- Email: [email protected]
Visual Outcome and Tumor Control Following Conformal Radiotherapy for Patients With Optic Nerve Sheath Meningioma
I. J. Radiation Oncology d Biology d Physics
S256
2093
Volume 69, Number 3, Supplement, 2007
Long Term Experience With WHO Grade III Meningiomas at the Cleveland Clinic Foundation
L. A. Rosenberg, R. A. Prayson, J. Lee, C. A. Reddy, S. T. Chao, G. Barnett, M. Vogelbaum, J. H. Suh Cleveland Clinic Foundation, Cleveland, OH Purpose/Objective(s): Malignant meningiomas are rare, aggressive tumors that are associated with poor patient outcomes. Few programs have published their experience with malignant, or grade III, meningiomas using the current World Health Organization (WHO) definition. We present the experience of the Cleveland Clinic Foundation (CCF) with grade III meningiomas exclusively using the year 2000 WHO criteria. Materials/Methods: Twenty-two patients were initially identified with malignant meningiomas at CCF who were treated between 1981 and 2006. Slides from 18 patients diagnosed with malignant tumors prior to 2000 were reviewed by a single pathologist; 9 did not satisfy the WHO 2000 criteria for grade III tumors. The remaining 13 patients were used for this study. Patients were diagnosed between the ages of 37 and 87 years (median = 66), and 8 were male. Six patients had a history of a prior local lower grade meningioma. Seven patients received post-surgical radiation therapy to a partial brain volume as a component of primary or salvage therapy (5040–6000 cGy; median = 5940 cGy; 180 cGy/fx). Stereotactic radiosurgery employing a Gamma Knife was used as salvage therapy for 3 patients (1500–2400 cGy; 4–13 isocenters). Four patients were alive at last follow up. Results: From the time of primary surgery, overall median survival was 3.4 years, 5 year survival was 47.2%, and median time to recurrence was 9.6 months. Patients who received adjuvant radiotherapy after their first surgery had median survival of 5.4 years (n = 3) whereas those not receiving radiotherapy survived to a median of 2.5 years (n = 10); this difference was not statistically significant. No other variable affected survival or time to recurrence including age, KPS at diagnosis, prior diagnosis of lower grade meningioma, degree of resection, or mode of salvage therapy. Notably, a single individual whose tumor has not recurred for 105 months had gross total resection with adjuvant radiotherapy to 5900 cGy. Conclusions: Our results are consistent with published data for malignant meningiomas that report 5 year survival from 32 to 64%. We found that half of 18 meningiomas diagnosed as malignant prior to 2000 failed to satisfy the new criteria for grade III tumors. This finding suggests that the new definition is substantially different than the prior one. Patient outcome remains unsatisfactory for malignant meningiomas. More studies are necessary to develop more effective interventions. Author Disclosure: L.A. Rosenberg, None; R.A. Prayson, None; J. Lee, None; C.A. Reddy, None; S.T. Chao, None; G. Barnett, None; M. Vogelbaum, None; J.H. Suh, None.
2094
The Efficiency of Radiotherapy in the Treatment of Newly Diagnosed Intracranial Oligodendroglioma: Prognostic Factors for Tumor Recurrence and Survival
H. Kang, K. Eom, I. Kim, C. Park Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea Purpose/Objective(s): To retrospectively analyze the outcomes and benefits from radiation therapy as a component of multimodal treatment for oligodendroglioma, assessing local control and survival rates and evaluating prognostic factors. Materials/Methods: Between January 1983 and December 2003, total of 120 patients with oligodendroglioma (ODG; 61 patients) and anaplastic oligodendroglioma (AODG; 59 patients) were treated with postoperative radiotherapy at Seoul National University Hospital. Variation in the clinical-therapeutic features in two histologic groups were evaluated. Results: Follow-up ranged from 2 to 231 months (median 65). Median overall survival (OS) and progression-free survival (PFS) were 68 months (range, 3–235 months) and 49 months (range, 3–235 months), respectively. With regard to histologic grade, progression free survival rates at 5 and 10 years were ODG: 83% and 45%; AODG: 55% and 48%. Univariate analysis of several clinical variables showed that age (p = 0.049) and extent of resection (p = 0.04) correlated significantly with PFS of patients with AODG. Overall survival rates at 5 and 10 years were ODG: 94% and 64%; AODG: 72% and 64%. Age (p = 0.005) and performance status (p = 0.019) were significant factor for OS of patients with AODG in univariate analysis. No significant factor was found that correlated with PFS or OS in patients with ODG. Conclusions: Patients with ODG/AODG have a better prognosis after therapy compared with those who have other gliomas. Patients with AODG should continue to receive postoperative radiotherapy as component of multimodal treatment to obtain long-term survival. Author Disclosure: H. Kang, None; K. Eom, None; I. Kim, None; C. Park, None.
