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Trend of Declining Radiotherapy Use in Pediatric Low Grade Glioma
Proceedings of the 53rd Annual ASTRO Meeting
2932
Trend of Declining Radiotherapy Use in Pediatric Low Grade Glioma
M. M. Poppe, J. D. Tward, D. C. Shrieve Huntsman Cancer Hospital, Salt Lake City, UT Purpose/Objective(s): Recent publications confirm that radiotherapy (RT) is an effective treatment for unresectable or recurrent pediatric low grade glioma (LGG), with 5 and 10 year progression free survival (PFS) estimates of 80% and 70%, respectively. Despite recent data demonstrating less RT-associated toxicity than previously reported, and progression free survival data from chemotherapy similar to that of surveillance (5yr PFS around 50%), the nationwide trend is a dramatic decrease in RT utilization in this disease. Materials/Methods: Subjects were identified using the NCI’s Surveillance, Epidemiology and End Results (SEER) Program diagnosed between the years 1973 and 2007 with WHO grade I or II glioma. Subjects included in the analysis were children aged 0 18 with primary glioma and more than 2 months of follow-up. Descriptive statistics were performed, and cause specific survival (CSS) and overall survival (OS) were estimated using the methods of Kaplan and Meier. As SEER only reports on the use of surgery and RT used in the initial management of cancer therapy, we limited the trend analysis in RT to children 10 years and older at the time of diagnosis who underwent less than an initial subtotal resection of their disease (debulking, or biopsy only). Results: A total of 1739 subjects were identified. The median age at diagnosis was 9 years and median f/u time was 95 months (range 2 - 414 months). The 10, 20 and 30 yr CSS children with WHO grade I LGG was 94%, 89%, and 79%, with OS 91%, 83% and 67%, respectively. The 10, 20 and 30 yr CSS for children with WHO grade II LGG was 88%, 84%, and 80%, with OS 84%, 78%, and 67% respectively. JPA and oligodendroglioma histologies had equivalent CSS, with a HR 2.17 (1.53 - 3.07) for non-JPA astrocytic subtypes. Linear regression over 20 yrs for reporting of 269 older children with limited surgery yields an increasing slope of 0.75 (0.38 to 1.12), while the use of RT over the same period of time yields a flat slope of 0.124 (-0.16 to 0.40). Conclusions: Pediatric LGG is a chronic disease, in which the majority of patients will be living 30 years after their diagnosis. Short of a gross total resection, RT offers the most effective treatment to delay progression of this disease. Despite this fact, the use of RT in pediatric LGG has dramatically fallen in the United States. Even in older patients who are less prone to RT side effects and underwent only limited initial surgery, there appears to be a 6 fold decrease in the use of upfront RT over the last 20 years. Analysis needs to be performed to determine if quality of life is improved by preventing or delaying recurrence with early RT versus chemo-observation and an increased risk of recurrence. Author Disclosure: M.M. Poppe: None. J.D. Tward: None. D.C. Shrieve: None.
2933
Supratentorial Ependymoma: Disease Control and Functional Outcomes after Irradiation
E. Landau, F. A. Boop, T. E. Merchant St. Jude Children’s Research Hospital, Memphis, TN Purpose/Objective(s): Ependymoma is less commonly found in the supratentorial brain and is known to have clinical and molecular features that are unique compared to ependymoma arising in the infratentorial brain. Children with supratentorial ependymoma (STEP) treated with focal post-operative irradiation are unique among pediatric brain tumor patients and represent a group from which valuable information may be obtained about the side effects of supratentorial irradiation. Materials/Methods: A total of 50 children with newly diagnosed STEP and a median age of 6.3 yrs (range 1.0 - 18.9 yrs) were treated with adjuvant irradiation at St. Jude Children’s Research Hospital since 1972; 35 were irradiated during the conformal treatment era after 1997 and prospectively followed for CNS effects. The group was characterized according to gender (27 female), race (42 white), tumor location (22 parietal, 19 frontal) extent of resection (36 GTR) and tumor grade (37 anaplastic). The modern cohort was prospectively evaluated for neurological, cognitive and endocrine effects. Results: With a median follow-up of 7.4 years (range 0.5 - 23 yrs) the 10 year progression-free (PFS) and overall survival (OS) were 74% ± 7% and 76% ± 6%. The PFS (P = 0.014) and OS (P = 0.003) were influenced by extent of resection and not tumor grade. Distant failure was a component of failure in 11 of 14 patients with progressive disease. Eleven patients died from disease and one from CNS necrosis. Seizure disorders were present in 13 patients and 4 of these children were considered to be clinically disabled. Clinically significant cognitive effects were limited to children with difficult to control seizures. Average values for IQ and academic achievement (reading, spelling, math) were within the range of normal through 10 years of follow-up. Central hypothyroidism was the most commonly treated endocrinopathy and observed in 12 patients. Height (-0.33) and weight (0.39) zscores and body mass index (15.5, range 12.45 - 26.18) were within the range of normal with few outliers. Conclusions: Investigators have concluded that radiation therapy may be administered with acceptable risks for complications in young children with infratentorial ependymoma but remained concerned about young children with supratentorial tumor location. These results suggest that the outcome for children with supratentorial ependymoma are improving and that treatment complications after irradiation may be limited use focal methods of irradiation. Author Disclosure: E. Landau: None. F.A. Boop: None. T.E. Merchant: None.
