Initial SRS for Patients With 5 to 15 Brain Metastases: Results of a Multi-Institutional Experience

Hughes, Ryan T.; Masters, Adrianna Henson; McTyre, E.; Farris, Michael; Chung, Caroline; Page, B.R.; Kleinberg, Lawrence; Hepel, Jaroslaw T.; Contessa, Joseph N.; Chiang, Veronica; Ruiz, Jimmy; Watabe, Kounosuke; Su, Jing; Fiveash, John B.; Braunstein, Steve; Chao, Samuel T.; Attia, Albert; Ayala-Peacock, D.N.; Chan, Michael D.

doi:10.1016/j.ijrobp.2019.03.052

Cited by 110 publications

(87 citation statements)

References 22 publications

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“…Although series on BMs are heterogeneous in terms of primary tumors, prognosis, treatments and patients clinical characteristics, outcome in our cohort are similar to the one reported in other studies [22,23].…”

Section: Discussionsupporting

confidence: 81%

Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases

et al. 2020

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Background The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods Ninety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Results After a median follow-up of 11.9 months (range 0.7–29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53% (p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03). Conclusion SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.

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Section: Discussionsupporting

confidence: 81%

Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases

et al. 2020

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“…In patients with > 4 brain lesions, WBRT remains the standard of care although the role of SRS is fast emerging. A prospective observational study and a large retrospective multi-institutional study have shown that the total number of brain metastases (up to 15 lesions) treated with SRS did not seem to affect the survival outcome and could be considered instead of WBRT [ 21 , 22 ]. Despite this, there remains some controversy in giving SRS for multiple brain metastases.…”

Section: Discussionmentioning

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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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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“…However, in single‐isocenter SRS treatment planning, larger separations can be encountered, exceeding 10 cm in a few cases . In addition, up to four targets per patient were studied, despite the fact that the number of lesions considered treatable by SRS has recently increased . Assuming a larger number of metastases per case would result in increased average lesion‐to‐isocenter distances, and tolerance of rotational uncertainties is expected to be much more stringent in such distant targets and adjacent OARs.…”

Section: Discussionmentioning

confidence: 99%

“…Stereotactic radiosurgery (SRS) is a well‐established radiotherapy technique for the treatment of a variety of lesions, mainly in the brain . Regarding the management of multiple brain metastases, SRS is being increasingly employed even in cases with more than 10 lesions . However, increased conformity and presence of steep dose gradients in SRS treatment plans demand increased spatial accuracy in order to ensure effective treatment delivery, as spatial errors of just a few millimeters can induce considerable target underdosage, especially in tiny brain lesions …”

Section: Introductionmentioning

confidence: 99%

Dosimetric impact of rotational errors on the quality of VMAT‐SRS for multiple brain metastases: Comparison between single‐ and two‐isocenter treatment planning techniques

Prentou

Pappas

Logothetis

et al. 2020

J Applied Clin Med Phys

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Purpose In the absence of a 6D couch and/or assuming considerable intrafractional patient motion, rotational errors could affect target coverage and OAR‐sparing especially in multiple metastases VMAT‐SRS cranial cases, which often involve the concurrent irradiation of off‐axis targets. This work aims to study the dosimetric impact of rotational errors in such applications, under a comparative perspective between the single‐ and two‐isocenter treatment techniques. Methods Ten patients (36 metastases) were included in this study. Challenging cases were only considered, with several targets lying in close proximity to OARs. Two multiarc VMAT plans per patient were prepared, involving one and two isocenters, serving as the reference plans. Different degrees of angular offsets at various orientations were introduced, simulating rotational errors. Resulting dose distributions were evaluated and compared using commonly employed dose‐volume and plan quality indices. Results For single‐isocenter plans and 1⁰ rotations, plan quality indices, such as coverage, conformity index and D95%, deteriorated significantly (>5%) for distant targets from the isocenter (at> 4–6 cm). Contrarily, for two‐isocenter plans, target distances to nearest isocenter were always shorter (≤4 cm), and, consequently, 1⁰ errors were well‐tolerated. In the most extreme case considered (2⁰ around all axes) conformity index deteriorated by on‐average 7.2%/cm of distance to isocenter, if one isocenter is used, and 2.6%/cm, for plans involving two isocenters. The effect is, however, strongly associated with target volume. Regarding OARs, for single‐isocenter plans, significant increase (up to 63%) in Dmax and D0.02cc values was observed for any angle of rotation. Plans that could be considered clinically unacceptable were obtained even for the smallest angle considered, although rarer for the two‐isocenter planning approach. Conclusion Limiting the lesion‐to‐isocenter distance to ≤4 cm by introducing additional isocenter(s) appears to partly mitigate severe target underdosage, especially for smaller target sizes. If OAR‐sparing is also a concern, more stringent rotational error tolerances apply.

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Initial SRS for Patients With 5 to 15 Brain Metastases: Results of a Multi-Institutional Experience

Cited by 110 publications

References 22 publications

Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases

Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases

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

Dosimetric impact of rotational errors on the quality of VMAT‐SRS for multiple brain metastases: Comparison between single‐ and two‐isocenter treatment planning techniques

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