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Combined Proton and Photon Conformal Radiotherapy for Skull-Base Atypical and Malignant Meningioma
I. J. Radiation Oncology d Biology d Physics
S252
Volume 69, Number 3, Supplement, 2007
performance uncertainties of the two imaging modalities. Sensitivity and specificity are used to quantify the performance characteristics of an imaging device. The purpose of this project is to develop a framework that integrates performance characteristics of MRA and OXA into AVM radiosurgery planning and evaluation. Materials/Methods: Ten patients with AVM located in critical areas such as occipital or left temple lobe were recruited in this retrospective planning study. The image findings of the 10 patients were first utilized to estimate the sensitivity and specificity of MRA and OXA. Instead of accepting the observation from imaging as a binary (yes or no) mapping of AVM location, our alternative is to translate the image into an AVM probability distribution map by incorporating the sensitivity and specificity of the imaging devices, and use such a map as a basis for treatment planning and evaluation. Three sets of radiosurgery plans, targeting at the MRA and OXA positive overlap, at MRA positive only, and at OXA positive only were optimized for best conformality via the GammaPlanÒ system. AVM obliteration rate (ORAVM) was calculated using the dose volume histogram and AVM probability distribution. Late toxicity to brain tissue was evaluated using the volume receiving more than 12 Gy (V12). Both ORAVM and V12 served as end points for plan comparison. Results: In our 10 patient study, the positive overlap of MRA and OXA accounted for 90.5 ± 8.1% of the MRA positive only volume, and 61.9 ± 7.8% of the OXA positive only volume. The sensitivities and specificities of MRA and OXA were estimated to be (0.95, 0.74) and (0.71, 0.95), respectively. The probability of being true AVM was estimated to be 0.994 ± 0.005 in the MRA and OXA positive overlap zone, 0.560 ± 0.261 in the MRA positive and OXA negative zone, 0.642 ± 0.125 in the MRA negative and XA positive zone, and 0.083 ± 0.071 in the MRA and OXA negative overlap zone, respectively. Compared to plans targeting at the MRA and OXA positive overlap, plans targeting at the MRA positive and at the OXA positive improved ORAVM by 4.1 ± 1.9% and 15.7 ± 8.3%, respectively, while also increasing V12 1.88 ± 1.36 cc and 6.91 ± 2.14 cc, respectively. Attempts of shaping the dose distribution according to the AVM probability map suggested that dose reductions of 2–3 Gy in the zone where MRA and OXA disagree could be applied to spare the surrounding critical brain tissue. Conclusions: The sensitivity and specificity of MRA and OXA should be incorporated into AVM radiosurgery planning to better assist clinicians’ decision making with regard to target definition and plan evaluation. Author Disclosure: P. Zhang, None; L. Wu, None; S. Isaacson, None; T. Liu, None; G. Kutcher, None.
2087
Prognostic Factors of Patients With Glioblastoma (Recursive Partitioning Analysis: RPA Classes 5 6)
N. Shikama, S. Sasaki, A. Shinoda Shinshu University, Matsumoto, Japan Background: The prognosis of patients with glioblastoma (GBM) is poor, and radiotherapy at a dose of 60 Gy over 6 weeks represents a significant burden for patients with poor prognoses. Although some investigators have conducted clinical trials with shortcourse radiotherapy, an appropriate schedule has yet to be established for this disease. The appropriate inclusion criteria for clinical trials are important to avoid severe late adverse effects induced by large fraction size, and the homogeneity of patient characteristics is important to avoid interactions between prognostic variables. Recursive partitioning analysis (RPA) proposed by RTOG is a useful tool to estimate prognosis. However, a portion of patients with poor prognoses (classes 5 or 6) show long-term survival. Purpose/Objective(s): The present study was performed to clarify the predictive factors of long-term survivors among patients in RPA classes 5 6. Materials/Methods: Eighty-six patients with GBM were analyzed in the present study. The median age was 59 years (9 76). Forty-six patients (53%) showed good performance status (PS 0 1), and 40 (47%) showed poor PS (2 4). The median preoperative tumor size was 4.5 cm (1.4 8 cm). Fifty-two patients (60%) underwent total or subtotal resection and 34 (40%) underwent partial resection or biopsy. The median radiation dose was 54 Gy (30 70), and the daily fraction size was 2.0 Gy. Radiation fields included the primary lesion and the high intensity areas on T2-weighted MR image. Seventy-three patients (85%) received systemic chemotherapy and/or interferon. Results: The median survival time (MST) of 35 patients in classes 3 4 was 17 months, while that of 51 patients in classes 5 6 was 10 months (p \ .001). Two-year survival rates of these two groups were 29% and 6%, respectively. Among the patients in classes 5 6, MST of the patients with small tumors (less than 5 cm) was 14 months, while that of patients with large tumors (more than 5 cm) was 9 months (p = .03). Fifteen percent of the patients with small tumors, but none of the patients with large tumors, survived for longer than 2 years. All 14 elderly patients older than 70 years were grouped into classes 5 6, and their MST was 10 months. Nine elderly patients (69%) had small tumors, and eight (57%) received total or subtotal resection. However, 2-year survival rate of all 14 elderly patients was 0%. Conclusions: RPA is a useful tool to estimate the prognosis of patients with GBM. The prognosis of patients in classes 5 6 was poor, but that of patients with small tumors was relatively good. Thus, careful management is required if short-course radiotherapy using a large fraction size is applied for patients with small tumors. On the other hand, the prognosis of elderly patients in classes 5 6 older than 70 years was poor, and these patients may be suitable for short-course radiotherapy regardless of preoperative tumor size. Author Disclosure: N. Shikama, None; S. Sasaki, None; A. Shinoda, None.
