Stereotactic radiosurgery for pilocytic astrocytomas part 1: outcomes in adult patients

To assess outcomes when stereotactic radiosurgery (SRS) is used during multimodality management of pilocytic astrocytomas in adult patients. Fourteen patients (six male and eight females) with pilocytic astrocytomas underwent SRS between 1994 and 2006. The median patient age was 32 years (range, 19–52 years). Initial surgical management included stereotactic biopsy (N = 4), gross total resection (N = 1), and partial resection (N = 9). Fractionated radiation therapy had failed in six patients. The median radiosurgery target volume was 4.7 cc (range, 0.6–33.7 cc) and the median margin dose was 13.3 Gy (range, 10–20 Gy). At a median follow-up of 36.3 months (range 6.1–109 months), three patients died and 11 were alive. The overall survival after SRS for the entire series was 100%, 88.9% and 88.9% at 1, 3 and 5 years, respectively. Localized solid tumor progression was seen in two patients. Cyst progression was noted in three of nine patients with cystic tumors and mixed solid and cyst progression was noted in two with cystic tumors. The progression free survival after SRS (including tumor growth and cyst enlargement) for the entire series was 83.9%, 31.5% and 31.5% at 1, 3 and 5 years, respectively. Prior surgical resection was associated with better progression free survival after SRS (P = 0.027). Despite their purported benign nature, pilocytic astrocytomas in adult patients often do not behave benignly. Unresectable pilocytic astrocytomas that are located in critical or deep areas of the brain require additional management approaches. In this preliminary experience obtained over a 12 year interval, SRS is most valuable for patients after maximal feasible surgical resection. Delayed cyst progression contributes to late loss of tumor control.     

Early or delayed radiosurgery for WHO grade II astrocytomas

To evaluate the role of gamma knife stereotactic radiosurgery (SRS) in the management of newly diagnosed (early) or progressive (delayed) WHO grade II astrocytomas, the authors reviewed 25 patients who underwent SRS for pathologically proven WHO grade II astrocytomas between 1987 and 2009 at the University of Pittsburgh. The median patient age was 30 years (range 8–68 years). Sixteen patients had early SRS after stereotactic biopsy (n = 14), resection (n = 1) or radiation therapy (n = 1), and 9 underwent delayed SRS for progression after surgical resection (n = 3), radiation therapy (n = 4) or both (n = 2). The median tumor volume was 3.7 cm³ (range 0.6–17.0 cm³) and the median margin dose was 14 Gy (range 11–20 Gy). At a median of 65 months of follow-up (range 6–208 months), tumor control was observed in 13 patients (52%). The progression-free survival rates after SRS at 1, 5 and 10 years were 91.3, 54.1 and 37.1%, respectively. On both univariate and multivariate analysis smaller tumor volume (<6 cm³), higher marginal dose (≥15 Gy) and absence of contrast enhancement on imaging studies were associated with better progression free-survival. Gamma knife SRS is an additional option for patients with small volume, deep seated, non-enhancing and well-demarcated WHO grade II astrocytomas and does not preclude later conventional fractionated radiation therapy, cyst aspiration, or cautious debulking if feasible. It may also benefit patients with residual or recurrent tumors that have progressed after surgery, radiation therapy or both.     

Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women’s Cancer Center experience

To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan–Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8–16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02–2.39). The median age was 57 years (range, 42–92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8–21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.     

