1. Feasibility of hippocampal sparing radiation therapy for glioblastoma using helical Tomotherapy
Dr Kamalram THIPPU JAYAPRAKASH1,2,3, Dr Raj JENA1,4 and Mrs Karen WILDSCHUT5
1Department of Oncology, Cambridge University Hospitals, Cambridge, United Kingdom
2Department of Oncology, St Luke’s Cancer Centre, Guildford, United Kingdom, 3Department of Clinical and Experimental Medicine, University of Surrey, Guildford, United Kingdom
4Department of Oncology, University of Cambridge, Cambridge, United Kingdom, 5Department of Radiation Physics, Cambridge University Hospitals, Cambridge, United Kingdom
Purpose/Objective
With improvements in survival for good performance status patients with glioblastoma, some patients will survive to develop significant neurocognitive dysfunction. This retrospective planning study quantifies hippocampal radiation doses in twenty-five patients with glioblastoma receiving radical
chemo-radiation therapy, and evaluates the potential for dose reduction using helical Tomotherapy.
Material and Methods
We identified twenty-five glioblastoma patients treated with Helical IMRT (Tomotherapy HI-ART, Accuray, Sunnyvale CA, USA) with concurrent and adjuvant temozolomide between October 2011 and December 2013 from our radiotherapy electronic database and conducted a retrospective analysis. Hippocampi (HC) were contoured in CT and MRI co-registered image data sets used for clinical radiotherapy planning and hippocampus planning risk volumes (HC-PRV) were created by adding five-millimetre isotropic margin which were checked by a neuro radiologist* (fig 1). Clinical treatment dosimetry plans were overlaid to obtain dose statistics (fig 2). Four selected patients were planned for hippocampus avoidance radiotherapy (HA) without compromising tumour planning target volume (PTV) coverage using currently established hippocampus dose volume histogram (DVH) based constraints$ (figs 3 & 4).
Fig 1 – HC contouring
Fig 2 – DVH dose statistics
Fig 3 – Treatment plan
Fig 4 – HA plan
Results
Mean HC-PRV maximum, minimum and mean radiation doses were 54.7, and Gy respectively (table 1). HC-PRV V7.3, V14.9 and V20 (volumes receiving 7.3, 19.9 and 20 Gy respectively) were 99.95%, 98.41% and 95.72% and hippocampus V3 was 100% (table 2). In seventeen
patients ipsilateral hippocampi were within PTVs and in seven patients both hippocampi were outside PTVs with only minimal overlapping volumes but DVH based dose constraints were not achieved (tables 3 & 4).
Max dose
Min dose
Mean dose
HC-PRV Max dose
66.81
37.80
54.70
HC-PRV Min dose
43.07
6.21
24.15
HC-PRV Ave dose
50.85
20.58
38.62
HC Max dose
60.32
34.16
51.71
HC Min dose
46.13
8.12
28.18
HC Ave dose
49.98
20.98
38.83
Max volume
Min volume
Mean volume
HC-PRV, V 7.3Gy
100
99.15
99.95
HC-PRV, V 14.9Gy
73.59
98.41
HC-PRV, V 20Gy
47.50
95.72
HC, V 3Gy
Max volume
Min volume
Mean volume
HC-PRV in PTV (cc)
10.16
1.55
HC-PRV, V 7.3Gy (%)
100
HC-PRV, V 14.9Gy (%)
HC-PRV, V 20Gy (%)
95.55
99.74
HC, V 3Gy (%)
Max volume
Min volume
Mean volume
HC-PRV in PTV (cc)
20.19
9.34
Rt HC-PRV in PTV (cc)
19.14
5.36
Lt HC-PRV in PTV (cc)
10.11
3.93
HC-PRV, V 7.3Gy (%)
100
99.15
99.81
HC-PRV, V 14.9Gy (%)
73.59
94.55
HC-PRV, V 20Gy (%)
47.50
85.98
HC, V 3Gy (%)
HC & HC-PRV doses
DVH constraints analysis
Volumetric analysis
Volumetric analysis
With hippocampus avoidance radiotherapy planning, in four patients HC-PRV minimum doses and in three patients mean HC-PRV doses were reduced and significant reductions in DVH based dose constraints were achieved in three patients when compared to clinical treatment plans (table 5).
Location
Right frontal
Right temporal
Left parietal
Posterior fossa
Group
Treatment HA
HC-PRV max dose
53.17
51.88
51.28
45.33
56.88
55.91
52.63
61.02
HC-PRV min dose
14.96
2.27
12.4
2.85
31.63
4.11
25.34
6.28
HC-PRV mean dose
33.39
9.09 28
6.71
43.09
15.55
42.79
37.79
V 7.3Gy
100
58.7
29.17
67.43
99.29
V 14.9Gy
25.51
98.24 16
38.91
91.4
V 20Gy
16.22 82
12.12
28.68 80
Conclusion
Our analysis showed hippocampus PRVs received significant radiation doses and currently established hippocampus DVH parameters were not achieved during cranial radiotherapy for glioblastoma using Helical IMRT without hippocampus avoidance planning. Our planning study demonstrated significant dose reductions were possible with hippocampus avoidance radiotherapy planning in selected patients. More clinically correlated DVH objectives for hippocampus are required for better optimisation for hippocampus avoidance cranial radiotherapy in glioblastoma for this to be considered for all patients.
*Hippocampal-Sparing Whole Brain Radiotherapy: A “How-To” Technique, Utilizing Helical Tomotherapy and LINAC-based Intensity Modulated Radiotherapy; Int J Radiation Oncol Biol Phys, Vol. 78, Issue 4, 1244–1252, 2010
$Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors; Int J Radiation Oncol Biol Phys, Vol. 85, No. 2, , 2013
$Preservation of Memory With Conformal Avoidance of the Hippocampal Neural Stem-Cell Compartment During Whole-Brain Radiotherapy for Brain Metastases (RTOG 0933); A Phase II Multi-Institutional Trial; JCO, Vol. 32, No , 2014
Contact:
Key words; glioblastoma, hippocampus avoidance radiotherapy, neurocognitive function