- Email: [email protected]
Clinical Outcome and Prognostic Factors for Central Neurocytoma
I. J. Radiation Oncology d Biology d Physics
S288
Volume 81, Number 2, Supplement, 2011
cases had primary RS. Treatment was planned on a Fisher-Leibinger system until Feb 2009, thereafter on a BrainLAB System, using multiple non-coplanar arcs and circular collimators. A dose of 12 or 14 Gy was prescribed to the 70-90% isodose envelope encompassing the gross tumor volume. Sustained changes $ 2mm in any diameter were deemed significant and useful hearing was defined as inter-aural pure tone average (PTA) # 50 dB. The Kaplan-Meier method was used to estimate hearing retention, possible prognostic factors for which were tested by dividing the patients at reasonable cutpoints specified before examining the hearing data viz: age (60 years), maximum tumor diameter (20mm), initial PTA (20 dB), dose (12 vs 14 Gy). Results: Eighty-four of the 91 sporadic primary RS cases were evaluable for tumor control (at least one post-treatment MRI). Their median follow-up was 65 mo (range 10-184 mo). Eighty-two of the 84 tumors (97.6%) remained stable (30) or decreased (52), the remaining two requiring salvage surgery for progression at 5.8 and 9.8 years. Also, one of the post-operative cases required surgery at 2.1 years after RS. Fifty of the 91 primary RS patients had initially useful hearing. Their median age was 56 (range 21-76), median initial PTA 16 dB (range -11 to +45 dB) and median tumor diameter 21mm (range 10-33mm). Four received 14 Gy, the rest 12 Gy. After RS, 31 patients lost useful hearing (crude preservation rate 19/50 = 38%). The Kaplan-Meier estimated preservation rate at 5 years was 50% (95% CI 36-64%) but by 10 years, this had fallen to 23% (95% CI 12-41%). On univariate analysis, the only significant factor of the four variables tested was initial PTA (P \ 0.0001). The estimated risk of hearing loss after RS for patients with initial PTA $ 20 dB was 5.0 (95% CI 2.2-11.2) times that with PTA \ 20 dB. New or worsened V neuropathies occurred in 15 of the 102 patients (15%), and VII neuropathies in 9 (9%), all transient. Conclusions: Tumor control was excellent (99/102 = 97% freedom from surgical salvage) and cranial neuropathy rates were acceptable. Hearing preservation was strongly dependent on initial PTA, but there was a steady fall-off in hearing out to about 10 years. Author Disclosure: D.E. Roos: None. A.E. Potter: None. A.C. Zacest: None.
2158
External Beam Radiotherapy in Combination with Peptide Receptor Radionuclide Therapy (PRRT) in Irresectable or Recurrent Meningioma
B. Polat1, M. C. Kreissl2, H. Haenscheid2, R. Sweeney1, C. Reiners2, A. Buck2, M. Flentje1 1 Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany, 2Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
Purpose/Objective(s): Prognosis in patients with meningioma is normally very good. However, there are some cases in which recurrences are quite frequent or the tumors are not or only partially resectable. Here external beam radiotherapy (EBRT) remains the mainstay of treatment. An alternative approach uses the fact that meningiomas highly express somatostatin receptors which can be addressed by octreotide analogues that are linked to radionuclides like Lu-177 or Y-90. In this study we combined both treatment modalities for further dose escalation and for reduction of doses delivered to the surrounding organs at risk (OAR) with the use of internal irradiation. Materials/Methods: In 10 patients (8 female, 2 male) with recurrent or residual meningioma (6 grade I, 3 grade II, 1 grade III) have been treated with a combination of PRRT (Lu-177-DOTA-TOC or -TATE) and EBRT. Pre-therapeutic Ga-68-DOTA-TOC /-TATE-PET showed sufficient tracer uptake for the succeeding PRRT. For PRRT, 7.4 ± 0.3 GBq of Lu-177 was administered. Within one week after PRRT, EBRT was initiated and continued over 5-6 weeks using a linear accelerator (Elekta, Synergy S) with a Cone Beam CT for image guidance (IGRT). IMRT plans consisted of a simultaneous integrated boost or a conventional fractionation scheme. Median total doses of 50 Gy were applied. After at least 3 months a second PET was performed. Results: Median age of the patients was 55 years. Median tumor dose achieved by PRRT (6 Lu-177 DOTA-TOC, 4 DOTA-TATE) was 