Hippocampus‐avoidance whole‐brain radiation therapy with a simultaneous integrated boost for multiple brain metastases

Popp, Ilinca; Rau, Shane W.; Hintz, Mandy; Schneider, J.; Bilger, Angelika; Fennell, Jamina Tara; Heiland, Dieter Henrik; Rothe, Thomás; Egger, Karl; Nieder, Carsten; Urbach, Horst; Grosu, Anca L.

doi:10.1002/cncr.32787

Cited by 51 publications

(45 citation statements)

References 37 publications

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“…Several studies have shown that higher doses to target lesions could improve on local control rates and potentially reduce intracranial failure [ 9 , 20 , 23 ]. In turn, improving intracranial control could possibly result in improved performance status and reduced neurological death [ 8 , 9 , 12 ]. It would thus seem reasonable to consider giving tumours a simultaneous higher dose during HA-WBRT using HA-SIB-WBRT.…”

Section: Discussionmentioning

confidence: 99%

“…The reported intracranial PFS was noted to be as high as 13.5 months with few ≥Grade 3 toxicities (≤6.5%), making it a potentially viable option. In a propensity score-matched comparison against WBRT, Popp et al reported significantly improved local tumour control rates, intracranial PFS, reduction in neurological deaths and even better OS [ 12 ]. This has led the group to continue to a phase II HIPPORAD Trial comparing HA-WBRT+SIB against WBRT+SIB (German Clinical Trials Registry: DRKS00004598) [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Randomised prospective phase II trial in multiple brain metastases comparing outcomes between hippocampal avoidance whole brain radiotherapy with or without simultaneous integrated boost: HA-SIB-WBRT study protocol

et al. 2020

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Background Recent evidence supports hippocampal avoidance with whole brain radiotherapy (HA-WBRT) as the recommended treatment option in patients with good prognosis and multiple brain metastases as this results in better neurocognitive preservation compared to whole brain radiotherapy. However, there is often poor tumour control with this technique due to the low doses given. Stereotactic Radiosurgery (SRS), a form of focused radiotherapy which is given to patients who have a limited number of brain metastases, delivers a higher radiation dose to the metastases resulting in better target lesion control. With improvements in radiation technology, advanced dose-painting techniques now allow a simultaneous integrated boost (SIB) dose to lesions whilst minimising doses to the hippocampus to potentially improve brain tumour control and preserve cognitive outcomes. This technique is abbreviated to HA-SIB-WBRT or HA-WBRT+SIB. Methods We hypothesise that the SIB in HA-SIB-WBRT (experimental arm) will result in better tumour control compared to HA-WBRT (control arm). This may also lead to better intracranial disease control as well as functional and survival outcomes. We aim to conduct a prospective randomised phase II trial in patients who have good performance status, multiple brain metastases (4–25 lesions) and a reasonable life expectancy (> 6 months). These patients will be stratified according to the number of brain metastases and randomised between the 2 arms. We aim for a recruitment of 100 patients from a single centre over a period of 2 years. Our primary endpoint is target lesion control. These patients will be followed up over the following year and data on imaging, toxicity, quality of life, activities of daily living and cognitive measurements will be collected at set time points. The results will then be compared across the 2 arms and analysed. Discussion Patients with brain metastases are living longer. Maintaining functional independence and intracranial disease control is thus increasingly important. Improving radiotherapy treatment techniques could provide better control and survival outcomes whilst maintaining quality of life, cognition and functional capacity. This trial will assess the benefits and possible toxicities of giving a SIB to HA-WBRT. Trial registration Clinicaltrials.gov identifier: NCT04452084. Date of registration 30th June 2020.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Randomised prospective phase II trial in multiple brain metastases comparing outcomes between hippocampal avoidance whole brain radiotherapy with or without simultaneous integrated boost: HA-SIB-WBRT study protocol

et al. 2020

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“…One criticism of typical WBRT is poor local control of existing brain metastases after 30 Gy. A recent single-arm feasibility study investigated the utility of a simultaneous integrated boost (SIB) technique with WBRT [ 21 ]. The investigators prescribed 30 Gy in 12 fractions to the brain and simultaneously boosted metastases and resection cavities to 42 or 51 Gy.…”

