Abstract
Aim
To assess whether extent of surrounding edema correlates with acute adverse clinical outcomes within 3 months after stereotactic radiosurgery (SRS) for melanoma brain metastases (BM).
Methods
Patients with melanoma BM treated with SRS were included in a single center retrospective analysis. A contrast-enhanced magnetic resonance image (MRI) brain was acquired on the day of treatment and used to calculate the volume of the largest lesion (the index BM) and total volume of all BM. Their corresponding volume of surrounding edema was defined based on the fluid attenuated inversion recovery (FLAIR) sequence. After SRS, MRI was performed every 3 months for at least 2 years if the patient remained well enough to do so. Adverse neurologic events after SRS were defined using common terminology criteria for adverse events (CTCAE) version 5.0. Multivariate regression analyses assessed for associations between BM size and edema at baseline with increasing edema and neurologic adverse events within 3 months after SRS.
Results
Mean volume of the index BM reduced from 2.2 to 0.5 cm3 at 3 months after SRS (p = 0.03). Mean volume of edema surrounding the index BM was 6.4 cm3 at baseline, 10.2 cm3 at 3 months and 5.5 cm3 at 6 months. There were 7/43 (16%) patients that experienced an adverse neurological event within 3 months (attributable to any cause) and 4/43 (9%) were associated with an increase in BM edema. On univariate and multivariate analyses, there were no correlations between any baseline factors and volume of edema at 3 months. However, SRS dose delivered and systemic therapy use within 4 weeks of SRS both correlated with a reduction in edema surrounding the index BM.
Conclusion
A transient increase in mean volume of edema was apparent at 3 months after SRS. However, this resolved by 6 months and did not correlate with adverse events or dexamethasone requirement. Thus, the clinical significance is uncertain.
Similar content being viewed by others
References
Tio M, Wang X, Carlino MS, Shivalingam B, Fogarty GB, Guminski AD, Lo S, Hong AM, Menzies AM, Long GV (2018) Survival and prognostic factors for patients with melanoma brain metastases in the era of modern systemic therapy. Pigment Cell Melanoma Res. https://doi.org/10.1111/pcmr.12682
Sperduto PW, Jiang W, Brown PD, Braunstein S, Sneed P, Wattson DA, Shih HA, Bangdiwala A, Shanley R, Lockney NA, Beal K, Lou E, Amatruda T, Sperduto WA, Kirkpatrick JP, Yeh N, Gaspar LE, Molitoris JK, Masucci L, Roberge D, Yu J, Chiang V, Mehta M (2017) Estimating survival in melanoma patients with brain metastases: an update of the graded prognostic assessment for melanoma using molecular markers (Melanoma-molGPA). Int J Radiat Oncol Biol Phys 99(4):812–816
Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322(8):494–500
Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeko N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K (2014) Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15(4):387–395
Aiyama H, Yamamoto M, Kawabe T, Watanabe S, Koiso T, Sato Y, Higuchi Y, Ishikawa E, Yamamoto T, Matsumura A, Kasuya H, Barfod BE (2018) Complications after stereotactic radiosurgery for brain metastases: incidences, correlating factors, treatments and outcomes. Radiother Oncol 129(2):364–369
Harat M, Lebioda A, Lasota J, Makarewicz R (2017) Evaluation of brain edema formation defined by MRI after LINAC-based stereotactic radiosurgery. Radiol Oncol 51(2):137–141
Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA (2018) Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol 19(5):672–681
Colaco RJ, Yu JB, Bond JS, Bindra RS, Contessa JN, Knisely JPS, Chiang VL (2016) A contemporary dose selection algorithm for stereotactic radiosurgery in the treatment of brain metastases—An initial report. J Radiosurg SBRT 4(1):43–45
National Institute of Health- Cancer Therapy Evaluation Program (2017) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 %3chttps://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf%3e
Kothari RU, Brott T, Broderick JP, Brasan WG, Sauerbeck LR, Zuccarello M, Khoury J (2018) The ABCs of measuring intracerebral hemorrhage volumes. Stroke 27:1304–1305
Krishnan K, Mukhtar SF, Lingard J (2015) Performance characteristics of methods for quantifying spontaneous intracerebral haemorrhage: data from the efficacy of nitric oxide in stroke (ENOS) trial. J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2014-309845
Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Márquez-Rodas I, Del Vecchio M, Lebbé C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV (2017) Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol 18(7):863–873
Hanna A, Boggs DH, Kwok Y, Simard M, Regine WF, Mehta M (2016) What predicts early volumetric oedema increase following stereotactic radiosurgery for brain metastases? J Neurooncology. 127:303–311
Qian JM, Yu JB, Kluger HM, Chiang VL (2016) Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 122(19):3051–3058
Minniti G, Scaringi C, Paolini S, Lanzetta G, Romano A, Cicone F, Osti M, Enrici RM, Esposito V (2016) Single-fraction versus multifraction (3 × 9 Gy) stereotactic radiosurgery for large (%3e2 cm) brain metastases: a comparative analysis of local control and risk of radiation-induced brain necrosis. Int J Radiat Oncol Biol Phys 95(4):1142–1148
Pires da Silva I, Glitza IC, Haydu LE, Johnpulle R, Banks PD, Grass GD, Goldinger SMA, Smith JL, Everett AS, Koelblinger P, Roberts-Thomson R, Millward M, Atkinson VG, Guminski A, Kapoor R, Conry RM, Carlino MS, Wang W, Shackleton MJ, Eroglu Z, Lo S, Hong AM, Long GV, Johnson DB, Menzies AM (2019) Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti-PD-1 antibodies. Pigment Cell Melanoma Res 32(4):553–563
Kruser TJ, Gondi V, Sperduto PW, Brown PD (2018) Omitting radiosurgery in melanoma brain metastases: a drastic and dangerous de-escalation. Lancet Oncol 19(8):366
Funding
No funding was received for this project.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflict of interest.
Informed consent
All patient data was de-identified prior to review and its use approved by Institutional Review Board from the Princess Alexandra Ethics Committee.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethics approval to conduct research at the Princess Alexandra Hospital was granted by the Centers for Health Research on the 18/07/2017. The approval was subject to researcher compliance throughout the duration of the research with requirements as outlines in the National Statement on Ethical Conduct in Human Research 2007 and Australian Code for the Responsible Conduct of Research. HREC/17/QPAH/379-SSA/17/QPAH/380
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Jardim, A., Scott, J., Drew, Z. et al. Extent of surrounding edema does not correlate with acute complications after radiosurgery for melanoma brain metastases. J Neurooncol 145, 581–585 (2019). https://doi.org/10.1007/s11060-019-03330-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-019-03330-9