Local Recurrence Patterns Following Postoperative Stereotactic Radiosurgery to Resected Brain Metastases: A Quantitative Analysis to Guide Target Delineation

OBJECTIVEThe optimal margin size in postoperative stereotactic radiosurgery (SRS) for brain metastases is unknown. Herein, the authors investigated the effect of SRS planning target volume (PTV) margin on local recurrence and symptomatic radiation necrosis postoperatively.METHODSRecords of patients who received postoperative LINAC-based SRS for brain metastases between 2006 and 2016 were reviewed and stratified based on PTV margin size (1.0 or > 1.0 mm). Patients were treated using frameless and framed SRS techniques, and both single-fraction and hypofractionated dosing were used based on lesion size. Kaplan-Meier and cumulative incidence models were used to estimate survival and intracranial outcomes, respectively. Multivariate analyses were also performed.RESULTSA total of 133 patients with 139 cavities were identified; 36 patients (27.1%) and 35 lesions (25.2%) were in the 1.0-mm group, and 97 patients (72.9%) and 104 lesions (74.8%) were in the > 1.0–mm group. Patient characteristics were balanced, except the 1.0-mm cohort had a better Eastern Cooperative Group Performance Status (grade 0: 36.1% vs 19.6%), higher mean number of brain metastases (1.75 vs 1.31), lower prescription isodose line (80% vs 95%), and lower median single fraction–equivalent dose (15.0 vs 17.5 Gy) (all p < 0.05). The median survival and follow-up for all patients were 15.6 months and 17.7 months, respectively. No significant difference in local recurrence was noted between the cohorts. An increased 1-year rate of symptomatic radionecrosis was seen in the larger margin group (20.9% vs 6.0%, p = 0.028). On multivariate analyses, margin size > 1.0 mm was associated with an increased risk for symptomatic radionecrosis (HR 3.07, 95% CI 1.13–8.34; p = 0.028), while multifraction SRS emerged as a protective factor for symptomatic radionecrosis (HR 0.13, 95% CI 0.02–0.76; p = 0.023).CONCLUSIONSExpanding the PTV margin beyond 1.0 mm is not associated with improved local recurrence but appears to increase the risk of symptomatic radionecrosis after postoperative SRS.

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Predicting Local Recurrence of Stereotactic Radiosurgery Brain Metastases Using MRI Radiomics Features

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2018.07.1564 ◽

2018 ◽

Vol 102 (3) ◽

pp. e563-e564 ◽

Cited By ~ 1

Author(s):

H. Wang ◽

D. Barbee ◽

J. Xue ◽

I.J. Das ◽

D. Kondziolka

Keyword(s):

Local Recurrence ◽

Brain Metastases ◽

Stereotactic Radiosurgery

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45. DELAY OR FAILURE TO ADMINISTER STEREOTACTIC RADIOSURGERY TO THE CAVITY AFTER SURGERY FOR BRAIN METASTASES. AN INTENTION-TO-TREAT ANALYSIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.033 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii8-ii9

Author(s):

Diana Roth O’Brien ◽

Sydney Kaye ◽

Phillip Poppas ◽

Sean Mahase ◽

Anjile An ◽

...

Keyword(s):

Local Recurrence ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Systemic Disease ◽

Tumor Diameter ◽

Intention To Treat ◽

Cancer Pathology ◽

Number Of Patients ◽

The Relationship ◽

Treat Analysis

Abstract BACKGROUND Data regarding the efficacy of adjuvant stereotactic radiosurgery (SRS) for resected brain metastases (BM) is often limited to patients completing SRS within a specified timeframe. We performed an intention-to-treat analysis to determine local recurrence (LR) for all BM patients referred for SRS. METHODS We retrospectively identified resected BM patients referred for SRS between 2012 and 2018. Patients were divided based on delay to SRS into four categories: 1) ≤4 weeks, 2) >4–8 weeks, 3) >8 weeks, and 4) never received. We investigated the relationship between delay to SRS and LR, local recurrence-free survival (LRFS), and overall survival, as well as the predictors of and reason for delays. RESULTS In our cohort of 159 patients, median age was 64.0 years, 56.5% patients were female, median tumor diameter was 2.9 cm, and gross total resection was achieved in 83.0%. On intention-to-treat analysis, LR was 22.6%. Delays to SRS correlated with LR: 2.3% with SRS ≤4 weeks postoperatively, 14.5% with SRS at >4–8 weeks (p=0.03), 48.5% with SRS at >8 weeks (p<0.001). No LR difference was observed with SRS delayed by >8 weeks, vs. never completed, 48.5% vs. 50.0% (p=0.91). 53 (33.3%) patients comprised these latter two categories. A similar relationship emerged between delay to SRS and LRFS (p<0.01). Non-small cell lung cancer pathology (p=0.04) and earlier year of treatment (p<0.01) were predictive of delays. Common reasons for delays included logistics, management of systemic disease, complications, or comorbidities. CONCLUSION A significant number of patients referred for SRS never receive it, or are treated with a delay >8 weeks, conferring equivalent LR risk. Accordingly, the actual efficacy of adjuvant SRS may need reassessment. Reasons for delays and mechanisms for reducing them are discussed. For patients likely to experience significant delays, other techniques, such as preoperative SRS or intraoperative brachytherapy, may be considered.

