Resection and brain brachytherapy with permanent iodine ...1750 Volume 126 • June 2017 B rain metastasis is the most common intracranial tumor and is found in approximately 30% of

CLINICAL ARTICLEJ Neurosurg 126:1749–1755, 2017

ABBREVIATIONS 125I = iodine-125; FFN = freedom from necrosis; GTR = gross-total resection; LFFP = local freedom from progression; MRI-1, first postoperative MRI; OS = overall survival; RPA = recursive partitioning analysis; SRS = stereotactic radiosurgery; UCSF = University of California, San Francisco; WBRT = whole-brain radio-therapy.SUBMITTED October 30, 2015. ACCEPTED April 14, 2016.INCLUDE WHEN CITING Published online July 1, 2016; DOI: 10.3171/2016.4.JNS152530.* Drs. Raleigh and Seymour contributed equally to this work.

Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis*David R. Raleigh, MD, PhD,1 Zachary A. Seymour, MD,2 Bryan Tomlin, PhD,3 Philip V. Theodosopoulos, MD,4 Mitchel S. Berger, MD,4 Manish K. Aghi, MD, PhD,4 Sarah E. Geneser, PhD,5 Devan Krishnamurthy, PhD,1 Shannon E. Fogh, MD,1 Penny K. Sneed, MD,1 and Michael W. McDermott, MD4

Departments of 1Radiation Oncology and 4Neurological Surgery, University of California San Francisco; 2Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan; 3Department of Economics, California State University Chanel Islands, Camarillo; and 5Department of Therapeutic Radiology, Yale University, New Haven, Connecticut

OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS be-cause of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive mor-bidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases.METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between Septem-ber 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by crani-otomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models.RESULTS The median age at surgery was 59 years (range 29.9–81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21–76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4–93), and the median activity was 0.73 mCi (range 0.34–1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0–22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clini-cal follow-up time in living patients was 14.4 months (range 0.02–13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05).CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric param-eters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associ-ated with minimal toxicity and can result in long-term survival for some patients.■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV. https://thejns.org/doi/abs/10.3171/2016.4.JNS152530KEY WORDS brain metastasis; brachytherapy; iodine-125; radiotherapy; oncology

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D. R. Raleigh et al.

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Brain metastasis is the most common intracranial tumor and is found in approximately 30% of all patients with cancer at autopsy.17 Resection can

prolong survival in select cases, but subsequent radia-tion is required to reduce the rate of local recurrence and neurological death.13 Stereotactic radiosurgery (SRS) is often chosen for postoperative radiation of resection cavi-ties, but it has limited efficacy in the setting of large or recurrent lesions and is associated with an increased risk of radionecrosis when used for large lesions.12,20,22 Whole-brain radiation (WBRT) can further reduce the risk of re-currence at the resection site and distantly, but it seems to have no impact on overall survival (OS) and is associated with significant neurocognitive morbidity.2,6

Because of these conflicts, therapeutic options for pa-tients with large or recurrent brain metastases are limited. Permanent brachytherapy after resection for the treatment of both newly diagnosed and recurrent brain metastases that may be unsuitable for SRS has been associated with high rates of local control.5,7,9,14,18,23,24 Temporary brachy-therapy for brain metastases has been reported also, and although this technique can have dosimetric advantages, permanent implantation is preferable logistically, and there are no data available to suggest that their outcomes differ.4,10,11,15,16 Iodine-125 (125I) is most commonly used for permanent intracranial brachytherapy, but this isotope has come under criticism because of its relatively long half-life (59.4 days) and for concern that resection cavity remodel-ing over time might impair local control and promote ra-dionecrosis.3,19 Indeed, the rate of radionecrosis with per-manent 125I brachytherapy for brain metastasis has been reported to be as high as 23%.9 As a result of these con-cerns, suture-stranded cesium-131 has been prospectively investigated in a limited number of patients, and the initial results have been encouraging.23

The purpose of this study was to investigate the safety and efficacy of resection and permanent 125I brachytherapy for both newly diagnosed and recurrent brain metastases in a large cohort of patients with extended follow-up to better characterize the outcomes and generalizability of this treatment.

