favorable time to progression andsurvival outcomes in the combined surgery and interferonarm of their study as well.8 However, both studies wereperformed before the advent of modern targeted systemictherapy options. Although there is no published ran-domized evidence to support cytoreductive surgery inpatients receiving targeted therapies, large modern retro-spective studies have demonstrated survival outcomesfavoring surgery in this setting.9,10 However, patientswith RCC with brain metastases generally have a guardedprognosis, and invasive surgery may not be a viable op-tion for this subset of patients. Alternatives to surgeryinclude cryoablation and radiofrequency ablation, butthese are limited to smaller tumor volumes and are stillinvasive procedures.11 Thus, in patients who are medi-cally inoperable or decline invasive procedures, SBRTmay be an option to deliver noninvasive therapy to theprimary renal tumor.Currently, SBRT is a feasible treatment modality fornonmetastatic RCC, as described by the InternationalRadiosurgery Oncology Consortium for Kidneyconsensus statement, and provides excellent long-termlocal control.12,13 This technique allows for high doses ofradiation to be delivered to the tumor while attempting tospare surrounding normal tissue. Most RT clinics usefluoroscopic imaging and cone beam CT to help alignpatients for SBRT treatments. Unfortunately, the ability ofboth prior imaging modalities to discern tumor fromnormal kidney and surrounding OARs can be poor in theabdomen.14 MRI-guided RT provides excellent soft-tissuecontrast, which reduces this uncertainty. In addition toimproving accuracy of patient set-up, MRI can becontinuously acquired during treatment, without addi-tional ionizing radiation, to confirm tumor location withinthe gating boundary when the beam is on. This eliminatesthe need for fiducial marker placement in a classicallyhighly vascular tumor. Treatment with this novel systemmay improve the therapeutic ratio by improving tumorcoverage while reducing unnecessary dose to OARs. Thisis of particular importance with SBRT treatments wherehigh doses of radiation are delivered with sharp dose falloff outside the target volumes.This case demonstrates that MRI-guided SBRT is areasonable approach to locally ablate the primary renaltumor in the setting of stable metastatic RCC with con-current nivolumab. Kerkhof et al initially reported thetechnical feasibility of MRI-guided radiation for renaltumor ablation by evaluating renal movement during free-breathing and breath-hold imaging.15 Correa et al reporteda prospective phase 1 dose-escalation study for conven-tional SBRT to the primary renal mass in metastatic pa-tients with RCC; they were able to escalate to a regimenof 35 Gy delivered in 5 fractions with acceptable toxicityoutcomes.16 Our patient was treated to 40 Gy in 5 frac-tions with no reported toxicity at 6-month follow-up,stable renal function, and no evidence of progression.Of note, the benefits of SBRT may go beyond localcontrol. Radiation delivered in large fraction sizes isknown to boost the antitumor immune response in pre-clinical studies.17,18 Singh et al showed that SBRT to theprimary renal mass in patients with metastatic RCC canalter immunomodulatory markers in the primary tumor.19The combination of high dose per fraction and immuno-therapy in animal models has demonstrated responses inboth irradiated and nonirradiated sites of disease, sug-gesting a role for SBRT in improving local and distantcontrol.20 As a result, prospective clinical evaluation ofthe combination of SBRT with immunotherapy in patientswith RCC is underway (NCT02855203).To our knowledge, this is the first report of MRI-guided SBRT for the primary mass in a patient withmetastatic RCC. A prior case report demonstrated use ofthe MRI-guided system on a spleen tumor with a moreconventionally fractionated radiation regimen.21 In thepresent report, we detail the simulation and treatmentFigure 3 Sagittal magnetic resonance image view of respiratory-gated radiation delivery with gross tumor volume (yellow) within3-mm gating boundary (light blue) (A) and outside gating boundary (B).Advances in Radiation Oncology: OctobereDecember 2019 MRI-guided SBRT in renal cell carcinoma 569Downloaded for Anonymous User (n/a) at Washington University in Saint Louis Bernard Becker Medical Library from ClinicalKey.com by Elsevier on October 23, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.planning parameters used for MRI-guided SBRT to thekidney at our institution. Additional prospective studiesare needed to identify subgroups of patients with RCCwho may benefit from SBRT to not only metastatic dis-ease, but also the primary site.References1. Juusela H, Malmio K, Alfthan O, et al. Preoperative irradiation inthe treatment of renal adenocarcinoma. Scand J Urol Nephrol. 