2095
Visual Outcome and Tumor Control Following Conformal Radiotherapy for Patients With Optic Nerve Sheath Meningioma
N. D. Arvold1, S. Lessell2, J. F. Rizzo2, N. J. Liebsch1, T. I. Yock1, J. S. Loeffler1, H. A. Shih1 1
Massachusetts General Hospital, Boston, MA, 2Massachusetts Eye and Ear Infirmary, Boston, MA
Background: Optic nerve sheath meningioma (ONSM) is a rare tumor that almost uniformly leads to visual dysfunction and blindness without intervention. Since attempts at surgical extirpation carry a high risk of post-operative blindness, vision-sparing treatment strategies are desirable. Recent reports suggest a beneficial role for conformal fractionated radiation therapy in the management of ONSM. We report the outcomes of 25 patients treated at a single institution with highly conformal fractionated radiation therapy, including the use of photon and/or proton radiation. Materials/Methods: We retrospectively reviewed the outcomes of twenty-five patients (25 optic nerves) with ONSM, treated with conformal fractionated radiation therapy by either stereotactic photon radiotherapy or fractionated proton radiation. Primary endpoints assessed were local control and visual acuity. Secondary endpoints included visual field, color vision, other reported symptoms, and examination findings.
Proceedings of the 49th Annual ASTRO Meeting Results: The patients presented with symptoms of visual loss (21), orbital pain (3), or were incidentally diagnosed by imaging studies (3). Mean age was 42 years, and 16/25 (64%) were female. Indication for treatment was development or progression of symptoms, most commonly visual deterioration. Thirteen patients were treated with photons, 9 patients were treated with protons, and 3 patients received a combination of photons and protons. Median dose delivered was 50.4 GyE (range 45–59.4 GyE). Mean gross tumor volume was 2.91 cc (range 0.28–13.60 cc). Median patient follow-up after radiation therapy was 30 months (range 3– 168 months), with 3 patients lost to follow-up. All patients (100%) experienced improvement or stability of symptoms during treatment. At most recent follow up, 21 of the 22 (95%) patients available for evaluation had improved (14) or stable (7) visual acuity. Nine patients had improvement in visual field. Color vision improved in 8 patients. One patient had worsened visual acuity after initial post-irradiation improvement. Three patients had evidence of retinopathy that was likely related to treatment, and 1 patient had recurrent ONSM 11 years after treatment. Treatment-related morbidity was approximately equal between patients treated with photons and patients treated with protons. To date, no case of secondary tumor formation has occurred. Conclusions: Highly conformal, fractionated radiation therapy is an effective noninvasive treatment for primary ONSM, with improvement in visual function in the majority of cases. Treatment-induced morbidity including visual loss is uncommon. Longer follow-up is needed to assess durability of tumor control and treatment-related late effects. Author Disclosure: N.D. Arvold, None; S. Lessell, None; J.F. Rizzo, None; N.J. Liebsch, None; T.I. Yock, None; J.S. Loeffler, None; H.A. Shih, None.
