- Email: [email protected]
Adult Supratentorial Ependymoma: The Mayo Clinic Experience
Proceedings of the 53rd Annual ASTRO Meeting respectively prior to SRS. The median prescription dose was 18 Gy (12 - 27 Gy) delivered in 1 - 3 fractions for a median target volume of 7.6 cm3 (0.5 - 59 cm3). The 6-month, 1-year and 2-year LC rates were 75.9%/75.9%/73.7%, respectively. The 6month, 1-year, and 2-year IC rates were 75.5%/53%/42.8%, respectively. With a median follow-up of 13.1 months, the median OS was 14.4 months (1.9 - 51.4 months) after SRS. The overall 6-month, 1-year and 2-year OS rates were 91%/61.7%/43%, respectively. The median OS for RPA classes 1 (n = 17), 2 (n = 45) and 3 (n = 16) were not reached, 21.9, and 6.2 months, respectively. The median OS for GPA scores [0-1] (n = 9), [1.5-2.5] (n = 54), and [3-4] (n = 15) were 6.2, 18.2 months and not reached, respectively. On multivariate analysis, target volume (p = 0.01) significantly predicted LC, whereas no factors were significant predictors of IC. Factors that significantly influenced OS on multivariate analysis were age (p = 0.001), GPA score (p = 0.01) and RPA class (p = 0.02). Complications included 2 patients with radiation necrosis. WBRT was offered in 21 patients (26.9%) at 8.8 months following SRS for local and/or intracranial recurrence. Conclusions: Adjuvant SRS to the tumor cavity of resected brain metastases is well-tolerated and achieves LC in the majority of patients. RPA class and GPA are highly predictive of clinical outcomes. Author Disclosure: J. Rwigema: None. R.E. Wegner: None. A.H. Mintz: None. S.A. Burton: None. D.E. Heron: None.
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Volumetric Based Thresholds to Define Local Control of Brain Metastases following Gamma Knife Radiosurgery and Predictors of Local Control and Overall Survival
M. J. Follwell1, K. Hu2, W. Xu1, L. Cheng1, N. Laperriere1, M. Bernstein2, A. Sahgal1 1
Princess Margaret Hospital, Toronto, ON, Canada, 2Toronto Western Hospital, Toronto, ON, Canada
Purpose/Objective(s): To define volume based thresholds using segmentation software for local control of brain metastases following Gamma Knife radiosurgery (RS) using RECIST criteria as the benchmark, and determine predictors of local control and overall survival in this patient cohort. Materials/Methods: One hundred nineteen patients with 287 brain metastases (BM) were identified with newly diagnosed brain metastases treated with Gamma Knife RS alone or those with brain metastases that had recurred or developed after previous whole brain radiotherapy (WBRT). BM were excluded if they were located in the brainstem, had been treated with the intent of boost RS or if no follow-up imaging was performed. 70 patients with 178 metastases that met these criteria were included in the final analysis. All tumors treated were characterized at baseline and at each follow-up MRI according to widest diameter, calculated sphere volume (Vc) and segmented volume (Vs) using ITK-SNAP 1.8.0 image segmentation software. Results: The median age of the patients was 56 years (range, 25-79), median KPS was 90 (range, 50-100), median RPA was 2 (range, 1-3) and median GPA was 3 (range, 1-4). Thirty-seven patients presented with a solitary metastasis while 33 patients had multiple metastases (range 2-18). Most metastases were supra-tentorial (87%) and received Gamma Knife RS as salvage following prior WBRT (95%). Median tumor diameter was 1.2cm (range, 0.2-4.5cm), Vc was 0.70cc (range, 0.004-47.7cc) and Vs was 0.73cc (range, 0.01-22.7cc). Based on RECIST criteria, at 1 year the rate of progressive disease (PD, $20% increase) was 18%, 47% for stable disease (SD, \30% decrease or \20% increase), 22% for partial response (PR, $30% decrease) and 14% for complete response (CR, 100% decrease). The corresponding changes in volume required to match these rates for Vs were a $71.5% increase for PD, \58.5% decrease or \71.5% increase for SD and $58.5% decrease for PR. Factors that predicted local control were a baseline diameter .3.0cm (p = 0.006) and a baseline Vs of .6.0cc (p = 0.043). At the time of analysis 26 patients had died and the median survival after RS was 15.3 months (range 4.6-22.3 months). The one and two year survival probabilities were 0.54 and 0.10. Only baseline cumulative volume of .3.0 cc (p = 0.020) was identified as negative predictive of overall survival despite RPA and GPA classification. Conclusions: We defined volumetric criteria for response based on the current standard of RECIST criteria for brain metastases treated with RS, and accordingly identified a Vs of .6.0 cc and diameter of .3.0 cm as predictors for local failure and a cumulative volume of disease .3.0 cc as a predictor of shorter overall survival. Author Disclosure: M.J. Follwell: None. K. Hu: None. W. Xu: None. L. Cheng: None. N. Laperriere: None. M. Bernstein: None. A. Sahgal: None.