Multidrug resistance proteins expression in glioma patients with epilepsy

This report shows the results of stereotactic radiation therapy for progressive residual pilocytic astrocytomas. Medical records of patients who had undergone stereotactic radiation therapy for a progressive residual pilocytic astrocytoma were reviewed. Between 1995 and 2010, 12 patients with progression of a residual pilocytic astrocytoma underwent stereotactic radiation therapy at UCLA. Presentation was headache (4), visual defects (3), hormonal disturbances (2), gelastic seizures (2) and ataxia (1). MRI showed a cystic (9), mixed solid/cystic (2) or solid tumor (1); located in the hypothalamus (5), midbrain (3), thalamus (2), optic chiasm (1) or deep cerebellum (1). Median age was 21 years (range 5-41). Nine tumors received stereotactic radiotherapy (SRT). Three tumors received stereotactic radiosurgery (SRS), two of them to their choline positive regions. SRT median total dose was 50.4 Gy (40-50.4 Gy) in a median of 28 fractions (20-28), using a median fraction dose of 1.8 Gy (1.8-2 Gy) to a median target volume of 6.5 cm(3). (2.4-33.57 cm(3)) SRS median dose was 18.75 Gy (16.66-20 Gy) to a median target volume of 1.69 cm(3) (0.74-2.22 cm(3)). Median follow-up time was 37.5 months. Actuarial long-term progression-free and disease-specific survival probabilities were 73.3 and 91.7 %, respectively. No radiation-induced complications were observed. Stereotactic radiation therapy is a safe and effective modality to control progressive residual pilocytic astrocytomas. Better outcomes are obtained with SRT to entire tumor volumes than with SRS targeting choline positive tumor regions.     

A phase I dose-escalation study of fractionated stereotactic radiosurgery in combination with gefitinib in patients with recurrent malignant gliomas

PURPOSE: To determine the maximum tolerated dose (MTD) of fractionated stereotactic radiosurgery (SRS) with gefitinib in patients with recurrent malignant gliomas. METHODS AND MATERIALS: A Phase I clinical trial was performed. Eligible patients had pathologically proved recurrent anaplastic astrocytoma or glioblastoma. Patients started gefitinib (250 mg/day) 7 days before SRS and continued for 1 year or until disease progression. SRS was delivered in three fractions over 3 days. The planning target volume (PTV) was the T1-weighted MRI postcontrast enhancing lesion+2 mm. The first cohort received an SRS dose of 18 Gy, and subsequent cohorts received higher doses up to the maximum dose of 36 Gy. Dose-limiting toxicity (DLT) was any Grade 3 toxicity. The MTD was exceeded if 2 of 6 patients in a cohort experienced DLT. RESULTS: Characteristics of the 15 patients enrolled were: 9 men, 6 women; median age, 47 years (range, 23-65 years); 11 glioblastoma, 4 AA; median prior RT dose, 60 Gy (range, 54-61.2 Gy); median interval since RT, 12 months (range, 3-57 months); median PTV, 41 cc (range, 12-151 cc). Median follow-up time was 7 months (range, 2-28 months). Median time on gefitinib was 5 months (range, 2-12 months). No patient experienced a DLT, and the SRS dose was escalated from 18 to 36 Gy. Grade 1-2 gefitinib-related dermatitis and diarrhea were common (10 and 7 patients, respectively). CONCLUSION: Fractionated SRS to a dose of 36 Gy in three fractions is well tolerated with gefitinib at daily dose of 250 mg. Further studies of SRS and novel molecular targeted agents are warranted in this challenging clinical setting.     

Feasibility,safety, and outcome of frameless image-guided robotic radiosurgery for brain metastases

We prospectively analyzed the safety and outcome of frameless image-guided robotic stereotactic radiosurgery (SRS) for treatment of brain metastases in patients that would have otherwise been treated with frame-based techniques. During a three-year period, 333 patients with 783 brain metastases of various histologies underwent 391 outpatient SRS procedures. Fifty-five percent of patients had multiple brain metastases. The median (mean) tumor volume was 1.0 cc (2.7 cc). The mean prescribed tumor dose was 18.5 Gy (±1.3 Gy). Local/distant tumor recurrences were treated by additional SRS for patients with stable systemic disease. Survival and freedom from local tumor recurrence was analyzed with the Kaplan–Meier method. Prognostic factors were obtained from the Cox proportional hazards model. System accuracy tests (end-to-end tests) were performed with a standard head phantom. Overall median survival was 12.2 months after SRS. The actuarial one-year local control rate was 95.2% (95% CI: 92.0–97.2); the distant brain tumor control rate was 67% (95% CI: 61.0–71.2). Most patients died from systemically progressing cancer (69%). A Karnofsky performance score (KPS) > 70 was related to prolonged survival in the univariate and multivariate analysis. Recursive partition analysis (RPA) classes I and II were related to prolonged survival in the univariate analysis. Twenty-one patients (6.3%) developed treatment-related neurotoxic effects; no patient died because of complications of SRS. Forty-five end-to-end tests documented a mean targeting accuracy of 0.48 ± 0.22 mm. Single-session, frameless robotic SRS is feasible, accurate, and safe in selected patients with brain metastases of various primary tumors. There seems to be no difference in patient selection, adverse effects, treatment outcomes, or system accuracy compared with frame-based SRS.     