2096
Helical Tomotherapy Provides Significant Normal Brain Sparing Using a Simultaneous Integrated Boost
J. M. Baisden, K. Sheng, A. F. McIntosh, P. W. Read, J. Sheehan, J. Larner University of Virginia Medical Center, Charlottesville, VA Purpose/Objective(s): Conventional radiation treatment plans for primary brain tumors as well as metastatic disease often involve the treatment of an initial larger volume followed by a reduced volume known as a ‘‘boost’’. A simultaneous integrated boost (SIB) in which the boost is incorporated into the treatment of the larger volume is easily achieved with Helical Tomotherpay (HT) based inverse treatment planning due to its increased degrees of freedom (multiple beamlets) compared to other forms of radiation delivery. SIB has the potential to improve patient outcome (decreased radiation induced-neuro-cognitive decline) by reducing dose to normal brain. We therefore quantified the dosimetric advantage of a HT based IMRT SIB technique versus a conventional HT based sequential (SEQ) boost technique for hypothetical primary brain tumors as well as for metastatic disease. Materials/Methods: Hypothetical lesions (PTV) were contoured within CT scans from normal controls. For primary brain tumors, two centrally placed cylindrical PTVS were created. A dose of 50 Gy was prescribed to the larger PTV1 while the PTV boost received a total of 60 Gy. Twenty plans were compared with PTV1 ranging from 3 to 6 cm diameter and PTV boost ranging from 2 to 5 cm diameter. For metastatic brain tumors, a dose of 32.5 Gy was prescribed to the entire brain, while the PTV boost received a dose of 40 Gy. Twenty-two plans were compared with either solitary or 3 lesions (PTV boost from 2 to 151 cc total volume). Plans were optimized with similar prescriptions to targets as well as similar constraints on normal tissue to minimize planning bias in the analysis of dosimitry. Composite dosimetry from the SEQ plans was compared to SIB plans. Results: For primary brain lesions the average reduction in mean and median brain dose with the SIB plan compared to the SEQ plan was 11.0% (Standard Error = 0.5) and 11.5% (SE = 0.6), respectively. The average decrease in V45 was 14.4% (SE = 1.0). This sparing was weakly dependent on target volume. For metastatic lesions the SIB techniques resulted in a decrease in mean and median dose of 1% for the smallest volumes to 11% for the largest volumes. PTVboost volumes greater than 25 cc were associated with .5% reduction in mean and median brain doses. The basis for brain sparing provided by SIB technique is due in part to the ability of the planning software to consider and compensate for the dose spillage from treatment of the boost volume in the treatment of the primary volume. Conclusions: The HT SIB technique provides significant sparing of normal brain for both primary and metastatic lesions compared with a conventional sequential boost. Defining the clinical benefit of the SIB technique requires further investigation. Author Disclosure: J.M. Baisden, None; K. Sheng, None; A.F. McIntosh, None; P.W. Read, Tomotherapy, D. Speakers Bureau/ Honoraria; Tomotherapy, F. Consultant/Advisory Board; J. Sheehan, None; J. Larner, None.
2097
Tumor Specific Targeting of Intravenous 131I-chlorotoxin (TM-601) in Patients With Recurrent Glioma
J. B. Fiveash, L. B. Nabors, J. J. Raizer, N. Avgeropoulos, H. Modarresifar, S. Shen University of Alabama Medical Center, Birmingham, AL Purpose/Objective(s): Previous clinical trials of 131I-chlorotoxin in patients with recurrent glioblastoma multiforme administered this targeted peptide locally into a tumor resection cavity. In this trial the distribution of intravenous (IV) 131I-chlorotoxin was examined to determine if the IV route of administration would be feasible and show intratumoral uptake in patients with inoperable malignant gliomas. Materials/Methods: Five patients with recurrent gliomas were enrolled in a prospective clinical trial of IV 131I-chlorotoxin that also included patients with other advanced solid tumors. The glioma patients are the subject of this report. All patients received a test dose of 10 mCi (0.2 mg peptide) 131I-chlorotoxin IV. Five, sequential, whole body gamma camera images were acquired at immediate, 3 hours, 24 hours, 48–72 hours, and 168 hours post 131I-chlorotoxin injection for tumor localization and dosimetry analysis. Patients showing tumor localization by gamma camera or SPECT imaging received a second therapeutic dose of 30 mCi (0.6 mg peptide) 131I-chlorotoxin one week later. Patients not showing uptake were re-treated a week later with 20 mCi (0.4 mg peptide) 131I-chlorotoxin to determine possible localization at a higher dose. Results: All five patients with glioma demonstrated tumor specific localization on follow-up gamma camera or SPECT imaging after IV administration of 131I-chlorotoxin. Dose limiting toxicity was not observed. MRI imaging on one patient at the day 28 evaluation demonstrated a reduction in the T1 enhancing volume and T2 volume. The mean radiation dose was 0.24 cGy/mCi
