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Patterns of Failure Following Proton Therapy in Medulloblastoma: LET Distributions and RBE Associations for Relapses
S720
International Journal of Radiation Oncology Biology Physics
ranks will receive bonuses. In this study, we present an analysis of factors that predict for PG scores. Materials/Methods: PG scores were analyzed over a time span of 7 months including 71 patients and 1409 survey questions for an academic institution with two satellite centers. Multiple variables (i.e., age, performance status, diagnosis, treatment venue, presence of pain, concurrent chemotherapy) were analyzed for correlations with scores using the Independent T Test, Pearson Chi Square, and Fisher Exact Test. Results: 26 patients (36%) filled out all questions with scores of all 5, 16 patients (22%) had all 5s but incomplete survey, 39 patients (55%) had at least one non-5 score. 4 patients had a single non-5 score while 35 patients had multiple non-5 scores. For complete surveys, the median score was 104 (range 84 to 105), the average score was 102.5. Pain, increasing age, and treatment venue were predictive for non-5 scores. Conclusions: PG scores are becoming a vital metric as department reimbursement is tied into these scores. Patients with unsatisfactory scores tended to give non-5 scores across multiple questions, patients are seldom dissatisfied in a single area. We found several modifiable (treatment venue) and non-modifiable (older age and presence of pain) factors related to poor scores. While there is some potential methods for improving PG scores there are limitations, departments that see a disproportionate number of elderly palliative cases will likely have lower scores. Author Disclosure: A.B. Patel: None. T. LaCouture: None. K. Hunter: None. A. Tartaglia: None. G.J. Kubicek: None.
Conclusions: Preliminary findings suggest right hippocampal dose is associated with steeper IQ decline post-PRT in this cohort of patients. Author Disclosure: A. Mahajan: None. D. Grosshans: None. D. Ris: None. M. Chintagumpala: None. F. Okcu: None. M. McAleer: None. B. Moore: None. H. Stancel: None. C. Minard: None. D. Guffey: None. L. Kahalley: None.
3294 Neurocognitive Outcomes in Relationship to Hippocampal and Brain Doses After Partial Brain Proton Radiation Therapy in Children A. Mahajan,1,2 D. Grosshans,1 D. Ris,2 M. Chintagumpala,2 F. Okcu,2 M. McAleer,1 B. Moore,1 H. Stancel,2 C. Minard,2 D. Guffey,2 and L. Kahalley2; 1M.D. Anderson Cancer Center, Houston, TX, 2Baylor College of Medicine, Houston, TX Purpose/Objective(s): We evaluated the relationship between IQ and hippocampal RT doses in pediatric patients with brain tumors treated with proton radiation therapy (PRT). Materials/Methods: IQ scores were abstracted for patients treated with partial brain PRT who underwent serial neurocognitive testing. Hippocampal delineation was performed according to RTOG guidelines. The PRT dosimetric data were compiled. The relationships between IQ and 1) median hippocampal doses and 2) percentage of hippocampus receiving 50, 30 and 10 GyRBE were evaluated using general linear mixed models while controlling for mean brain-GTV dose, CTV volume, tumor location, and age-at-RT. Results: Data were collected for 25 patients (13 males, 12 females) receiving PRT from 2007-2012. The mean interval between first-last IQ testing was 2.1 y (range 0.9-6.0). The median age-at-PRT was 9.4 y (range 1.7-15.4 y). Tumors were supratentorial in 17 patients (9 glial, 5 craniopharyngioma, 2 germinoma, 1 meningeal tumors) and infratentorial in 7 patients (3 anaplastic ependymoma, 2 medulloblastoma, 2 glial tumor). 17, 2 and 6 tumors were midline, right and left, respectively. The median dose was 50.4 GyRBE (range 45.0-60.0 GyRBE). The median CTV volume was 43.3 cc (range 12.3-234.4 cc). The median mean brain-GTV dose was 9.4 GyRBE (range 3.9-19.7 GyRBE). The median mean right and left hippocampal doses were 17.0 and 16.3 GyRBE (range 0.2-54.8 and 0.0-46.2 GyRBE), respectively. After controlling for the factors mentioned above, patients who received any right hippocampal dose >50 GyRBE exhibited significant IQ decline (6.4 points/y, p Z 0.01). Patients who received 30 GyRBE to 10% of the right hippocampal volume also experienced significant IQ decline (4.0 points/y, p<0.01), while patients with less right hippocampal dose/volume maintained stable IQ over time (p Z 0.67). Left hippocampal dose/volume was not associated with IQ decline in this cohort.