Treatment with high marginal dose is mandatory to achieve long-term control of skull base chordomas and chondrosarcomas by means of stereotactic radiosurgery

Chordomas and chondrosarcomas of the skull base are rare. Since total resection of these tumors is difficult, adjuvant radiotherapy is necessary. This study was performed to evaluate the effect of stereotactic radiosurgery (SRS) for skull base chordomas and chondrosarcomas and to determine the optimal marginal dose for these tumors. Fourteen patients with histologically proven chordomas or chondrosarcomas underwent 16 sessions of SRS using gamma knife. The marginal doses ranged from 10 to 20 Gy (mean, 15 Gy). Lower marginal doses of 12 Gy on average (range, 10–12.5 Gy) were applied to four patients since they underwent prior fractionated radiotherapy, and partial treatment for which parts of tumors were excluded from planned target volume because of their proximity to critical structures was also applied to four patients. The whole tumors were covered with higher marginal doses of 18 Gy on average (range, 16–20 Gy) for six patients. The mean follow-up period was 65 months. Progression-free survival (PFS) rates at 3 and 5 years after SRS was 53 and 43%, respectively. Five-year PFS rates for patients who underwent SRS with higher and lower marginal doses were 80 and 14%, respectively, which were significantly different (P = 0.005). Tumor progression after partial irradiation mainly occurred from sites where delivered doses were reduced. Sufficient marginal doses at least 16 Gy appeared crucial. Proper combination with surgical resection to detach tumors from critical structures and to reduce tumor volume is necessary to completely deliver sufficient marginal doses for SRS.     

Gamma Knife radiosurgery for brainstem metastases: the UCSF experience

Purpose: To assess clinical and imaging outcomes in patients treated with Gamma Knife stereotactic radiosurgery (SRS) for brainstem metastases. Materials and methods: We reviewed all patients with brain metastases treated with SRS at the University of California, San Francisco from 1991–2005 to identify patients who had SRS to a brainstem metastasis. Survival time and freedom from progression (FFP) were calculated from date of SRS using the Kaplan–Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. Results: From 1991 through 2005, 42 consecutive patients with brainstem metastases had SRS to 44 lesions (seven midbrain, 31 pontine, and six medullary) in 42 sessions. Primary diagnoses included 14 cases of lung cancer (one small-cell), 10 melanoma, 12 breast cancer, five renal cell, and one unknown. The median age was 55 years (range, 25–79). The median survival time was 9 months after SRS. Longer survival time was associated with single metastasis, non-melanoma histology, and extracranial disease control. The median target volume was 0.26 ml (0.015–2.8 ml) and the median prescribed dose was 16.0 Gy (10.0–19.8 Gy). Brainstem lesion FFP was 90% at 6 months and 77% at 1 year. Four patients had brainstem complications following treatment. Poor brainstem outcome was associated with melanoma and renal cell histology as well as brainstem lesion volume ≥1 ml. Conclusions: In this series, SRS using a median dose of 16 Gy provided excellent local control with relatively low morbidity in patients with brainstem metastases less than 1 ml or non-melanoma, non-renal cell histology.     

