Survival and disease control after upfront stereotactic radiosurgery for brain metastases from breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14013-e14013
Author(s):  
Yan Wang ◽  
Ran An ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  

e14013 Background: As systemic therapy for metastatic breast cancer (BC) improves, effective treatment for central nervous system involvement has become a major concern, as 10%‒30% of such patients develop brain metastases (BMs). The survival benefit from hormonal and targeted therapy urges to treat patients with BMs with minimal toxicity and less systemic interruption. Here we assessed survival and disease control in patients who received upfront stereotactic radiosurgery (SRS). Methods: We retrospectively reviewed 236 patients who received upfront SRS with/without surgery for BMs from metastatic BC at a single large-volume cancer center from June 2007 to May 2018. We excluded patients who received SRS for surgical cavity alone. A total of 212 were evaluable, of whom 68 had triple-negative (TN), 66 HR+/HER2-, 46 HR+/HER2+, and 32 HER2+ molecular subtypes. Primary endpoints were overall survival (OS) from BM diagnosis and salvage radiation free survival (SRTFS), which were estimated by Kaplan-Meier survival analysis. Cox proportional hazard regression analysis was used to identify prognostic factors. Results: Median age at BM diagnosis was 52.5 y (range 25.6‒85.4); median Karnofsky Performance Score (KPS) was 90 (range 60‒100); and median number of BMs treated was 2 (range 1‒17). At a median follow-up time of 15.4 months (mo) (range, 0.8–119.6), the estimated median OS was 18.5 mo (95% CI, 14.9–21). Factors associated with OS on multivariate analysis (MVA) were subtype (12.2 mo for TN, 13.3 mo for HR+/HER2-, 36.4 mo for HR+/HER2+, and 28.1 mo for HER2+, p= 0.002), KPS ( p <0.0001), receipt of chemotherapy ( p= 0.016) or anti HER2+ therapy (0.029) after diagnosis of BM, and type of salvage radiation ( p <0.0001). Age, extracranial disease status at BM diagnosis, or receipt of upfront surgery was not associated with OS. OS was also comparable in patients who received upfront SRS to less or more than 4 lesions (19.3 mo for < 4 [n = 162] vs. 17.8 mo for > / = 4 [n = 50], p= 0.36). Of the 106 patients (50%) who received salvage therapy after initial SRS, 42 received salvage SRS, 28 received salvage whole-brain radiation therapy (WBRT), and 36 received both. The 12-month salvage RT rate was 25% for WBRT and 26.4% for SRS. The median SRTFS was 7.4 mo (95% CI, 6.5‒8.3). Factors associated with SRTFS on MVA were subtype ( p= 0.002), KPS ( p= 0.011), and receipt of Hormone therapy after a diagnosis of BM (p = 0.031). Conclusions: Molecular subtypes of HER2+ and HR+/HER2+, good KPS, and receipt of chemotherapy or anti-HER2 therapy predicted better OS for patients who received upfront SRS for BMs from BC. Number of BMs treated by upfront SRS was not associated with OS. Molecular subtype, KPS, and receipt of Hormone therapy were also associated with SRTFS. Prospective studies are needed to clarify the best treatment strategies for the various subgroups of patients with BMs from BC particularly in the era of increasing use of new systemic therapies.

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii21-iii22
Author(s):  
Yan Wang ◽  
Ran An ◽  
Fuchenchu Wang ◽  
Chao Gao ◽  
Akshara Singareeka Raghavendra ◽  
...  

Abstract Background As systemic therapy for metastatic breast cancer (BC) improves, the survival benefit from hormonal and targeted therapy urges treatment of brain metastases (BMs) with minimal toxicity and less systemic therapy interruption. Here we assessed clinical outcomes in BC patients who received upfront stereotactic radiosurgery (SRS). Methods We identified 236 patients who received upfront SRS with/without surgery for BMs from metastatic BC from 06/2007 to 05/2018. Twenty-four patients who received SRS for surgical cavity were excluded for analysis. Overall survival (OS) and salvage radiation-free survival (SRFS) were estimated using Kaplan-Meier analysis. Cox proportional hazard regression was used to identify prognostic factors. Results At a median follow-up time of 15.4 months (range, 0.8–119.6), the estimated median OS was 18.5 mo (95% CI, 14.9–21). Factors associated with OS on multivariate analysis (MVA) were molecular subtypes (12.2 months for triple-negative [n=68], 13.3 months for HR+/HER2- [n=66], 36.4 months for HR+/HER2+ [n=46], and 28.1 months for HER2+ [n=32], p=0.002), KPS &gt;80 (p&lt;0.0001), receipt of chemotherapy (p=0.016) or anti-HER2 therapy (p=0.029) after diagnosis of BM, and type of salvage radiation (p&lt;0.0001). OS was comparable in patients who received upfront SRS to less or more than 4 lesions (19.3 months for &lt;4 [n=162] vs. 17.8 months for &gt;/= 4 [n=50], p=0.36). The 12-month salvage RT rate was 25% for WBRT and 26.4% for SRS. The median SRFS was 7.4 months (95% CI, 6.5‒8.3). Factors associated with SRFS on MVA were subtypes (p=0.002), KPS (p=0.011), and receipt of hormone therapy after diagnosis of BM (p=0.031). Conclusions The median OS for BC patients who developed BM is over 15 months. Molecular subtypes (HER2+ and HR+/HER2+), good KPS, and anti-HER2 or hormone therapy predicted better OS and SRFS. Prospective studies are needed to verify these results and refine the best treatment strategies for these patients.


