Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery

Johnson, Matthew H.; Avkshtol, Vladimir; Baschnagel, Andrew M.; Meyer, K.; Ye, Hong; Grills, I.S.; Chen, Peter Y.; Maitz, Ann; Olson, Rick E.; Pieper, Daniel R.; Krauss, Daniel

doi:10.1016/j.ijrobp.2015.11.022

Cited by 107 publications

(45 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neither did we find a difference in the incidence of LMD between the study arms, but this study was underpowered to determine the effect of post-surgical SRS on LMD development. In a recent study, LMD adjacent to the surgical cavity after radiosurgical treatment was reported to be as high as 16.9%, a potential risk of local radiation that should be evaluated in future studies 15 . A predictor of freedom from DBM was an initial presentation with only one brain metastasis, suggesting that patients with multiple metastases on presentation were at higher risk for DBM.…”

Section: Discussionmentioning

confidence: 99%

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial

Mahajan

Ahmed

McAleer

et al. 2017

The Lancet Oncology

560

400

View full text Add to dashboard Cite

SUMMARYBackgroundAfter brain metastasis resection, whole-brain radiation therapy (WBRT) decreases local recurrence but may cause cognitive decline. We performed this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved local tumor tumor-free recurrence rates compared to surgical resection alone as an alternative to the need for immediate WBRT.MethodsThe main entry criteria for the study included patients >3 years of age, with a Karnofsky Performance Score ≥ 70, who were able to undergo an MRI scan and who had a complete resection of 1–3 brain metastases (the maximum diameter of the resection cavity had to be ≤4cm). Patients were assigned randomly to either SRS treatment of the resection cavity (within 30 days of surgery) or observation (OBS). Patients were stratified by histology, tumor size, and number of metastases. Patients were recruited at a single tertiary cancer center. The primary endpoint was time to local recurrence in the resection cavity assessed by blinded central review of brain MRI scans in the intention-to-treat population. The trial was registered at clinicaltrials.gov (Trial NCT00950001, status: closed to new participants).FindingsBetween 8/13/2009 and 2/16/2016, 132 patients were randomized to OBS (N=68) or SRS (N=64), with 128 patients available for analysis. We stratified by metastasis size (maximum diameter of ≥3 cm vs. <3 cm), histology (melanoma vs. other), and number of metastases (one vs. two or three). The 12-month local tumor recurrence-free rate was 43% (OBS) (95% CI 31%–59%) and 72% (SRS) (95% CI 60%–87%) (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.24–0.88, p=0.015).InterpretationThis prospective randomized trial of patients undergoing surgical resection for 1–3 brain metastases indicates that SRS administered to the resection cavity significantly lowers local recurrence compared to observation alone. Thus, the use of SRS after brain metastasis resection is an alternative to WBRT.

show abstract

Section: Discussionmentioning

confidence: 99%

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial

Mahajan

Ahmed

McAleer

et al. 2017

The Lancet Oncology

560

400

View full text Add to dashboard Cite

show abstract

“…Leptomeningeal disease was diagnosed by imaging results consistent with this condition (either local or diffuse leptomeningeal disease) or by examination of spinal fluid positive for malignant cells. 9 …”

Section: Methodsmentioning

confidence: 99%

Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial

Brown

Ballman

Cerhan

et al. 2017

The Lancet Oncology

879

656

View full text Add to dashboard Cite

Summary Background Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. Methods In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12–20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. Findings Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1–18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45–5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86–3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35–0·63]; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference −33·6% [95% CI −45·3 to −21·8], p<0·00031). Median overall survival was 12·2 months (95% CI 9·7–16·0, 69 deaths) for SRS and 11·6 months (9·9–18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76–1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. Interpretation Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative...

show abstract

“…A possible advantage of WBRT over HFRT in the post operative setting is the risk of leptomeningeal disease. The rate of leptomeningeal spread to meninges and cerebrospinal fluid in patients treated with WBRT is 5–12% ( 65 , 66 ) vs. 14–28% ( 66 , 67 ).…”

Section: Post Operative Treatment Of Large Cavitiesmentioning

confidence: 99%

Hypofractionated Radiation Therapy for Large Brain Metastases

Masucci

2018

Front. Oncol.

View full text Add to dashboard Cite

Single fraction radiosurgery (SRS) treatment is an effective and recognized alternative to whole brain radiation for brain metastasis. However, SRS is not always possible, especially in tumors of a larger diameter where the administration of high dose in a single fraction is limited by the possibility of acute and late side effects and the dose to the surrounding organs at risk. Hypofractionated radiation therapy allows the delivery of high doses of radiation per fraction while minimizing adverse events, all the while maintaining good local control of lesions. The optimal dose fractionation has however not been established. This overwiew presents available evidence and rationale supporting usage of hypofractionated radiation therapy in the treatment of large brain metastases.

show abstract

Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery

Cited by 107 publications

References 22 publications

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial

Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial

Hypofractionated Radiation Therapy for Large Brain Metastases

Contact Info

Product

Resources

About