Dosimetric evaluation of four whole brain radiation therapy approaches with hippocampus and inner ear avoidance and simultaneous integrated boost for limited brain metastases

Aijun Jiang, Weipeng Sun, Fen Zhao, Zhenxuan Wu, Dongping Shang, Qingxi Yu, Suzhen Wang, Jian Zhu, Fengchang Yang, Shuanghu Yuan, Aijun Jiang, Weipeng Sun, Fen Zhao, Zhenxuan Wu, Dongping Shang, Qingxi Yu, Suzhen Wang, Jian Zhu, Fengchang Yang, Shuanghu Yuan

Abstract

Aims: To perform a dosimetric evaluation of four different simultaneous integrated boost whole brain radiotherapy modalities with hippocampus and inner ear avoidance in the treatment of limited brain metastases.

Methods: Computed tomography/magnetic resonance imaging data of 10 patients with limited (1-5) brain metastases were used to replan step-and-shoot intensity-modulated radiotherapy (sIMRT), dynamic intensity-modulated radiation therapy (dIMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (Tomo). The prescribed doses of 40-50 Gy in 10 fractions and 30 Gy in 10 fractions were simultaneously delivered to the metastatic lesions and the whole-brain volume, respectively. The hippocampal dose met the RTOG 0933 criteria for hippocampal avoidance (Dmax ≤17 Gy, D100% ≤10 Gy). The inner ear dose was restrained to Dmean ≤15 Gy. Target coverage (TC), homogeneity index (HI), conformity index (CI), maximum dose (Dmax), minimum dose (Dmin) and dose to organs at risk (OARs) were compared.

Results: All plans met the indicated dose restrictions. The mean percentage of planning target volume of metastases (PTVmets) coverage ranged from 97.1 to 99.4%. For planning target volume of brain (PTVbrain), Tomo provided the lowest average D2% (37.5 ± 2.8 Gy), the highest average D98% (25.2 ± 2.0 Gy), and the best TC (92.6% ± 2.1%) and CI (0.79 ± 0.06). The two fixed gantry IMRT modalities (step and shot, dynamic) provided similar PTVbrain dose homogeneity (both 0.76). Significant differences across the four approaches were observed for the maximum and minimum doses to the hippocampus and the maximum doses to the eyes, lens and optic nerves.

Conclusion: All four radiotherapy modalities produced acceptable treatment plans with good avoidance of the hippocampus and inner ear. Tomo obtained satisfactory PTVbrain coverage and the best homogeneity index.

Trial registration: Clinicaltrials.gov, NCT03414944 . Registered 29 January 2018.

Keywords: Brain metastases; Dosimetry; Hippocampus; Inner ear; Intensity-modulated radiation therapy; Tomotherapy; Volumetric-modulated arc therapy.

Conflict of interest statement

Ethics approval and consent to participate

The clinical research committee of the study institute approved the study protocol, and written informed consent was waived by the Institutional Review Board .

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Color wash comparison of dose distributions for four modalities in a representative patient. sIMRT: step-and-shoot intensity-modulated radiotherapy, dIMRT: dynamic intensity-modulated radiation therapy, VMAT: volumetric-modulated arc therapy, Tomo: helical tomotherapy
Fig. 2
Fig. 2
Dose–volume histograms for treatment planning with the four modalities for a representative patient. sIMRT: step-and-shoot intensity-modulated radiotherapy, dIMRT: dynamic intensity-modulated radiation therapy, VMAT: volumetric-modulated arc therapy, Tomo: helical tomotherapy