Section: Discussionmentioning

confidence: 99%

Automated contouring and planning pipeline for hippocampal-avoidant whole-brain radiotherapy

et al. 2020

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Background Whole-brain radiotherapy (WBRT) remains an important treatment for over 200,000 cancer patients in the United States annually. Hippocampal-avoidant WBRT (HA-WBRT) reduces neurocognitive toxicity compared to standard WBRT, but HA-WBRT contouring and planning are more complex and time-consuming than standard WBRT. We designed and evaluated a workflow using commercially available artificial intelligence tools for automated hippocampal segmentation and treatment planning to efficiently generate clinically acceptable HA-WBRT radiotherapy plans. Methods We retrospectively identified 100 consecutive adult patients treated for brain metastases outside the hippocampal region. Each patient’s T1 post-contrast brain MRI was processed using NeuroQuant, an FDA-approved software that provides segmentations of brain structures in less than 8 min. Automated hippocampal segmentations were reviewed for accuracy, then converted to files compatible with a commercial treatment planning system, where hippocampal avoidance regions and planning target volumes (PTV) were generated. Other organs-at-risk (OARs) were previously contoured per clinical routine. A RapidPlan knowledge-based planning routine was applied for a prescription of 30 Gy in 10 fractions using volumetric modulated arc therapy (VMAT) delivery. Plans were evaluated based on NRG CC001 dose-volume objectives (Brown et al. in J Clin Oncol, 2020). Results Of the 100 cases, 99 (99%) had acceptable automated hippocampi segmentations without manual intervention. Knowledge-based planning was applied to all cases; the median processing time was 9 min 59 s (range 6:53–13:31). All plans met per-protocol dose-volume objectives for PTV per the NRG CC001 protocol. For comparison, only 65.5% of plans on NRG CC001 met PTV goals per protocol, with 26.1% within acceptable variation. In this study, 43 plans (43%) met OAR constraints, and the remaining 57 (57%) were within acceptable variation, compared to 42.5% and 48.3% on NRG CC001, respectively. No plans in this study had unacceptable dose to OARs, compared to 0.8% of manually generated plans from NRG CC001. 8.4% of plans from NRG CC001 were not scored or unable to be evaluated. Conclusions An automated pipeline harnessing the efficiency of commercially available artificial intelligence tools can generate clinically acceptable VMAT HA-WBRT plans with minimal manual intervention. This process could improve clinical efficiency for a treatment established to improve patient outcomes over standard WBRT.

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“…Hopefully the open question regarding the role of hippocampal avoidance in PCI will be settled by ongoing trials ( Table 2). Another option that may improve both local and distant brain control could be adding a simultaneous integrated boost with WBRT, although recent trials have excluded SCLC [47]. ICIs with CNS efficacy either alone or in combination with RT were also discussed, although existing data is mainly from preclinical and NSCLC studies and ongoing SCLC trials are limited ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

Stereotactic radiosurgery (SRS) – A new normal for small cell lung cancer?

Pereira

Slotman²,

Rusthoven

et al. 2020

Clinical and Translational Radiation Oncology

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Hippocampus‐avoidance whole‐brain radiation therapy with a simultaneous integrated boost for multiple brain metastases

Cited by 51 publications

References 37 publications

Randomised prospective phase II trial in multiple brain metastases comparing outcomes between hippocampal avoidance whole brain radiotherapy with or without simultaneous integrated boost: HA-SIB-WBRT study protocol

Randomised prospective phase II trial in multiple brain metastases comparing outcomes between hippocampal avoidance whole brain radiotherapy with or without simultaneous integrated boost: HA-SIB-WBRT study protocol

Automated contouring and planning pipeline for hippocampal-avoidant whole-brain radiotherapy

Stereotactic radiosurgery (SRS) – A new normal for small cell lung cancer?

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