A simple score to estimate the likelihood of pseudoprogression vs. recurrence following stereotactic radiosurgery for brain metastases: The Bergen Criteria.

BACKGROUND: A major challenge in the follow-up of patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) is to distinguish pseudoprogression (PP) from tumor recurrence (TR). The aim of the study was to develop a clinical risk assessment score. METHODS: Follow-up images of 87 of 97 consecutive patients treated with SRS for 348 BM were analyzed. Of these, 100 (28.7%) BM in 48 (53.9%) patients responded with either TR (n = 53, 15%) or PP (n = 47, 14%). Differences between the 2 groups were analyzed and used to develop a risk assessment score (the Bergen Criteria). RESULTS: Factors associated with a higher incidence of PP vs. TR were as follows: prior radiation with whole brain radiotherapy or SRS (P = .001), target cover ratio ≥98% (P = .048), BM volume ≤2 cm3 (P = .054), and primary lung cancer vs. other cancer types (P = .084). Based on the presence (0) or absence (1) of these 5 characteristics, the Bergen Criteria was established. A total score <2 points was associated with 100% PP, 2 points with 57% PP and 43% TR, 3 points with 57% TR and 43% PP, whereas >3 points were associated with 84% TR and 16% PP, P < .001. CONCLUSION: Based on 5 characteristics at the time of SRS the Bergen Criteria could robustly differentiate between PP vs. TR following SRS. The score is user-friendly and provides a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.

Quality of life is maintained using Gamma Knife radiosurgery: a prospective study of a brain metastases patient cohort.

OBJECTIVE Gamma Knife radiosurgery (GKRS) is increasingly used in the management of brain metastases (BMs), but few studies have evaluated how GKRS impacts quality of life (QOL). The aim of this study was to monitor QOL as the primary end point following GKRS in a patient cohort with BM. METHODS The study included 97 consecutive patients with 1-6 BMs treated with GKRS between May 2010 and September 2011. QOL was assessed at baseline and at 1, 3, 6, 9, and 12 months postoperatively using the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire with the brain cancer subscale (BRCS) questionnaire. Factors predicting QOL were identified by mixed linear regression analyses. Local control and toxicity were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) and the European Organisation for Research and Treatment/Radiation Therapy Oncology Group (EORTC/RTOG) criteria of late effects, respectively. RESULTS Compliance was high from baseline (97%) to 12-month follow-up (78%). Mean BRCS scores remained high during follow-up: they improved in 66% of patients and remained unchanged in 6% at 9 months. Local control (p = 0.018), improved symptoms (p = 0.005), and stable extracerebral disease (p = 0.001) correlated with high QOL-BRCS score. High baseline recursive partitioning analysis class predicted improved QOL (p = 0.031), whereas high Karnofsky Performance Scale score (p = 0.017), asymptomatic BMs (p = 0.001), and no cognitive deficits (p = 0.033) or seizures (p = 0.040) predicted high, stable QOL-BRCS during the 12-month follow-up. CONCLUSIONS QOL remained stable for up to 12 months following GKRS for the total cohort. High QOL was reported if local control occurred, cerebral symptoms improved/stabilized, or the need for steroids declined, which all reflected successful GKRS. Conversely, low QOL accompanied progression of intra- and extracerebral disease. Based on the study findings, GKRS appears to be a safe and effective treatment option for patients with BMs.

Gamma knife surgery as monotherapy with clinically relevant doses prolongs survival in a human GBM xenograft model.

OBJECT: Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs). However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS. METHODS: GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12 Gy or 18 Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test. RESULTS: In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls (P < 0.001). In a second experiment, survival was 72 days in the treatment group versus 54 days in controls (P < 0.006). Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment (P = 0.04). CONCLUSION: GKS administered with clinically relevant doses prolongs survival in rats harboring GBM xenografts, and the associated toxicity is mild.

γ knife surgery versus reoperation for recurrent glioblastoma multiforme.

BACKGROUND: The optimal management of patients with recurrent glioblastoma multiforme (GBM) is a subject of controversy. These patients may be candidates for both reoperation and/or gamma knife surgery (GKS). Few studies have addressed the role of GKS for relapsing gliomas, and the results have not been compared with reoperation. To validate the efficacy and safety of GKS, we compared the survival and complication rates of GKS and reoperation for recurrent GBMs. METHODS: This study retrospectively reviewed 77 consecutive patients with histopathologically confirmed GBMs retreated for recurrent GBM between 1996 and 2007. Thirty-two patients underwent GKS, 26 reoperation and 19 both procedures. RESULTS: The median time from the second intervention to tumor progression was longer after GKS than after resection, P = 0.009. Median survival after retreatment was 12 months for the 51 patients receiving GKS compared with 6 months for reoperation only (P = 0.001, hazard ratio [HR] 2.4), and 19 months versus 16 months from the time of primary diagnosis (P = 0.021, HR 1.8). A multivariate analysis adjusted for possible confounding factors (tumor volume, recursive partitioning analysis class, neurological deficits, time to recurrence, adjuvant therapy, and tumor location) showed significantly longer survival for patients treated with GKS, both from retreatment (P = 0.013, HR 4.1) and from primary diagnosis (P = 0.002, HR 5.8). The adjusted results were still significant after separate analysis according to tumor volume <5 mL, 5 to 20 mL, and >20 mL. The complications rate was 9.8% after GKS and 25.2% after reoperation. CONCLUSIONS: GKS may be an alternative to open surgery for small GBMs at the time of recurrences, with a significantly lower complication rate and a possible survival benefit compared with reoperation.

Gamma knife surgery in brain melanomas: absence of extracranial metastases and tumor volume strongest indicators of prolonged survival.

OBJECTIVE: To review a series of patients who underwent Gamma Knife surgery (GKS) to identify prognostic factors for local growth control and survival. METHODS: During the period 1996-2006, 77 patients (42 men and 35 women) with a total of 143 metastases underwent GKS. A solitary lesion was present in 40 patients (51.9%). RESULTS: Growth control was achieved in 114 of 128 (89.1%) tumors and 59 of 70 (84.3%) patients. The median survival was 7 months (range 0-73 months) after GKS and 67 months (range 4-327 months) from the time of diagnosis. Patients with absence of extracranial disease lived longer than patients with more widespread disease-median 16 months (range 3-52 months) versus 6 months (range 0-73 months; P = 0.014). A total tumor volume of less than 5 cc was associated with longer survival (P = 0.041). Survival was significantly longer in recursive partitioning analysis (RPA) class 1 (22 months) than RPA class 2 (7 months) and RPA class 3 (3 months; P = 0.008). Even in cases of treatment failure with tumor growth or appearance of new metastases, GKS slowed down the cerebral disease with no significant reduction in the duration of survival. CONCLUSIONS: GKS for melanoma brain metastasis provides a high rate of local tumor control. Survival is longest for well-functioning patients with absence of extracranial metastases or with an intracerebral total tumor volume less than 5 cc.