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 3 (Supplement_3) ◽  
pp. iii21-iii21
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of developing brain metastases (BM). Clinical outcomes and prognostic factors after stereotactic radiosurgery (SRS) for BM were not well defined. Methods We identified 57 consecutive TNBC patients (pts) treated with single fraction SRS for BM during 05/2008–04/2018. Overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS were evaluated. BM progression was defined as local and/or distant brain failure (LBF, DBF) after SRS. Kaplan-Meier analyses and Cox proportional hazard regression were used to estimate survival outcomes and identify prognostic factors. Results The median time to BM development from TNBC diagnosis was 23.7 months (mo) (range 0.7‒271.1). Median OS was 13.1 mo (95%CI 8.0‒19.5). On univariate analysis, Karnofsky performance score (KPS) &gt;70 (p=0.03), number of BMs &lt;3 (p=0.016), and BM among the first metastatic sites (p=0.04) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p=0.03). Of 46 pts with adequate imaging follow-up, 29 (63%) had intracranial progression with a median FFBMP of 7.4 mo (95% CI 5.7–12.7). At 12 mo the estimated cumulative DBF rate was 61.1% (95%CI 40.8%–74.4%) and LBF rate was 17.8% (95%CI 2%–31.1%). Number of BMs (≥3 vs &lt;3) was not associated with FFBMP (p=0.7). Of the 29 pts with BM progression, additional radiation therapy (RT) (vs. no RT) was associated with improved survival (21.7 vs. 7.0 mo, p&lt;0.0001). Conclusions TNBC pts with BM treated with SRS had an OS of 13.1 mo and FFBMP of 7.4 mo. Good KPS was an independent prognostic factor for OS. Further studies with more pts or conducted prospectively are needed to better understand and to improve treatment outcomes in this pt population.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i10-i10
Author(s):  
In Ah Kim ◽  
Kathryn Winter ◽  
David Peereboom ◽  
Paul Sperduto ◽  
Jennifer De Los Santos ◽  
...  

Abstract The addition of trastuzumab to cytotoxic chemotherapy has improved outcomes for patients with HER2 positive breast cancer. Increased survival coupled with limited blood-brain barrier (BBB) penetration of trastuzumab may contribute to the increased incidence of brain metastasis in these patients. Half of these patients die of intracranial disease progression rather than extracranial disease. Therefore, strategies to improve survival must include increased CNS disease control in these patients. Lapatinib crosses the BBB and demonstrates modest activity against intracranial metastases. Based upon preclinical data and results of a phase I study, we hypothesized that lapatinib plus WBRT /SRS can improve the intracranial disease control compared to WBRT / SRS alone. A randomized phase II trial of WBRT (37.5 Gy/3 weeks) or SRS plus or minus concurrent lapatinib (daily 1000 mg for 6 weeks) was initiated. CNS penetrating HER2 targeted therapy is permitted throughout the study, but patients not on trastuzumab, pertuzumab or any other breast cancer therapy at study entry are not permitted to begin this therapy while on protocol treatment, but may begin it 24 hours after completion of protocol treatment. Eligibility includes HER2+ breast cancer with at least one measurable, unirradiated parenchymal brain metastasis. The two populations targeted for accrual include patients with 1) newly diagnosed, multiple brain metastases or 2) progressive brain metastases after stereotactic radiosurgery (SRS) or surgical resection of 1–3 metastases. Prior lapatinib is allowed. Patients are stratified by breast-specific graded prognostic assessment; use of non-CNS penetrating HER2 targeted therapy; and prior SRS or surgical resection. The primary endpoint is complete response rate in the brain 12 weeks after WBRT. Secondary endpoints include objective response rate, lesion-specific response rate, CNS progression-free survival, and overall survival. 140 of 143 target accrual have enrolled (4/22/2019).


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14014-e14014
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  

