High Initial Brain Metastasis Velocity Is Associated With Shorter Brain Progression Free Survival After Stereotactic Radiosurgery For Brain Metastases

Author(s):  
J.W. Ho ◽  
L. Aznar-Garcia
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2022-2022
Author(s):  
Mohammad Khurram Khan ◽  
Tahseen Nasti ◽  
Troy Kleber ◽  
David H. Lawson ◽  
Melinda Lynne Yushak ◽  
...  

2022 Background: The safety and efficacy of concurrent pembrolizumab (anti-PD1) and stereotactic radiosurgery (SRS) for brain metastases (BM) is unknown. Methods: Patients with melanoma or NSCLC, 1-10 brain metastases, ≥ 1 extra-cranial lesion, age ≥ 18, and ECOG 0-1 were treated with anti-PD1 every 3 weeks. SRS was administered 1-2 days after starting anti-PD1. SRS used three different radiation arms: Arm A used 6 Gray (Gy) in 5 fractions (fx), Arm B used 9 Gy in 3 fx, and Arm C used 18-21 Gy in single fx. Primary endpoint was grade 3 CNS toxicity at 3 months (CTCAE v 4.0). Secondary endpoints were overall survival (OS), local control (LC) within the SRS field, intra-cranial progression free survival (IC-PFS), extra-cranial progression free survival (EC-PFS), rate of extra-cranial clinical benefit, and immunological changes. OS, LC, IC-PFS, and EC-PFS were estimated using the Kaplan-Meier method, and covariates were compared using log-rank tests. 95% confidence intervals for 6-month and 12-month were estimated using Greenwood’s formula. Results: 25 patients were treated from 2016 until 2020. The mean age was 61. The mean number of CNS lesions was 2.7. The mean number of extra-cranial lesions was 2.5. Six were enrolled on Arm A, 12 on Arm B, and 7 on Arm C. 21 had melanoma. 4 had NSCLC. Of the melanoma, 8 were BRAF-, 10 were BRAF+, and 3 had unknown mutation status. 12 patients (48%) had progressed on prior immunotherapy and/or other oncological therapies. The trial met its primary endpoint, with no grade 3 CNS toxicity at 3 months. Two patients (8%) experienced ≥ Grade 3 anti-PD1 related toxicity, and no grade 5 toxicity was noted. The median OS was 32.8 months. The 6 and 12 month OS were 79.1% (56.5-90.8%) and 67.8% (43.3-83.5%), respectively. The 1 year OS was similar between previously treated and treatment naïve patients (71.8% vs. 65.6%), suggesting some role for SRS in overcoming therapy resistance. However, with longer follow-up, the OS trended worse (p=0.07) for previously treated patients. LC was 95.7% (72.9-99.4%) at 6 and 12 months. IC-PFS at 6 months was 69.1% (45.8-83.9%), and at 12 months was 57.5% (33.7-75.5%). The EC-PFS at 6 and 12 month was 54.5% (32.1-72.4%) and 43.6% (22.3-63.2%), respectively. Clinical benefit, which was defined as a best overall response of stable disease or better according to RECIST 1.1, occurred in 12 patients (48%). No outcome differences were noted amongst the three different SRS arms. 70% of the patients demonstrating early activation (within 3 weeks of starting SRS/anti-PD1) of CD8+PD1+Ki67+ T cells demonstrated a clinical benefit. 100% of patients that failed to show early activation of CD8+PD1+Ki67+ T cells progressed. Conclusions: Concurrent pembrolizumab (Anti-PD-1) and SRS is safe and effective. Early activation of CD8+PD1+Ki67+ T cells correlates with improved outcome. Further trials testing pembrolizumab and SRS are justified. Clinical trial information: NCT02858869.


2016 ◽  
Vol 34 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Kimberly L. Johung ◽  
Norman Yeh ◽  
Neil B. Desai ◽  
Terence M. Williams ◽  
Tim Lautenschlaeger ◽  
...  

Purpose We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). Conclusion Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.


Author(s):  
Fred Hsu ◽  
Alan Nichol ◽  
Roy Ma ◽  
Para Kouhestani ◽  
Brian Toyota ◽  
...  

AbstractBackground: To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. Methods: We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. Results: For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Conclusions: Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.


Neurosurgery ◽  
2013 ◽  
Vol 73 (6) ◽  
pp. 1001-1006 ◽  
Author(s):  
Neal Luther ◽  
Douglas Kondziolka ◽  
Hideyuki Kano ◽  
Seyed H. Mousavi ◽  
Johnathan A. Engh ◽  
...  

Abstract BACKGROUND: Stereotactic radiosurgery (SRS) to the resection bed of a brain metastasis is an important treatment option. OBJECTIVE: To identify factors associated with tumor progression after SRS of the resection bed of a brain metastasis and to evaluate patterns of failure for patients who eventually had tumor progression. METHODS: We performed a retrospective analysis of 120 patients who underwent tumor bed radiosurgery after an initial gross total resection. The mean imaging follow-up time was 55 weeks. The median margin dose was 16 Gy. Forty-seven patients (39.2%) underwent whole-brain radiation therapy before or shortly after SRS. RESULTS: Local tumor control was achieved in 103 patients (85.8%). Progression-free survival was 96% at 6 months, 87% at 12 months, and 74% at 24 months. Recurrence most commonly occurred deep in the cavity (65%) outside the planned treatment volume (PTV) margin (53%). PTV, cavity diameter, and a margin dose &lt; 16 Gy significantly correlated with local failure. For patients with PTVs ≥ 8.0 cm3, local progression-free survival declined to 93% at 6 months, 83% at 12 months, and 65% at 24 months. Development or progression of distant metastases occurred in 40% of patients. Whole-brain radiation therapy was not associated with improved local control. CONCLUSION: Resection bed SRS for brain metastases provided excellent local control. The cavity PTV is predictive of tumor control. Because failure usually occurs outside the PTV, inclusion of a judicious 2- to 3-mm margin beyond the area of postoperative enhancement may be prudent.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii129-ii129
Author(s):  
Kallol Bhadra ◽  
Omar Al-Salihi ◽  
Sheila Hassan ◽  
Angela Swampillai ◽  
Kirsty Blythe ◽  
...  