Gamma Knife stereotactic radiosurgery for intracranial hemangiopericytomas

The purpose of this study is to determine the efficacy of Gamma Knife stereotactic radiosurgery (GK SRS) for intracranial hemangiopericytomas, and to investigate the optimal dose for successful tumor control without adverse effects. We evaluated 17 hemangiopericytomas of nine patients treated with GK SRS between 1999 and 2008. The mean tumor volume was 2.2 cm³ (range 0.2–9.9 cm³), and the mean and median marginal doses were 18.1 and 20 Gy (range 11–22 Gy), respectively, at the 50% isodose line. Mean clinical and radiological follow-up periods were 49 and 34 months, respectively. Successful tumor control was achieved in 14 of 17 lesions (82.4%) at time of last follow-up after GK SRS. Actuarial local tumor control rates at 1, 2, and 5 years after GK SRS were 100%, 84.6%, and 67.7%, respectively. No adverse effects, such as radiation necrosis or marked peritumoral edema, were observed in any patient. Marginal dose (≥17 Gy) was the only statistically significant factor for local tumor control on univariate analysis. Extended analysis using lesion data available from previous studies revealed that higher marginal dose (≥17 Gy) was also significant (P = 0.028). GK SRS provides an effective and safe adjuvant management option for patients with recurrent or residual hemangiopericytomas. Our results suggest that doses higher than previously used (around 15 Gy) are desirable to achieve better local tumor control of hemangiopericytomas. Close radiological follow-up is also necessary for early detection of small recurrent lesions.     

Stereotactic radiosurgery for intracranial chondrosarcoma

To assess outcomes after stereotactic radiosurgery (SRS) for chondrosarcomas of the skull base, we reviewed 22 patients with cranial base chondrosarcomas who underwent SRS between 1987 and 2009. The median patient age was 42 years (range, 15-75). The median SRS target volume was 8.0 cc (range, 0.9-28.2) and median margin dose was 15.0 Gy (range, 10.5-20). 15 patients (68 %) underwent one or more tumor resections and 3 of these patients also had fractionated radiation therapy. At a median follow-up of 75 months after SRS, seven patients died due to tumor progression. The actuarial overall survival after SRS for the entire group of chondrosarcoma patients was 95, 76, 70 and 56 % at 1, 3, 5 and 10 years, respectively. Factors associated with longer survival after SRS included patient age >40 years, a shorter interval (<6 months) between diagnosis and SRS, and either no or a single prior resection. Treated tumor control rates were 91, 72, 72 and 54 % at 1, 3, 5 and 10 years, respectively. Factors associated with longer progression-free survival after SRS included patient age >40 years and no prior RT. Symptomatic adverse radiation effects occurred in two patients (10 %). Stereotactic radiosurgery may provide a benefit to patients as either a primary or adjuvant therapy. The ability to achieve tumor control in patients with chondrosarcoma is likely to be enhanced by earlier timing of SRS after diagnosis and multimodal management, beginning with resection when feasible followed by early SRS for progressive residual tumor.     

Overall and progression-free survival and visual and endocrine outcomes for patients with parasellar lesions treated with intensity-modulated stereotactic radiosurgery

Linear accelerator single-fraction radiosurgery (SRS) for skull base lesions is usually delivered with dynamic conformal arcs (DCAs), but intensity-modulated radiosurgery (IMRS) is another option when SRS dose is limited by proximity of the optic nerve and chiasm. We review the long-term outcome of patients treated with IMRS for parasellar lesions. Fourteen patients with parasellar lesions were treated with IMRS when standard DCA radiosurgery was limited by optic nerve tolerance. Prospective patient data included endocrine function, visual acuity and field testing, nonoptic nerve cranial neuropathy, and overall survival. In addition, tumor control on serial magnetic resonance imaging is reported as progression-free survival (PFS). Six patients with cavernous sinus meningiomas and eight with recurrent pituitary adenomas were treated. Three of the pituitary tumors were hormonally active (two with Cushing disease, one with acromegaly). The median patient age was 50 years (range 24–70 years). Median follow-up was 54 months. Average tumor treatment volume was 4.99 ml (average dose 16 Gy, average of 10 IMRS fields). Tumor control was achieved in 11 of 14 (79%) patients. Median PFS has not been reached in our patient population. Thirteen patients are alive (one died of an unrelated cancer). No patients developed new endocrinological, ophthalmological, or cranial nerve deficits. IMRS allows for treatment of parasellar lesions when standard DCA SRS is limited by optic nerve tolerance. Although our follow-up period was relatively short and the number of patients was small, it appears that this can be accomplished with a high tumor control rate and survival without new endocrinopathies, optic neuropathies, or other complications in patients who have failed other therapies.     

