Dose specification for hippocampal sparing whole brain radiotherapy (HS WBRT): considerations from the UK HIPPO trial QA programme

Abstract

Objective: The HIPPO trial is a UK randomized Phase II trial of hippocampal sparing (HS) vs conventional wholebrain radiotherapy after surgical resection or radiosurgery in patients with favourable prognosis with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS intensity-modulated radiotherapy (IMRT) in a multicentre trial setting. Methods: Submitted planning benchmark cases were reviewed using visualization for radiotherapy software (VODCA) evaluating plan quality and compliance in relation to the HIPPO radiotherapy planning and delivery guidelines. Results: Comparison of the planning benchmark data highlighted a plan specified using dose to medium as an outlier by comparison with those specified using dose to water. Further evaluation identified that the reported plan statistics for dose to medium were lower as a result of the dose calculated at regions of PTV inclusive of bony cranium being lower relative to brain. Conclusion: Specification of dose to water or medium remains a source of potential ambiguity and it is essential that as part of a multicentre trial, consideration is given to reported differences, particularly in the presence of bone. Evaluation of planning benchmark data as part of an RTQA programme has highlighted an important feature of HS IMRT dosimetry dependent on dose being specified to water or medium, informing the development and undertaking of HS IMRT as part of the HIPPO trial. Advances in knowledge: The potential clinical impact of differences between dose to medium and dose to water are demonstrated for the first time, in the setting of HS whole-brain radiotherapy.

Improving on whole-brain radiotherapy in patients with large brain metastases: A planning study to support the AROMA clinical trial

“…Normal brain volumes were defined as whole brain volume with the subtraction of the GTV. Dose constraints followed the general constraints presented in Supplement Table 1 [28][29][30], and in particular, we constrained V24.4 to be less than 10 cm 3 of normal brain to limit the predicted risk of radionecrosis to 5% for fivefraction radiation [31]. We considered dose constraints on all OARs prior to the dose on PTVs.…”

“…All HS-WBRT plans were planned using VMAT based on a monoisocentric technique with two coplanar 360°-arcs of Truebeam Linac 6MV flattened beam. Hippocampal avoidance regions were developed with a geometrical isotropic expansion of 5 mm to the hippocampus [29,30] unless there was a lesion within 5 mm of a hippocampus, in which case we only spared the contralateral hippocampus. We prescribed 20 Gy in 5 fractions to the whole brain with 3 mm expansion, sparing the hippocampal avoidance regions (Fig.…”

“…All the models had to meet the requirement that 98% of the target volumes were irradiated with at least 20 Gy as mandatory without an upper dose limit within the target volumes. We followed a combination of guidance from the UK Consensus guidance for stereotactic radiotherapy, HyTEC reports, AAPM report and the HIPPO phase 2 RCT protocol to set dose constraints on the OARs [28,[30][31][32]; where an OAR had differing dose constraints in two sets of guidance, we took the more conservative (lower) dose limit. All VMAT plans used a mono-isocenter technique with two coplanar 360°-arcs.…”

A new dose quantity for evaluation and optimisation of MV photon dose distributions when using advanced algorithms: proof of concept and potential applications

“…The use of D w,m * can also be helpful in multi-centre activities, such as clinical trials, audits, benchmarking, and shared models for automation. In these environments, several dose reporting modes can coexist and consistency is crucial for the significance and robustness of the results (Megias et al 2017, Palmer et al 2017, Lehmann et al 2018, Lee et al 2019, Panettieri et al 2019. Sometimes, one dose quantity is imposed on all centres, but this is not the case in most situations.…”

The Effect of Hippocampal Avoidance Whole Brain Radiotherapy on the Preservation of Long-Term Neurocognitive Function in Non-Small Cell Lung Cancer Patients With Brain Metastasis

“…HIPPO hypothesized that irradiation of the bilateral hippocampi may cause part of the adverse neurocognitive effect from WBRT, and reducing dosage to the hippocampi may help preserve NCF. 8 HA-WBRT may delay onset, or reduce severity of NCF decline without decreased intracranial disease control, therefore it improves outcome of the patients. 9 Previous studies revealed that cells of the hippocampus were highly sensitive to radiation even at low doses.…”