- Department of Neurosurgery, Rush University Medical Center, Chicago, IL, USA
- Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL, USA
- Medical College, Rush University, Chicago, IL, USA
- Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA
Robert G. Kellogg
Department of Neurosurgery, Rush University Medical Center, Chicago, IL, USA
DOI:10.4103/2152-7806.121632Copyright: © 2013 Kellogg RG. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Kellogg RG, Straus DC, Choi M, Chaudhry TA, Diaz AZ, Lorenzo F. Muñoz. Stereotactic radiosurgery boost to the resection cavity for cerebral metastases: Report of overall survival, complications, and corticosteroid protocol. Surg Neurol Int 20-Nov-2013;4:
How to cite this URL: Kellogg RG, Straus DC, Choi M, Chaudhry TA, Diaz AZ, Lorenzo F. Muñoz. Stereotactic radiosurgery boost to the resection cavity for cerebral metastases: Report of overall survival, complications, and corticosteroid protocol. Surg Neurol Int 20-Nov-2013;4:. Available from: http://sni.wpengine.com/surgicalint_articles/stereotactic-radiosurgery-boost-to-the-resection-cavity-for-cerebral-metastases-report-of-overall-survival-complications-and-corticosteroid-protocol/
Background:This report focuses on the overall survival and complications associated with treatment of cerebral metastases with surgical resection followed by stereotactic radiosurgery (SRS). Management and complications of corticosteroid therapy are underreported in the literature but represent an important source of morbidity for patients.
Methods:Fifty-nine consecutive patients underwent surgical resection of a cerebral metastasis followed by SRS to the cavity. Patient charts were reviewed retrospectively to ascertain overall survival, local control, surgical complications, SRS complications, and corticosteroid complications.
Results:Our mean follow-up was 14.4 months (median 12.0 months, range 0.9-62.9 months). Median overall survival in this series was 15.25 months and local control was 98.3%. There was a statistically significant survival benefit conferred by Radiation Therapy Oncology Group recursive partitioning analysis Classes 1 and 2. The surgical complication rate was 6.8% while the SRS complication rate was 2.4%. Corticosteroid complications are reported and dependence at 1 month was 20.3%, at 3 months 6.8%, at 6 months 1.7%, and at 12 months no patients remained on corticosteroid therapy.
Conclusions:Overall survival and local control with this treatment paradigm compare well to the other published literature. Complications associated with this patient population are low. A corticosteroid tapering protocol is proposed and demonstrated lower rates of steroid-related complications and dependence than previously reported.
Keywords: Cerebral metastases, corticosteroids, stereotactic radiosurgery
Cerebral metastasis is the most common intracranial tumor in the adult population and the incidence is rising.[
Historically, cerebral metastases were managed with palliative therapy and were considered the end stage of a patient's disease.[
Corticosteroid use for the management of symptomatic peritumoral edema is a mainstay of treatment.[
The present study examines the overall survival and complications for patients with cerebral metastases treated by surgical resection followed by SRS to the cavity. We also propose a protocol for the management of corticosteroid therapy in this population.
During a 2-year period from 2010 to 2012, 59 consecutive patients who underwent surgical resection of a cerebral metastasis followed by SRS to the resection cavity were identified. This time period was selected because it represents the initiation of this protocol to the start of the study period. Metastatic lesions at our institution are treated exclusively by the two senior authors (LM and AD) and the cases selected were identified from a prospectively maintained database.
Patient information was obtained from the hospital chart and outpatient records from the Departments of Neurosurgery, Oncology, and Radiation Oncology. This work was conducted as part of studies approved by the institutional review board at Rush University Medical Center (Chicago, IL) (ORA #12121105-IRB01-AM02).
