Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases—Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept

Shafie, Rami A El; Tonndorf-Martini, Eric; Schmitt, Daniela; Weber, Dorothea; Celik, Aylin; Dresel, Thorsten; Bernhardt, Denise; Lang, Kristin; Hoegen, Philipp; Adeberg, Sebastian; Paul, Angela; Debus, Jürgen; Rieken, Stefan

doi:10.3390/cancers11030294

Cited by 27 publications

(18 citation statements)

References 47 publications

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“…Target volume delineation and treatment planning for SRT were based on high-resolution contrast-enhanced computed tomography (CT), as well as magnetic resonance imaging (MRI) scans and carried out as previously described. 27 , 28 Employed safety margins depended on treatment technique and ranged between 1 mm for CyberKnife and 2-3 mm for LINAC-based radiosurgery. The target volume for post-operative SRT encompassed the resection cavity with a safety margin of 3-4 mm.…”

Section: Methodsmentioning

confidence: 99%

Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer

et al. 2021

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Background The improved efficacy of tyrosine kinase inhibitors (TKI) mandates reappraisal of local therapy (LT) for brain metastases (BM) of oncogene-driven non-small-cell lung cancer (NSCLC). Patients and methods This study included all epidermal growth factor receptor-mutated (EGFR + , n = 108) and anaplastic lymphoma kinase-rearranged (ALK + , n = 33) TKI-naive NSCLC patients diagnosed with BM in the Thoraxklinik Heidelberg between 2009 and 2019. Eighty-seven patients (62%) received early LT, while 54 (38%) received delayed ( n = 34; 24%) or no LT ( n = 20; 14%). LT comprised stereotactic (SRT; n = 40; 34%) or whole-brain radiotherapy (WBRT; n = 77; 66%), while neurosurgical resection was carried out in 19 cases. Results Median overall survival (OS) was 49.1 months for ALK + and 19.5 months for EGFR + patients ( P = 0.001), with similar median intracranial progression-free survival (icPFS) (15.7 versus 14.0 months, respectively; P = 0.80). Despite the larger and more symptomatic BM ( P < 0.001) of patients undergoing early LT, these experienced longer icPFS [hazard ratio (HR) 0.52; P = 0.024], but not OS (HR 1.63; P = 0.12), regardless of the radiotherapy technique (SRT versus WBRT) and number of lesions. High-risk oncogene variants, i.e. non-del19 EGFR mutations and ‘short’ EML4-ALK fusions (mainly variant 3, E6:A20), were associated with earlier intracranial progression (HR 2.97; P = 0.001). The longer icPFS with early LT was also evident in separate analyses of the EGFR + and ALK + subsets. Conclusions Despite preferential use for cases with poor prognostic factors, early LT prolongs the icPFS, but not OS, in TKI-treated EGFR + /ALK + NSCLC. Considering the lack of survival benefit, and the neurocognitive effects of WBRT, patients presenting with polytopic BM may benefit from delaying radiotherapy, or from radiosurgery of multiple or selected lesions. For SRT candidates, the improved tumor control with earlier radiotherapy should be weighed against the potential toxicity and the enhanced intracranial activity of newer TKI. High-risk EGFR / ALK variants are associated with earlier intracranial failure and identify patients who could benefit from more aggressive management.

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Section: Methodsmentioning

confidence: 99%

Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer

et al. 2021

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“…The potential advantages of pre-operative SRS are as follows: (1) tumor is easy to identify and contour; (2) expansion margin is not required for target delineation uncertainty; (3) dose is often reduced by 20% given better oxygenation of intact tumor and planned surgery; and (4) there is potentially a reduction in leptomeningeal disease (LMD) risk following surgery [ 37 ]. When treating intact brain metastases with planned pre-operative SRS, the expansion margin is typically 0–1 mm with no utilization of volumetric expansion (i.e., GTV = PTV) being most commonly employed [ 37 , 49 , 54 ]. The lack of PTV margin and radiation dose reduction with planned pre-operative SRS reduces the volume of healthy brain tissue receiving 10–12 Gy, which are volumes that have been associated with increased RN [ 10 , 27 , 29 , 37 , 49 , 55 , 56 ].…”