4.3 Gy (1.9 - 14.4). Mean MRI and PET based tumor volumes were 38.4 and 37.3 ml, respectively. During PRRT, no severe side effects occurred. EBRT was also well tolerated in most patients with no grade III/IV side effects. In one patient with a large grade III tumor, a continuous deterioration of symptoms at the end of EBRT was observed. In all other patients, a stabilization or improvement of tumor associated symptoms was noted after a median follow up of 5 months. In five patients tracer uptake at the second PET scan was still elevated or slightly increasing (mean SUVmax PET1 22, PET2 23.4). Conclusions: These preliminary data suggest that PRRT can safely be added to EBRT to increase radiation dose or for a better preservation of OAR. The treatment sequence in this study was PRRT first followed by EBRT, but as shown by the second PET scan it could possibly be reversed. Further long-term follow-up and a larger number of recruited patients in a randomized study are needed to confirm this treatment approach. Author Disclosure: B. Polat: None. M.C. Kreissl: None. H. Haenscheid: None. R. Sweeney: None. C. Reiners: None. A. Buck: None. M. Flentje: None.
2159
Clinical Outcome and Prognostic Factors for Central Neurocytoma
F. Y. Wu, N. Boehling, N. Nabavizadeh, K. Lamborn, M. Barnes, S. Chang, M. McDermott, D. Haas-Kogan University of California San Francisco, San Francisco, CA Purpose/Objective(s): Central neurocytomas are intraventricular neoplasms of the central nervous system that comprise 0.250.5% of brain tumors and their optimal management remains controversial due to their rarity. We assessed clinical outcome for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, tumor size, extent of resection (EOR), and adjuvant radiation (RT). Materials/Methods: Progression-free survival (PFS) was measured from date of first surgical resection. Differences in PFS were measured by Kaplan-Meier and proportional hazard ratio methods. Tumor atypia was defined as MIB-1 index .2%, focal necrosis, or microvascular proliferation, as previously established. Results: A total of 22 patients (14 males, 8 females) were treated between 1995 and 2009, with a median age at diagnosis of 24 years (range 11-62). A total of 8 patients experienced recurrent/progressive disease. Median follow-up by MRI was 38 month (range 0.1-183) for those who have not progressed. Overall 3-yr PFS was 70% (CI 41-86%). Only three patients died and all
Proceedings of the 53rd Annual ASTRO Meeting
S289
had atypical tumors. For the remaining patients, median follow-up for survival was 51 month (range 0.1-183). We examined effects of tumor atypia and MIB-1 labeling. Ten of 22 tumors had atypical features. There was near 100% concordance between tumor atypia and MIB-1 labeling: only 1 tumor was atypical based on microvascular proliferation but had MIB-1 # 2%. Three-year PFS was 78% for MIB labeling # 2% and 39% for MIB labeling .2% (HR 7.7, CI 2 - 40, p = 0.016). Median tumor diameter was 4.3 cm (range 0.8-8.6 cm). Three-yr PFS was 48% (CI 21-77%) for tumor .4.3 cm and 74.1% (CI 29-93%) for tumor #4.3 cm (HR 1.6, CI 0.5 - 6.6, p = 0.49). We examined influence of EOR and adjuvant RT. Five patients had gross total resection (GTR), and 17 had subtotal resection (STR). No patient had a biopsy only. Seven patients progressed after STR, and one patient recurred after GTR. None of the GTR patients received adjuvant RT and four of the STR patients received adjuvant RT. Three-year PFS rates by extent of resection and adjuvant RT are shown (in table below). Conclusions: For patients with central neurocytoma, MIB-1 labeling index .2% significantly predicts worse outcome. The additional criteria for tumor atypia did not add useful prognostic information. Although patient numbers are too small for conclusive confirmation, our data indicate that lesser EOR and larger tumors size may confer worse prognosis and adjuvant RT after STR may improve PFS. 3-yr PFS Rates by Extent of Resection and Adjuvant RT
3-yr PFS (%) (CI)
GTR/No RT (5 pts)
STR/All (17 pts)
STR/No RT (13 pt)
STR/RT (4 pts)
80% (CI 20-97%)
63% (CI 32-83%)
48% (CI 16-74%)
67% (CI 5-95%)
Author Disclosure: F.Y. Wu: None. N. Boehling: None. N. Nabavizadeh: None. K. Lamborn: None. M. Barnes: None. S. Chang: None. M. McDermott: None. D. Haas-Kogan: None.