S257
S256
2093
Volume 69, Number 3, Supplement, 2007
Long Term Experience With WHO Grade III Meningiomas at the Cleveland Clinic Foundation
L. A. Rosenberg, R. A. Prayson, J. Lee, C. A. Reddy, S. T. Chao, G. Barnett, M. Vogelbaum, J. H. Suh Cleveland Clinic Foundation, Cleveland, OH Purpose/Objective(s): Malignant meningiomas are rare, aggressive tumors that are associated with poor patient outcomes. Few programs have published their experience with malignant, or grade III, meningiomas using the current World Health Organization (WHO) definition. We present the experience of the Cleveland Clinic Foundation (CCF) with grade III meningiomas exclusively using the year 2000 WHO criteria. Materials/Methods: Twenty-two patients were initially identified with malignant meningiomas at CCF who were treated between 1981 and 2006. Slides from 18 patients diagnosed with malignant tumors prior to 2000 were reviewed by a single pathologist; 9 did not satisfy the WHO 2000 criteria for grade III tumors. The remaining 13 patients were used for this study. Patients were diagnosed between the ages of 37 and 87 years (median = 66), and 8 were male. Six patients had a history of a prior local lower grade meningioma. Seven patients received post-surgical radiation therapy to a partial brain volume as a component of primary or salvage therapy (5040–6000 cGy; median = 5940 cGy; 180 cGy/fx). Stereotactic radiosurgery employing a Gamma Knife was used as salvage therapy for 3 patients (1500–2400 cGy; 4–13 isocenters). Four patients were alive at last follow up. Results: From the time of primary surgery, overall median survival was 3.4 years, 5 year survival was 47.2%, and median time to recurrence was 9.6 months. Patients who received adjuvant radiotherapy after their first surgery had median survival of 5.4 years (n = 3) whereas those not receiving radiotherapy survived to a median of 2.5 years (n = 10); this difference was not statistically significant. No other variable affected survival or time to recurrence including age, KPS at diagnosis, prior diagnosis of lower grade meningioma, degree of resection, or mode of salvage therapy. Notably, a single individual whose tumor has not recurred for 105 months had gross total resection with adjuvant radiotherapy to 5900 cGy. Conclusions: Our results are consistent with published data for malignant meningiomas that report 5 year survival from 32 to 64%. We found that half of 18 meningiomas diagnosed as malignant prior to 2000 failed to satisfy the new criteria for grade III tumors. This finding suggests that the new definition is substantially different than the prior one. Patient outcome remains unsatisfactory for malignant meningiomas. More studies are necessary to develop more effective interventions. Author Disclosure: L.A. Rosenberg, None; R.A. Prayson, None; J. Lee, None; C.A. Reddy, None; S.T. Chao, None; G. Barnett, None; M. Vogelbaum, None; J.H. Suh, None.
2094
The Efficiency of Radiotherapy in the Treatment of Newly Diagnosed Intracranial Oligodendroglioma: Prognostic Factors for Tumor Recurrence and Survival
H. Kang, K. Eom, I. Kim, C. Park Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea Purpose/Objective(s): To retrospectively analyze the outcomes and benefits from radiation therapy as a component of multimodal treatment for oligodendroglioma, assessing local control and survival rates and evaluating prognostic factors. Materials/Methods: Between January 1983 and December 2003, total of 120 patients with oligodendroglioma (ODG; 61 patients) and anaplastic oligodendroglioma (AODG; 59 patients) were treated with postoperative radiotherapy at Seoul National University Hospital. Variation in the clinical-therapeutic features in two histologic groups were evaluated. Results: Follow-up ranged from 2 to 231 months (median 65). Median overall survival (OS) and progression-free survival (PFS) were 68 months (range, 3–235 months) and 49 months (range, 3–235 months), respectively. With regard to histologic grade, progression free survival rates at 5 and 10 years were ODG: 83% and 45%; AODG: 55% and 48%. Univariate analysis of several clinical variables showed that age (p = 0.049) and extent of resection (p = 0.04) correlated significantly with PFS of patients with AODG. Overall survival rates at 5 and 10 years were ODG: 94% and 64%; AODG: 72% and 64%. Age (p = 0.005) and performance status (p = 0.019) were significant factor for OS of patients with AODG in univariate analysis. No significant factor was found that correlated with PFS or OS in patients with ODG. Conclusions: Patients with ODG/AODG have a better prognosis after therapy compared with those who have other gliomas. Patients with AODG should continue to receive postoperative radiotherapy as component of multimodal treatment to obtain long-term survival. Author Disclosure: H. Kang, None; K. Eom, None; I. Kim, None; C. Park, None.