Section: Optimal Approach For Utilizing Surgery and Srsmentioning

confidence: 99%

The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases

Gutschenritter

Venur²,

Combs³

et al. 2020

Cancers

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Brain metastases are the most common intracranial malignant tumor in adults and are a cause of significant morbidity and mortality for cancer patients. Large brain metastases, defined as tumors with a maximum dimension >2 cm, present a unique clinical challenge for the delivery of stereotactic radiosurgery (SRS) as patients often present with neurologic symptoms that require expeditious treatment that must also be balanced against the potential consequences of surgery and radiation therapy—namely, leptomeningeal disease (LMD) and radionecrosis (RN). Hypofractionated stereotactic radiotherapy (HSRT) and pre-operative SRS have emerged as novel treatment techniques to help improve local control rates and reduce rates of RN and LMD for this patient population commonly managed with post-operative SRS. Recent literature suggests that pre-operative SRS can potentially half the risk of LMD compared to post-operative SRS and that HSRT can improve risk of RN to less than 10% while improving local control when meeting the appropriate goals for biologically effective dose (BED) and dose-volume constraints. We recommend a 3- or 5-fraction regimen in lieu of SRS delivering 15 Gy or less for large metastases or resection cavities. We provide a table comparing the BED of commonly used SRS and HSRT regimens, and provide an algorithm to help guide the management of these challenging clinical scenarios.

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“…Improved systemic cancer treatment has resulted in prolonged survival of patients with brain metastases, thereby demanding long-term local control after the treatment course is completed. The brain metastases are usually delineated by referring to contrast-enhanced 3D T1-weighted (CE-3D-T1W) MRI, which is subsequently co-registered to the planning CT [1]. Recently, the importance of contrast-enhanced 3D fluid-attenuated inversion recovery (CE-3D-FLAIR) MRI was demonstrated in various intracranial pathological disorders by comparing with CE-3D-T1W [2,3].…”

Section: Introductionmentioning

confidence: 99%

A New Tumor Delineation Method for Brain Metastases Radiotherapy by Jointly Referring to Contrast-Enhanced T1-Weighted and Fluid-Attenuated Inversion Recovery MRI

Soyama

Azumi

2020

Cureus

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A new tumor delineation technique for brain metastases has been proposed by jointly referring to thin-slice contrast-enhanced T1-weighted and thin-slice contrast-enhanced fluidattenuated inversion recovery magnetic resonance (MR) images. A single-isocenter six-arc noncoplanar volumetric modulated arc radiotherapy (VMAT) plan for 16 brain metastases was created by the Monaco treatment planning system (Elekta AB, Stockholm, Sweden) with a photon energy of 6 MV. Each gross target volume (GTV) was very carefully delineated on all three orthogonal planes of the above two different MR images. A dose of 37.5 Gy was prescribed to 96% of the whole brain in 15 fractions with a simultaneous integrated boost (SIB) dose of 57 Gy to 95% of each of the eight GTVs each having a volume larger than 0.05 cm 3 and another SIB dose of 52.5 Gy to 90% of each of the remaining eight smaller GTVs. For accurate tumor localization, an in-house thermoplastic mask was developed by modifying a commercial thermoplastic shell, in such a way that a portion of the thermoplastic shell was pushed into a patient mouth so that the patient can bite it with the lips and the teeth. The outer cylinder of a syringe was additionally pushed into the resulting mouthpiece portion, thereby providing an air duct for easier mouth breathing. Immediately before the VMAT delivery, bone matching was performed between planning CT and on-board cone-beam CT images; thereafter, a sixdegrees-of-freedom couch was activated to correct the translational and rotational setup errors. The treatment time per fraction was approximately 30 minutes including the couch rotations.

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Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases—Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept

Cited by 27 publications

References 47 publications

Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer

Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer

The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases

A New Tumor Delineation Method for Brain Metastases Radiotherapy by Jointly Referring to Contrast-Enhanced T1-Weighted and Fluid-Attenuated Inversion Recovery MRI

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