2088
Combined Proton and Photon Conformal Radiotherapy for Skull-Base Atypical and Malignant Meningioma
C. S. Boskos1, L. Feuvret2, G. Noe¨l3, J. Habrand3, P. Pommier4, C. Alapetite5, H. Mammar5, R. Ferrand3, G. Boisserie6, J. J. Mazeron2 1 Hoˆpital Pitie´ Salpeˆtrie`re, General Hospital of Hellenic Airforce, Paris, France, 2Hoˆpital Pitie´ Salpeˆtrie`re, Institut Curie–Centre de Protonthe´rapie d’Orsay, Paris, France, 3Institut Curie–Centre de Protonthe´rapie d’Orsay, Paris, France, 4 Centre Le´on Be´rard, Lyon, France, 5Institut Curie, Paris, France, 6Hoˆpital Pitie´ Salpeˆtrie`re, Paris, France
Purpose/Objective(s): Atypical and malignant meningiomas are at high risk for local failure. Limited data are available concerning the outcome of these patients. The focal and also aggressive character of these meningiomas makes conformal radiotherapy
Proceedings of the 49th Annual ASTRO Meeting with protons (PRT), combined or not with photons (PHRT), an attractive adjuvant treatment modality to surgical resection. The purpose is to evaluate the efficacy of external conformal fractionated radiotherapy combining protons and photons, after primary surgery in the treatment of skull-base atypical and malignant meningiomas. Materials/Methods: Between September 1999 and October 2006, 25 patients (13 males, 12 females) with skull-base pathologically proven meningioma (atypical 20, malignant 5) received postoperative adjuvant combined radiotherapy by 201 MeV proton beam at the Centre Protontherapie d’Orsay (CPO) and high energy photon beam in Pitie Salpetriere Hospital (PS) and Institute Gustave Roussy (IGR). One patient(male-atypical) was excluded from the study(not existed data). Six patients underwent gross total resection (GTR), eighteen had a subtotal resection (STR). Mean total irradiation dose (TD) was 65.01 CGE (cobalt gray equivalent) with mean protons total dose (PRTD) 34.05 CGE and mean photons total dose (PHTD) 30.96 CGE. TD, PRTD, PHTD administrated to the atypical and malignant meningiomas were 64.24/32.28/31.95 CGE and 68/40.8/27.2 CGE respectively. Median duration of the treatment was 50 days [38–58]. Results: The median follow up interval was 32.2 months [1–72]. Median Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) were 44.7 cc and 153.3 cc, respectively. Median time for freedom from progression for the atypical and malignant meningiomas was 28 (9–70) and 29.3 (4–72) months, respectively. One, 2-, 3-, 4-, 5-years local control (LC) rate for atypical and malignant meningiomas were 87.5%, 81.3%, 51.6%, 51.6%, 34.4% and 80%, 53.3%, 26.7%, 26.7%, 26.7% respectively. One, 2-, 3-, 4-, 5-years overall survival (OS) for atypical and malignant were 100%, 94.1%, 73.9%, 60.5%, 50.4% and 100%, 100%, 50%, 50%, 50% respectively. All the patients reveal complete or partial clinical improvement. Maximum radiological response was stable disease. The radiotherapy was well tolerated. Conclusions: The postoperative combination conformal radiotherapy with protons and photons for aggressive meningiomas like the atypical and the malignant, is a well-tolerated treatment with a considerable clinical improvement and long-term radiological proven stabilization. Author Disclosure: C.S. Boskos, None; L. Feuvret, None; G. Noe¨l, None; J. Habrand, None; P. Pommier, None; C. Alapetite, None; H. Mammar, None; R. Ferrand, None; G. Boisserie, None; J.J. Mazeron, None.