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A case-matched study of stereotactic radiosurgery for patients with multiple brain metastases: comparing treatment results for 1–4 vs ≥ 5 tumors

Journal of Neurosurgery ◽

10.3171/2013.3.jns121900 ◽

2013 ◽

Vol 118 (6) ◽

pp. 1258-1268 ◽

Cited By ~ 41

Author(s):

Masaaki Yamamoto ◽

Takuya Kawabe ◽

Yasunori Sato ◽

Yoshinori Higuchi ◽

Tadashi Nariai ◽

...

Keyword(s):

Local Recurrence ◽

Brain Metastases ◽

Survival Time ◽

Stereotactic Radiosurgery ◽

Median Survival ◽

Median Survival Time ◽

Free Survival ◽

Group A ◽

Group B ◽

Matched Study

Object Although stereotactic radiosurgery (SRS) alone for patients with 4–5 or more tumors is not a standard treatment, a trend for patients with 5 or more tumors to undergo SRS alone is already apparent. The authors' aim in the present study was to reappraise whether SRS results for ≥ 5 tumors differ from those for 1–4 tumors. Methods This institutional review board–approved retrospective cohort study used the authors' database of prospectively accumulated data that included 2553 consecutive patients who underwent SRS, not in combination with concurrent whole-brain radiotherapy, for brain metastases (METs) between 1998 and 2011. These 2553 patients were divided into 2 groups: 1553 with tumor numbers of 1–4 (Group A) and 1000 with ≥ 5 tumors (Group B). Because there was considerable bias in pre-SRS clinical factors between Groups A and B, a case-matched study was conducted. Ultimately, 1096 patients (548 each in Groups A and B) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival and the post-SRS neurological death–free survival times. Competing risk analysis was applied to estimate cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications. Results The post-SRS median survival time was significantly longer in the 548 Group A patients (7.9 months, 95% CI 7.0–8.9 months) than in the 548 Group B patients (7.0 months 95% [CI 6.2–7.8 months], HR 1.176 [95% CI 1.039–1.331], p = 0.01). However, incidences of neurological death were very similar: 10.6% in Group A and 8.2% in Group B (p = 0.21). There was no significant difference between the groups in neurological death–free survival intervals (HR 0.945, 95% CI 0.636–1.394, p = 0.77). Furthermore, competing risk analyses showed that there were no significant differences between the groups in cumulative incidences of local recurrence (HR 0.577, 95% CI 0.312–1.069, p = 0.08), repeat SRS (HR 1.133, 95% CI 0.910–1.409, p = 0.26), neurological deterioration (HR 1.868, 95% CI 0.608–1.240, p = 0.44), and major SRS-related complications (HR 1.105, 95% CI 0.490–2.496, p = 0.81). In the authors' cohort, age ≤ 65 years, female sex, a Karnofsky Performance Scale score ≥ 80%, cumulative tumor volume ≤ 10 cm3, controlled primary cancer, no extracerebral METs, and neurologically asymptomatic status were significant factors favoring longer survival equally in both groups. Conclusions This retrospective study suggests that increased tumor number is an unfavorable factor for longer survival. However, the post-SRS median survival time difference, 0.9 months, between the two groups is not clinically meaningful. Furthermore, patients with 5 or more METs have noninferior results compared to patients with 1–4 tumors, in terms of neurological death, local recurrence, repeat SRS, maintenance of good neurological state, and SRS-related complications. A randomized controlled trial should be conducted to test this hypothesis.

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43. DELAYS IN ADJUVANT STEREOTACTIC RADIOSURGERY REDUCE LOCAL CONTROL FOR RESECTED BRAIN METASTASES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.031 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii8-ii8

Author(s):

Diana Roth O’Brien ◽

Phillip Poppas ◽

Sydney Kaye ◽

Sean Mahase ◽

Anjile An ◽

...

Keyword(s):

Local Recurrence ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Median Time ◽

Distant Recurrence ◽

Consecutive Series ◽

Inclusion Criteria ◽

Free Survival ◽

The Relationship ◽

Local Recurrence Free Survival

Abstract OBJECTIVE For resected brain metastases (BM), stereotactic radiosurgery (SRS) is often offered to minimize local recurrence (LR). Although the aim is to deliver SRS within a few weeks of surgery, a variety of socioeconomic, medical, and procedural issues can cause delays. We evaluated the relationship between timing of postoperative SRS and LR. METHODS We retrospectively identified a consecutive series of BM patients managed with resection and adjuvant SRS, recommended within two weeks of surgery, at our institution from 2012–2018. We assessed the correlation between time to SRS, as well as other demographic, disease, and treatment variables, and LR, distant recurrence (DR), and overall survival (OS). RESULTS 133 patients met inclusion criteria. Median age was 64.5 years. Approximately half of patients had a single BM, and median BM size was 2.9 cm. Gross total resection was achieved in 111 (83.6%) patients, and >90% received fractionated SRS. Median time to adjuvant SRS was 37.0 days and LR rate was 16.4%. The factor most predictive of LR was time from surgery to SRS. Median time from surgery to SRS was 34.0 days for patients without LR, versus 61.0 days for those with LR (p<0.01). LR was 2.3% with SRS administered ≤4 weeks postoperatively, compared to 23.6% if delayed >4 weeks (p<0.01). Local recurrence-free survival (LRFS) was also improved for patients who had SRS at ≤4 weeks (p=0.02). Delayed SRS was also predictive of DR (p=0.02), but not OS. CONCLUSIONS We demonstrate that the strongest predictor of failure of postoperative SRS for BM is the delay to SRS. A cut-off of 4 weeks is a reliable predictor of increased LR. Every effort should be made to perform SRS within 4 weeks of surgery, and if this cannot be achieved, other RT modalities, such as brachytherapy or preoperative SRS, should be strongly considered.

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