3295 Patterns of Failure Following Proton Therapy in Medulloblastoma: LET Distributions and RBE Associations for Relapses R. Sethi,1 D. Giantsoudi,2 M. Raiford,2 I. Malhi,2 A. Niemierko,2 O. Rapalino,3 P. Caruso,1 T.I. Yock,2 N.J. Tarbell,2 H. Paganetti,2 and S. MacDonald2; 1Harvard Medical School, Boston, MA, 2 Massachusetts General Hospital, Boston, MA, 3Massachussetts General Hospital, Boston, MA Purpose/Objective(s): The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to modern photon series. It has been suggested this pattern may differ from photons due to variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal (CSI) radiation may influence patterns of relapse. We seek to report the patterns of failure following protons, compare to the available photon literature, and determine the LET and RBE values in areas of recurrence. Materials/Methods: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at *** between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: One hundred and nine patients were followed for a median of 38.8 months (range, 1.4 to 119.2). Sixteen (16) patients experienced relapse. Relapse involved the supratentorial compartment (n Z 8), spinal compartment (n Z 11) and posterior fossa (n Z 5). Eleven failures were isolated to a single compartment; six failures in the spine, four failures in the supratentorium and one failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of two fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not differ from patients treated with photon therapy. Author Disclosure: R. Sethi: None. D. Giantsoudi: None. M. Raiford: None. I. Malhi: None. A. Niemierko: None. O. Rapalino: None. P. Caruso: None. T.I. Yock: None. N.J. Tarbell: K. Advisory Board; Spouse is on medical advisory board of ProCure. NJT was on medical advisory board until 2008. H. Paganetti: None. S. MacDonald: None.
3296 Impact of Molecular Subtype and Craniospinal Irradiation (CSI) Dose on Relapse of Medulloblastoma A. Wang,1 S. Partap,1 K. Yeom1, M. Martinez,2 H. Vogel,1 S. S. Donaldson,1 P. G. Fisher,1 S. Perreault,3 Y.-J. Cho,1 and I. C. Gibbs1; 1 Stanford University/Lucile Packard Children’s Hospital, Stanford, CA,
International Journal of Radiation Oncology Biology Physics
ranks will receive bonuses. In this study, we present an analysis of factors that predict for PG scores. Materials/Methods: PG scores were analyzed over a time span of 7 months including 71 patients and 1409 survey questions for an academic institution with two satellite centers. Multiple variables (i.e., age, performance status, diagnosis, treatment venue, presence of pain, concurrent chemotherapy) were analyzed for correlations with scores using the Independent T Test, Pearson Chi Square, and Fisher Exact Test. Results: 26 patients (36%) filled out all questions with scores of all 5, 16 patients (22%) had all 5s but incomplete survey, 39 patients (55%) had at least one non-5 score. 4 patients had a single non-5 score while 35 patients had multiple non-5 scores. For complete surveys, the median score was 104 (range 84 to 105), the average score was 102.5. Pain, increasing age, and treatment venue were predictive for non-5 scores. Conclusions: PG scores are becoming a vital metric as department reimbursement is tied into these scores. Patients with unsatisfactory scores tended to give non-5 scores across multiple questions, patients are seldom dissatisfied in a single area. We found several modifiable (treatment venue) and non-modifiable (older age and presence of pain) factors related to poor scores. While there is some potential methods for improving PG scores there are limitations, departments that see a disproportionate number of elderly palliative cases will likely have lower scores. Author Disclosure: A.B. Patel: None. T. LaCouture: None. K. Hunter: None. A. Tartaglia: None. G.J. Kubicek: None.
Conclusions: Preliminary findings suggest right hippocampal dose is associated with steeper IQ decline post-PRT in this cohort of patients. Author Disclosure: A. Mahajan: None. D. Grosshans: None. D. Ris: None. M. Chintagumpala: None. F. Okcu: None. M. McAleer: None. B. Moore: None. H. Stancel: None. C. Minard: None. D. Guffey: None. L. Kahalley: None.