Gamma knife radiosurgery for metastatic brain tumors from thyroid cancer

Objective We report our experience using gamma knife radiosurgery (GKR) for brain metastasis from thyroid cancer, which is extremely rare. Methods Between 1995 and 2007, 9 patients with 26 metastatic brain tumor(s) from thyroid cancer underwent GKR. The mean patient age was 58 years (range: 10–78). Seven patients had metastases from papillary thyroid cancer, and two from medullary thyroid cancer. Five patients had solitary tumors, and four patients had multiple metastases. Three patients who had multiple metastases also underwent whole brain radiation therapy (WBRT). The mean tumor volume was 2.4 cc (range: 0.03–14.0). A median margin dose of 18.0 Gy (range: 12–20) was delivered to the tumor margin. Results Tumor control was obtained in 25 out of 26 tumors (96%). The median progression-free period after GKR was 12 months (range: 4–53). The overall median survival after GKR was 33 months (range: 5–54). There were no procedure-related complications and six patients are still living 5–54 months after GKR. Conclusions Radiosurgery is an effective and minimally invasive strategy for management of brain metastases form thyroid cancer.     

Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival

Purpose To determine the radiographic and clinical efficacy of stereotactic single dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) as salvage therapy for glioblastoma (GBM) at recurrence. Methods Thirty-six patients with pathologically proven recurrent GBM were treated with salvage reirradiation by either SRS or FSRT between March of 2001 and August of 2006. Thirty-one patients had an initial diagnosis of GBM. Five patients had a malignant transformation. All patients had received radiotherapy with a dose of 50–60 Gy, a median 13.6 months prior to reirradiation (range: 0.8–119 months). At the time of recurrence, 26 patients were treated with SRS with a median dose of 18 Gy (range: 12–20 Gy). FSRT was performed in ten patients with a dose of 36 Gy in six fractions, twice weekly. Follow-up included MRI and clinical examination every 2 months. Results Median survival time after SRS was 8.5 months, compared to 7.4 months after FSRT (P = 0.81). Of 26 patients treated with SRS, radiographic tumor response or stable disease was observed in eight (35%) patients and tumor progression was seen in 18 (65%) patients. Of 10 patients treated by FSRT, radiographic tumor response or stable disease was observed in four (40%) patients and tumor progression was observed in four (40%) patients (two lost to follow-up). Patients who responded to treatment had statistically improved survival compared to non-responders, with median survival of 15.8 vs. 7.3 months (P < 0.05). Conclusion Salvage reirradiation with SRS or FSRT for recurrent GBM results in radiographic response in a proportion of patients. Survival was significantly improved among patients who either responded or had stable disease after salvage reirradiation, compared to non-responders. Further study is warranted to investigate the method and time of reirradiation for recurrent GBM.     

The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases

PURPOSE: To better analyze how whole-brain radiotherapy (WBXRT) affects long-term tumor control and toxicity from the initial stereotactic radiosurgery (SRS) for brain metastases, we studied these outcomes in patients who had survived at least 1 year from SRS. METHODS AND MATERIALS: We evaluated the results of gamma knife radiosurgery for 160 brain metastases in 110 patients who were followed for a median of 18 months (range, 12-122 months) after SRS. Eighty-two patients had a solitary brain metastasis and 28 patients had multiple metastases. Seventy patients (116 tumors) were treated with initial radiosurgery and WBXRT, whereas 40 patients (44 lesions) initially received radiosurgery alone. Median treatment volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group, and 1.6 cc in the SRS alone group. Median tumor dose was 16 Gy (range, 12-21 Gy). RESULTS: At 1, 3, and 5 years, local tumor control was 84.1% +/- 5.5%, 68.6% +/- 8.7%, and 68.6% +/- 8.7% with SRS alone compared with 93.1% +/- 2.4%, 87.7% +/- 4.9%, and 65.7% +/- 10.2%. with concurrent WBXRT and SRS (p = 0.0228, univariate). We found that WBXRT improved local control in patient subsets tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and lung cancer metastases (p = 0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal intracranial failure developed at 1, 3, and 5 years in 26.0% +/- 7.1%, 74.5% +/- 9.4%, and 74.5% +/- 9.4% with SRS alone compared with 20.7% +/- 4.9%, 49.0% +/- 8.7%, and 61.8% +/- 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a trend for improved distal intracranial control with WBXRT for only nonradioresistant tumors (p = 0.054). Postradiosurgery complications developed in 2.8% +/- 1.2% and 10.7% +/- 3.5% at 1 and 3-5 years and was unaffected by WBXRT (p = 0.7721). WBXRT did not improve survival in the entire series (p = 0.5027) or in any subsets. CONCLUSIONS: In this retrospective study of 1-year survivors of SRS for brain metastases, the addition of concurrent WBXRT to SRS was associated with an improved local control rate in patient subsets with tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and specifically lung cancer metastases. A trend was noted for improved distal intracranial control for patients having nonradioresistant tumors. Distant intracranial relapse >1 year posttreatment is a significant problem with or without initial WBXRT.     