e14014 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of brain metastases (BM). Outcomes after upfront stereotactic radiosurgery (SRS) for BM from TNBC patients are not well defined. We evaluated outcomes and identified prognostic factors for such patients. Methods: We reviewed 57 consecutive patients treated with upfront SRS for BM from TNBC in May 2008–April 2018 at a large-volume cancer center. Endpoints were overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS. BM progression was defined as local and/or distant brain failure (LBF or DBF) after initial SRS; LBF was radiographic progression of treated lesions, assessed by a neuroradiologist or treating physician excluding post-radiation changes or radiation necrosis. Kaplan-Meier and Cox proportional hazard regression analyses were used to estimate survival outcomes and identify prognostic factors. Results: In this cohort of 57 patients with a median age of 53 y (range 26–82) at BM diagnosis and follow-up time of 12.2 months (mo, range 0.8–97.5), median time to BM development from TNBC diagnosis was 23.7 mo (range 0.7‒271.1). Estimated median OS time from initial BM diagnosis was 13.1 mo (95% CI 8.0‒19.5). In univariate analysis, Karnofsky performance score (KPS) > 70 (p = 0.03), having < 3 BMs (p = 0.016) at BM diagnosis, and BM as first site of metastasis (p = 0.041) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p = 0.03). Of 46 patients with imaging follow-up for FFBMP assessment, 29 (63%) developed BM progression after initial SRS with an estimated median FFBMP of 7.4 mo (95% CI 5.7–12.7). Median times to LBF and DBF were 10 mo (range 0.3–97) and 5.9 mo (range 0.3–90.8). Estimated cumulative LBF rate was 17.8% (95% CI 2%–31.1%) and DBF 61.1% (95% CI 40.8%–74.4%) at 12 mo. Number of BMs at BM diagnosis (≥3 vs < 3) was not associated with FFBMP (p = 0.7). Of the 29 patients with BM progression, 5 did not receive salvage radiation therapy (RT) and 24 received salvage RT (SRS, whole-brain radiation [WBRT], or both SRS+WBRT). Receipt of salvage RT was associated with longer survival (median 21.7 mo vs. 7.0 mo for no salvage RT, p < 0.0001) and did not differ by type of salvage RT (median OS 18.6 mo for WBRT; 26.2 mo for SRS+WBRT; 35.9 mo for SRS, p = 0.08). Conclusions: We reported a median OS of 13.1 mo and FFBMP of 7.4 mo in TNBC patients with good local control. Good KPS was independent prognostic factor for better OS. FFBMP did not differ by number of SRS-treated brain lesions ( < 3 vs ≥3). Further prospective studies of larger numbers of patients needed for more accurate comparisons of treatment types.


2011 ◽  
Vol 114 (3) ◽  
pp. 792-800 ◽  
Author(s):  
Douglas Kondziolka ◽  
Hideyuki Kano ◽  
Gillian L. Harrison ◽  
Huai-che Yang ◽  
Donald N. Liew ◽  
...  

Object To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from breast cancer, the authors assessed clinical outcomes and prognostic factors for survival. Methods The records from 350 consecutive female patients who underwent SRS for 1535 brain metastases from breast cancer were reviewed. The median patient age was 54 years (range 19–84 years), and the median number of tumors per patient was 2 (range 1–18 lesions). One hundred seventeen patients (33%) had a single metastasis to the brain, and 233 patients (67%) had multiple brain metastases. The median tumor volume was 0.7 cm3 (range 0.01–48.9 cm3), and the median total tumor volume for each patient was 4.9 cm3 (range 0.09–74.1 cm3). Results Overall survival after SRS was 69%, 49%, and 26% at 6, 12, and 24 months, respectively, with a median survival of 11.2 months. Factors associated with a longer survival included controlled extracranial disease, a lower recursive partitioning analysis (RPA) class, a higher Karnofsky Performance Scale score, a smaller number of brain metastases, a smaller total tumor volume per patient, the presence of deep cerebral or brainstem metastases, and HER2/neu overexpression. Sustained local tumor control was achieved in 90% of the patients. Factors associated with longer progression-free survival included a better RPA class, fewer brain metastases, a smaller total tumor volume per patient, and a higher tumor margin dose. Symptomatic adverse radiation effects occurred in 6% of patients. Overall, the condition of 82% of patients improved or remained neurologically stable. Conclusions Stereotactic radiosurgery was safe and effective in patients with brain metastases from breast cancer and should be considered for initial treatment.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 638-638
Author(s):  
Muhammet Ali Kaplan ◽  
Abdurrahman Isikdogan ◽  
Dogan Koca ◽  
Mehmet Kucukoner ◽  
Ozge Gumusay ◽  
...  

638 Background: In the present study, we investigate that which treatment choice is more effective in the human epidermal growth factor receptor 2 (HER2) positive breast cancer patients with brain metastases. Methods: Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 111 patients treated with lapatinib or trastuzumab after brain metastases eligible for the analyses were identified. Patients received both drugs consecutively or sequentially were excluded from the study. Results: Median age was 44 years (27-76) and 46 of the 111 patients (41.5%) had received lapatinib. Median time to development of brain metastases was 12.2 months (0-71). Sixteen patients (14.4%) had undergone surgery, 33 (29.7%) radiosurgery, and 108 (97.2%) whole brain radiation therapy (WBRT). Median overall survival (OS) after brain metastases was 15 months(95% confidence interval (CI): 12.3-17.6). Lapatinib usage was prolonged OS over trastuzumab alone (19.1 months vs 12 months, p=0.039).Other parameters affecting the survival were Karnofsky performance score (KPS, >70), number of brain metastases (>3), extracranial metastases (≥2), performed neurosurgery, and received radiosurgery. After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival [Odds ratio (OR), 0.57; p=0.02). Conclusions: Although this retrospective multi-center study had several limitations, study results suggest that the usage of lapatinib after brain metastases prolonged survival compared to the usage of trastuzumab. This result should be support with prospective studies.


2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.


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