2934
Spot-Scanning Based Proton Radiation Therapy for Children with Ependymoma: Clinical Outcome of 25 Patients Treated at Paul Scherrer Institute (PSI)
C. Ares, A. Staab, E. B. Hug, G. Goitein, T. Koch, F. Albertini, A. J. Lomax, B. Timmermann Center for Proton Therapy - Paul Scherrer Institute, Villigen, Switzerland Purpose/Objective(s): To assess the clinical results of spot scanning based proton therapy (PT) in the treatment of children with ependymoma. Materials/Methods: Between July-04 and September-10, 25 patients with Grade 3 (24 patients) or Grade 2 (1 patient) ependymoma were treated with PT. Tumors were localized infratentorially in 17 patients and supratentorially in 8 patients. Eight patients presented with macroscopic residual disease after subtotal resection before starting PT. Mean age was 3.2 years (range: 1.1 - 15.2), 23 patients (92%) were younger than 4 years requiring general anesthesia. Median prescribed dose was 59.4 Gy(RBE) (range, 54 60) delivered in 1.8 - 2 Gy(RBE) dose per fraction. Late toxicity was assessed according to CTCAE version 4.0.
S657
2932
Trend of Declining Radiotherapy Use in Pediatric Low Grade Glioma
M. M. Poppe, J. D. Tward, D. C. Shrieve Huntsman Cancer Hospital, Salt Lake City, UT Purpose/Objective(s): Recent publications confirm that radiotherapy (RT) is an effective treatment for unresectable or recurrent pediatric low grade glioma (LGG), with 5 and 10 year progression free survival (PFS) estimates of 80% and 70%, respectively. Despite recent data demonstrating less RT-associated toxicity than previously reported, and progression free survival data from chemotherapy similar to that of surveillance (5yr PFS around 50%), the nationwide trend is a dramatic decrease in RT utilization in this disease. Materials/Methods: Subjects were identified using the NCI’s Surveillance, Epidemiology and End Results (SEER) Program diagnosed between the years 1973 and 2007 with WHO grade I or II glioma. Subjects included in the analysis were children aged 0 18 with primary glioma and more than 2 months of follow-up. Descriptive statistics were performed, and cause specific survival (CSS) and overall survival (OS) were estimated using the methods of Kaplan and Meier. As SEER only reports on the use of surgery and RT used in the initial management of cancer therapy, we limited the trend analysis in RT to children 10 years and older at the time of diagnosis who underwent less than an initial subtotal resection of their disease (debulking, or biopsy only). Results: A total of 1739 subjects were identified. The median age at diagnosis was 9 years and median f/u time was 95 months (range 2 - 414 months). The 10, 20 and 30 yr CSS children with WHO grade I LGG was 94%, 89%, and 79%, with OS 91%, 83% and 67%, respectively. The 10, 20 and 30 yr CSS for children with WHO grade II LGG was 88%, 84%, and 80%, with OS 84%, 78%, and 67% respectively. JPA and oligodendroglioma histologies had equivalent CSS, with a HR 2.17 (1.53 - 3.07) for non-JPA astrocytic subtypes. Linear regression over 20 yrs for reporting of 269 older children with limited surgery yields an increasing slope of 0.75 (0.38 to 1.12), while the use of RT over the same period of time yields a flat slope of 0.124 (-0.16 to 0.40). Conclusions: Pediatric LGG is a chronic disease, in which the majority of patients will be living 30 years after their diagnosis. Short of a gross total resection, RT offers the most effective treatment to delay progression of this disease. Despite this fact, the use of RT in pediatric LGG has dramatically fallen in the United States. Even in older patients who are less prone to RT side effects and underwent only limited initial surgery, there appears to be a 6 fold decrease in the use of upfront RT over the last 20 years. Analysis needs to be performed to determine if quality of life is improved by preventing or delaying recurrence with early RT versus chemo-observation and an increased risk of recurrence. Author Disclosure: M.M. Poppe: None. J.D. Tward: None. D.C. Shrieve: None.