2160
Treatment of Vestibular Schwannomas Utilizing Fractionated LINAC Stereotactic Radiosurgery: Updated 12 Year Results
V. Dest1, F. S. Cardinale1, R. Sinha2, I. Goodrich1, J. Haas3, P. Dickey1 1
Hospital of Saint Raphael, New Haven, CT, 2El Camino Hospital, Mountainview, CA, 3Winthrop Hospital, Mineola, NY
Purpose/Objective(s): Vestibular schwannomas are the most common primary cerebellopontine (CP) angle tumor occurring in the United States. Between 2500 and 3000 new cases are diagnosed each year. A variety of therapies have been utilized in the past for this tumor, including observation, surgery and stereotactic radiosurgery/radiotherapy. In 2004, we reported on our initial experience of results with fractionated LINAC stereotactic radiotherapy for vestibular schwannomas at the (ASTRO) Annual Meeting and our 8 year results in 2008. The purpose of this paper is to provide a follow-up of previously reported cases, as well as additional cases compiled since then. Materials/Methods: Retrospective review of all patients who underwent fractionated stereotactic radiosurgery for vestibular schwannomas at the Hospital of Saint Raphael in New Haven, Connecticut between 1998 and 2008 was accomplished. A total of 67 patients were identified. Patient age ranged from 26 to 81 (median 55). 46 (68.6%) patients had useful hearing prior to treatment. Therapy was accomplished with a VarianÒ 600C linear accelerator with an attached BrainLabÒ micro-multileaf collimator. The total dose of radiation varied from 46.8 Gy to 54 Gy (median 50.4 Gy). Daily fractions of 1.8 Gy prescribed to the 90th percentile isodose line were utilized. Target volumes ranged from 0.17 cc to 21.34 cc (median 1.47 cc). In all cases, the percent isodose volume/target volume ranged from 1.39 to 3.17 (median 2.07). Results: The median follow-up was 52.7 months (range 5 to 129.9 months). Local control was achieved in 65 of 67 patients (97%). Twenty-five (37.3%) patients had a decrease in size of their tumor and 19 (28.3%) patients exhibited evidence of central tumor necrosis on follow-up MRI scans. Thirty-seven (80.4%) patients retained useful hearing. Long term side effects are infrequent in this population. However, two (2.9%) patients developed cranial nerve V and VII dysfunction. Approximately, fifteen percent of patients have noted a decrease of previous useful hearing. Conclusions: Fractionated LINAC stereotactic radiotherapy utilizing a micro-multileaf collimator is a useful treatment option for patients with appropriately sized (\2.5 cm in diameter) vestibular schwannomas that is very well tolerated. Over a median period of 52.7 months, useful hearing can be preserved in the vast majority of patients with functional hearing. Local control rates with other cranial nerve preservation thus far are excellent. Still further follow-up will be required to ascertain the durability of these results. Author Disclosure: V. Dest: D. Speakers Bureau/Honoraria; Myriad Laboratories, EUSA Pharma. F.S. Cardinale: None. R. Sinha: None. I. Goodrich: None. J. Haas: None. P. Dickey: None.
