Brain metastases are a common occurrence, with literature supporting the treatment of a limited number of brain metastases with stereotactic radiosurgery (SRS), as opposed to whole brain radiotherapy ...(WBRT). Less well understood is the role of SRS in patients with ≥10 brain metastases.
Patients treated with SRS to ≥10 brain metastases without concurrent WBRT between March 1999 and December 2016 were reviewed. Analysis was performed for overall survival, treated lesion freedom from progression (FFP), freedom from new metastases (FFNMs), and adverse radiation effect. Hippocampal volumes were retrospectively generated in patients treated with up-front SRS for evaluation of dose volume metrics.
A total of 143 patients were identified with 75 patients having up-front SRS and 68 patients being treated as salvage therapy after prior WBRT. The median number of lesions per patient was 13 (interquartile range IQR, 11–17). Median total volume of treatment was 4.1 cm3 (IQR, 2.0–9.9 cm3). The median 12-month FFP for up-front and salvage treatment was 96.8% (95% confidence interval CI, 95.5–98.1) and 83.6% (95% CI, 79.9–87.5), respectively (P < 0.001). Twelve-month FFNMs for up-front and salvage SRS was 18.8% (95% CI, 10.9–32.3) versus 19.2% (95% CI, 9.7–37.8), respectively (P = 0.90). The mean hippocampal dose was 150 cGy (IQR, 100–202 cGy).
Excellent rates of local control can be achieved when treating patients with >10 intracranial metastases either in the up-front or salvage setting. Hippocampal sparing is readily achievable with expected high rates of new metastatic lesions in treated patients.
Introduction
Recurrent intracranial epidermoid cysts may be difficult to address surgically given their proximity to critical neurovascular structures of the skull base. There are emerging reports of ...using radiotherapy (RT) for the treatment of recurrent epidermoid cysts. Here, we report a case series of adjuvant fractionated external beam RT for recurrent intracranial epidermoid cysts.
Methods
A single-institution review of all recurrent epidermoid cysts treated with adjuvant therapy between 2000 and 2017 was performed.
Results
Eight patients with recurrent epidermoid cysts who underwent adjuvant external beam RT were identified. Average age at initial diagnosis was 42.2 years, and median clinical follow-up after initial diagnosis and RT was 16.4 and 2.9 years, respectively. The median number of surgical resections prior to RT was 3 (range 2–5). Rationale for RT included multiple recurrent disease, rapid recurrence following prior resection, increased risk of further surgical morbidity, and patient preference. Median dose was 50.4 delivered in 1.8 Gy fractions (median 28 fractions). By the date of last follow-up, no patient has demonstrated progression, and there have been no cases of malignant degeneration.
Conclusion
Adjuvant RT should be considered in the context of recurrent epidermoid cysts to decrease the likelihood of further recurrences.
Abstract
BACKGROUND
Prognostic markers for meningioma are needed to risk-stratify patients and guide postoperative surveillance and adjuvant therapy.
OBJECTIVE
To identify a prognostic gene signature ...for meningioma recurrence and mortality after resection using targeted gene-expression analysis.
METHODS
Targeted gene-expression analysis was used to interrogate a discovery cohort of 96 meningiomas and an independent validation cohort of 56 meningiomas with comprehensive clinical follow-up data from separate institutions. Bioinformatic analysis was used to identify prognostic genes and generate a gene-signature risk score between 0 and 1 for local recurrence.
RESULTS
We identified a 36-gene signature of meningioma recurrence after resection that achieved an area under the curve of 0.86 in identifying tumors at risk for adverse clinical outcomes. The gene-signature risk score compared favorably to World Health Organization (WHO) grade in stratifying cases by local freedom from recurrence (LFFR, P < .001 vs .09, log-rank test), shorter time to failure (TTF, F-test, P < .0001), and overall survival (OS, P < .0001 vs .07) and was independently associated with worse LFFR (relative risk RR 1.56, 95% CI 1.30-1.90) and OS (RR 1.32, 95% CI 1.07-1.64), after adjusting for clinical covariates. When tested on an independent validation cohort, the gene-signature risk score remained associated with shorter TTF (F-test, P = .002), compared favorably to WHO grade in stratifying cases by OS (P = .003 vs P = .10), and was significantly associated with worse OS (RR 1.86, 95% CI 1.19-2.88) on multivariate analysis.
CONCLUSION
The prognostic meningioma gene-expression signature and risk score presented may be useful for identifying patients at risk for recurrence.
Abstract
BACKGROUND: The role of stereotactic radiosurgery (SRS) for recurrent glioblastoma and the radionecrosis risk in this setting remain unclear.
OBJECTIVE: To perform a large retrospective ...study to help inform proper indications, efficacy, and anticipated complications of SRS for recurrent glioblastoma.
METHODS: We retrospectively analyzed patients who underwent Gamma Knife SRS between 1991 and 2013. We used the partitioning deletion/substitution/addition algorithm to identify potential predictor covariate cut points and Kaplan-Meier and proportional hazards modeling to identify factors associated with post-SRS and postdiagnosis survival.
RESULTS: One hundred seventy-four glioblastoma patients (median age, 54.1 years) underwent SRS a median of 8.7 months after initial diagnosis. Seventy-five percent had 1 treatment target (range, 1-6), and median target volume and prescriptions were 7.0 cm3 (range, 0.3-39.0 cm3) and 16.0 Gy (range, 10-22 Gy), respectively. Median overall survival was 10.6 months after SRS and 19.1 months after diagnosis. Kaplan-Meier and multivariable modeling revealed that younger age at SRS, higher prescription dose, and longer interval between original surgery and SRS are significantly associated with improved post-SRS survival. Forty-six patients (26%) underwent salvage craniotomy after SRS, with 63% showing radionecrosis or mixed tumor/necrosis vs 35% showing purely recurrent tumor. The necrosis/mixed group had lower mean isodose prescription compared with the tumor group (16.2 vs 17.8 Gy; P = .003) and larger mean treatment volume (10.0 vs 5.4 cm3; P = .009).
CONCLUSION: Gamma Knife may benefit a subset of focally recurrent patients, particularly those who are younger with smaller recurrences. Higher prescriptions are associated with improved post-SRS survival and do not seem to have greater risk of symptomatic treatment effect.
A previous analysis showed that brain metastases that are treated with frameless stereotactic radiation surgery (SRS) and planned with magnetic resonance imaging (MRI) >14 days before SRS had worse ...local control (LC). To evaluate if worse LC may be due to unaccounted interval metastasis growth and radiosurgical marginal miss, we quantified growth before SRS on preradiosurgical imaging.
We reviewed data from patients who were treated with fixed-frame SRS for brain metastases at our institution between 2010 and 2013 and had pretreatment diagnostic brain MRI and SRS-planning MRI scans available. Metastases were contoured on the pretreatment MRI scan and the day-of-treatment planning MRI scan for volumetric comparison. Growth rates were calculated. Serial volumetric contour expansions on the pretreatment MRI scans were used to determine the minimum margin necessary to encompass the entire metastasis on day of the SRS. LC was estimated by Kaplan-Meier method.
Among 411 brain metastases in 165 patients, the time between pretreatment and treatment MRI was associated with metastasis growth (P < .001) with a mean growth rate of 0.02 ml/day (95% confidence interval, 0.01-0.03) and a 1.35-fold volume increase at 14 days. Time between MRI scans was associated with the amount of margin that was needed to target the entire brain metastasis volume on the day of the SRS (P < .001), as were volume of metastasis on the pre-treatment MRI (P < .001) and melanoma histology (P < .001). LC was not associated with growth rate among patients who underwent fixed-frame SRS.
Time between pretreatment MRI and SRS is associated with brain metastasis growth, but LC is not compromised when patients receive fixed-frame SRS with same-day MRI planning. Margins may be needed for metastases that are treated with frameless SRS to account for growth between the planning MRI and SRS delivery.
In this study, we quantify brain metastasis growth over time by taking advantage of the availability of 2 pretreatment magnetic resonance imaging scans taken at 2 time points among patients treated with frame-fixed radiation surgery. We found that metastasis growth is associated with time, initial metastasis size, melanoma histology, and concurrent chemotherapy. Performing serial margin expansions demonstrated factors that are associated with the amount of margin that is needed to target the entire metastasis on the day of radiation surgery.
Stereotactic radiosurgery (SRS) is a potentially important option for patients with skull base chondrosarcomas. The object of this study was to analyze the outcomes of SRS for chondrosarcoma patients ...who underwent this treatment as a part of multimodality management.
Seven participating centers of the North American Gamma Knife Consortium (NAGKC) identified 46 patients who underwent SRS for skull base chondrosarcomas. Thirty-six patients had previously undergone tumor resections and 5 had been treated with fractionated radiation therapy (RT). The median tumor volume was 8.0 cm3 (range 0.9-28.2 cm3), and the median margin dose was 15 Gy (range 10.5-20 Gy). Kaplan-Meier analysis was used to calculate progression-free and overall survival rates.
At a median follow-up of 75 months after SRS, 8 patients were dead. The actuarial overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. Local tumor progression occurred in 10 patients. The rate of progression-free survival (PFS) after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with shorter PFS. Eight patients required salvage resection, and 3 patients (7%) developed adverse radiation effects. Cranial nerve deficits improved in 22 (56%) of the 39 patients who deficits before SRS. Clinical improvement after SRS was noted in patients with abducens nerve paralysis (61%), oculomotor nerve paralysis (50%), lower cranial nerve dysfunction (50%), optic neuropathy (43%), facial neuropathy (38%), trochlear nerve paralysis (33%), trigeminal neuropathy (12%), and hearing loss (10%).
Stereotactic radiosurgery for skull base chondrosarcomas is an important adjuvant option for the treatment of these rare tumors, as part of a team approach that includes initial surgical removal of symptomatic larger tumors.
•Margin dose per volume stage and compact architecture are favorable in terms of response with VS-SRS.•Diffuse nidus architecture is associated with a threshold dose of 17 Gy for response.•Dose ...escalation for compact nidus architecture may improve rates of cure as well.•Future efforts should evaluate continued dose escalation with smaller volumes per volume-stage.
Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult.
This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3–6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival.
With a median age of 33 years old at the time of first SRS volume stage, patients received 2–4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7–94.4 cc) with a median margin dose per stage of 17 Gy (range: 12–20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy.
VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.
The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported ...efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs).
This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic.
Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE.
Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.
The most common treatment protocol for whole-brain radiation therapy (WBRT) is 30 Gy in 10 fractions. This regimen entails a low risk of radiation retinopathy, with fewer than a dozen reported cases. ...We describe a case of radiation retinopathy that was confined to the superior retinae. These regions were the only portions of the eyes that were included in the treatment field.
Observational case report consisting of clinical examination, review of radiation treatment planning and implementation, computerized visual field testing, and fundus photography.
A 36-year-old man with metastatic lung adenocarcinoma developed radiation retinopathy 16 months after WBRT to 30 Gy in 10 fractions. The retinopathy was largely confined to the superior halves of the retinae. There was corresponding geographic inferior visual field loss in both eyes. Review of the patient's treatment protocol revealed that the superior retinae received a substantial radiation dose, approaching 30 Gy, whereas the inferior retinae were essentially outside the treatment field.
In this patient, the correlation between the treatment field and the resulting local development of radiation retinopathy demonstrated unequivocally that the relatively low dose used in routine WBRT (ie, 30 Gy in 10 fractions) can induce radiation retinopathy.
Purpose: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone ...reserving WBRT for salvage as needed. We reviewed results of RS ± WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial.
Methods and Materials: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site.
Results: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjusted
p = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted
p = 0.56).
Conclusions: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases.
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