2089
Regression Pattern of Intracranial Meningiomas to Primary Definitive Radiotherapy by Volumetric Response Analysis
N. Jang1, I. Kim1, C. Park1, A. Chang1, H. Jung2 1 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea, 2Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea
Purpose/Objective(s): To evaluate the response and effectiveness of definitive radiotherapy for patients with primary intracranial meningiomas. Materials/Methods: The records of 28 patients with intracranial meningiomas who underwent definitive radiotherapy between 1994 and 2003 were analyzed. Median follow-up duration was 54 months. Three patients had pathologically confirmed benign meningiomas and others were clinically diagnosed. The dose ranged 48.6 to 61.2 Gy (median 54) over 3–7 weeks. The tumor volume was calculated by the formula, p/6 * X * Y * Z or using software (Osiris, the University Hospital of Geneva) based on sum-of-areas method. Results: Follow-up tumor volume at 1 and 3 years ranged from 12 to 123%, from 12 to 92% by p/6 * X * Y * Z and from 11 to 126%, from 10 to 93% by sum-of-areas method. There were 2 cases of excellent response, which showed more than 65% decrease in tumor volume. Even though we excluded 2 cases, the mean tumor volume at 1, 3 and 5 years were 84, 72 and 66% by p/6 * X * Y * Z and 86, 68 and 60% by sum-of-areas method, respectively. There were 3 cases of progression. The 5-year overall and progression-free survival rates were 72 and 88%, respectively. Except two grade 3 middle ear effusions, there was no documented severe toxicity. Conclusions: Intracranial meningioma showed slow but continuous regression without severe toxicity after definitive radiotherapy. External beam radiotherapy is a well tolerated and effective treatment for inoperable intracranial meningioma with various reasons, and its efficacy can be further improved with high precision techniques (Fig.).
Author Disclosure: N. Jang, None; I. Kim, None; C. Park, None; A. Chang, None; H. Jung, None.
S253
S252
Volume 69, Number 3, Supplement, 2007
performance uncertainties of the two imaging modalities. Sensitivity and specificity are used to quantify the performance characteristics of an imaging device. The purpose of this project is to develop a framework that integrates performance characteristics of MRA and OXA into AVM radiosurgery planning and evaluation. Materials/Methods: Ten patients with AVM located in critical areas such as occipital or left temple lobe were recruited in this retrospective planning study. The image findings of the 10 patients were first utilized to estimate the sensitivity and specificity of MRA and OXA. Instead of accepting the observation from imaging as a binary (yes or no) mapping of AVM location, our alternative is to translate the image into an AVM probability distribution map by incorporating the sensitivity and specificity of the imaging devices, and use such a map as a basis for treatment planning and evaluation. Three sets of radiosurgery plans, targeting at the MRA and OXA positive overlap, at MRA positive only, and at OXA positive only were optimized for best conformality via the GammaPlanÒ system. AVM obliteration rate (ORAVM) was calculated using the dose volume histogram and AVM probability distribution. Late toxicity to brain tissue was evaluated using the volume receiving more than 12 Gy (V12). Both ORAVM and V12 served as end points for plan comparison. Results: In our 10 patient study, the positive overlap of MRA and OXA accounted for 90.5 ± 8.1% of the MRA positive only volume, and 61.9 ± 7.8% of the OXA positive only volume. The sensitivities and specificities of MRA and OXA were estimated to be (0.95, 0.74) and (0.71, 0.95), respectively. The probability of being true AVM was estimated to be 0.994 ± 0.005 in the MRA and OXA positive overlap zone, 0.560 ± 0.261 in the MRA positive and OXA negative zone, 0.642 ± 0.125 in the MRA negative and XA positive zone, and 0.083 ± 0.071 in the MRA and OXA negative overlap zone, respectively. Compared to plans targeting at the MRA and OXA positive overlap, plans targeting at the MRA positive and at the OXA positive improved ORAVM by 4.1 ± 1.9% and 15.7 ± 8.3%, respectively, while also increasing V12 1.88 ± 1.36 cc and 6.91 ± 2.14 cc, respectively. Attempts of shaping the dose distribution according to the AVM probability map suggested that dose reductions of 2–3 Gy in the zone where MRA and OXA disagree could be applied to spare the surrounding critical brain tissue. Conclusions: The sensitivity and specificity of MRA and OXA should be incorporated into AVM radiosurgery planning to better assist clinicians’ decision making with regard to target definition and plan evaluation. Author Disclosure: P. Zhang, None; L. Wu, None; S. Isaacson, None; T. Liu, None; G. Kutcher, None.
