RadiosurgeryStereotactic radiosurgery as single-modality treatment of incidentally identified renal cell carcinoma brain metastases☆
Introduction
Each year, 30 000 new cases of RCC are diagnosed [17]; 60% of these patients will develop metastatic disease [34]. Approximately 4% to 17% of metastatic RCCs involve the brain [32], for an estimated incidence of 1200 to 5100 cases annually. Most of the brain lesions are clinically asymptomatic [31] and are discovered during routine staging evaluation; such cases pose a unique therapeutic challenge. Because effective treatment of brain metastases can improve both quality of life and outcomes in selected patients, as well as influence eligibility for clinical trials, patients stand to benefit from early, aggressive control of their CNS disease. Conversely, the benefits of early treatment of brain metastases must be weighed against the delays that such interventions, particularly those associated with surgery or whole brain irradiation (WBI), may cause for the management of the primary malignancy; and so, strategies must maximize CNS control and minimize delays in systemic therapy.
Optimal management of brain metastasis has not been defined and generally must be conducted on an individual basis. Essentially all clinical studies reported involve symptomatic patients. The median survival of patients with untreated RCC brain metastases averages 3 to 4 months [9]. Monotherapy with WBI confers benefit in many patients, with median survival of 8.5, 3.0, and 0.6 months for RPA (Table 1) class 1, 2, and 3 patients, respectively, [5]. Surgical resection of RCC brain metastases has resulted in reported mean survival times ranging from 2.5 to 27.5 months [25], [29], [35]. These data must be viewed with caution, however, as selection bias toward patients with good performance status, limited systemic disease, and only a single metastasis may influence these results. Surgery and adjuvant WBI, which decreases recurrence and improves survival in patients with metastatic brain lesions, are generally applied in concert [27].
The modest response of RCC brain metastases to WBI alone has traditionally been considered the result of a “relatively radioresistant” phenotype. Current thinking suggests that this resistance may be a dose-dependent outcome, and RCC lesions may be effectively treated with higher radiation doses [4], [10], [11]. Until the advent of SRS, however, the clinical significance of this distinction was limited by the radiosensitivity of the normal brain. Overall survival for patients undergoing monotherapy with SRS has been reported at 7.5 to 12.5 months [6], [15], [19], [28], [30], [33]; and survival stratified by RPA class has been reported at 18 to 24, 8.5 to 9.2, and 5.3 to 7.5 months for classes 1, 2, and 3, respectively [14], [23]. Furthermore, local control rates lie in the 80% to 98% range [4], [22], [23], [24], [33]. Adding WBI to SRS may not improve either overall survival or local or distant recurrence rates [1], [2], [12], [13], [16], [22].
Although not directly comparable, these studies suggest that survival is similar when RCC brain metastases are managed either with SRS or with surgery and WBI. In general, most patients with metastatic tumors, including RCC, die of complications related to their primary malignancy or to additional, distant CNS metastases. Neither the major study of WBI with or without SRS (RTOG 9508) nor a recent randomized trial of SRS with or without WBI included significant numbers of patients with RCC (4/331 and 10/132 patients, respectively), so the optimal method of managing RCC metastases to the brain remains unclear [1], [2]. Finally, neither study examined asymptomatic patients, a significant proportion of RCC patients (as many as 86% of patients may have minimal or no neurologic symptoms at the time of diagnosis [31]); and the number of patients with brain metastasis, symptomatic or not, may likely grow, as an increasing number of patients with metastases outside the CNS survive because of improved control with newer, molecularly targeted agents [7].
Stereotactic radiosurgery is an attractive option to patients with incidentally discovered RCC brain metastases, as it combines the potential for definitive or extended local control with a favorable adverse effect profile, a brief recovery period, and minimal delay of treatment of the primary malignancy and may be repeated or have WBI added subsequently. Because of the inherent limitations of the RPA system, specific outcomes data for such patients are lacking. We analyzed the outcomes of patients with incidentally discovered RCC brain metastases who were managed initially with SRS monotherapy.
