Basic Original ReportBrain metastasis growth on preradiosurgical magnetic resonance imaging
Introduction
Brain metastases are a significant cause of morbidity and mortality among patients with advanced cancer. The neurocognitive morbidity that results from whole brain radiation therapy (WBRT)1 has led to stereotactic radiation surgery (SRS) frequently being used in the management of a limited number of brain metastases,2 and many radiation oncologists would consider this standard of care in the modern era.3 In addition, growing evidence supports the feasibility of SRS without WBRT for patients with multiple brain metastases.[4], [5]
SRS may be administered using either a fixed-frame or frameless approach. With fixed-frame SRS at our institution, planning magnetic resonance imaging (MRI) is acquired after placement of a treatment immobilization frame, and SRS is delivered on the same day. No planning treatment volume (PTV) margin is added because the SRS-planning MRI scan (ie, treatment MRI) and SRS delivery are both performed under same-day, head frame-fixation with sub-millimeter accuracy.6 However, with the frameless approach, a planning MRI is often obtained days to weeks before SRS delivery.7 A PTV margin of 1 to 2 mm may be used to account for uncertainty in patient position between planning and treatment for frameless SRS,8 but image guided SRS delivery systems with intrafraction motion may obviate any PTV from being used. A clinical target volume (CTV) margin of 1 mm may be employed to account for infiltration9 but not necessarily growth between SRS planning and delivery.
Given the precisely targeted and highly conformal nature of SRS, successful treatment relies on adequate target coverage with rapid radiation dose falloff. Seymour et al. reported 95% versus 56% 6-month local control (LC) of brain metastases for <14 versus ≥14 days between the planning MRI and the delivery of the frameless SRS.10 This raises the question, is worse LC due to a marginal miss from brain metastasis growth between SRS planning and SRS delivery not accounted for by the PTV margin?
Herein, we sought to quantify brain metastasis growth on MRI scans leading up to delivery of SRS and evaluate the need for CTV margins necessary to account for such growth, which has not been previously reported.
Section snippets
Methods and materials
We reviewed data from all patients who were treated with fixed-frame SRS for previously untreated brain metastases at our institution between January 2010 and December 2013 and had documentation and imaging available in the electronic medical record system. Patients who were diagnosed with 1 to 10 brain metastases and had a fixed-frame SRS planning MRI (treatment MRI) at the time of the SRS as well as a prior diagnostic MRI (pretreatment MRI) available for comparison were chosen for analysis.
Results
We identified 165 patients with a total of 411 brain metastases who met the inclusion criteria. The median age at time of SRS was 63 years (range, 25-97 years). The most common cancer histologies were nonsmall cell lung cancer (30%), melanoma (27%), breast (24%), and renal cell carcinoma (5%). With regard to the extent of disease at the time of referral for fixed-frame SRS, 8% of patients had brain metastases without evidence of extracranial disease, 42% had controlled extracranial metastatic
Discussion
In an era where SRS without WBRT is becoming a more conventional approach to treat multiple brain metastases,[1], [5], [12], [13], [14], [15] the accurate targeting of brain metastases is paramount for intracranial disease control.
Given that ≥2 weeks between SRS-planning MRI and frameless SRS delivery was associated with worse LC in a prior study,10 one logical explanation is that interval tumor growth that is not addressed during planning leads to a radiosurgical marginal miss.
Herein, we
Conclusions
Time between pretreatment and treatment MRI scans is associated with brain metastasis growth. LC does not appear compromised when patients receive fixed-frame SRS with same-day imaging and planning. Given the inherent workflow of frameless radiation surgery with time between planning MRI and treatment delivery, adding a CTV margin to account for potential growth may preserve LC, but must be measured against the potential treatment of excess uninvolved brain tissue.
In addition, larger brain
References (22)
- et al.
Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: A randomised controlled trial
Lancet Oncol
(2009) - et al.
Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: Individual patient data meta-analysis
Int J Radiat Oncol Biol Phys
(2015) - et al.
Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): A multi-institutional prospective observational study
Lancet Oncol
(2014) - et al.
Inter- and intrafraction patient positioning uncertainties for intracranial radiotherapy: A study of four frameless, thermoplastic mask-based immobilization strategies using daily cone-beam CT
Int J Radiat Oncol Biol Phys
(2011) - et al.
Interval from imaging to treatment delivery in the radiosurgery age: How long is too long?
Int J Radiat Oncol Biol Phys
(2015) - et al.
Stereotactic radiosurgery alone for brain metastases
Lancet Oncol
(2015) - et al.
A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases
Int J Radiat Oncol Biol Phys
(2002) - et al.
Discovery of additional brain metastases on the day of stereotactic radiosurgery: risk factors and outcomes
J Neurosurg
(July 2016) - et al.
A pathology-based substrate for target definition in radiosurgery of brain metastases
Int J Radiat Oncol Biol Phys
(2006) ASTRO releases second list of five radiation oncology treatments to question, as part of national Choosing Wisely campaign
Whole brain radiotherapy for brain metastases: Is the debate over?
JAMA
Cited by (20)
Stereotactic Radiosurgery in the Management of Brain Metastases: A Case-Based Radiosurgery Society Practice Guideline
2024, Advances in Radiation OncologyA Comparison of Single Fraction and Multi Fraction Radiosurgery on the Gamma Knife ICON: A Single Institution Review
2023, Advances in Radiation OncologyAccuracy of MRI-CT registration in brain stereotactic radiotherapy: Impact of MRI acquisition setup and registration method
2022, Zeitschrift fur Medizinische PhysikCitation Excerpt :The MRI images are then co-registered to the planning CT images, and so the contoured target volumes are brought onto the CT frame-of-reference. Due to the different acquisition sites and the time interval between the MRI and CT acquisition (±5 days), multiple uncertainties are introduced due to tumor growth and displacement as well as the differences in positioning between MRI acquisition and treatment delivery [5,6]. One important uncertainty derives from the MRI-CT registration inaccuracy.
Cerebral metastases
2022, Progress in Brain ResearchCitation Excerpt :Gamma Knife users have long been familiar with the finding that there are more tumors in the dose-planning MR images than were to be seen in the referral images (Garcia et al., 2017; Patel et al., 2012). A more recent finding is that tumors may grow in volume from referral to treatment (Garcia et al., 2018; Plunkett et al., 2019). The increase in number and volume of tumors to receive radiosurgery emphasizes the need to avoid delay as much as possible.
The Effect of Slice Thickness on Contours of Brain Metastases for Stereotactic Radiosurgery
2021, Advances in Radiation OncologyCitation Excerpt :Our results indicate that if an image with a large slice thickness is used for pretreatment evaluation, small lesions can be missed, and patients may be excluded from receiving SRS who would otherwise be candidates. Similarly, there is a chance that MRI with slice thickness greater than 1 mm may not identify patients with numerous tiny metastases and may lead to an aborted SRS treatment when thin slices are acquired on the day of treatment after frame placement.25 When thick-slice images are used in follow-up, small lesions may be missed entirely or the lesion volume may be overestimated, making it appear to have grown.
The authors report no funding in support of this study.
Conflicts of interest: The authors report no conflicts of interest with regard to the materials, methods, or results in this study.