ESTRO 2020 Abstract Book

S42 ESTRO 2020

Verbal Learning Test (HVLT) – a test of verbal learning and memory. A second aim was to elucidate relationships between RT dose to the whole brain, thalamus, left, right, and total hippocampus, temporal and frontal lobes, and neurocognitive function based on a priori hypothesized structure-function relationships. Material and Methods Neurocognitive function was assessed cross-sectionally in 78 progression-free patients with a primary brain tumour grade I-III or medulloblastoma treated with RT between 2007 and 2016. RT was administered in 1.8-2.0 Gy per fraction with total doses ranging from 45-60 Gy. Doses were converted to biologically equivalent doses in 2 Gy fractions (EQD 2 ) assuming an α/β ratio of 3 Gy. Dose Volume Histograms were generated for the delineated structures. Neurocognitive function was assessed a median of 4.6 years after completion of RT with a battery of 7 neuropsychological tests covering multiple neurocognitive domains. Results were converted to z-scores using available normative data adjusted for age and, when available, level of education. Domain-specific impairment was defined as a z-score ≤ -1.5 standard deviation (SD). Results To examine the effect of doses to various brain structures and their function, mean EDQ 2 to the structure and test z- scores as a binary outcome variables were fitted to a logistic regression model. A p-value < 0.05 was considered significant. Domain-specific neurocognitive impairment was evident in the entire group of patients. High mean EQD 2 to the left hippocampus was associated with verbal learning and memory impairment (p=0.04). High mean EQD 2 to the left hippocampus (p=0.03), left temporal lobe (p=0.04), left frontal lobe (p<0.01), and total frontal lobe (p=0.02) were associated with verbal fluency impairment (figure 1). High mean EQD 2 to left frontal lobe (p=0.01) and thalamus (p=0.03) were associated with impairment in executive function (p=0.01). High mean EQD 2 to the total brain (p=0.05) and thalamus (p=0.02) were associated with processing speed impairment. Conclusion The present study finds associations between impaired performance in verbal learning and memory, verbal fluency, executive function and processing speed, in patients who had received RT to left hippocampus and temporal lobe, left frontal lobe, thalamus and the total brain. Validation of these findings is being undertaken in a prospective study that will include pre-treatment neurocognitive assessment. OC-0093 Hippocampus-avoidance whole-brain irradiation with dose escalation on multiple brain metastases I. Popp 1 , S. Rau 1 , M. Hintz 1 , J. Schneider 1 , A. Bilger 1 , J.T. Fennell 1 , D.H. Heiland 2 , T. Rothe 1 , K. Egger 3 , C. Nieder 4,5 , H. Urbach 3 , A.L. Grosu 1,6 1 University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany ; 2 Medical Center - University of Freiburg, Department of Neurosurgery, Freiburg im Breisgau, Germany ; 3 Medical Center - University of Freiburg, Department of Neuroradiology, Freiburg im Breisgau, Germany ; 4 Nordland Hospital, Department of Oncology and Palliative Medicine, Bodø, Germany ; 5 Faculty of Health Sciences- University of Tromsø, Department of Clinical Medicine, Tromsø, Norway ; 6 German Cancer Consortium DKTK- German Cancer Research Center DKFZ- Heidelberg- Germany, Partner Site Freiburg, Freiburg im Breisgau, Germany Purpose or Objective Whole brain radiation therapy (WBRT) is the standard treatment for multiple brain metastases. However, WBRT ensures a relatively poor local tumor control and can lead to a significant neurocognitive decline. The aim of the current study was to investigate the efficacy of a

hippocampus-avoidance WBRT with simultaneous integrated boost on the metastases (HA-WBRT+SIB) in patients with multiple cerebral metastases. Material and Methods Between May 2012 and December 2016, 66 patients were prospectively enrolled and treated with HA-WBRT+SIB analog to the constraints of the experimental arm of the HIPPORAD trial protocol (DRKS00004598). The HA- WBRT+SIB was performed with 30 Gy in 12 fractions and D98% in hippocampus ≤ 9 Gy, D2% ≤ 17 Gy. A SIB (51/42 Gy) was applied on metastases (2-16) and/or resection cavities (0-2). The 66 patients were further analyzed regarding survival, tumor control, occurrence of metastases in the HA-area, and toxicity. After 1:1 propensity score matching analysis, 62 HA-WBRT patients and 62 additional patients having received conventional whole-brain irradiation (WBRT, mostly 10x3 Gy) were selected and compared. Results Median follow-up time was 44.1 months (3.7 years) in the HA-WBRT+SIB group and was not reached in the WBRT group. The local tumor control of existing metastases was significantly higher in the HA-WBRT+SIB group (96% vs. 77% at 1 year, p=.004). At the last follow-up, from a total of 380 boosted lesions in the HA-WBRT+SIB cohort, 103 (27.6%) had a complete remission, 153 (40.3%) a partial remission, 47 (12.4%) were stable and 11 (2.9%) were progressive. The distant intracranial tumor control was significantly higher in the WBRT group (68% vs. 81% at 1 year, p=.016), corresponding to higher applied biologically effective doses (60.6 Gy vs. 42.1 Gy and 42.1 Gy vs. 37.5 Gy). Intracranial progression-free (12.8 vs. 5.8 months, p=.02) and overall survival (9 vs. 4.9 months, p=.0003) were significantly better in the HA-WBRT+SIB cohort. Five patients (7.6%) developed hippocampal or perihippocampal metastases after HA. The acute toxicity profile of HA-WBRT+SIB proved acceptable and derived primarily from the SIB. Serious adverse events within the first year of follow-up were comparable in type and frequency (6.1%) to those following radiosurgery alone. The neurologic death rate after HA-WBRT+SIB was 27.4%. Conclusion HA-WBRT with SIB is a safe and effective therapeutic option for patients with multiple brain metastases and shows improved local tumor control of existing metastases and overall intracranial progression-free survival compared to WBRT alone. The potential to avoid neurocognitive side effects is being further explored in the multicenter phase II HIPPORAD trial. OC-0094 Patterns of Failure in Pediatric Medulloblastoma and Implications for Hippocampal Sparing S. Baliga 1 , B. Bajaj 2 , L. Vanbenthuysen 2 , J. Adams 2 , S. Gallotto 2 , E.A. Weyman 2 , M.P. Lawell 2 , N.J. Tarbell 2 , S.M. MacDonald 2 , T.I. Yock 2 1 The Ohio State University Comprehensive Cancer Center, Radiation Oncology, Columbus, USA ; 2 Massachusetts General Hospital/Harvard Medical School, Radiation Oncology, Boston, USA Purpose or Objective Hippocampal Sparing (HS) has been associated with preservation of memory in adult patients with brain metastases. This approach has not yet been prospectively evaluated in the pediatric population due to concerns of increased disease relapse in the peri-hippocampal region. We aim to determine the patterns of local, distant, and peri-hippocampal failures in a cohort of patients treated with proton beam therapy (PBT) for pediatric We performed a retrospective review and identified patients with histologically confirmed standard-risk (SR) or high-risk (HR) MB, who were treated with PBT at the Massachusetts General Hospital from January 2000- medulloblastoma (MB). Material and Methods

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