2933
Supratentorial Ependymoma: Disease Control and Functional Outcomes after Irradiation
E. Landau, F. A. Boop, T. E. Merchant St. Jude Children’s Research Hospital, Memphis, TN Purpose/Objective(s): Ependymoma is less commonly found in the supratentorial brain and is known to have clinical and molecular features that are unique compared to ependymoma arising in the infratentorial brain. Children with supratentorial ependymoma (STEP) treated with focal post-operative irradiation are unique among pediatric brain tumor patients and represent a group from which valuable information may be obtained about the side effects of supratentorial irradiation. Materials/Methods: A total of 50 children with newly diagnosed STEP and a median age of 6.3 yrs (range 1.0 - 18.9 yrs) were treated with adjuvant irradiation at St. Jude Children’s Research Hospital since 1972; 35 were irradiated during the conformal treatment era after 1997 and prospectively followed for CNS effects. The group was characterized according to gender (27 female), race (42 white), tumor location (22 parietal, 19 frontal) extent of resection (36 GTR) and tumor grade (37 anaplastic). The modern cohort was prospectively evaluated for neurological, cognitive and endocrine effects. Results: With a median follow-up of 7.4 years (range 0.5 - 23 yrs) the 10 year progression-free (PFS) and overall survival (OS) were 74% ± 7% and 76% ± 6%. The PFS (P = 0.014) and OS (P = 0.003) were influenced by extent of resection and not tumor grade. Distant failure was a component of failure in 11 of 14 patients with progressive disease. Eleven patients died from disease and one from CNS necrosis. Seizure disorders were present in 13 patients and 4 of these children were considered to be clinically disabled. Clinically significant cognitive effects were limited to children with difficult to control seizures. Average values for IQ and academic achievement (reading, spelling, math) were within the range of normal through 10 years of follow-up. Central hypothyroidism was the most commonly treated endocrinopathy and observed in 12 patients. Height (-0.33) and weight (0.39) zscores and body mass index (15.5, range 12.45 - 26.18) were within the range of normal with few outliers. Conclusions: Investigators have concluded that radiation therapy may be administered with acceptable risks for complications in young children with infratentorial ependymoma but remained concerned about young children with supratentorial tumor location. These results suggest that the outcome for children with supratentorial ependymoma are improving and that treatment complications after irradiation may be limited use focal methods of irradiation. Author Disclosure: E. Landau: None. F.A. Boop: None. T.E. Merchant: None.
2934
Spot-Scanning Based Proton Radiation Therapy for Children with Ependymoma: Clinical Outcome of 25 Patients Treated at Paul Scherrer Institute (PSI)
C. Ares, A. Staab, E. B. Hug, G. Goitein, T. Koch, F. Albertini, A. J. Lomax, B. Timmermann Center for Proton Therapy - Paul Scherrer Institute, Villigen, Switzerland Purpose/Objective(s): To assess the clinical results of spot scanning based proton therapy (PT) in the treatment of children with ependymoma. Materials/Methods: Between July-04 and September-10, 25 patients with Grade 3 (24 patients) or Grade 2 (1 patient) ependymoma were treated with PT. Tumors were localized infratentorially in 17 patients and supratentorially in 8 patients. Eight patients presented with macroscopic residual disease after subtotal resection before starting PT. Mean age was 3.2 years (range: 1.1 - 15.2), 23 patients (92%) were younger than 4 years requiring general anesthesia. Median prescribed dose was 59.4 Gy(RBE) (range, 54 60) delivered in 1.8 - 2 Gy(RBE) dose per fraction. Late toxicity was assessed according to CTCAE version 4.0.
S657