2087
Prognostic Factors of Patients With Glioblastoma (Recursive Partitioning Analysis: RPA Classes 5 6)
N. Shikama, S. Sasaki, A. Shinoda Shinshu University, Matsumoto, Japan Background: The prognosis of patients with glioblastoma (GBM) is poor, and radiotherapy at a dose of 60 Gy over 6 weeks represents a significant burden for patients with poor prognoses. Although some investigators have conducted clinical trials with shortcourse radiotherapy, an appropriate schedule has yet to be established for this disease. The appropriate inclusion criteria for clinical trials are important to avoid severe late adverse effects induced by large fraction size, and the homogeneity of patient characteristics is important to avoid interactions between prognostic variables. Recursive partitioning analysis (RPA) proposed by RTOG is a useful tool to estimate prognosis. However, a portion of patients with poor prognoses (classes 5 or 6) show long-term survival. Purpose/Objective(s): The present study was performed to clarify the predictive factors of long-term survivors among patients in RPA classes 5 6. Materials/Methods: Eighty-six patients with GBM were analyzed in the present study. The median age was 59 years (9 76). Forty-six patients (53%) showed good performance status (PS 0 1), and 40 (47%) showed poor PS (2 4). The median preoperative tumor size was 4.5 cm (1.4 8 cm). Fifty-two patients (60%) underwent total or subtotal resection and 34 (40%) underwent partial resection or biopsy. The median radiation dose was 54 Gy (30 70), and the daily fraction size was 2.0 Gy. Radiation fields included the primary lesion and the high intensity areas on T2-weighted MR image. Seventy-three patients (85%) received systemic chemotherapy and/or interferon. Results: The median survival time (MST) of 35 patients in classes 3 4 was 17 months, while that of 51 patients in classes 5 6 was 10 months (p \ .001). Two-year survival rates of these two groups were 29% and 6%, respectively. Among the patients in classes 5 6, MST of the patients with small tumors (less than 5 cm) was 14 months, while that of patients with large tumors (more than 5 cm) was 9 months (p = .03). Fifteen percent of the patients with small tumors, but none of the patients with large tumors, survived for longer than 2 years. All 14 elderly patients older than 70 years were grouped into classes 5 6, and their MST was 10 months. Nine elderly patients (69%) had small tumors, and eight (57%) received total or subtotal resection. However, 2-year survival rate of all 14 elderly patients was 0%. Conclusions: RPA is a useful tool to estimate the prognosis of patients with GBM. The prognosis of patients in classes 5 6 was poor, but that of patients with small tumors was relatively good. Thus, careful management is required if short-course radiotherapy using a large fraction size is applied for patients with small tumors. On the other hand, the prognosis of elderly patients in classes 5 6 older than 70 years was poor, and these patients may be suitable for short-course radiotherapy regardless of preoperative tumor size. Author Disclosure: N. Shikama, None; S. Sasaki, None; A. Shinoda, None.
2088
Combined Proton and Photon Conformal Radiotherapy for Skull-Base Atypical and Malignant Meningioma
C. S. Boskos1, L. Feuvret2, G. Noe¨l3, J. Habrand3, P. Pommier4, C. Alapetite5, H. Mammar5, R. Ferrand3, G. Boisserie6, J. J. Mazeron2 1 Hoˆpital Pitie´ Salpeˆtrie`re, General Hospital of Hellenic Airforce, Paris, France, 2Hoˆpital Pitie´ Salpeˆtrie`re, Institut Curie–Centre de Protonthe´rapie d’Orsay, Paris, France, 3Institut Curie–Centre de Protonthe´rapie d’Orsay, Paris, France, 4 Centre Le´on Be´rard, Lyon, France, 5Institut Curie, Paris, France, 6Hoˆpital Pitie´ Salpeˆtrie`re, Paris, France
Purpose/Objective(s): Atypical and malignant meningiomas are at high risk for local failure. Limited data are available concerning the outcome of these patients. The focal and also aggressive character of these meningiomas makes conformal radiotherapy
Proceedings of the 49th Annual ASTRO Meeting with protons (PRT), combined or not with photons (PHRT), an attractive adjuvant treatment modality to surgical resection. The purpose is to evaluate the efficacy of external conformal fractionated radiotherapy combining protons and photons, after primary surgery in the treatment of skull-base atypical and malignant meningiomas. Materials/Methods: Between September 1999 and October 2006, 25 patients (13 males, 12 females) with skull-base pathologically proven meningioma (atypical 20, malignant 5) received postoperative adjuvant combined radiotherapy by 201 MeV proton beam at the Centre Protontherapie d’Orsay (CPO) and high energy photon beam in Pitie Salpetriere Hospital (PS) and Institute Gustave Roussy (IGR). One patient(male-atypical) was excluded from the study(not existed data). Six patients underwent gross total resection (GTR), eighteen had a subtotal resection (STR). Mean total irradiation dose (TD) was 65.01 CGE (cobalt gray equivalent) with mean protons total dose (PRTD) 34.05 CGE and mean photons total dose (PHTD) 30.96 CGE. TD, PRTD, PHTD administrated to the atypical and malignant meningiomas were 64.24/32.28/31.95 CGE and 68/40.8/27.2 CGE respectively. Median duration of the treatment was 50 days [38–58]. Results: The median follow up interval was 32.2 months [1–72]. Median Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) were 44.7 cc and 153.3 cc, respectively. Median time for freedom from progression for the atypical and malignant meningiomas was 28 (9–70) and 29.3 (4–72) months, respectively. One, 2-, 3-, 4-, 5-years local control (LC) rate for atypical and malignant meningiomas were 87.5%, 81.3%, 51.6%, 51.6%, 34.4% and 80%, 53.3%, 26.7%, 26.7%, 26.7% respectively. One, 2-, 3-, 4-, 5-years overall survival (OS) for atypical and malignant were 100%, 94.1%, 73.9%, 60.5%, 50.4% and 100%, 100%, 50%, 50%, 50% respectively. All the patients reveal complete or partial clinical improvement. Maximum radiological response was stable disease. The radiotherapy was well tolerated. Conclusions: The postoperative combination conformal radiotherapy with protons and photons for aggressive meningiomas like the atypical and the malignant, is a well-tolerated treatment with a considerable clinical improvement and long-term radiological proven stabilization. Author Disclosure: C.S. Boskos, None; L. Feuvret, None; G. Noe¨l, None; J. Habrand, None; P. Pommier, None; C. Alapetite, None; H. Mammar, None; R. Ferrand, None; G. Boisserie, None; J.J. Mazeron, None.
2089
Regression Pattern of Intracranial Meningiomas to Primary Definitive Radiotherapy by Volumetric Response Analysis
N. Jang1, I. Kim1, C. Park1, A. Chang1, H. Jung2 1 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea, 2Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea
Purpose/Objective(s): To evaluate the response and effectiveness of definitive radiotherapy for patients with primary intracranial meningiomas. Materials/Methods: The records of 28 patients with intracranial meningiomas who underwent definitive radiotherapy between 1994 and 2003 were analyzed. Median follow-up duration was 54 months. Three patients had pathologically confirmed benign meningiomas and others were clinically diagnosed. The dose ranged 48.6 to 61.2 Gy (median 54) over 3–7 weeks. The tumor volume was calculated by the formula, p/6 * X * Y * Z or using software (Osiris, the University Hospital of Geneva) based on sum-of-areas method. Results: Follow-up tumor volume at 1 and 3 years ranged from 12 to 123%, from 12 to 92% by p/6 * X * Y * Z and from 11 to 126%, from 10 to 93% by sum-of-areas method. There were 2 cases of excellent response, which showed more than 65% decrease in tumor volume. Even though we excluded 2 cases, the mean tumor volume at 1, 3 and 5 years were 84, 72 and 66% by p/6 * X * Y * Z and 86, 68 and 60% by sum-of-areas method, respectively. There were 3 cases of progression. The 5-year overall and progression-free survival rates were 72 and 88%, respectively. Except two grade 3 middle ear effusions, there was no documented severe toxicity. Conclusions: Intracranial meningioma showed slow but continuous regression without severe toxicity after definitive radiotherapy. External beam radiotherapy is a well tolerated and effective treatment for inoperable intracranial meningioma with various reasons, and its efficacy can be further improved with high precision techniques (Fig.).
Author Disclosure: N. Jang, None; I. Kim, None; C. Park, None; A. Chang, None; H. Jung, None.
S253