References

    1. Tsao MN, Xu W, Wong RK, Lloyd N, Laperriere N, Sahgal A, et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2018. 10.1002/14651858.
    1. Soffietti R, Ruda R, Trevisan E. Brain metastases: current management and new developments. Curr Opin Oncol. 2008;20:676–684. doi: 10.1097/CCO.0b013e32831186fe.
    1. Kong W, Jarvis CR, Sutton DS, Ding K, Mackillop WJ. The use of palliative whole brain radiotherapy in the management of brain metastases. Clin Oncol (R Coll Radiol). 2012. 10.1016/j.clon.2012.08.004.
    1. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10:1037–1044. doi: 10.1016/S1470-2045(09)70263-3.
    1. Rades D, Kueter JD, Hornung D, Veninga T, Hanssens P, Schild SE, et al. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT+SRS) for one to three brain metastases. Strahlenther Onkol. 2008;184:55–62.
    1. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295:2483–2491. doi: 10.1001/jama.295.21.2483.
    1. Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011;29:134–141. doi: 10.1200/JCO.2010.30.1655.
    1. Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014;32:3810–3816. doi: 10.1200/JCO.2014.57.2909.
    1. Hajisafari A, Bakhshandeh M, Aghamiri SMR, Houshyari M, Rakhsha A, Bolokat ER, et al. Prospective evaluation of the early effects of radiation on the auditory system frequencies of patients with head and neck cancers and brain tumors after radiotherapy. Ear Nose Throat J. 2018;97:E10–E17. doi: 10.1177/014556131809700302.
    1. Abayomi OK. Pathogenesis of irradiation-induced cognitive dysfunction. Acta Oncol. 1996;35:59–63. doi: 10.3109/02841869609083995.
    1. Tang FR, Loke WK, Khoo BC. Postnatal irradiation-induced hippocampal neuropathology, cognitive impairment and aging. Brain and Development. 2017;39:277–293. doi: 10.1016/j.braindev.2016.11.001.
    1. Ji S, Tian Y, Lu Y, Sun R, Ji J, Zhang L, et al. Irradiation-induced hippocampal neurogenesis impairment is associated with epigenetic regulation of bdnf gene transcription. Brain Res. 2014;1577:77–88. doi: 10.1016/j.brainres.2014.06.035.
    1. Tan PX, Du SS, Ren C, Yao QW, Yuan YW. Radiation-induced cochlea hair cell death: mechanisms and protection. Asian Pac J Cancer Prev. 2013;14:5631–5635. doi: 10.7314/APJCP.2013.14.10.5631.
    1. Hitchcock YJ, Tward JD, Szabo A, Bentz BG, Shrieve DC. Relative contributions of radiation and cisplatin-based chemotherapy to sensorineural hearing loss in head-and-neck cancer patients. Int J Radiat Oncol Biol Phys. 2009;73:779–788. doi: 10.1016/j.ijrobp.2008.05.040.
    1. Dobi Á, Fodor E, Maráz A, Együd Z, Cserháti A, Tiszlavicz L, et al. Boost Irradiation Integrated to Whole Brain Radiotherapy in the Management of Brain Metastases. Pathol Oncol Res. 2018. 10.1007/s12253-018-0383-y.
    1. Rodrigues G, Yartsev S, Tay KY, Pond GR, Lagerwaard F, Bauman G. A phase II multi-institutional study assessing simultaneous in-field boost helical tomotherapy for 1-3 brain metastases. Radiat Oncol. 2012;7:42. doi: 10.1186/1748-717X-7-42.
    1. Ferro M, Cilla S, Macchia G, Deodato F, Pierro A, Digesu’ C, et al. On the cutting edge of intensity modulated radiotherapy and simultaneous integrated boost (IMRT-SIB): the case of a patient with 8 brain metastases. Rep Pract Oncol Radiother. 2015;20(4):316–319. doi: 10.1016/j.rpor.2014.09.001.
    1. Sood S, Pokhrel D, McClinton C, Lominska C, Badkul R, Jiang H, et al. Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk. Med Dosim. 2017;42:375–383. doi: 10.1016/j.meddos.2017.07.005.
    1. Gutiérrez AN, Westerly DC, Tomé WA, Jaradat HA, Mackie TR, Bentzen SM, et al. Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. Int J Radiat Oncol Biol Phys. 2007;69:589–597. doi: 10.1016/j.ijrobp.2007.05.038.
    1. Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012. 10.1002/14651858.
    1. Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys. 1982;8:1981–1997. doi: 10.1016/0360-3016(82)90459-X.
    1. Paddick I. A simple scoring ratio to index the conformity of radiosurgical treatment plans. Technical note. J Neurosurg. 2000;93(Suppl 3):219–222. doi: 10.3171/jns.2000.93.supplement_3.0219.
    1. Kataria T, Sharma K, Subramani V, Karrthick KP, Bisht SS. Homogeneity index: an objective tool for assessment of conformal radiation treatments. J Med Phys. 2012;37:207–213. doi: 10.4103/0971-6203.103606.
    1. Zhou L, Liu J, Xue J, Xu Y, Gong Y, Deng L, et al. Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer. Radiat Oncol. 2014;9:117. doi: 10.1186/1748-717X-9-117.
    1. Prokic V, Wiedenmann N, Fels F, Schmucker M, Nieder C, Grosu AL. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: a planning study on treatment concepts. Int J Radiat Oncol Biol Phys. 2013;85:264–270. doi: 10.1016/j.ijrobp.2012.02.036.
    1. Cozzi L, Clivio A, Bauman G, Cora S, Nicolini G, Pellegrini R, et al. Comparison of advanced irradiation techniques with photons for benign intracranial tumours. Radiother Oncol. 2006;80:268–273. doi: 10.1016/j.radonc.2006.07.012.
    1. Kothavade V, Jamema SV, Gupta T, Pungavkar S, Upasani M, Juvekar S, et al. Which is the most optimal technique to spare hippocampus?-Dosimetric comparisons of SCRT, IMRT, and tomotherapy. J Cancer Res Ther. 2015;11:358–363. doi: 10.4103/0973-1482.157310.
    1. Rong Y, Evans J, Xu-Welliver M, Pickett C, Jia G, Chen Q, et al. Dosimetric evaluation of intensity-modulated radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for hippocampal-avoidance whole brain radiotherapy. PLoS One. 2015. 10.1371/journal.pone.0126222.
    1. Pokhrel D, Sood S, Lominska C, Kumar P, Badkul R, Jiang H, et al. Potential for reduced radiation-induced toxicity using intensity-modulated arc therapy for whole-brain radiotherapy with hippocampal sparing. J Appl Clin Med Phys. 2015;16:131–141. doi: 10.1120/jacmp.v16i5.5587.
    1. Liu SH, Murovic J, Wallach J, Cui G, Soltys SG, Gibbs IC, et al. CyberKnife radiosurgery for brainstem metastases: management and outcomes and a review of the literature. J Clin Neurosci. 2016;25:105–110. doi: 10.1016/j.jocn.2015.10.013.
    1. Yamamoto M, Serizawa T, Higuchi Y, Sato Y, Kawagishi J, Yamanaka K, et al. A multi-institutional prospective observational study of stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901 study update): irradiation-related complications and long-term maintenance of mini-mental state examination scores. Int J Radiat Oncol Biol Phys. 2017;99:31–40. doi: 10.1016/j.ijrobp.2017.04.037.

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