2095
Visual Outcome and Tumor Control Following Conformal Radiotherapy for Patients With Optic Nerve Sheath Meningioma
N. D. Arvold1, S. Lessell2, J. F. Rizzo2, N. J. Liebsch1, T. I. Yock1, J. S. Loeffler1, H. A. Shih1 1
Massachusetts General Hospital, Boston, MA, 2Massachusetts Eye and Ear Infirmary, Boston, MA
Background: Optic nerve sheath meningioma (ONSM) is a rare tumor that almost uniformly leads to visual dysfunction and blindness without intervention. Since attempts at surgical extirpation carry a high risk of post-operative blindness, vision-sparing treatment strategies are desirable. Recent reports suggest a beneficial role for conformal fractionated radiation therapy in the management of ONSM. We report the outcomes of 25 patients treated at a single institution with highly conformal fractionated radiation therapy, including the use of photon and/or proton radiation. Materials/Methods: We retrospectively reviewed the outcomes of twenty-five patients (25 optic nerves) with ONSM, treated with conformal fractionated radiation therapy by either stereotactic photon radiotherapy or fractionated proton radiation. Primary endpoints assessed were local control and visual acuity. Secondary endpoints included visual field, color vision, other reported symptoms, and examination findings.
Proceedings of the 49th Annual ASTRO Meeting Results: The patients presented with symptoms of visual loss (21), orbital pain (3), or were incidentally diagnosed by imaging studies (3). Mean age was 42 years, and 16/25 (64%) were female. Indication for treatment was development or progression of symptoms, most commonly visual deterioration. Thirteen patients were treated with photons, 9 patients were treated with protons, and 3 patients received a combination of photons and protons. Median dose delivered was 50.4 GyE (range 45–59.4 GyE). Mean gross tumor volume was 2.91 cc (range 0.28–13.60 cc). Median patient follow-up after radiation therapy was 30 months (range 3– 168 months), with 3 patients lost to follow-up. All patients (100%) experienced improvement or stability of symptoms during treatment. At most recent follow up, 21 of the 22 (95%) patients available for evaluation had improved (14) or stable (7) visual acuity. Nine patients had improvement in visual field. Color vision improved in 8 patients. One patient had worsened visual acuity after initial post-irradiation improvement. Three patients had evidence of retinopathy that was likely related to treatment, and 1 patient had recurrent ONSM 11 years after treatment. Treatment-related morbidity was approximately equal between patients treated with photons and patients treated with protons. To date, no case of secondary tumor formation has occurred. Conclusions: Highly conformal, fractionated radiation therapy is an effective noninvasive treatment for primary ONSM, with improvement in visual function in the majority of cases. Treatment-induced morbidity including visual loss is uncommon. Longer follow-up is needed to assess durability of tumor control and treatment-related late effects. Author Disclosure: N.D. Arvold, None; S. Lessell, None; J.F. Rizzo, None; N.J. Liebsch, None; T.I. Yock, None; J.S. Loeffler, None; H.A. Shih, None.