Treatment of brainstem metastases with gamma-knife radiosurgery

The aim was to investigate the efficacy and safety of gamma-knife stereotactic radiosurgery (SRS) for treating brainstem metastases. The cases of 44 patients who underwent SRS as treatment for 46 brainstem metastases were retrospectively evaluated. The median age was 57 years (range 42–82 years) and the median Karnofsky performance score (KPS) was 80 (range 60–90). The primary tumor was lung carcinoma in 28 cases, breast carcinoma in 7 cases, colon carcinoma in 3 cases, renal cell carcinoma in 3 cases, malignant melanoma in 1 case, and unknown origin in 2 cases. Of the 46 metastases, 30 were in the pons, 14 were in the mesencephalon, and 2 were in the medulla oblongata. The median volume of the 46 metastases was 0.6 cc (range 0.34–7.3 cc). The median marginal dose of radiation was 16 Gy (range 10–20 Gy). Twenty-three patients (52 %) received whole brain radiotherapy prior to SRS, and 6 (14 %) received this therapy after SRS. In the remaining 15 cases (34 %), SRS was applied as the only treatment. Recursive partitioning analysis, graded prognostic assessment, and basic score for brain metastases were used to predict survival time. Local control was achieved for all but two of the 46 metastases (96 %). The overall survival time after SRS was 8 months. Female gender, KPS >70, mesencephalon tumor location, and response to treatment were associated with longer survival. Basic score for brain metastases class I and recursive partitioning analysis classification were associated with better prognosis. Peri-tumoral changes were detected radiologically at 2 (4 %) of the metastatic lesion sites but neither of these patients exhibited symptoms. Gamma-knife radiosurgery is effective for treating brainstem metastases without a higher risk for radiation necrosis.     

Repeat stereotactic radiosurgery for the management of locally recurrent brain metastases

Purpose

Stereotactic radiosurgery (SRS) is a well-established treatment option for brain metastases (BM). Repeat SRS for progressive BM is an increasingly used paradigm, although little data is available to support this practice. The goal of this study was to assess the safety and efficacy of a second SRS procedure on a previously treated BM.

Methods

We performed a retrospective metastasis-level analysis of patients who underwent two SRS procedures on the same lesion and for whom at least 6 months of radiological follow-up was available. The data collected included patient characteristics, clinical symptoms at time of treatment, SRS parameters, radiological response per RANO-BM criteria, clinical evolution and survival.

Results

Seventy-five BM in 56 patients were included in the analysis. Most frequent primary histologies were non-small-cell lung cancer (59%) and breast cancer (19%). At the second SRS, median treatment volume was 1.19 cc (range 0.07–20.6) treated with a median margin dose of 18 Gy (range 12–20) at the 50% isodose line (range 30–80%). Median follow-up was 11 months. Progression per RANO-BM criteria occurred in 31%, yielding actuarial local control at 1, 2, and 5 years of 68%, 54% and 54% respectively. At last follow-up, 10 patients (18%) had improved relative to the initial presentation, while 21 (38%) were stable and 25 (44%) were deteriorated. Radiation-induced edema and radionecrosis occurred in 8.3% and 5% respectively. The median survival from the diagnosis of BM was 30 months.

Conclusion

Repeat SRS is a safe and effective novel therapeutic approach to consider in carefully selected patients.

     

Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case–control study

We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46–72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5–34.5 months). The median tumor volume was 13.6 cm³ (range 1.2–45.1 cm³) and the median margin dose of GKSR was 16 Gy (range 13–18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6–28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5–23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1–25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy.