Clinical StudyStereotactic radiosurgery for large brain metastases
Introduction
Nearly 1.7 million new diagnoses of cancer were expected in the USA in 2014, and 20–40% of patients will develop brain metastases [1], [2]. Stereotactic radiosurgery (SRS) is an effective treatment for patients with limited brain metastases. SRS has been shown to improve local tumor control better than whole brain irradiation alone, and in a subset of patients with favorable prognosis, it has been shown to improve the overall survival [3]. Furthermore, SRS has been evaluated as a sole treatment modality for patients with limited brain metastases, as a strategy to prevent the neurocognitive effects attributed to whole brain irradiation [4], [5], [6], [7], [8]. However, SRS is constrained by target size and is limited to tumors <3.5–4.0 cm. Additionally, for tumors ⩾3 cm, a dose reduction is required to reduce the unacceptably high risk of radiation injury [9]. As a result, treatment outcomes for this subgroup of patients with large metastases are suboptimal [10], [11], [12], [13]. Here, we report our institutional experience of SRS treatment for brain metastases ⩾3 cm.
Section snippets
Methods
All patients treated with SRS for brain metastases at Rhode Island Hospital between 2003 and 2013 were analyzed with approval from the Internal Review Board. Patients with baseline Karnofsky performance status (KPS) <70%, or those without adequate follow-up, were excluded. The size of the treated metastases was evaluated, and patients with large metastases, defined as ⩾3 cm in maximum diameter, were included for comparative analysis. Patient, disease, and treatment characteristics were obtained
Results
A total of 343 patients with 754 brain metastases were treated with SRS. Of these, 93 patients had large metastases (⩾3 cm). The demographics for all patients and those with large metastases are shown in Table 1. For patients with large metastases, the median age was 61 years. The most common primary diagnoses were non-small cell lung cancer (48%), breast cancer (17%), and melanoma (14%). These were not significantly different from patients with smaller lesions. Tumor size was 3–3.5, 3.5–4, and ⩾4
Discussion
CNS metastases can have a devastating effect on the quality of life of cancer patients. The impact of brain metastases will increase as novel systemic treatments lead to controlled extracranial disease and prolonged survival. As such, a reliable treatment to control brain disease is necessary to limit both disease morbidity and mortality.
SRS effectively treats small brain metastases. However, a chief difficulty in treating large brain metastases is that as tumor size increases, the volume of
Conclusion
For patients with large brain metastases, SRS can achieve local CNS disease control in the majority of patients, and extended survival in some. However, the local control rate for these large lesions is suboptimal. Surgery can be helpful to reduce symptoms or reduce target volumes, but it does not appear to improve the local disease control. Other strategies to improve outcomes in this subgroup of patients are needed.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
References (32)
The management of brain metastases
Cancer Treat Rev
(2003)- et al.
Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial
Lancet
(2004) - 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.
Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05
Int J Radiat Oncol Biol Phys
(2000) - et al.
What is the optimal treatment of large brain metastases? An argument for a multidisciplinary approach
Int J Radiat Oncol Biol Phys
(2012) - et al.
Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05
Int J Radiat Oncol Biol Phys
(2000) - et al.
Factors influencing local control and survival in patients treated with radiosurgery following surgical resection of CNS metastases
Int J Radiat Oncol Biol Phys
(2013) - et al.
Postoperative stereotactic radiosurgery without whole-brain radiation therapy for brain metastases: potential role of preoperative tumor size
Int J Radiat Oncol Biol Phys
(2013) - et al.
Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases
Int J Radiat Oncol Biol Phys
(2003) - et al.
Radiation dose-volume effects in the brain
Int J Radiat Oncol Biol Phys
(2010)
Radiation associated brainstem injury
Int J Radiat Oncol Biol Phys
Radiation dose-volume effects of optic nerves and chiasm
Int J Radiat Oncol Biol Phys
Multidose stereotactic radiosurgery (9 Gy × 3) of the postoperative resection cavity for treatment of large brain metastases
Int J Radiat Oncol Biol Phys
Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors
Int J Radiat Oncol Biol Phys
Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases
J Clin Oncol
Cited by (29)
Brain metastases: An update on the multi-disciplinary approach of clinical management
2022, NeurochirurgieCitation Excerpt :This is because the size of the tumor(s) influences the amount of radiation delivered to the surrounding, normal tissue and as the tumor size increases, so does the incidental irradiation delivered to the surrounding tissues [106]. Several studies have evaluated the maximum size of metastatic lesions that can be successfully treated with SRS to achieve sufficient local control without exposing the surrounding, normal tissue to unacceptable levels of radiation [116–123]. The Radiation Therapy Oncology group (RTOG 90-05), previously determined the maximum tolerated dose for non-brainstem BM with diameters ≤2 cm, >2–3 cm and > 3–4 cm to be 24 Gy, 18 Gy and 15 Gy, respectively [121,122].
Standalone gamma knife radiosurgery for brain metastasis of malignant peripheral nerve sheath tumor
2021, Interdisciplinary Neurosurgery: Advanced Techniques and Case ManagementTumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases
2021, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Our searches identified only 2 groups that modeled data from pooled studies: Wiggenraad et al27 and Shuryak et al.29 Of 1500 articles published on radiosurgery for brain metastases in radiation-naïve patients and patients previously treated with WBRT up to 2011, the Wiggenraad 2011 review only included 12 data points from 11 papers in the dose-response model. As can be seen from Table 114,30-84 and Tables EA1 to EA3, our literature search confirmed the small number of reports that provided sufficient stratification of dose, fractionation, and size to be modeled; we only found 2 additional usable data points from that period. All dose-response models in this HyTEC review were logistic85 (Table EA4).
Stereotactic radiotherapy of brain metastases in complex situations
2019, Cancer/RadiotherapieTailored Treatment Options for Patients with Brain Metastases by a Relocatable Frame System with Gamma Knife Radiosurgery
2018, World NeurosurgeryCitation Excerpt :It can increase the risk with traditional single-fraction high-dose GKRS for large treatment volumes.14,15 Several studies23-27 reported that single session GKRS achieved reasonable local control with acceptable central nervous system toxicity in selected patients with large brain metastases. However, lower radiation doses may prevent adverse effects, which are associated with a relatively inferior control rate compared with smaller tumors when a higher radiation dose is needed to eradicate tumor clonogens.
Very Large Metastases to the Brain: Retrospective Study on Outcomes of Surgical Management
2018, World NeurosurgeryCitation Excerpt :Although they do not isolate patients with metastases larger than 4 cm, they mention on multivariate analysis that age younger than 65 years was the only metric associated with improved survival. They did not identify a significant difference on overall survival based on size when comparing metastases of 3–4 cm with those greater than 4 cm.12 Lee et al.27 also reviewed SRS for intracranial metastases, focusing on those larger than 3 cm in diameter.