Day Of Radiosurgery Research Articles

P.013 Symptom stability in de novo and rollover patients with bipolar I disorder receiving aripiprazole once-monthly in a 52-week, open-label study

To evaluate the efficacy and safety of Gamma Knife Radiosurgery (GKRS) in the treatment of single and multiple brain metastases.From October 2012 to June 2014 106 patients were treated with Radiosurgery (RS) for brain metastases at University of Florence. 77 out of 106 patients had a radiological follow up and their data were analyzed. The target was defined as the enhancing lesion. The prescription dose was defined depending on tumor volume and tumor location. Each patient performed an MRI one month after GKRS for the first three months and every 3 months thereafter. Overall survival was calculated from the day of RS until death. Local recurrence (LR) was defined as radiologic growth of the irradiated lesion, while distant brain recurrence (DBR) was the evidence of brain lesion outside the previous irradiated field. Both the LR and DBR were calculated from the RS till the day of radiological evidence of relapse. The correlations within patient and disease characteristics and the outcomes of survival and disease control were analyzed.Mean follow up was 7.2 ± 4.8 months (range: 2.4–22.8 months). At the time of analysis 21 patients (27.3%) were dead. The overall survival (OS) at 1 year was 74%. On univariate Cox Regression analysis female gender (p = 0.043, HR: 0.391, 95% CI: 0.157–0.972) and age >65 years (p = 0.003 HR: 4.623, 95% CI: 1.687–12.663) were predictive for survival. On multivariate analysis, age older than 65 years (p = 0.005HR: 4.254, 95% CI: 1.544–11.721) was confirmed as associated with worsened overall survival. 19 patients (24.7%) had recurrence in the radiosurgery field. The median time to local failure was 4.8 ± 2.0 months (range: 1.8–9.4 months) from GKRS. On Cox Regression univariate analysis, the only factor associated with higher risk of local failure was a number of treated lesions more than 4 (p = 0.015, HR: 3.813, 95% CI: 1.298–11.202), no significant parameters were found at the multivariate analysis. The median time to develop distant brain failure was 6 ± 4.32 months (range: 1.08–21.6 months). Median distant brain control was 74% at 1 year. None of the factors analyzed was statistically significant for the distant brain relapse. The radiosurgery treatment was well tolerated. One patient treated for seven metastases developed seizures 8 h after GKRS, he was treated with steroids and anticonvulsants. One patient had radiologic evidence of radionecrosis without any neurological symptoms.In well-performing patients with stable systemic disease radiosurgery can be performed as an exclusive treatment for brain metastases. Younger patients could have a greater benefit from the RS, on the other hand our finding confirm no correlation between the survival outcome and the number of lesions treated.

Additional brain metastases on the day of radiosurgery does not preclude a favorable outcome

Additional brain metastases on the day of radiosurgery does not preclude a favorable outcome

Increasing time to postoperative stereotactic radiation therapy for patients with resected brain metastases: investigating clinical outcomes and identifying predictors associated with time to initiation.

We sought todetermine the impact of time to initiation (TTI) of post-operative radiosurgery on clinical outcomes for patients with resected brain metastases and to identify predictors associated with TTI. All patients with resected brain metastases treated with postoperative SRS or fractionated stereotactic radiation therapy (fSRT) from 2012 to 2016at a single institution were reviewed. TTI was defined as the interval from resection to first day of radiosurgery. Receiver operating characteristic (ROC) curves were used to identify an optimal threshold for TTI with respect to local failure (LF). Survival outcomes were estimated using the Kaplan-Meier method and analyzed using the log-rank test and Cox proportional hazards models. Logistic regression models were used to identify factors associated with ROC-determined TTI covariates. A total of 79 resected lesions from 73 patients were evaluated. An ROC curve of LF and TTI identified an optimal threshold for TTI of 30.5 days, with an area under the curve of 0.637. TTI > 30days was associated with an increased hazard of LF (HR 4.525, CI 1.239-16.527) but was not significantly associated with survival (HR 1.002, CI 0.547-1.823) or distant brain failure (DBF, HR 1.943, CI 0.989-3.816). Fifteen patients (20.5%) required post-operative inpatient rehabilitation. Post-operative rehabilitation was associated with TTI > 30 days (OR 1.48, CI 1.142-1.922). In our study of resected brain metastases, longer time to initiation of post-operative radiosurgery was associated with increased local failure. Ideally, post-op SRS should be initiated within 30 days of resection if feasible.

Discovery of additional brain metastases on the day of stereotactic radiosurgery: risk factors and outcomes.