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) commenced at Guy’s Cancer Hospital in August 2017. We report our first seventeen months’ data (August 2017 to December 2018) for brain metastases SRS. METHOD Patients referred via Neuro Oncology MDT were assessed for suitability for SRS via clinical review and 1mm-slice MRI. Treatment was planned on Eclipse v15.6 and delivered using Truebeam STx Linac(FFF) and Align RT v5.1 for matching. Dose prescription, according to departmental protocol, was set at 100% isodose, ranging from 18Gy to 25Gy, with fractionation varying from single to five fractions depending on factors including size, volume and locations. Post-treatment, patients were discharged back to their primary treating team for 3-monthly MRI. RESULTS Between Aug-17 to Dec-18, 70 patients with brain metastases were treated with a total of 122 lesions. Mean age was 66 years (range 37-93) and Median follow-up 9 months. Primary tumour sites mainly included lung 34(48.5%), breast 16(22.8%) and melanoma 17(24.3%). Brain-only metastases, including small volume primary with brain metastases were found in 85.4% cases, whilst visceral disease with brain metastases were found in 14.5% patients. Out of 122 lesions, the majority were treated in the primary setting; 95(77.8%) vs 27(22.1%) in the adjuvant setting. At 9-months follow up, local failure rate was in 26(21.3%) sites and 17 new sites in distant brain appeared. 31(44.2%) patients received no systemic therapy after SRS, whilst immunotherapy was received by 14(20%), with the remaining receiving hormones or chemotherapy. Median Overall Survival was 9.2 months (95% CI: 4.5-13.8) and Median progression-free survival was 5.9 months (95% CI: 7.0-10.4). CONCLUSION Overall Survival results were encouraging with initial auditing proving SRS as effective approach. Local control rates correlate well with randomized control trials results for SRS in brain metastases.


2020 ◽  
Vol 10 (2) ◽  
pp. 97-100
Author(s):  
N. V. Sevian ◽  
A. Kh. Bekyashev ◽  
E. V. Prozorenko ◽  
N. A. Kozlov ◽  
D. R. Naskhletashvili ◽  
...  

Esophageal cancer spreads locally via the circulatory and lymphatic systems and can, extremely rarely, form brain metastases. The development of intracranial metastases is a long-term adverse event indicating poor prognosis. In this paper, we present a case of esophageal cancer with a brain metastasis in a patient who received combination therapy and demonstrated long-term progression-free survival.


2014 ◽  
Vol 121 (Suppl_2) ◽  
pp. 26-34 ◽  
Author(s):  
Benjamin Farnia ◽  
K. Ranh Voong ◽  
Paul D. Brown ◽  
Pamela K. Allen ◽  
Nandita Guha-Thakurta ◽  
...  

ObjectThe authors' institution previously reported a 69% rate of crude local control for surgical management of lateral ventricle metastases at the University of Texas MD Anderson Cancer Center. For comparison, the authors here report their institutional experience with use of stereotactic radiosurgery (SRS) to treat intraventricular metastases.MethodsTo identify patients with intraventricular metastases for this retrospective review, the authors queried an institutional SRS database containing the medical records of 1962 patients with 5800 brain metastases who consecutively underwent SRS from June 2009 through October 2013. End points assessed were local control (crude and locoregional), distant failure–free survival, progression-free survival, and overall survival.ResultsOf the 1962 records examined, those for 25 (1.3%) patients with 30 (0.52%) intraventricular metastases were identified. Median patient age at SRS was 55.8 years. The most common primary malignancy was renal cell carcinoma (n = 13), followed by melanoma (n = 7) and breast adenocarcinoma (n = 5). Median tumor volume was 0.75 cm3 (range 0.01–5.6 cm3). Most lesions were located in the lateral ventricles (n = 25, 83.3%) and were treated to a median dose of 20 Gy (range 14–20 Gy). A total of 12 (48%) patients received whole-brain radiation therapy, most (n = 10) before SRS. With a median follow-up of 11.4 months (range 1.6–39.2 months), the rate of crude local control was 93.3%, and the rates of 6-month and 1-year actuarial locoregional control were 85.2% and 56.2%, respectively. The median overall survival time after SRS was 11.6 months (range 1.3–38.9 months), and the 6-month and 1-year actuarial rates were 87.1% and 46.7%, respectively. Disease dissemination developed in 7 (28%) patients as a second intraventricular metastatic lesion (n = 3, 12%), leptomeningeal disease (n = 3, 12%), or both (n = 1, 4%). Radiographic changes developed in 5 (20%) patients and included necrosis (n = 2, 8%) and hemorrhage (n = 3, 12%). A primary diagnosis of renal cell carcinoma was associated with an improved rate of distant failure–free survival (p = 0.05) and progression-free survival (p = 0.08).ConclusionsSRS provides excellent local control for intraventricular metastases, with acceptable treatment-related toxicity, thereby supporting nonsurgical treatment for these lesions. The propensity for intraventricular dissemination among intraventricular metastases seems to be histologically dependent.


Sign in / Sign up

Export Citation Format

Share Document