scholarly journals 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

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Brendan Seng Hup Chia ◽  
Jing Yun Leong ◽  
Ashley Li Kuan Ong ◽  
Cindy Lim ◽  
Shi Hui Poon ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Target Lesion ◽  
Whole Brain ◽  
Tumour Control ◽  
Multiple Brain Metastases ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance ◽  
Integrated Boost

Abstract 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.

scholarly journals RTHP-26. DOSIMETRIC FEASIBILITY STUDY USING HIPPOCAMPAL AVOIDANCE WITH SIMULTANEOUS INTEGRATED BOOST WHOLE BRAIN RADIOTHERAPY (HA-SIB-WBRT)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi215-vi215 ◽  
Author(s):  
Brendan Seng Hup Chia ◽  
Ashley Li Kuan Ong ◽  
Zubin Master
Keyword(s):  
Brain Metastases ◽  
Brain Mri ◽  
Whole Brain Radiotherapy ◽  
Good Prognosis ◽  
Simultaneous Integrated Boost ◽  
Conformity Index ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance ◽  
Integrated Boost

Abstract BACKGROUND Recently Hippocampal Avoidance (HA-) WBRT has become a recommended treatment option in patients with multiple (≥ 5) brain metastases and good prognosis. We wanted to investigate the dosimetric feasibility of dose painting technique combining HA-WBRT with a simultaneous integrated boost (SIB) to tumours. METHOD 5 patients who had a CT simulation fused with brain MRI with fine cuts, were selected for this study. Volumes were contoured on T1w contrast images. Whole brain prescription dose was 30Gy in 12 fractions. A PTV margin of 2mm was applied to lesions, except when these were ≤5mm from organs at risks (OARs). A simultaneous integrated boost (SIB) of 48Gy and 40.2Gy was prescribed to these volumes respectively. Hippocampal constraints followed RTOG 0933 protocol. For lesions ≤5mm from OARs, the acceptable D0.03cc≤42Gy was allowed. All plans were planned on EclipseTM v.13.6 TPS using 6MV photons, VMAT technique with 3 coplanar and 1 non-coplanar arcs for Varian TrueBeam machine. RESULTS Plans had between 6–24 lesions with GTV and PTV of 3.02–11.32cc and 7.05–31.74cc respectively. 3 of the plans had lesions within/adjacent to brainstem or hippocampus. The achieved PTV_40.2Gy D95% 37.42–39.05Gy with Conformity Index (CI)(95%) 0.63–1.06, PTV_48Gy D95% 44.64–47.04Gy with CI(95%) 0.75–0.97 and GTV_48Gy D95% 47.44–50.16Gy. Whole brain Dmean 31.87–33.15Gy with a Homogeneity Index (D2%-D98%/Dmean) 0.18–0.58. Hippocampal D100% 8.69–10.1Gy, D0.03cc 16.5–40.43Gy and Dmean 12.66–24.68Gy. SUMMARY: There was a steep learning curve when adopting this technique and multiple plan iterations were made to achieve target constraints. To meet acceptable OAR constraints, SIB coverage was compromised. Lesions ≤5mm from hippocampus resulted in higher Hippocampal average Dmean 22.8Gy vs. 12.8Gy. The significance of this value should be tested in clinical trials. Overall, HA-SIB-WBRT seems feasible even with ≥ 5 brain metastases and could result in better brain metastases control then HA-WBRT alone.

scholarly journals A Dutch phase III randomized multicenter trial: whole brain radiotherapy vs. stereotactic radiotherapy for 4-10 brain metastases

2021 ◽  
Author(s):  
Dianne Hartgerink ◽  
Anna Bruynzeel ◽  
Danielle Eekers ◽  
Ans Swinnen ◽  
Coen Hurkmans ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Brain Metastases ◽  
Survival Rates ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
One Year

Abstract Background The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods Patients with 4 to 10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at three months post-treatment. Results The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range, 4-9) and the median total treatment volume was 13.0 cc 3 (range, 1.8-25.9 cc 3). QOL at three months decreased in the SRS group by 0.1 (SD=0.2), compared to 0.2 (SD=0.2) in the WBRT group (p=0.23). The actuarial one-year survival rates were 57% (SRS) and 31% (WBRT) (p=0.52). The actuarial one-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (p=0.22). Conclusion In patients with 4 to 10 BM, SRS alone resulted in one-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

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