OBJECTIVE High-resolution double-dose gadolinium-enhanced Gamma Knife (GK) radiosurgery-planning MRI (GK MRI) on the day of GK treatment can detect additional brain metastases undiagnosed on the prior diagnostic MRI scan (dMRI), revealing increased intracranial disease burden on the day of radiosurgery, and potentially necessitating a reevaluation of appropriate management. The authors identified factors associated with detecting additional metastases on GK MRI and investigated the relationship between detection of additional metastases and postradiosurgery patient outcomes. METHODS The authors identified 326 patients who received GK radiosurgery at their institution from 2010 through 2013 and had a prior dMRI available for comparison of numbers of brain metastases. Factors predictive of additional brain metastases on GK MRI were investigated using logistic regression analysis. Overall survival was estimated by Kaplan-Meier method, and postradiosurgery distant intracranial failure was estimated by cumulative incidence measures. Multivariable Cox proportional hazards model and Fine-Gray regression modeling assessed potential risk factors of overall survival and distant intracranial failure, respectively. RESULTS The mean numbers of brain metastases (SD) on dMRI and GK MRI were 3.4 (4.2) and 5.8 (7.7), respectively, and additional brain metastases were found on GK MRI in 48.9% of patients. Frequencies of detecting additional metastases for patients with 1, 2, 3-4, and more than 4 brain metastases on dMRI were 29.5%, 47.9%, 55.9%, and 79.4%, respectively (p < 0.001). An index brain metastasis with a diameter greater than 1 cm on dMRI was inversely associated with detecting additional brain metastases, with an adjusted odds ratio of 0.57 (95% CI 0.4-0.9, p = 0.02). The median time between dMRI and GK MRI was 22 days (range 1-88 days), and time between scans was not associated with detecting additional metastases. Patients with additional brain metastases did not have larger total radiosurgery target volumes, and they rarely had an immediate change in management (abortion of radiosurgery or addition of whole-brain radiation therapy) due to detection of additional metastases. Patients with additional metastases had a higher incidence of distant intracranial failure than those without additional metastases (p = 0.004), with an adjusted subdistribution hazard ratio of 1.4 (95% CI 1.0-2.0, p = 0.04). Significantly worse overall survival was not detected for patients with additional brain metastases on GK MRI (log-rank p = 0.07), with the relative adjusted hazard ratio of 1.07, (95% CI 0.81-1.41, p = 0.65). CONCLUSIONS Detecting additional brain metastases on GK MRI is strongly associated with the number of brain metastases on dMRI and inversely associated with the size of the index brain metastasis. The discovery of additional brain metastases at time of GK radiosurgery is very unlikely to lead to aborting radiosurgery but is associated with a higher incidence of distant intracranial failure. However, there is not a significant difference in survival. ▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class IV.

Gamma Knife Radiosurgery in the management of single and multiple brain metastases

ObjectivesTo evaluate the efficacy and safety of Gamma Knife Radiosurgery (GKRS) in the treatment of single and multiple brain metastases. Patients and methodsFrom October 2012 to June 2014 106 patients were treated with Radiosurgery (RS) for brain metastases at University of Florence. 77 out of 106 patients had a radiological follow up and their data were analyzed. The target was defined as the enhancing lesion. The prescription dose was defined depending on tumor volume and tumor location. Each patient performed an MRI one month after GKRS for the first three months and every 3 months thereafter. Overall survival was calculated from the day of RS until death. Local recurrence (LR) was defined as radiologic growth of the irradiated lesion, while distant brain recurrence (DBR) was the evidence of brain lesion outside the previous irradiated field. Both the LR and DBR were calculated from the RS till the day of radiological evidence of relapse. The correlations within patient and disease characteristics and the outcomes of survival and disease control were analyzed. ResultsMean follow up was 7.2±4.8 months (range: 2.4–22.8 months). At the time of analysis 21 patients (27.3%) were dead. The overall survival (OS) at 1 year was 74%. On univariate Cox Regression analysis female gender (p=0.043, HR: 0.391, 95% CI: 0.157–0.972) and age >65 years (p=0.003 HR: 4.623, 95% CI: 1.687–12.663) were predictive for survival. On multivariate analysis, age older than 65 years (p=0.005HR: 4.254, 95% CI: 1.544–11.721) was confirmed as associated with worsened overall survival. 19 patients (24.7%) had recurrence in the radiosurgery field. The median time to local failure was 4.8±2.0 months (range: 1.8–9.4 months) from GKRS. On Cox Regression univariate analysis, the only factor associated with higher risk of local failure was a number of treated lesions more than 4 (p=0.015, HR: 3.813, 95% CI: 1.298–11.202), no significant parameters were found at the multivariate analysis. The median time to develop distant brain failure was 6±4.32 months (range: 1.08–21.6 months). Median distant brain control was 74% at 1 year. None of the factors analyzed was statistically significant for the distant brain relapse. The radiosurgery treatment was well tolerated. One patient treated for seven metastases developed seizures 8h after GKRS, he was treated with steroids and anticonvulsants. One patient had radiologic evidence of radionecrosis without any neurological symptoms. ConclusionsIn well-performing patients with stable systemic disease radiosurgery can be performed as an exclusive treatment for brain metastases. Younger patients could have a greater benefit from the RS, on the other hand our finding confirm no correlation between the survival outcome and the number of lesions treated.

