Neuroimaging and quality-of-life outcomes in patients with brain metastasis and peritumoral edema who undergo Gamma Knife surgery

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Gamma Knife surgery (GKS) has been shown to be effective for treating many patients with brain metastasis. Some brain metastases demonstrate significant peritumoral edema; radiation may induce cerebral edema or worsening preexisting edema. This study was conducted to evaluate the imaging and neurobehavioral outcomes in patients with preexisting peritumoral edema who then undergo GKS.


Between August 2003 and January 2008, 63 cases of brain metastasis with significant peritumoral edema (> 20 cm3) were prospectively studied. The study inclusion criteria were as follows: 1) a single metastatic lesion with significant edema (perilesional edema signal volume on FLAIR > 20 cm3); and 2) inclusion of only 1 lesion > 20 cm3 in the study (in cases of multiple lesions noted on FLAIR images). All patients received MR imaging with pulse sequences including T1-weighted imaging and FLAIR with or without contrast and T2-weighted imaging at an interval of 3 months. A neurological assessment and Brain Cancer Module (BCM-20) questionnaire were obtained every 2–3 months. Kaplan–Meier, Cox regression, and logistic regression were used for analysis of survival and associated factors.


At the time of GKS, the median Karnofsky Performance Scale (KPS) score was 70 (range 50–90), and the mean BCM-20 score was 45.5 ± 6.1. The mean tumor volume (± standard deviation) was 5.2 ± 4.6 cm3 with corresponding T2-weighted imaging and FLAIR volumes of 59.25 ± 37.3 and 62.1 ± 38.8 cm3, respectively (R2 = 0.977, p < 0.001). The mean edema index (volume of peritumoral edema/tumor volume) was 17.5 ± 14.5. The mean peripheral and maximum GKS doses were 17.4 ± 2.3 and 35 ± 4.7 Gy, respectively. The median survival was 11 months. The longer survival was related to KPS scores ≥ 70 (p = 0.008), age < 65 years (p = 0.022), and a reduction of > 6 in BCM-20 score (p = 0.007), but survival was not related to preexisting edema or tumor volume. A reduction in BCM-20 score of > 6 was related to decreased volume in T1-weighted and FLAIR imaging (p < 0.001). Thirty-eight (79.2%) of 48 patients demonstrated decreased tumor volume and accompanied by decreased T2-weighted imaging and FLAIR volume. Eight (16.7%) of the 48 patients exhibited increased or stable tumor volume. A margin dose > 18 Gy was more likely to afford tumor reduction and resolution of peritumoral edema (p = 0.005 and p = 0.006, respectively). However, prior external-beam radiation therapy correlated with worsened preexisting peritumoral edema (p = 0.013) and longer maintenance of corticosteroids (p < 0.001).


Patients demonstrating a reduction in the BCM-20 score > 6, age < 65 years, and KPS score ≥ 70 exhibited longer survival. Significant preexisting edema did not influence the tumor response or clinical outcome. The resolution of edema was related to better quality of life but not to longer survival.

Abbreviations used in this paper: BCM-20 = Brain Cancer Module-20; GKS = Gamma Knife surgery; QOL = quality of life; WBRT = whole-brain radiotherapy.

Article Information

Address correspondence to: Jason Sheehan, M.D., Ph.D., Department of Neurosurgery, University of Virginia Health System, Box 800-212, Charlottesville, Virginia 22908. email:

© AANS, except where prohibited by US copyright law.



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    Magnetic resonance images obtained in this 78-year-old man who presented with left limb weakness that had persisted for 2 weeks. A stereotactic biopsy revealed non–small cell lung cancer. Axial FLAIR sequence obtained at the time of GKS, revealing peritumoral brain edema in the left parietal region (A). Axial T1-weighted image with contrast demonstrating a heterogeneously enhancing partially cystic lesion in the left parietal lobe (B). The patient underwent GKS with treatment volume of 6.1 ml and margin dose of 18 Gy to the 50% isodose curve. Six months after GKS, the FLAIR (C) and T1-weighted imaging (D) volumes were decreased. Eighteen months after GKS, the volume in FLAIR (E) and T1-weighted imaging (F) showed a paralleling increase. G and H: Twenty-one months after GKS, the volume in FLAIR (G) and T1-weighted imaging with contrast administration (H) shows a further increase. The patient is still alive; at last follow-up, he has a KPS score of 90 and BMC-20 of 29. V = tumor volume.

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    Three years previously, renal cell carcinoma had been diagnosed in this 60-year-old man. The patient presented with a 1-month history of left limb weakness, and a brain metastasis was diagnosed. He underwent GKS with a treatment volume of 1.8 ml and a margin dose of 18 Gy to the 65% isodose line. Axial T2-weighted (A) and FLAIR (B) images showing severe brain edema. Axial T1-weighted image with contrast revealing a homogeneous enhancing metastatic deposit (C). D–F: Three months later, the T2-weighted and FLAIR volume showed an initial increase. Six months later, the T2-weighted (G) and FLAIR (H) imaging volumes demonstrated paralleling decreases along with that of the T1-weighted image with contrast (I). The patient died of aspiration pneumonia 8 months after GKS.

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    Breast carcinoma had been diagnosed in this 32-year-old woman 5 years previously. She had undergone a mastectomy followed by chemotherapy. Multiple brain metastases had been observed 2.5 years ago. She received WBRT with a dose of 30 Gy in 10 fractions. She suffered a lancinating headache for 1 month, and a tumor recurrence was diagnosed. An FLAIR sequence MR imaging showing the severe brain edema (A). Axial T1-weighted MR image with contrast (B) revealing a homogeneous enhancing mass. The patient received GKS with treatment volume 19.2 ml and margin dose of 12 Gy to the 40% isodose curve. Three months after GKS, the FLAIR imaging volume increased in size (C). Axial T1-weighted image (D) with contrast administration showing that the tumor volume is decreased in size. Six months after GKS, the FLAIR (E), T2-weighted image (F), and T1-weighted image with contrast (G) volumes revealing accompanying increases. The patient's condition deteriorated and she underwent a craniotomy and tumor resection. Postoperative CT (H) revealing no residual tumor. Photomicrographs (I and J) showing the tumor recurrence. H & E, original magnification × 200 (I) and × 400 (J). Estrogen receptor staining (K) was positive in the resected tumor. Original magnification × 400 (K). The patient died of multiple brain metastases 8 months after the craniotomy.

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    This 59-year-old woman with endometrial carcinoma underwent a total hysterectomy and bilateral oophorectomy followed by chemotherapy 3 years previously. Multiple brain metastases occurred 6 months prior to presentation for radiosurgery. She had undergone WBRT of 30 Gy in 10 fractions. Left leg weakness was observed 2 months after radiation therapy. A and B: T2 and FLAIR sequence MR imaging revealing severe brain edema. C: T1 with contrast MR imaging showed multiple cystic lesions. She underwent GKS with a treatment volume of 18 ml and margin dose of 14 Gy in 40% isodose curve. D and E: Six months after GKS, T2 and FLAIR volumes were not altered. F: The T1 with contrast volume was reduced. The patient remains alive with a KPS score of 80 and BCM-20 of 35.



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