2096
Helical Tomotherapy Provides Significant Normal Brain Sparing Using a Simultaneous Integrated Boost
J. M. Baisden, K. Sheng, A. F. McIntosh, P. W. Read, J. Sheehan, J. Larner University of Virginia Medical Center, Charlottesville, VA Purpose/Objective(s): Conventional radiation treatment plans for primary brain tumors as well as metastatic disease often involve the treatment of an initial larger volume followed by a reduced volume known as a ‘‘boost’’. A simultaneous integrated boost (SIB) in which the boost is incorporated into the treatment of the larger volume is easily achieved with Helical Tomotherpay (HT) based inverse treatment planning due to its increased degrees of freedom (multiple beamlets) compared to other forms of radiation delivery. SIB has the potential to improve patient outcome (decreased radiation induced-neuro-cognitive decline) by reducing dose to normal brain. We therefore quantified the dosimetric advantage of a HT based IMRT SIB technique versus a conventional HT based sequential (SEQ) boost technique for hypothetical primary brain tumors as well as for metastatic disease. Materials/Methods: Hypothetical lesions (PTV) were contoured within CT scans from normal controls. For primary brain tumors, two centrally placed cylindrical PTVS were created. A dose of 50 Gy was prescribed to the larger PTV1 while the PTV boost received a total of 60 Gy. Twenty plans were compared with PTV1 ranging from 3 to 6 cm diameter and PTV boost ranging from 2 to 5 cm diameter. For metastatic brain tumors, a dose of 32.5 Gy was prescribed to the entire brain, while the PTV boost received a dose of 40 Gy. Twenty-two plans were compared with either solitary or 3 lesions (PTV boost from 2 to 151 cc total volume). Plans were optimized with similar prescriptions to targets as well as similar constraints on normal tissue to minimize planning bias in the analysis of dosimitry. Composite dosimetry from the SEQ plans was compared to SIB plans. Results: For primary brain lesions the average reduction in mean and median brain dose with the SIB plan compared to the SEQ plan was 11.0% (Standard Error = 0.5) and 11.5% (SE = 0.6), respectively. The average decrease in V45 was 14.4% (SE = 1.0). This sparing was weakly dependent on target volume. For metastatic lesions the SIB techniques resulted in a decrease in mean and median dose of 1% for the smallest volumes to 11% for the largest volumes. PTVboost volumes greater than 25 cc were associated with .5% reduction in mean and median brain doses. The basis for brain sparing provided by SIB technique is due in part to the ability of the planning software to consider and compensate for the dose spillage from treatment of the boost volume in the treatment of the primary volume. Conclusions: The HT SIB technique provides significant sparing of normal brain for both primary and metastatic lesions compared with a conventional sequential boost. Defining the clinical benefit of the SIB technique requires further investigation. Author Disclosure: J.M. Baisden, None; K. Sheng, None; A.F. McIntosh, None; P.W. Read, Tomotherapy, D. Speakers Bureau/ Honoraria; Tomotherapy, F. Consultant/Advisory Board; J. Sheehan, None; J. Larner, None.
2097
Tumor Specific Targeting of Intravenous 131I-chlorotoxin (TM-601) in Patients With Recurrent Glioma
J. B. Fiveash, L. B. Nabors, J. J. Raizer, N. Avgeropoulos, H. Modarresifar, S. Shen University of Alabama Medical Center, Birmingham, AL Purpose/Objective(s): Previous clinical trials of 131I-chlorotoxin in patients with recurrent glioblastoma multiforme administered this targeted peptide locally into a tumor resection cavity. In this trial the distribution of intravenous (IV) 131I-chlorotoxin was examined to determine if the IV route of administration would be feasible and show intratumoral uptake in patients with inoperable malignant gliomas. Materials/Methods: Five patients with recurrent gliomas were enrolled in a prospective clinical trial of IV 131I-chlorotoxin that also included patients with other advanced solid tumors. The glioma patients are the subject of this report. All patients received a test dose of 10 mCi (0.2 mg peptide) 131I-chlorotoxin IV. Five, sequential, whole body gamma camera images were acquired at immediate, 3 hours, 24 hours, 48–72 hours, and 168 hours post 131I-chlorotoxin injection for tumor localization and dosimetry analysis. Patients showing tumor localization by gamma camera or SPECT imaging received a second therapeutic dose of 30 mCi (0.6 mg peptide) 131I-chlorotoxin one week later. Patients not showing uptake were re-treated a week later with 20 mCi (0.4 mg peptide) 131I-chlorotoxin to determine possible localization at a higher dose. Results: All five patients with glioma demonstrated tumor specific localization on follow-up gamma camera or SPECT imaging after IV administration of 131I-chlorotoxin. Dose limiting toxicity was not observed. MRI imaging on one patient at the day 28 evaluation demonstrated a reduction in the T1 enhancing volume and T2 volume. The mean radiation dose was 0.24 cGy/mCi
S257