Angioarchitecture Determines Obliteration Rate After Radiosurgery in Brain Arteriovenous Malformations

Radiosurgery as a potential treatment modality for brain arteriovenous malformations (AVM) has 60% to 90% obliteration rates. To test whether AVM angioarchitecture determines obliteration rate after radiosurgery. This study was a retrospective analysis of 139 patients with AVM who underwent radiosurgery. Multiple angioarchitectural characteristics were reviewed on conventional angiogram on the day of radiosurgery: enlargement of feeding arteries, flow-related or intranidal aneurysms, perinidal angiogenesis, arteriovenous transit time, nidus type, venous ectasia, focal pouches, venous rerouting, and presence of a pseudophlebitic pattern. The radiation plan was reviewed for nidus volume and eloquence of AVM location. A chart review was performed to determine clinical presentation and previous treatment. Outcome was dichotomized into complete/incomplete obliteration, and various statistics were performed, examining whether outcome status was associated with the investigated factors. Marginal dose ranged from 15 to 25 Gy (mean, 18.8 Gy), with lower doses prescribed in eloquent locations. Sizes of AVMs ranged from 0.08 to 21 cm (mean, 3.78 ± 4.19 cm). Complete AVM obliteration was achieved in 92 patients (66%) and was related to these independent factors: noneloquent location (odds ratio [OR], 3.20), size (OR, 0.88), low flow (OR, 3.47), no or mild arterial enlargement (OR, 3.32), and absence of perinidal angiogenesis (OR, 2.61). Concerning the 3 last angioarchitectural characteristics, if no or only a single factor was present in an individual patient (n = 92 patients), obliteration was observed in 74 (80%); if 2 or 3 factors were present (n = 47), obliteration was observed in 18 patients (38%; OR, 6.62). Angioarchitectural factors that indicate high flow are associated with a lower rate of AVM obliteration after radiosurgery.

SU-FF-T-541: Registration Strategy in Trigeminal Neuralgia Gamma Knife Radiosurgery Using T1-Weighted and FIESTA MRI Sequences

Purpose/Objective(s): Targeting precision is particularly crucial in Gamma Knife radiosurgery for trigeminal neuralgia. The purpose of this study was to develop a standardized image definition strategy to improve target registration. Materials/Methods: We conducted a study on 54 patients who underwent Gamma Knife radiosurgery treatment for trigeminal neuralgia. All patients were scanned with two magnetic resonance imaging(MRI)sequences on the day of radiosurgery: contrast‐enhanced T1‐weighted MRI and three‐dimensional fast imaging employing steady‐state acquisition (3‐D FIESTA) MRI.MRIimages were imported into the Elekta Leksell GammaPlan for radiosurgerytreatment planning. The trigeminal nerves for all patients were contoured by one experienced neurosurgeon. Image registration of T1‐weighted and FIESTA MRI scans was achieved through definition of the fiducial markers. We evaluated four registration methods: automatic image definition, manual definition through superior slices, middle slices, and inferior slices. Target discrepancies were measured by the deviations of an intracranial landmark on T1‐weighted and FIESTA MRIimages. We verified our results with in‐house software using a landmark‐based rigid registration algorithm. Results: For T1‐weighted MRI, automatic image definition was achieved in 50 (93%) of 54 patients and no difference was found in the coordinates of the intracranial landmark using T1‐weighted automatic or manual definition. For FIESTA MRI, automatic image definition was achieved in 7 patients (13%). The most accurate registration strategy for FIESTA MRI was achieved using middle slice definition with mean error of 0.45 ± 0.41 mm (p<0.01). We confirmed these clinical findings with a landmark‐based MRI registration algorithm. Conclusion: Our study demonstrated that T1‐weighted and FIESTA MRI registration through image definition in GammaPlan affected targeting accuracy in Gamma knife radiosurgery for trigeminal neuralgia. We recommend a standardized registration strategy using manual definition of middle slices for T1‐weighted and FIESTA MRI to further improve targeting.