Seven patients had received prior cranial radiation therapy and were offered surgery because of the development of new intracranial lesions. The SRS was delivered to the operative bed within 1 month of surgery in most cases. The patient records were reviewed retrospectively and data regarding the following variables were recorded: age, sex, primary pathology, extent of extracranial disease (based on preoperative staging enhanced computed tomography scan (CT) of the chest, abdomen, and pelvis), the number and size of cerebral metastases, extent of resection (gross vs. subtotal as evidenced by 24-hour postoperative magnetic resonance imaging (MRI) scan), post operative complications, duration of corticosteroid use, corticosteroid-related complications, and SRS dose and treatment volume. Additionally, all patients were classified according to the Radiation Oncology Therapy Group (RTOG) Recursive Partioning Analysis (RPA).[
The prerequisite for neurosurgical treatment was stable systemic disease and life expectancy greater than 6 months as determined by the patient's oncologist. The choice to proceed with surgical resection was made based upon lesion size, peritumoral edema, and presence of mass effect and/or symptoms. The lesions were all classified by the Sawaya criteria:[
All patients underwent craniotomy and resection with the assistance of preoperative MRI images for frameless stereotactic guidance. After surgery, a new MRI brain was obtained for SRS planning. Patients were generally mobilized on postoperative day #1 and were seen as outpatients by neurosurgery between 2 and 4 weeks after surgery. SRS typically was given within one month of surgery. Post-SRS patients were seen initially at 6 weeks and then every 3 months with repeat MRI studies at each visit. Additional or expedited neuroimaging was obtained if central nervous system-related signs or symptoms developed. The patient's oncologist provided all systemic cancer care.
On the day of SRS, a stereotactic head frame was placed under local anesthesia and a simulation CT of the head obtained and fused with the MRI scan. The edges of the operative bed were delineated by the neurosurgeon and radiation oncologist on the MR images. Treatment plans for patients treated before March 2012 were designed using a conformal arc technique on a Varian Trilogy linear accelerator with a Brainlab treatment planning system (Westchester, IL). After March 2012 treatments were conducted on a Varian TruBeam STx (Palo Alto, CA) system with the Brainlab treatment planning system (Westchester, IL) and a frameless technique. All surgical cavities were treated with 1500 to 1600 cGy, and dose selection was based upon the RTOG 90-05 volume dependent SRS guidelines.[
Follow-up MRI scans were obtained 1 month after treatment and at 2 to 3 month intervals thereafter. If up to four new lesions were identified on follow-up imaging, they were treated with SRS using the RTOG 90-05 dose/volume scheme[
A corticosteroid tapering protocol was utilized that enables patients to be discontinued from this therapy in a timely fashion. The MRI scans of all patients are evaluated for the degree of cerebral edema surrounding a given metastasis, and this is one of the variables considered when deciding to proceed with surgical resection. Patients are started on dexamethasone 4 mg every 6 hours until the first postoperative day. At that time the dose is reduced to dexamethasone 4 mg every 12 hours and then dexamethasone 2 mg every 12 hours the next day. On postoperative day 3 the dose is reduced to 2 mg daily until SRS is completed. After SRS all patients are sent home with a methylprednisolone dose pack that contains 21 tablets of 4 mg each; the dosing regimen can be found in
Complications were surgical if they occurred within 30 days or, if later than 30 days, were a direct result of surgical intervention. Complications were transient if they resolved within 30 days of surgery or definitive management, or prolonged if they persisted until last follow-up or death. The criteria proposed by Sawaya et al. for classifying complications is applied.[
Overall survival and local control were determined by the method of Kaplan and Meier.[
Fifty-nine consecutive patients were treated in the above manner. We present the overall survival (OS), local control (LC), and treatment-related complications for this group of patients.
The tumors originated from different primary cancers [
Operative complications are presented in
Patients underwent SRS treatment at a mean of 3.5 weeks (1-224 days) after surgery. The postoperative bed was treated with a mean dose of 1600 cGy (range 1500 cGy in a single fraction to 3000 cGy given in 5 fractions) to the 90% isodose line. The mean target volume was 13.1 cm3. Three thousand centigray in 5 fractions were used when the target volume was equivalent to a sphere larger than 3 cm in diameter.