MethodsPatient Characteristics

A total of 95 consecutive patients with 105 brain me-tastases treated at the University of California, San Fran-cisco (UCSF), between September 1997 and July 2013 were identified retrospectively for this analysis, which was approved by the institutional review board. Patients who were undergoing craniotomy for resection of large or re-current brain metastases were considered for brachyther-apy by a multidisciplinary team consisting of a neurosur-geon and a radiation oncologist. Given the retrospective nature of this study, inclusion criteria were heterogeneous and varied with patient- and operation-specific conditions. Our results with fractionated radiosurgery or repeat SRS for large lesions previously treated with resection and SRS were disappointing.20 As such, our institutional preference is for resection and permanent 125I brachytherapy in pa-tients with large brain metastases and otherwise minimal

disease burden. As a consequence, this series included metastases up to 76 cm3. On the opposite end of the spec-trum, 1 subject received brachytherapy for a 0.2-cm3 me-tastasis that was easily accessible by the same craniotomy site used to access an 11.6-cm3 metastasis, which also was treated with brachytherapy.

Treatment CharacteristicsEach patient underwent preoperative MRI followed

by standard craniotomy with maximal safe resection of metastasis and placement of permanent 125I sources into the resection cavity (Oncura, GE Healthcare). The rate of necrosis in an initial report of short-term outcomes from 40 patients within this cohort was 23%, which in 2005 prompted more consistent usage of lower-activity sources.9 During the later era, our experience taught us that place-ment of ≤ 0.73-mCi sources 6–10 mm apart achieves ad-equate target coverage. In all patients treated before 2005 (55% of the lesions), sources were secured in place with fi-brin glue. From 2005 to the present, sources were inserted end-on into the brain tissue and secured in place with Tis-seel (Baxter). Postoperative stereotactic CT for dosimetric calculations was completed in 89 patients within 24 hours of surgery. In brief, 125I sources were identified and marked on each slice by a medical physicist (D.K. and S.E.G.) and a radiation oncologist (D.R.R.) using MIM software, and the prescription was determined based on source activity, calibration date, and implantation date. The extent of re-section was scored as gross total (no evidence of residual disease on postoperative MRI), near total (< 10% residual metastasis on postoperative MRI as defined by only a thin enhancing rim of tumor ≤ 2 mm, with or without docu-mentation of surgical gross residual disease), or subtotal (> 10% residual metastasis or nodular enhancement > 2 mm on postoperative MRI).

Clinical and Radiographic Follow-UpDemographic and clinical follow-up data for all the pa-

■ CLASSIFICATION OF EVIDENCETYPE OF QUESTION TherapeuticSTUDY DESIGN Retrospective Case SeriesEVIDENCE Class IVRaleigh and colleagues report their experience in treating 95 consecutive patients with 105 resected brain metastases (53% of whom had been treated previously with stereotactic radiosurgery, whole-brain irradiation, or both) with permanent iodine-125 (125I) brachytherapy. Because of the lack of a con-trol group, this study provides Class IV evidence that perma-nent 125I brachytherapy is an effective strategy for achieving local control of brain metastases. The authors also investi-gated potential predictors of posttherapy radiation necrosis. Because of the absence of masked assessment and prospec-tively established diagnostic criteria, this study provides Class III evidence for an association between previous stereotactic radiosurgery and radiation necrosis after 125I brachytherapy. Predictors of improved survival were not identified by multi-variable analysis.


Resection and 125I brachytherapy for brain metastasis

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tients were extracted from the medical records and institu-tional cancer registry. The patients were followed with se-rial surveillance MRI, and all volumetric data were calcu-lated by a radiation oncologist (D.R.R.) from 3D contours on T1-weighted postcontrast images using MIM software. The timing of surveillance MRI was heterogeneous with-in the overall patient population but occurred at regular intervals for each patient. As such, imaging data were pooled from peak surveillance intervals for volumetric analyses. Resection cavity location was scored according to anatomical position within the brain and with respect to the ventricular system, lobar tips (temporal, frontomedial, and lateral cerebellar), and proximity to the cerebral/cer-ebellar surface. Both symptomatic and radiographically discovered necroses were recorded, although all cases of adverse radiation effects were both symptomatic and had imaging findings consistent with radionecrosis. Most cases of radionecrosis were treated with long-term corti-costeroids. Resection of necrotic lesions was performed in select cases when permitted by patient and operative con-ditions. No evidence of seed migration within CSF path-ways was observed in follow-up imaging. However, the majority of patients were followed with only MRI and not CT, which enables improved identification of 125I sources.