3294 Neurocognitive Outcomes in Relationship to Hippocampal and Brain Doses After Partial Brain Proton Radiation Therapy in Children A. Mahajan,1,2 D. Grosshans,1 D. Ris,2 M. Chintagumpala,2 F. Okcu,2 M. McAleer,1 B. Moore,1 H. Stancel,2 C. Minard,2 D. Guffey,2 and L. Kahalley2; 1M.D. Anderson Cancer Center, Houston, TX, 2Baylor College of Medicine, Houston, TX Purpose/Objective(s): We evaluated the relationship between IQ and hippocampal RT doses in pediatric patients with brain tumors treated with proton radiation therapy (PRT). Materials/Methods: IQ scores were abstracted for patients treated with partial brain PRT who underwent serial neurocognitive testing. Hippocampal delineation was performed according to RTOG guidelines. The PRT dosimetric data were compiled. The relationships between IQ and 1) median hippocampal doses and 2) percentage of hippocampus receiving 50, 30 and 10 GyRBE were evaluated using general linear mixed models while controlling for mean brain-GTV dose, CTV volume, tumor location, and age-at-RT. Results: Data were collected for 25 patients (13 males, 12 females) receiving PRT from 2007-2012. The mean interval between first-last IQ testing was 2.1 y (range 0.9-6.0). The median age-at-PRT was 9.4 y (range 1.7-15.4 y). Tumors were supratentorial in 17 patients (9 glial, 5 craniopharyngioma, 2 germinoma, 1 meningeal tumors) and infratentorial in 7 patients (3 anaplastic ependymoma, 2 medulloblastoma, 2 glial tumor). 17, 2 and 6 tumors were midline, right and left, respectively. The median dose was 50.4 GyRBE (range 45.0-60.0 GyRBE). The median CTV volume was 43.3 cc (range 12.3-234.4 cc). The median mean brain-GTV dose was 9.4 GyRBE (range 3.9-19.7 GyRBE). The median mean right and left hippocampal doses were 17.0 and 16.3 GyRBE (range 0.2-54.8 and 0.0-46.2 GyRBE), respectively. After controlling for the factors mentioned above, patients who received any right hippocampal dose >50 GyRBE exhibited significant IQ decline (6.4 points/y, p Z 0.01). Patients who received 30 GyRBE to 10% of the right hippocampal volume also experienced significant IQ decline (4.0 points/y, p<0.01), while patients with less right hippocampal dose/volume maintained stable IQ over time (p Z 0.67). Left hippocampal dose/volume was not associated with IQ decline in this cohort.
3295 Patterns of Failure Following Proton Therapy in Medulloblastoma: LET Distributions and RBE Associations for Relapses R. Sethi,1 D. Giantsoudi,2 M. Raiford,2 I. Malhi,2 A. Niemierko,2 O. Rapalino,3 P. Caruso,1 T.I. Yock,2 N.J. Tarbell,2 H. Paganetti,2 and S. MacDonald2; 1Harvard Medical School, Boston, MA, 2 Massachusetts General Hospital, Boston, MA, 3Massachussetts General Hospital, Boston, MA Purpose/Objective(s): The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to modern photon series. It has been suggested this pattern may differ from photons due to variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal (CSI) radiation may influence patterns of relapse. We seek to report the patterns of failure following protons, compare to the available photon literature, and determine the LET and RBE values in areas of recurrence. Materials/Methods: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at *** between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: One hundred and nine patients were followed for a median of 38.8 months (range, 1.4 to 119.2). Sixteen (16) patients experienced relapse. Relapse involved the supratentorial compartment (n Z 8), spinal compartment (n Z 11) and posterior fossa (n Z 5). Eleven failures were isolated to a single compartment; six failures in the spine, four failures in the supratentorium and one failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of two fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not differ from patients treated with photon therapy. Author Disclosure: R. Sethi: None. D. Giantsoudi: None. M. Raiford: None. I. Malhi: None. A. Niemierko: None. O. Rapalino: None. P. Caruso: None. T.I. Yock: None. N.J. Tarbell: K. Advisory Board; Spouse is on medical advisory board of ProCure. NJT was on medical advisory board until 2008. H. Paganetti: None. S. MacDonald: None.
3296 Impact of Molecular Subtype and Craniospinal Irradiation (CSI) Dose on Relapse of Medulloblastoma A. Wang,1 S. Partap,1 K. Yeom1, M. Martinez,2 H. Vogel,1 S. S. Donaldson,1 P. G. Fisher,1 S. Perreault,3 Y.-J. Cho,1 and I. C. Gibbs1; 1 Stanford University/Lucile Packard Children’s Hospital, Stanford, CA,