Mean follow-up was 14.4 months (median 12.0 months, range 0.9-62.9 months). The median OS was 15.25 months (95% CI: 11.74-24.20 months) [
Corticosteroids in the form of dexamethasone were given to all patients in the immediate preoperative period and then rapidly tapered postoperatively. Thereafter, the radiation oncologist managed the corticosteroid regimen. A standard methylprednisolone dose pack (6 days of therapy) was given to all patients after SRS treatment. All patients received gastrointestinal (GI) prophylaxis in the form of a proton pump inhibitor or H2-blocker. The mean duration of corticosteroid use from the time of diagnosis before surgery to after completion of SRS treatment was 3.4 weeks. At 1 month, 12 patients (20.3%) remained on corticosteroids, at 3 months 4 patients (6.8%), at 6 months 1 patient (1.7%), and at 12 months no patients remained on corticosteroid therapy. The reasons patients were maintained on corticosteroids past the end point of our protocol was due to peritumoral edema seen on MRI scan (8 patients), worsening neurological deficit upon wean (3 patients), and leptomeningeal disease (1 patient).
Complications related to corticosteroid therapy were seen in 91.5% of patients (54/59) and most commonly occurred in the form of hyperglycemia (34/59 patients, 57.6%). Peripheral edema and depression occurred in six patients each (10.2%). There were four (6.8%) DVT and one case (1.7%) of a PE. One patient (1.7%) experienced delayed wound healing, one patient had pneumonia, and there was one GI bleed. There were no cases of oropharyngeal candidiasis, gastritis, Cushing's syndrome, steroid psychosis, or steroid myopathy. A full listing of corticosteroid-related complications is found in
The use of adjuvant WBRT following resection in patients with cerebral metastases has been the standard of care,[
The local control rate at 1 year observed in this study, 98.3% (1 recurrence), compares favorably to the published literature. Karlovits et al. reported a local control of 92.3% while Robbins et al., reported 81.2%.[
Overall survival in this series was 15.25 months and compares well to the literature. Most contemporary series report an OS of 10-20 months.[
Salvage WBRT was required in 42.4% of patient in this study and in all cases was due to the detection of new distant metastases. There was no statistically significant factor associated with this but it can be attributed to the inevitable progression of the disease course.
Corticosteroids remain a mainstay of therapy for cerebral metastases and their effectiveness at reducing symptoms from cerebral edema in this patient population is well documented.[
The corticosteroid tapering protocol implemented by our group has proven to be very effective at weaning patients from this therapy. There are very few other reports in the literature that address this topic[
Side effects of corticosteroid therapy and their impact on the patient are important considerations as they are frequent and confer morbidity.[
The overall prevalence of side effects in this study is high (91.5% of patients). This is expected in a patient population treated with high-dose dexamethasone. The incidence of specific side effects such as hyperglycemia, DVT, and PE are in line with what literature has been published on the topic.[
The complication rate as related to surgery was 6.8% in this series and compares well to that reported by Sawaya et al.[
Two of the complications in this series required further surgery. All complications are presented in
There were two complications associated with SRS therapy in this series (2.4%). One patient developed a MRSA infection in the head frame pin site and underwent a course of antibiotics. Another patient who harbored a pontine metastasis that was not resected and was treated concurrently with the resection cavity experienced exacerbation of a preexisting hemiparesis. This complication rate is lower than other published reports that utilized SRS without surgical resection.[
Cerebral metastases can be treated with a variety of modalities. While the standard of care for resected lesions remains postoperative WBRT, SRS to the resection cavity has been shown to be effective with a better side effect profile. Corticosteroid therapy is a cornerstone of treatment for symptomatic metastases but has significant side effects. The corticosteroid tapering protocol used at our institution has been effective at reducing corticosteroid dependency in this patient population.
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