Statistical AnalysisAll statistical analyses were performed according to

lesion except for those that pertained to extracranial dis-ease progression and OS. Multinomial logistic regression models were used to examine the relationships between outcomes of local progression or necrosis and independent variables of preoperative metastasis volume, resection cavity volume, rate of cavity remodeling, lesion histology, lesion location, treatment setting (newly diagnosed versus recurrent lesion), source activity, and extent of resection. For regression modeling of resection cavity volume and rate of remodeling, patient age, preoperative metasta-sis volume, implantation technique, histology, location, treatment setting, source number and activity, and extent of resection were used as independent variables. Follow-up, local freedom from progression (LFFP) (defined as tumor recurrence within or immediately adjacent to the brachytherapy cavity), freedom from progression (defined as tumor progression at any site), freedom from necrosis (FFN), and OS were measured from the date of resec-tion, estimated by using the Kaplan-Meier method, and compared with the results of log-rank tests. Cavities were censored from volumetric analyses at the time of tumor progression or necrosis and censored from LFFP and FFN analyses at last follow-up or the time of local progression or necrosis, respectively. Ordinary least-squares, logistic, and linear probability regression models were used to ex-amine dependent variables of LFFP, FFN, and OS with respect to independent variables of histology, metastasis volume, treatment setting, extent of resection, source ac-tivity, radiation dose, and treatment volume. Additional independent variables of total brain metastasis (median 1; range 1–13) and recursive partitioning analysis (RPA) class were added for OS analyses.8 The p values were cal-culated from t statistics with the appropriate degrees of freedom, and p values less than 0.05 were considered sta-

tistically significant. Statistical analyses were performed by using GraphPad Prism 6 and Stata v13.

ResultsPatient and disease characteristics are presented in

Table 1. The median age at the time of treatment was 59.4 years (range 29.9–81.6 years), 41% of the patients were male, and the median Karnofsky Performance Scale (KPS) score was 80 (range 50–90). The most common his-tology results were lung cancer (38%), melanoma (27%), and breast cancer (23%). Although the site of primary disease was controlled in the majority of cases (78%), ex-tracranial metastases were present in 64% of the patients. Forty-seven percent of the lesions were newly diagnosed, and 53% were recurrent. In cases of recurrence, previous treatments included SRS (40%), WBRT (25%), and resec-tion (17%). The median metastasis volume was 13.5 cm3 (range 0.2–76 cm3), and gross-total resection (GTR) was achieved in 82% of the patients (Table 2). The median number of sources implanted per cavity was 28, and the median source activity was 0.73 mCi. The median brachy-therapy dose over the lifetime of sources was 540 Gy at 3-mm, 263 Gy at 5-mm, and 135 Gy at 10-mm depth into brain tissue measured outward from the resection cavity edge, which corresponded to median treatment volumes of 6.8 cm3, 12.8 cm3, and 33 cm3, respectively. Thirteen per-

TABLE 1. Patient and disease characteristics

Characteristic Value (%)*

No. of patients (no. of lesions) 95 (105)Median age (range), yrs 59.4 (29.9–81.6)Sex Male 39 (41) Female 56 (59)KPS score 50 1 (1) 60 8 (8) 70 26 (27) 80 31 (33) 90 28 (30)Primary cancer Lung 36 (38) Melanoma 26 (27) Breast 22 (23) Other 11 (12)Primary disease controlled 75 (79)Extracranial metastases 61 (64)Newly diagnosed lesion 49 (47)Recurrent lesion 56 (53) Previous SRS 38 (36) Previous WBRT 26 (25) Previous resection 18 (17)

KPS = Karnofsky Performance Scale. * Values represent the number (%) of patients unless otherwise specified.




cent of the patients underwent adjuvant SRS to additional lesions around the time of surgery and brachytherapy, and none of them underwent WBRT.

A total of 476 brain MRIs were analyzed. All the pa-tients underwent preoperative MRI, and 93 (98%) patients were followed with serial postoperative MRI scans (me-dian 3 per patient; range 1–22 per patient) beginning at a median of 1 day after surgery (MRI-1). The median resec-tion cavity volume seen on MRI-1 was 5.2 cm3 (Table 2). At medians of 1.7 (n = 32), 3.6 (n = 27), 5.9 (n = 38), 11.7 (n = 30), and 20.5 (n = 22) months after surgery and brachy-therapy, resection cavity volumes decreased by 25%, 35%, 42%, 47%, and 60%, respectively, on average, relative to MRI-1 (Fig. 1A).