2161
Clinical Characteristics of Malignant Meningioma: An Analysis from the Surveillance, Epidemiology, and End Result (SEER) Registry
H. M. Yu Y. Tsai H. Lee Moffitt Cancer Center, Tampa, FL Purpose/Objective(s): Malignant meningioma is a rare benign primary brain tumor not well characterized in the literature. It comprises of about 5 to 10% of meningioma and its rapid growth results in morbidity and mortality despite the therapeutic intervention. We investigated the clinical and survival outcomes of patients with malignant meningioma using the Surveillance, Epidemiology and End Result (SEER) registry. Materials/Methods: A total of 997 patients age 18 or greater diagnosed with malignant meningioma between 1987 and 2007 identified through the population-based SEER registry data were included. Demographic and clinical variables included gender,
S288
Volume 81, Number 2, Supplement, 2011
cases had primary RS. Treatment was planned on a Fisher-Leibinger system until Feb 2009, thereafter on a BrainLAB System, using multiple non-coplanar arcs and circular collimators. A dose of 12 or 14 Gy was prescribed to the 70-90% isodose envelope encompassing the gross tumor volume. Sustained changes $ 2mm in any diameter were deemed significant and useful hearing was defined as inter-aural pure tone average (PTA) # 50 dB. The Kaplan-Meier method was used to estimate hearing retention, possible prognostic factors for which were tested by dividing the patients at reasonable cutpoints specified before examining the hearing data viz: age (60 years), maximum tumor diameter (20mm), initial PTA (20 dB), dose (12 vs 14 Gy). Results: Eighty-four of the 91 sporadic primary RS cases were evaluable for tumor control (at least one post-treatment MRI). Their median follow-up was 65 mo (range 10-184 mo). Eighty-two of the 84 tumors (97.6%) remained stable (30) or decreased (52), the remaining two requiring salvage surgery for progression at 5.8 and 9.8 years. Also, one of the post-operative cases required surgery at 2.1 years after RS. Fifty of the 91 primary RS patients had initially useful hearing. Their median age was 56 (range 21-76), median initial PTA 16 dB (range -11 to +45 dB) and median tumor diameter 21mm (range 10-33mm). Four received 14 Gy, the rest 12 Gy. After RS, 31 patients lost useful hearing (crude preservation rate 19/50 = 38%). The Kaplan-Meier estimated preservation rate at 5 years was 50% (95% CI 36-64%) but by 10 years, this had fallen to 23% (95% CI 12-41%). On univariate analysis, the only significant factor of the four variables tested was initial PTA (P \ 0.0001). The estimated risk of hearing loss after RS for patients with initial PTA $ 20 dB was 5.0 (95% CI 2.2-11.2) times that with PTA \ 20 dB. New or worsened V neuropathies occurred in 15 of the 102 patients (15%), and VII neuropathies in 9 (9%), all transient. Conclusions: Tumor control was excellent (99/102 = 97% freedom from surgical salvage) and cranial neuropathy rates were acceptable. Hearing preservation was strongly dependent on initial PTA, but there was a steady fall-off in hearing out to about 10 years. Author Disclosure: D.E. Roos: None. A.E. Potter: None. A.C. Zacest: None.
2158
External Beam Radiotherapy in Combination with Peptide Receptor Radionuclide Therapy (PRRT) in Irresectable or Recurrent Meningioma
B. Polat1, M. C. Kreissl2, H. Haenscheid2, R. Sweeney1, C. Reiners2, A. Buck2, M. Flentje1 1 Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany, 2Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
Purpose/Objective(s): Prognosis in patients with meningioma is normally very good. However, there are some cases in which recurrences are quite frequent or the tumors are not or only partially resectable. Here external beam radiotherapy (EBRT) remains the mainstay of treatment. An alternative approach uses the fact that meningiomas highly express somatostatin receptors which can be addressed by octreotide analogues that are linked to radionuclides like Lu-177 or Y-90. In this study we combined both treatment modalities for further dose escalation and for reduction of doses delivered to the surrounding organs at risk (OAR) with the use of internal irradiation. Materials/Methods: In 10 patients (8 female, 2 male) with recurrent or residual meningioma (6 grade I, 3 grade II, 1 grade III) have been treated with a combination of PRRT (Lu-177-DOTA-TOC or -TATE) and EBRT. Pre-therapeutic Ga-68-DOTA-TOC /-TATE-PET showed sufficient tracer uptake for the succeeding PRRT. For PRRT, 7.4 ± 0.3 GBq of Lu-177 was administered. Within one week after PRRT, EBRT was initiated and continued over 5-6 weeks using a linear accelerator (Elekta, Synergy S) with a Cone Beam CT for image guidance (IGRT). IMRT plans consisted of a simultaneous integrated boost or a conventional fractionation scheme. Median total doses of 50 Gy were applied. After at least 3 months a second PET was performed. Results: Median age of the patients was 55 years. Median tumor dose achieved by PRRT (6 Lu-177 DOTA-TOC, 4 DOTA-TATE) was 4.3 Gy (1.9 - 14.4). Mean MRI and PET based tumor volumes were 38.4 and 37.3 ml, respectively. During PRRT, no severe side effects occurred. EBRT was also well tolerated in most patients with no grade III/IV side effects. In one patient with a large grade III tumor, a continuous deterioration of symptoms at the end of EBRT was observed. In all other patients, a stabilization or improvement of tumor associated symptoms was noted after a median follow up of 5 months. In five patients tracer uptake at the second PET scan was still elevated or slightly increasing (mean SUVmax PET1 22, PET2 23.4). Conclusions: These preliminary data suggest that PRRT can safely be added to EBRT to increase radiation dose or for a better preservation of OAR. The treatment sequence in this study was PRRT first followed by EBRT, but as shown by the second PET scan it could possibly be reversed. Further long-term follow-up and a larger number of recruited patients in a randomized study are needed to confirm this treatment approach. Author Disclosure: B. Polat: None. M.C. Kreissl: None. H. Haenscheid: None. R. Sweeney: None. C. Reiners: None. A. Buck: None. M. Flentje: None.