1977;11:277-281.2. van der Werf-Messing BH. Carcinoma of the kidney. Cancer. 1973;32:1056-1061.3. Svedman C, Sandström P, Pisa P, et al. A prospective phase II trialof using extracranial stereotactic radiotherapy in primary and met-astatic renal cell carcinoma. Acta Oncol. 2006;45:870-875.4. Siva S, Pham D, Gill S, et al. A systematic review of stereotacticradiotherapy ablation for primary renal cell carcinoma. BJU Int.2012;110:E737-E743.5. Chang JH, Cheung P, Erler D, et al. Stereotactic ablative bodyradiotherapy for primary renal cell carcinoma in non-surgical can-didates: Initial clinical experience. Clin Oncol. 2016;28:e109-e114.6. Siva S, Jackson P, Kron T, et al. Impact of stereotactic radiotherapyon kidney function in primary renal cell carcinoma: Establishing adose-response relationship. Radiother Oncol. 2016;118:540-546.7. Flanigan RC, Salmon SE, Blumenstein BA, et al. Nephrectomyfollowed by interferon alfa-2b compared with interferon alfa-2balone for metastatic renal-cell cancer. N Engl J Med. 2001;345:1655-1659.8. Mickisch GH, Garin A, van Poppel H, et al. Radical nephrectomyplus interferon-alfa-based immunotherapy compared with interferonalfa alone in metastatic renal-cell carcinoma: A randomised trial.Lancet. 2001;358:966-970.9. Heng DY, Wells JC, Rini BI, et al. Cytoreductive nephrectomy inpatients with synchronous metastases from renal cell carcinoma:Results from the International Metastatic Renal Cell CarcinomaDatabase Consortium. Eur Urol. 2014;66:704-710.10. Hanna N, Sun M, Meyer CP, et al. Survival analyses of patients withmetastatic renal cancer treated with targeted therapy with or withoutcytoreductive nephrectomy: A national cancer data base study. JClin Oncol. 2016;34:3267-3275.11. National Comprehensive Cancer Network. Kidney Cancer (version2.2019). Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney_blocks.pdf. Accessed February 9, 2019.12. Siva S, Ellis RJ, Ponsky L, et al. Consensus statement from theInternational Radiosurgery Oncology Consortium for Kidney forprimary renal cell carcinoma. Future Oncol. 2016;12:637-645.13. Siva S, Louie AV, Warner A, et al. Pooled analysis of stereotacticablative radiotherapy for primary renal cell carcinoma: A reportfrom the International Radiosurgery Oncology Consortium forKidney (IROCK). Cancer. 2018;124:934-942.14. Noel CE, Parikh PJ, Spencer CR, et al. Comparison of onboard low-field magnetic resonance imaging versus onboard computedtomography for anatomy visualization in radiotherapy. Acta Oncol.2015;54:1474-1482.15. Kerkhof EM, Raaymakers BW, van Vulpen M, et al. A new conceptfor non-invasive renal tumour ablation using real-time MRI-guidedradiation therapy. BJU Int. 2011;107:63-68.16. Correa RJM, Ahmad B, Warner A, et al. A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as analternative to cytoreductive nephrectomy for inoperable patientswith metastatic renal cell carcinoma. Radiat Oncol. 2018;13:47.17. Finkelstein SE, Timmerman R, McBride WH, et al. The confluenceof stereotactic ablative radiotherapy and tumor immunology. ClinDev Immunol. 2011;2011:439752.18. Siva S, Kothari G, Muacevic A, et al. Radiotherapy for renal cellcarcinoma: Renaissance of an overlooked approach. Nat Rev Urol.2017;14:549-563.19. Singh AK, Winslow TB, Kermany MH, et al. A pilot study ofstereotactic body radiation therapy combined with cytoreductivenephrectomy for metastatic renal cell carcinoma. Clin Cancer Res.2017;23:5055-5065.20. Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-inducedabscopal effect. Cancer Immunol Res. 2015;3:610-619.21. Fischer-Valuck BW, Green O, Mazur T, et al. Magnetic resonanceimage guided radiation therapy for primary splenic diffuse largeB-cell lymphoma. A teaching case. 2017;7:e23-e26.570 S. Rudra et al Advances in Radiation Oncology: OctobereDecember 2019Downloaded for Anonymous User (n/a) at Washington University in Saint Louis Bernard Becker Medical Library from ClinicalKey.com by Elsevier on October 23, 2019.For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

Magnetic resonance image guided stereotactic body radiation therapy to the primary renal mass in metastatic renal cell carcinoma

https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=9285&context=open_access_pubs

Magnetic resonance image guided stereotactic body radiation therapy to the primary renal mass in metastatic renal cell carcinoma

Abstract

Similar works

Full text

Available Versions

Digital Commons@Becker