Preoperative metastasis size was the strongest predictor of resection cavity volume (p < 0.001) and the rate of re-section cavity remodeling (p < 0.01) by multivariate linear regression modeling; a greater reduction in volume over time was found in larger cavities (Fig. 1B; Supplemental Table 1). Advanced patient age also was associated with comparatively larger resection cavity volumes (p < 0.05), and a periventricular location was associated with a higher rate of remodeling (p < 0.01). In contrast, the rate of resec-tion cavity remodeling was lower after GTR (p < 0.05). There was no association between lesion location and radionecrosis. Multinomial logistic regression modeling,

with or without controlling for source activity or previous SRS, failed to reveal an influence of metastasis volume, cavity volume, or the rate of cavity remodeling on the like-lihood of local progression or necrosis.

The median clinical follow-up time for all the patients was 8.8 months, and it was 14.4 months for those who were alive at the time of last follow-up (n = 24; range 0.023–13.6 years) (Table 3). Disease progression at the site of brachytherapy occurred in 10 lesions, for an overall local control rate of 90% (Fig. 2A). Intracranial salvage therapies at the site of brachytherapy or elsewhere includ-ed resection for 13 lesions, SRS for 8 lesions, WBRT in 3 patients, SRS and WBRT for 5 patients, and resection fol-lowed by WBRT in 1 patient. There were 64 deaths, and the median OS was 12 months. When analyzed according to interquartile range, the median OS times were 2.1, 6.8,

TABLE 2. Lesion and treatment characteristics

Characteristic Value

Median metastasis vol (range), cm3 13.5 (0.2–76)Resection cavity location (no. [%]) Frontal lobe 32 (30) Parietal lobe 17 (16) Temporal lobe 26 (25) Occipital lobe 17 (16) Cerebellum 13 (12) Cerebral/cerebellar convexity 94 (90) Periventricular 20 (19) Lobar tip 21 (20)Extent of resection (no. [%]) GTR 86 (82) STR 19 (18)No. of sources implanted (median [range]) 28 (4–93)Source activity (median [range]), mCi 0.73 (0.34–1.3)Total activity (median [range]), mCi 23.8 (6.5–69)Resection cavity vol (median [range]), cm3 5.2 (0.3–23.2)Brachytherapy dose (median [range]), Gy 3 mm 540 (135–1050) 5 mm 263 (67.5–600) 10 mm 135 (22.5–330)Brachytherapy vol (median [range]), cm3

3 mm 6.8 (0.9–28) 5 mm 12.8 (2–43) 10 mm 33 (7–90)

STR = subtotal resection.

FIG. 1. Resection cavity size and remodeling after resection and per-manent 125I brachytherapy for brain metastases. A: At medians of 1.7 (n = 32), 3.6 (n = 27), 5.9 (n = 38), 11.7 (n = 30), and 20.5 (n = 22) months after brachytherapy, resection cavity volumes decreased by 25% ± 6%, 35% ± 6.8%, 42% ± 7.7%, 47% ± 9.5%, and 60% ± 11.6%, respectively, on average, relative to each patient’s MRI-1, which was performed a median of 1 day after surgery. Data are displayed as means ± standard errors of the mean. Radiation dose deposition from 125I decay as a per-centage of the total dose accumulated over time (half-life = 59.4 days) is shown on the right y axis for reference. B: Metastasis volume predicts the rate of resection cavity remodeling over time according to multivari-ate linear regression modeling (p < 0.0001). Resection cavities were partitioned according to preoperative metastasis volume (median 13.5 cm3), and data are displayed as the mean ± standard error of the mean for each group.


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13.8, and 62.3 months (p < 0.0001, log-rank test) (Fig. 2B). We were unable to identify predictive factors for either LFFP or OS according to the extent of resection, metasta-sis size, RPA class,8 number of brain metastases, treatment setting, or dosimetric parameters with either log-rank tests or regression modeling. However, multivariate regression modeling revealed that the risk of radionecrosis increased with brachytherapy of recurrent lesions after SRS (25% crude risk) relative to that with newly diagnosed lesions (7% crude risk; p < 0.05) (Table 3; Fig. 2C; Supplemental Table 2). Excluding lesions previously treated with SRS, the risk of necrosis was no different for sources with an activity of ≤ 0.73 mCi than for those that delivered > 0.73 mCi. The median time to necrosis was 1 year (range 0.04–4.5 years). The risk of wound complications (all of which were Grade 3 or lower) was 6%.

DiscussionTherapeutic options for patients with large or recurrent

brain metastases are limited. Here we evaluate the out-comes of 95 patients treated with resection and permanent 125I brachytherapy for brain metastases at UCSF over the course of nearly 16 years, which to our knowledge repre-sents the largest collection of patients with either newly diagnosed or recurrent brain metastases treated with this technique. Our data suggest that this approach is associ-ated with excellent local control and might be especially valuable for metastases that are not amenable to SRS; for patients who wish to avoid the inherent neurocognitive sequelae of WBRT, as has been suggested by others14; or for those who have already received WBRT or conformal brain radiotherapy.6 In contrast to previous studies, we observed in our study a high rate of local control indepen-dent of metastasis size and an acceptably low rate of tox-icity.5,9,14 Notwithstanding, the rate of necrosis was signifi-cantly higher following treatment of recurrent metastases after SRS. It remains to be established if laser-interstitial thermal therapy, proton therapy, or other techniques can offer patients the same high rate of local control afforded by brachytherapy with a lower rate of radionecrosis. It also remains to be established if the efficacy or toxicity of brachytherapy for brain metastases is altered in patients receiving targeted or immunomodulatory agents. How-ever, treatment options for patients with recurrence after SRS are especially limited, because repeat treatment has

TABLE 3. Clinical outcomes

Outcome

No. of Lesions (%)Newly

Diagnosed (61 lesions)

Recurrent After SRS

(44 lesions) Overall

(105 lesions)

Local progression 6 (10) 4 (9) 10 (10)Distant progression 19 (42)* 22 (45)* 41 (43)*Death 26 (58)* 38 (78)* 64 (67)*Necrosis 4 (7)* 11 (25) 15 (14)

* Some patients experienced more than 1 outcome (i.e., some patients had both local and distant progression).

FIG. 2. Clinical outcomes after resection and permanent 125I brachy-therapy for brain metastases. A: The overall LFFP by lesion was 90% (median LFFP undefined; range 0.23–13.6 months). B: The median OS (dotted line) by patient was 12 months (range 0.23–13.6 months); the median OS times were 2.1, 6.8, 13.8, and 62.3 months when analyzed by quartiles (p < 0.0001, log-rank test). C: The crude risk of radionecro-sis was 14% and increased with brachytherapy of recurrent lesions after SRS relative to newly diagnosed lesions (p = 0.05, multivariate regres-sion). nec = necrosis; Q = quartile.






a lower likelihood of success than that expected for the first treatment. Thus, permanent brachytherapy may be considered for these patients with appropriate counseling concerning the risk of radionecrosis. These and all other conclusions should be considered with respect to the limi-tations of this study, which include a lack of generalizabil-ity, insofar as intracranial brachytherapy is available at only select centers, and the retrospective nature of patient selection.

The discovery that resection cavities from larger brain metastases undergo greater remodeling and size reduction after brachytherapy echoes findings from SRS treatment.3 In that regard, permanent 125I brachytherapy has been criti-cized for the relatively long half-life of 125I and potential for suboptimal dosimetric coverage with cavity remodel-ing. However, we found no association between the rate of resection cavity change and either local control or radio-necrosis, which suggests that radionecrosis observed after permanent 125I brachytherapy is likely a result of other fac-tors. As our data demonstrate, the most likely explanation is compounded toxicity from previous treatment.

Maximum radiographic follow-up in this series exceed-ed clinical follow-up because a number of the patients have remained alive more than 13 years after treatment and, at the time of this writing, have continued to send MRI stud-ies for evaluation at UCSF from afar. As has been reported by other investigators, these cases illustrate that resection and permanent 125I brachytherapy for brain metastases can be used to achieve long-term survival in select patients.4,14,18 In our series, 22% of the patients survived beyond 2 years after treatment. However, predictive factors for survival that might be used to guide therapeutic decisions relat-ing to permanent brain brachytherapy remain elusive. We detected no differences in survival for newly diagnosed versus recurrent lesions, as has been suggested by previ-ous reports.9,11 We also were unable to identify associa-tions between survival and extent of resection, metastasis size, RPA class, dosimetric parameters, or the number of brain metastases. However, we did detect an association between necrosis and improved OS that is likely a product of survivor bias, insofar as patients who live longer accrue a greater cumulative risk of radionecrosis. In support of this hypothesis, reverse causality was also identified be-tween local progression and OS in that brachytherapy was more likely to fail the longer the patients lived. Thus, as suggested by the high rate of distant disease progression observed in this study, extracranial metastases remain the primary barrier to long-term survival for patients who might otherwise benefit from aggressive local therapies for the treatment of brain metastases.15,16

The high rate of overall local control and relatively large metastasis size in our series is notable considering the poor efficacy of other available interventions. Prospec-tive randomized trials have demonstrated that local con-trol is approximately 63% for resection alone, 73% for SRS alone, 86% for resection and WBRT, and 82%–89% for SRS and WBRT.1,2,12,13 It is important to note that many of these studies imposed stringent criteria on lesion size for patient enrollment. In contrast, we observed 90% local control in the context of brain metastases that measured up to 76 cm3. Also, in contrast to SRS, we identified no

association between the risk of necrosis and treatment vol-ume.20 In summary, our data suggest that permanent 125I brachytherapy indeed might be preferable for adjuvant treatment of large brain metastases.

The risk of wound complications associated with resec-tion and permanent 125I brachytherapy for brain metastases is significantly lower than that observed for other intra-cranial purposes, such as recurrent atypical and anaplas-tic meningioma.21 Some of the risk associated with 125I brachytherapy for meningioma might result from tumor invasion of cranial bone, close proximity of radioactive sources to craniotomy sites, or complications related to previous surgery and/or radiation. We did not observe a significant number of wound complications despite the abundance of brain metastases immediately adjacent to the cerebral or cerebellar surface. This finding suggests that rapid dose fall-off from brachytherapy sources ac-cording to the inverse-square law is sufficient to prevent the majority of wound complications in patients with brain metastasis treated with permanent 125I sources, as has been demonstrated by other studies.15,18,19 Our surgeons are aware of this problem and use pedicle-based pericranial flaps when local dura or skin conditions suggest impaired healing.

ConclusionsResection and radiation therapy can be used to achieve

a high rate of local control for brain metastases, and to-gether, they seem to be an excellent option for large tumors for which SRS is unsuitable. Treatment of lesions that recur after SRS is associated with a greater risk of radionecro-sis. Resection cavity volume and remodeling vary directly with metastasis size, but none of these factors impact local control or the rate of necrosis.

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DisclosuresThe authors report no conflict of interest concerning the materi-als or methods used in this study or the findings specified in this paper.

Author ContributionsConception and design: McDermott, Raleigh, Seymour, Sneed. Acquisition of data: McDermott, Raleigh, Seymour, Geneser, Krishnamurthy, Sneed. Analysis and interpretation of data: McDermott, Raleigh, Seymour, Tomlin, Theodosopoulos, Aghi, Geneser, Krishnamurthy, Sneed. Drafting the article: McDermott, Raleigh, Seymour, Tomlin, Fogh, Sneed. Critically revising the article: McDermott, Raleigh, Seymour, Theodosopoulos, Berger, Aghi, Geneser, Krishnamurthy, Fogh, Sneed. Reviewed submitted version of manuscript: all authors. Statistical analysis: Raleigh, Tomlin, Sneed. Administrative/technical/material support: Raleigh. Study supervision: McDermott, Raleigh.

Supplemental InformationOnline-Only ContentSupplemental material is available with the online version of the article.

Supplemental Tables. https://thejns.org/doi/suppl/10.3171/ 2016.4.JNS152530.

Previous PresentationsPortions of this work were presented at the annual meetings of the American Society for Therapeutic Radiation Oncology held in San Francisco, CA, in September 2014, and the American Radium Society held in Kauai, HI, in May 2015.

CorrespondenceMichael W. McDermott, Department of Neurological Surgery, University of California San Francisco, 400 Parnassus Ave., San Francisco, CA 94122. email: [email protected].




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