2159
Clinical Outcome and Prognostic Factors for Central Neurocytoma
F. Y. Wu, N. Boehling, N. Nabavizadeh, K. Lamborn, M. Barnes, S. Chang, M. McDermott, D. Haas-Kogan University of California San Francisco, San Francisco, CA Purpose/Objective(s): Central neurocytomas are intraventricular neoplasms of the central nervous system that comprise 0.250.5% of brain tumors and their optimal management remains controversial due to their rarity. We assessed clinical outcome for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, tumor size, extent of resection (EOR), and adjuvant radiation (RT). Materials/Methods: Progression-free survival (PFS) was measured from date of first surgical resection. Differences in PFS were measured by Kaplan-Meier and proportional hazard ratio methods. Tumor atypia was defined as MIB-1 index .2%, focal necrosis, or microvascular proliferation, as previously established. Results: A total of 22 patients (14 males, 8 females) were treated between 1995 and 2009, with a median age at diagnosis of 24 years (range 11-62). A total of 8 patients experienced recurrent/progressive disease. Median follow-up by MRI was 38 month (range 0.1-183) for those who have not progressed. Overall 3-yr PFS was 70% (CI 41-86%). Only three patients died and all
Proceedings of the 53rd Annual ASTRO Meeting
S289
had atypical tumors. For the remaining patients, median follow-up for survival was 51 month (range 0.1-183). We examined effects of tumor atypia and MIB-1 labeling. Ten of 22 tumors had atypical features. There was near 100% concordance between tumor atypia and MIB-1 labeling: only 1 tumor was atypical based on microvascular proliferation but had MIB-1 # 2%. Three-year PFS was 78% for MIB labeling # 2% and 39% for MIB labeling .2% (HR 7.7, CI 2 - 40, p = 0.016). Median tumor diameter was 4.3 cm (range 0.8-8.6 cm). Three-yr PFS was 48% (CI 21-77%) for tumor .4.3 cm and 74.1% (CI 29-93%) for tumor #4.3 cm (HR 1.6, CI 0.5 - 6.6, p = 0.49). We examined influence of EOR and adjuvant RT. Five patients had gross total resection (GTR), and 17 had subtotal resection (STR). No patient had a biopsy only. Seven patients progressed after STR, and one patient recurred after GTR. None of the GTR patients received adjuvant RT and four of the STR patients received adjuvant RT. Three-year PFS rates by extent of resection and adjuvant RT are shown (in table below). Conclusions: For patients with central neurocytoma, MIB-1 labeling index .2% significantly predicts worse outcome. The additional criteria for tumor atypia did not add useful prognostic information. Although patient numbers are too small for conclusive confirmation, our data indicate that lesser EOR and larger tumors size may confer worse prognosis and adjuvant RT after STR may improve PFS. 3-yr PFS Rates by Extent of Resection and Adjuvant RT
3-yr PFS (%) (CI)
GTR/No RT (5 pts)
STR/All (17 pts)
STR/No RT (13 pt)
STR/RT (4 pts)
80% (CI 20-97%)
63% (CI 32-83%)
48% (CI 16-74%)
67% (CI 5-95%)
Author Disclosure: F.Y. Wu: None. N. Boehling: None. N. Nabavizadeh: None. K. Lamborn: None. M. Barnes: None. S. Chang: None. M. McDermott: None. D. Haas-Kogan: None.