Section snippets
Patient selection
Patients who were diagnosed with RCC and had one or more brain lesions consistent with metastases were eligible for inclusion in this study. For the purpose of this retrospective study, asymptomatic was defined as a Karnofsky Performance Score (KPS) greater than or equal to 90 and no neurologic symptoms or signs related to the brain lesion(s); patients with a KPS of 80 or lower were excluded. Patients younger than 18 years at the time of diagnosis; patients who harbored more than one active,
Dosimetry analysis
Dosimetry data were analyzed for all patients receiving radiotherapy to verify uniform treatment within the study groups and concordance with standard accepted therapeutic dosages. Patients in the SRS-only group received a mean prescribed dose of 21.3 Gy (95% CI, ±3.81 Gy) delivered to the mean 59.96% (95% CI, ±3.39%) isodose line. Patients treated with WBRT only received a mean total dose of 35 Gy (95% CI, ±0.35 Gy) with a mean fractionated dose of 262.5 cGy (95% CI, ±24.5 cGy). Patients
Outcomes after SRS for incidentally discovered brain metastases
Imaging of the neuraxis is becoming routine at many institutions as a part of initial staging workup for patients presenting with newly diagnosed RCC. Up to 86% of these patients may harbor clinically asymptomatic brain metastasis, generating the need for a management strategy for patients with incidentally discovered tumors [31]. At the time of diagnosis of their CNS disease, these patients often undergo local or systemic therapy for their newly diagnosed primary tumors and have concerns
Conclusions
Patients presenting with incidentally discovered brain metastases from RCC primary tumors managed with SRS have a mean survival of 21.46 ± 10.08 months (median, 12.58 months). This is at least comparable with survival after treatment with surgery ± WBRT. Stereotactic radiosurgery therefore represents a potential alternative to other therapeutic modalities for patients with incidentally discovered RCC brain metastases, as it confers comparable survival benefits without some of the risks and
Acknowledgments
This research was generously supported by the Melvin Burkhardt chair in neurosurgical oncology and the Karen Colina Wilson research endowment within the Brain Tumor Institute at the Cleveland Clinic Foundation.
References (35)
- 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.
Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone
Int J Radiat Oncol Biol Phys
(2007) - et al.
Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study
Int J Rad Oncol Biol Phys
(2004) - et al.
The role of whole brain radiotherapy and stereotactic radiosurgery on brain metastases from renal cell carcinoma
Int J Rad Oncol Biol Phys
(2000) - et al.
Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases
Int J Radiat Oncol Biol Phys
(1999) - et al.
LINAC radiosurgery for brain metastasis of renal cell carcinoma
Urologic Oncology: Seminars and Original Investigations,
(2004) - et al.
The treatment of renal cell carcinoma with solitary metastasis
J Urol
(1978) - et al.
Surgical resection of brain metastases from renal cell carcinoma in 50 patients
Urology
(1996) - et al.
Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial
JAMA
(2006) - et al.
Definitive, high-dose-per-fraction, conformal, stereotactic external radiation for renal cell carcinoma
Am J Clin Oncol
(2004)
Outcome variation among “radioresistant” brain metastases treated with stereotactic radiosurgery
Neurosurg
Recent advances in targeted therapy for renal cell carcinoma
Curr Opin Urol
Radiation-induced dementia in patients cured of brain metastases
Neurology
Brain metastases in patients with renal cell carcinoma: prognosis and treatment
J Clin Oncol
Radiation therapy in the management of brain metastases from renal cell carcinoma
Oncology
Improved survival duration in patients with unresected solitary brain metastasis using accelerated hyperfractionated radiation therapy at total doses of 54.4 gray and greater. Results of Radiation Therapy Oncology Group 85-28
Cancer
Radiosurgery of brain metastases from renal cell carcinoma: how can you improve on results like this?
Cancer J
Cited by (27)
Global management of brain metastasis from renal cell carcinoma
2022, Critical Reviews in Oncology/HematologyStereotactic Radiation Therapy for Renal Cell Carcinoma Brain Metastases in the Tyrosine Kinase Inhibitors Era: Outcomes of 120 Patients
2019, Clinical Genitourinary CancerBrain metastases in renal cell carcinoma, an unmet need
2018, Bulletin du CancerKidney cancer and radiotherapy: Radioresistance and beyond
2018, Bulletin du CancerBrain Metastasis from Renal Carcinoma: Locoregional and Systemic Treatments
2015, Brain Metastases from Primary Tumors: Epidemiology, Biology, and Therapy
- ☆
Authorization of copyright transfer: The authors hereby authorize transfer of copyright for this manuscript to the editorial board of the publishing journal at the time of print and/or electronic publication.
- 1
Reprint requests and other correspondence may be addressed to either LA or RJW: Lilyana Angelov, MD, Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195. Robert J. Weil, MD, Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195.