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Adult Supratentorial Ependymoma: The Mayo Clinic Experience
J. W. Rooney, M. Stauder, N. N. Laack Mayo Clinic, Rochester, MN Purpose/Objective(s): To examine the role of radiotherapy (RT) on survival and recurrence in adult patients diagnosed with supratentorial ependymoma. Materials/Methods: A retrospective search of a Mayo Clinic tumor registry was conducted to identify patients diagnosed with primary intracranial ependymoma between 1969 and 2008. The extent of surgical resection was determined by intraoperative impression and post-operative imaging. The external beam radiotherapy (EBRT) dose used ranged from 50 to 72 Gy delivered at 1.75-3.12 Gy per fraction. The EBRT treatment volumes consisted of tumor bed only, whole brain only, whole brain with boost, and the entire CNS with or without boost to the tumor bed. Estimates of overall survival (OS) and recurrence-free survival (RFS) were determined from the date of initial surgery using the Kaplan-Meier method. Results: A total of 42 adult patients (.18 y) were identified with a median age of 36.8 years (range 18.7-84.6). The median follow-up was 3.2 years (range 1.2 months to 13.9 years). 26 patients had Grade 2 and 14 had Grade 3 histology. At the time of analysis, 26 patients (62%) were alive. Kaplan-Meier estimates of OS and RFS at 5 years were 66% and 43%, respectively. The median survival was 9.7 years (range 1.2 months to 13.9 years). All patients (10) who had a subtotal resection (STR) received RT. 18 of 31 patients (58%) who underwent gross total resection (GTR) received RT. Twenty patients (48%) experienced a recurrence at a median of 3.2 years (range 1.2 months to 12.8 years). Three of 13 patients recurred after GTR without RT (range 0.9-4.6 yrs). Univariate analysis was performed to examine the role of presenting symptoms, grade, extent of resection, location, tumor size, radiation treatment, and chemotherapy treatment on OS and RFS. Significant factors predicting for improved OS included
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the extent of resection (p = 0.009), lack of recurrence (p = 0.02) and age\40 years (p = 0.05). There were no significant factors in our cohort associated with RFS, however there was a trend towards decreased recurrence in patients who had hemispheric location of their tumor (p = 0.08) and in patients who had undergone a GTR of their initial tumor (p = 0.15). Conclusions: Despite our small numbers, this is the largest cohort of patients with supratentorial ependymoma in the literature. OS was improved in younger patients with GTR and who were without recurrence. GTR was not associated with improvement in RFS, likely because all patients with STR received post-operative RT. Previously reported prognostic factors (i.e. age, grade) were not associated with risk of recurrence suggesting that a better understanding of the molecular characteristics of supratentorial ependymomas is necessary to determine patients who require adjuvant radiotherapy. Author Disclosure: J.W. Rooney: None. M. Stauder: None. N.N. Laack: None.
2183
Difference in Number of Brain Metastases Detected using 1.5T and 3T MRI in Patients Treated with Stereotactic Radiosurgery
L. G. Jensen, S. K. Nath, K. T. Murphy, J. F. Alksne, A. J. Mundt, J. D. Lawson University of California San Diego, La Jolla, CA Purpose/Objective(s): Brain metastases are the most common type of intracranial tumor and carry a poor prognosis. Recent retrospective series have suggested 3T magnetic resonance imaging (MRI) may detect more lesions when compared with 1.5T MRI. The aim of the current study is to compare the number of lesions detected by 1.5T and 3T MRI in patients planned for SRS using both imaging modalities. Materials/Methods: Records of patients treated with stereotactic radiosurgery for intracranial lesions at UCSD between December 2005 and December 2010 were reviewed. Patients were eligible if they had 1.5T MRI and a 3T MRI preceding treatment and the 1.5T MRI was performed first. The radiology reports were reviewed and the number of lesions recorded. Results: Fifty-nine pairs of scans (1.5T and 3T) were reviewed, with a median time between scans of 19 days (range 2-69). Tumor sites of origin were lung in 29 (49.2%), breast in 14 (23.7%), melanoma in 10 (16.9%), and other in 6 (10.2%). There was no increase in the number of lesions for 43 pairs (72.9%, 95% CI, 61.6-84.2%) and increased number of lesions for 16 pairs (27.1%, 95% CI, 15.8%-38.4). The difference in number of lesions ranged from 1-8. There was no difference in the proportion of breast (p = 0.495), lung (p = 0.937), and melanoma (p = 0.71) patients between the two groups. Mean time between scans for patients with increased number of lesions (28.8 days ± 20.7) was longer than patients with no increase (20.4 days, ± 12.9), but this difference did not reach statistical significance (p = 0.14). Conclusions: A significant number of patients were found to have an increased number of lesions on 3T MRI when compared to 1.5T MRI. This may have implications on symptom management and prognosis in patients with intracranial metastatic disease. Larger, prospective trials are needed to better establish the role of 3T MRI in detecting additional lesions prior to stereotactic radiosurgery. Author Disclosure: L.G. Jensen: None. S.K. Nath: None. K.T. Murphy: None. J.F. Alksne: None. A.J. Mundt: B. Research Grant; Varian Oncology Systems. D. Speakers Bureau/Honoraria; Varian Oncology Systems. J.D. Lawson: None.
2184
Half of Patients will Avoid Whole Brain Radiotherapy: Stereotactic Radiation Therapy for Multiple Brain Metastases
X. Chen, J. Xiao, X. Li Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China Purpose/Objective(s): To summarize the results of stereotactic radiation therapy (SRT) with or without whole-brain radiotherapy (WBRT) in the treatment of multiple brain metastases. Materials/Methods: From May 1995 to April 2010, totally 98 patients with newly diagnosed multiple (213 lesions) brain metastases were treated in our centre. Forty-four patients were treated with SRT alone for initial treatment and WBRT were used as salvage treatment for distant intracranial recurrence and 54 with SRT+WBRT. Dose fractionation schemes were 1526Gy in 1 fraction or 2452.5Gy in 215 fractions with 3.512Gy per fraction, which varied depending on the tumor volume, location, and history of prior irradiation. Kaplan-Meier and Cox proportional hazards regression analyses were used for survival analysis. Results: The median age of the patient population was 56 years. The most common primary tumor histologies were non-smallcell lung carcinoma (58.2%) and breast cancer (12.2%). The median overall survival time was 13.5 months from the time of treatment. for the whole group, there was no difference between SRT alone group and SRT+WBRT group (13 months vs.13.5 months, p = 0.578). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor factors for survival: those patients with a KPS# 70 had a median survival time (MST) of 10.0 months compared with 20.0 months (p = 0.025) for those with a KPS$ 80. The interval time (IT) between the diagnosis of the primary tumor and brain metastases was another significant predictor factors for survival: the MST was 19months for those patients with a IT.18months while it was 8 months for those patients with a IT#18months, and 15months for synchronous brain metastasis P = 0.012. The MST is 12 months and 20 months for patients with progressive extracranial metastases and stable or without extracranial metastases respectively (p = 0.018). The crude distant intracranial recurrence rate were 47.4% in the SRT group and 27.3% in the SRT + WBRT group (p = 0.018), 52.6% patients were free from distant intracranial recurrence in the SRT group and need no WBRT any more in their lifespan. Conclusions: Stereotactic radiation therapy is an effective treatment modality for multiple brain metastases and made half of patients avoid WBRT in their lifespan. SRT as the initial treatment while WBRT as salvage when distant intracranial recurrence occurred is an optional modality for multiple brain metastasis. Author Disclosure: X. Chen: None. J. Xiao: None. X. Li: None.
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Volumetric Based Thresholds to Define Local Control of Brain Metastases following Gamma Knife Radiosurgery and Predictors of Local Control and Overall Survival
M. J. Follwell1, K. Hu2, W. Xu1, L. Cheng1, N. Laperriere1, M. Bernstein2, A. Sahgal1 1
Princess Margaret Hospital, Toronto, ON, Canada, 2Toronto Western Hospital, Toronto, ON, Canada
Purpose/Objective(s): To define volume based thresholds using segmentation software for local control of brain metastases following Gamma Knife radiosurgery (RS) using RECIST criteria as the benchmark, and determine predictors of local control and overall survival in this patient cohort. Materials/Methods: One hundred nineteen patients with 287 brain metastases (BM) were identified with newly diagnosed brain metastases treated with Gamma Knife RS alone or those with brain metastases that had recurred or developed after previous whole brain radiotherapy (WBRT). BM were excluded if they were located in the brainstem, had been treated with the intent of boost RS or if no follow-up imaging was performed. 70 patients with 178 metastases that met these criteria were included in the final analysis. All tumors treated were characterized at baseline and at each follow-up MRI according to widest diameter, calculated sphere volume (Vc) and segmented volume (Vs) using ITK-SNAP 1.8.0 image segmentation software. Results: The median age of the patients was 56 years (range, 25-79), median KPS was 90 (range, 50-100), median RPA was 2 (range, 1-3) and median GPA was 3 (range, 1-4). Thirty-seven patients presented with a solitary metastasis while 33 patients had multiple metastases (range 2-18). Most metastases were supra-tentorial (87%) and received Gamma Knife RS as salvage following prior WBRT (95%). Median tumor diameter was 1.2cm (range, 0.2-4.5cm), Vc was 0.70cc (range, 0.004-47.7cc) and Vs was 0.73cc (range, 0.01-22.7cc). Based on RECIST criteria, at 1 year the rate of progressive disease (PD, $20% increase) was 18%, 47% for stable disease (SD, \30% decrease or \20% increase), 22% for partial response (PR, $30% decrease) and 14% for complete response (CR, 100% decrease). The corresponding changes in volume required to match these rates for Vs were a $71.5% increase for PD, \58.5% decrease or \71.5% increase for SD and $58.5% decrease for PR. Factors that predicted local control were a baseline diameter .3.0cm (p = 0.006) and a baseline Vs of .6.0cc (p = 0.043). At the time of analysis 26 patients had died and the median survival after RS was 15.3 months (range 4.6-22.3 months). The one and two year survival probabilities were 0.54 and 0.10. Only baseline cumulative volume of .3.0 cc (p = 0.020) was identified as negative predictive of overall survival despite RPA and GPA classification. Conclusions: We defined volumetric criteria for response based on the current standard of RECIST criteria for brain metastases treated with RS, and accordingly identified a Vs of .6.0 cc and diameter of .3.0 cm as predictors for local failure and a cumulative volume of disease .3.0 cc as a predictor of shorter overall survival. Author Disclosure: M.J. Follwell: None. K. Hu: None. W. Xu: None. L. Cheng: None. N. Laperriere: None. M. Bernstein: None. A. Sahgal: None.
2182
Adult Supratentorial Ependymoma: The Mayo Clinic Experience
J. W. Rooney, M. Stauder, N. N. Laack Mayo Clinic, Rochester, MN Purpose/Objective(s): To examine the role of radiotherapy (RT) on survival and recurrence in adult patients diagnosed with supratentorial ependymoma. Materials/Methods: A retrospective search of a Mayo Clinic tumor registry was conducted to identify patients diagnosed with primary intracranial ependymoma between 1969 and 2008. The extent of surgical resection was determined by intraoperative impression and post-operative imaging. The external beam radiotherapy (EBRT) dose used ranged from 50 to 72 Gy delivered at 1.75-3.12 Gy per fraction. The EBRT treatment volumes consisted of tumor bed only, whole brain only, whole brain with boost, and the entire CNS with or without boost to the tumor bed. Estimates of overall survival (OS) and recurrence-free survival (RFS) were determined from the date of initial surgery using the Kaplan-Meier method. Results: A total of 42 adult patients (.18 y) were identified with a median age of 36.8 years (range 18.7-84.6). The median follow-up was 3.2 years (range 1.2 months to 13.9 years). 26 patients had Grade 2 and 14 had Grade 3 histology. At the time of analysis, 26 patients (62%) were alive. Kaplan-Meier estimates of OS and RFS at 5 years were 66% and 43%, respectively. The median survival was 9.7 years (range 1.2 months to 13.9 years). All patients (10) who had a subtotal resection (STR) received RT. 18 of 31 patients (58%) who underwent gross total resection (GTR) received RT. Twenty patients (48%) experienced a recurrence at a median of 3.2 years (range 1.2 months to 12.8 years). Three of 13 patients recurred after GTR without RT (range 0.9-4.6 yrs). Univariate analysis was performed to examine the role of presenting symptoms, grade, extent of resection, location, tumor size, radiation treatment, and chemotherapy treatment on OS and RFS. Significant factors predicting for improved OS included
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the extent of resection (p = 0.009), lack of recurrence (p = 0.02) and age\40 years (p = 0.05). There were no significant factors in our cohort associated with RFS, however there was a trend towards decreased recurrence in patients who had hemispheric location of their tumor (p = 0.08) and in patients who had undergone a GTR of their initial tumor (p = 0.15). Conclusions: Despite our small numbers, this is the largest cohort of patients with supratentorial ependymoma in the literature. OS was improved in younger patients with GTR and who were without recurrence. GTR was not associated with improvement in RFS, likely because all patients with STR received post-operative RT. Previously reported prognostic factors (i.e. age, grade) were not associated with risk of recurrence suggesting that a better understanding of the molecular characteristics of supratentorial ependymomas is necessary to determine patients who require adjuvant radiotherapy. Author Disclosure: J.W. Rooney: None. M. Stauder: None. N.N. Laack: None.
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Difference in Number of Brain Metastases Detected using 1.5T and 3T MRI in Patients Treated with Stereotactic Radiosurgery
L. G. Jensen, S. K. Nath, K. T. Murphy, J. F. Alksne, A. J. Mundt, J. D. Lawson University of California San Diego, La Jolla, CA Purpose/Objective(s): Brain metastases are the most common type of intracranial tumor and carry a poor prognosis. Recent retrospective series have suggested 3T magnetic resonance imaging (MRI) may detect more lesions when compared with 1.5T MRI. The aim of the current study is to compare the number of lesions detected by 1.5T and 3T MRI in patients planned for SRS using both imaging modalities. Materials/Methods: Records of patients treated with stereotactic radiosurgery for intracranial lesions at UCSD between December 2005 and December 2010 were reviewed. Patients were eligible if they had 1.5T MRI and a 3T MRI preceding treatment and the 1.5T MRI was performed first. The radiology reports were reviewed and the number of lesions recorded. Results: Fifty-nine pairs of scans (1.5T and 3T) were reviewed, with a median time between scans of 19 days (range 2-69). Tumor sites of origin were lung in 29 (49.2%), breast in 14 (23.7%), melanoma in 10 (16.9%), and other in 6 (10.2%). There was no increase in the number of lesions for 43 pairs (72.9%, 95% CI, 61.6-84.2%) and increased number of lesions for 16 pairs (27.1%, 95% CI, 15.8%-38.4). The difference in number of lesions ranged from 1-8. There was no difference in the proportion of breast (p = 0.495), lung (p = 0.937), and melanoma (p = 0.71) patients between the two groups. Mean time between scans for patients with increased number of lesions (28.8 days ± 20.7) was longer than patients with no increase (20.4 days, ± 12.9), but this difference did not reach statistical significance (p = 0.14). Conclusions: A significant number of patients were found to have an increased number of lesions on 3T MRI when compared to 1.5T MRI. This may have implications on symptom management and prognosis in patients with intracranial metastatic disease. Larger, prospective trials are needed to better establish the role of 3T MRI in detecting additional lesions prior to stereotactic radiosurgery. Author Disclosure: L.G. Jensen: None. S.K. Nath: None. K.T. Murphy: None. J.F. Alksne: None. A.J. Mundt: B. Research Grant; Varian Oncology Systems. D. Speakers Bureau/Honoraria; Varian Oncology Systems. J.D. Lawson: None.
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Half of Patients will Avoid Whole Brain Radiotherapy: Stereotactic Radiation Therapy for Multiple Brain Metastases
X. Chen, J. Xiao, X. Li Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China Purpose/Objective(s): To summarize the results of stereotactic radiation therapy (SRT) with or without whole-brain radiotherapy (WBRT) in the treatment of multiple brain metastases. Materials/Methods: From May 1995 to April 2010, totally 98 patients with newly diagnosed multiple (213 lesions) brain metastases were treated in our centre. Forty-four patients were treated with SRT alone for initial treatment and WBRT were used as salvage treatment for distant intracranial recurrence and 54 with SRT+WBRT. Dose fractionation schemes were 1526Gy in 1 fraction or 2452.5Gy in 215 fractions with 3.512Gy per fraction, which varied depending on the tumor volume, location, and history of prior irradiation. Kaplan-Meier and Cox proportional hazards regression analyses were used for survival analysis. Results: The median age of the patient population was 56 years. The most common primary tumor histologies were non-smallcell lung carcinoma (58.2%) and breast cancer (12.2%). The median overall survival time was 13.5 months from the time of treatment. for the whole group, there was no difference between SRT alone group and SRT+WBRT group (13 months vs.13.5 months, p = 0.578). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor factors for survival: those patients with a KPS# 70 had a median survival time (MST) of 10.0 months compared with 20.0 months (p = 0.025) for those with a KPS$ 80. The interval time (IT) between the diagnosis of the primary tumor and brain metastases was another significant predictor factors for survival: the MST was 19months for those patients with a IT.18months while it was 8 months for those patients with a IT#18months, and 15months for synchronous brain metastasis P = 0.012. The MST is 12 months and 20 months for patients with progressive extracranial metastases and stable or without extracranial metastases respectively (p = 0.018). The crude distant intracranial recurrence rate were 47.4% in the SRT group and 27.3% in the SRT + WBRT group (p = 0.018), 52.6% patients were free from distant intracranial recurrence in the SRT group and need no WBRT any more in their lifespan. Conclusions: Stereotactic radiation therapy is an effective treatment modality for multiple brain metastases and made half of patients avoid WBRT in their lifespan. SRT as the initial treatment while WBRT as salvage when distant intracranial recurrence occurred is an optional modality for multiple brain metastasis. Author Disclosure: X. Chen: None. J. Xiao: None. X. Li: None.