2160
Treatment of Vestibular Schwannomas Utilizing Fractionated LINAC Stereotactic Radiosurgery: Updated 12 Year Results
V. Dest1, F. S. Cardinale1, R. Sinha2, I. Goodrich1, J. Haas3, P. Dickey1 1
Hospital of Saint Raphael, New Haven, CT, 2El Camino Hospital, Mountainview, CA, 3Winthrop Hospital, Mineola, NY
Purpose/Objective(s): Vestibular schwannomas are the most common primary cerebellopontine (CP) angle tumor occurring in the United States. Between 2500 and 3000 new cases are diagnosed each year. A variety of therapies have been utilized in the past for this tumor, including observation, surgery and stereotactic radiosurgery/radiotherapy. In 2004, we reported on our initial experience of results with fractionated LINAC stereotactic radiotherapy for vestibular schwannomas at the (ASTRO) Annual Meeting and our 8 year results in 2008. The purpose of this paper is to provide a follow-up of previously reported cases, as well as additional cases compiled since then. Materials/Methods: Retrospective review of all patients who underwent fractionated stereotactic radiosurgery for vestibular schwannomas at the Hospital of Saint Raphael in New Haven, Connecticut between 1998 and 2008 was accomplished. A total of 67 patients were identified. Patient age ranged from 26 to 81 (median 55). 46 (68.6%) patients had useful hearing prior to treatment. Therapy was accomplished with a VarianÒ 600C linear accelerator with an attached BrainLabÒ micro-multileaf collimator. The total dose of radiation varied from 46.8 Gy to 54 Gy (median 50.4 Gy). Daily fractions of 1.8 Gy prescribed to the 90th percentile isodose line were utilized. Target volumes ranged from 0.17 cc to 21.34 cc (median 1.47 cc). In all cases, the percent isodose volume/target volume ranged from 1.39 to 3.17 (median 2.07). Results: The median follow-up was 52.7 months (range 5 to 129.9 months). Local control was achieved in 65 of 67 patients (97%). Twenty-five (37.3%) patients had a decrease in size of their tumor and 19 (28.3%) patients exhibited evidence of central tumor necrosis on follow-up MRI scans. Thirty-seven (80.4%) patients retained useful hearing. Long term side effects are infrequent in this population. However, two (2.9%) patients developed cranial nerve V and VII dysfunction. Approximately, fifteen percent of patients have noted a decrease of previous useful hearing. Conclusions: Fractionated LINAC stereotactic radiotherapy utilizing a micro-multileaf collimator is a useful treatment option for patients with appropriately sized (\2.5 cm in diameter) vestibular schwannomas that is very well tolerated. Over a median period of 52.7 months, useful hearing can be preserved in the vast majority of patients with functional hearing. Local control rates with other cranial nerve preservation thus far are excellent. Still further follow-up will be required to ascertain the durability of these results. Author Disclosure: V. Dest: D. Speakers Bureau/Honoraria; Myriad Laboratories, EUSA Pharma. F.S. Cardinale: None. R. Sinha: None. I. Goodrich: None. J. Haas: None. P. Dickey: None.
2161
Clinical Characteristics of Malignant Meningioma: An Analysis from the Surveillance, Epidemiology, and End Result (SEER) Registry
H. M. Yu Y. Tsai H. Lee Moffitt Cancer Center, Tampa, FL Purpose/Objective(s): Malignant meningioma is a rare benign primary brain tumor not well characterized in the literature. It comprises of about 5 to 10% of meningioma and its rapid growth results in morbidity and mortality despite the therapeutic intervention. We investigated the clinical and survival outcomes of patients with malignant meningioma using the Surveillance, Epidemiology and End Result (SEER) registry. Materials/Methods: A total of 997 patients age 18 or greater diagnosed with malignant meningioma between 1987 and 2007 identified through the population-based SEER registry data were included. Demographic and clinical variables included gender,