A Virtual Frame System for Stereotactic Radiosurgery Planning

We describe a computerized (or virtual) model of a stereotactic head frame to enable planning prior to the day of radiosurgery. The location of the virtual frame acts as a guide to frame placement on the day of the procedure. The software consists of a triangular mesh representation of the essential frame hardware that can be overlaid with any MR scan of the patient and manipulated in three dimensions. The software calculates regions of the head that will actually be accessible for treatment, subject to the geometric constraints of the Leksell Gamma Knife hardware. DICOM-compliant MR images with virtual fiducial markers overlaid onto the image can then be generated for recognition by the treatment planning system. Retrospective evaluation of the software on 24 previously treated patients shows a mean deviation of the position of the virtual frame from the actual frame position of 1.6 +/- 1.3 mm. Initial clinical use on five patients indicates an average discrepancy of the virtual frame location and the actual frame location of <1 mm. MR images with virtual fiducial markers can be imported into radiosurgical treatment planning software and used to generate an initial treatment plan. The virtual frame provides a tool for prospective determination of lesion accessibility, optimization of the frame placement, and treatment planning before the day of the procedure. This promises to shorten overall treatment times, improve patient comfort, and reduce the need for repeat treatments due to suboptimally placed frames.

A phase II study of radiosurgery and temozolomide for patients with one to four brain metastases

2048 Background: To determine if temozolomide reduces the risk of distant brain failure (DBF, metachronous brain metastases) in patients with 1–4 brain metastases treated with radiosurgery without whole brain radiation therapy. Methods: Twenty-five patients with newly diagnosed brain metastases were enrolled in a single institution phase II trial of radiosurgery (15–24 Gy) and adjuvant temozolomide. Temozolomide was started within 14 days of radiosurgery and was administered 150–200 mg/m2 p.o. q day x 5 days in 28 day cycles. Temozolomide was continued for a total of 12 cycles unless the patient developed DBF, unacceptable toxicity, or systemic progression requiring other therapy. If more than 4 metastases were identified on the MRI performed on the day of radiosurgery, then the patient could still be treated on the clinical trial if all tumors could be treated with radiosurgery. In addition to clinical and radiographic follow-up, QOL was assessed utilizing the FACT-Br questionnaire. Results: Twenty-five patients were enrolled 2002–2005; three were not evaluable for determining DBF. Of the remaining twenty-two patients, tumor types included NSCLC (n=8), melanoma (n=7), other (n=7). Extracranial disease was present in ten (45%) patients. The median number of tumors was 3 (range 1–6). The median overall survival was 31 weeks. The median radiographic follow-up for patients that did not develop DBF was 33 weeks. Six patients developed DBF. The one year actuarial risk of DBF was 37%. Patients with melanoma had a higher risk of DBF than other patients (p&lt;0.001, log-rank). Only 1/15 patients without melanoma vs. 5/7 patients with melanoma developed DBF. 15 serious adverse events (SAEs) occurred in 10 of the patients, but none of the SAEs were judged to be likely related to temozolomide. Among patients that experienced DBF, no significant differences were seen in QOL when pretreatment FACT-Br and time of distant brain failure FACT-Br scores were compared. Conclusions: Adjuvant temolozomide after radiosurgery is associated with a low risk of distant brain failure in non-melanoma patients. Larger clinical trials should examine the relative efficacy and QOL of WBRT and temozolomide in non-melanoma brain metastases patients. No significant financial relationships to disclose.

Current radiosurgery practice: results of an astro survey

Purpose :Although there is increasing interest in radiosurgery, little quantitative data regarding current patterns of radiosurgery practice are available. We developed a radiosurgery questionnaire to obtain information on radiosurgery practice. Methods and Materials : We distributed the questionnaire to the entire membership of the American Society of Therapeutic Radiology and Oncology in early 1993. Responses were obtained from 74 facilities that practice radiosurgery, corresponding to over 6000 treatments carried out since 1983 by 135 radiation oncologists and 130 physicists. Results : Most respondents were found to work within a multidisciplinary team, consisting of the following specialists (Average hours devoted per patient on day of treatment in parentheses): radiation oncologist (3.8), neurosurgeon (3.2), physicist (6.1), radiologist (0.7), nurse (2.7), other (3.0). On average, neurosurgeons and nurses who perform Gamma Knife radiosurgery devote significantly more time-per-patient on the day of treatment than their peers who perform linac radiosurgery. On average, less experienced radiation oncologists and physicists (≤ 24 months experience, or ≤ 50 patients treated) devote significantly more time-per-patient on the day of treatment than their more experienced peers. Although there are many more linac radiosurgery facilities than Gamma Knife facilities, on average the number of patients treated per month per facility is significantly larger at the latter. On average, follow-up responsibilities are nearly equally shared by radiation oncologists and neurosurgeons, except at Gamma Knife facilities, where neurosurgeons assume a larger percentage of follow-up responsibility. The percentages of patients treated at linac facilities for metastases or primary CNS malignancy are larger than the corresponding percentages at Gamma Knife facilities; the opposite is true for arteriovenous malformation, acoustic neuroma, and meningioma. Conclusion : Current radiosurgery practice usually involves a team approach, with participation of specialists from radiation oncology, neurosurgery, physics, radiology, and nursing. The average number of M.D. and Ph.D. hours required per treatment on the day of radiosurgery is high.