PMID- 28937324 OWN - NLM STAT- MEDLINE DCOM- 20191010 LR - 20220317 IS - 1933-0693 (Electronic) IS - 0022-3085 (Linking) VI - 129 IP - 2 DP - 2018 Aug TI - Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases >/= 2 cm. PG - 366-382 LID - 2017.3.JNS162532 [pii] LID - 10.3171/2017.3.JNS162532 [doi] AB - OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases >/= 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases >/= 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases >/= 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm(3) (range 2.4-31.3 cm(3)) and 7.0 cm(3) (range 1.0-29.7 cm(3)). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm(3) (range 0.1-23.1 cm(3)). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% +/- 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% +/- 7% and 49% +/- 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases >/= 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS. FAU - Angelov, Lilyana AU - Angelov L AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. AD - 2Department of Neurosurgery, Neurological Institute. FAU - Mohammadi, Alireza M AU - Mohammadi AM AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. AD - 2Department of Neurosurgery, Neurological Institute. FAU - Bennett, Elizabeth E AU - Bennett EE AD - 2Department of Neurosurgery, Neurological Institute. FAU - Abbassy, Mahmoud AU - Abbassy M AD - 4Department of Neurosurgery, Alexandria University, Alexandria, Egypt. FAU - Elson, Paul AU - Elson P AD - 3Quantitative Health Sciences, Taussig Cancer Institute, and. FAU - Chao, Samuel T AU - Chao ST AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. AD - 5Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; and. FAU - Montgomery, Joshua S AU - Montgomery JS AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. FAU - Habboub, Ghaith AU - Habboub G AD - 2Department of Neurosurgery, Neurological Institute. FAU - Vogelbaum, Michael A AU - Vogelbaum MA AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. AD - 2Department of Neurosurgery, Neurological Institute. FAU - Suh, John H AU - Suh JH AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. AD - 5Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; and. FAU - Murphy, Erin S AU - Murphy ES AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. AD - 5Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; and. FAU - Ahluwalia, Manmeet S AU - Ahluwalia MS AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. FAU - Nagel, Sean J AU - Nagel SJ AD - 2Department of Neurosurgery, Neurological Institute. FAU - Barnett, Gene H AU - Barnett GH AD - 1Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute. AD - 2Department of Neurosurgery, Neurological Institute. LA - eng PT - Journal Article DEP - 20170922 PL - United States TA - J Neurosurg JT - Journal of neurosurgery JID - 0253357 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Brain Neoplasms/mortality/*pathology/*radiotherapy/secondary MH - Female MH - Humans MH - Male MH - Middle Aged MH - Radiosurgery/*methods MH - Retrospective Studies MH - Survival Rate MH - Treatment Outcome MH - Tumor Burden MH - Young Adult OTO - NOTNLM OT - 2-SSRS OT - 2-SSRS = 2-staged stereotactic radiosurgery OT - 2-staged radiosurgery OT - AE = adverse effect OT - BED = biologically effective dose OT - CTCAE = Common Terminology Criteria for Adverse Events OT - FSRS = fractionated stereotactic radiosurgery OT - GPA = graded prognostic assessment OT - Gamma Knife OT - KPS = Karnofsky Performance Scale OT - LBM = large brain metastases OT - LC = local control OT - MLD = maximum linear dimension OT - OS = overall survival OT - RN = radiation necrosis OT - RPA = recursive partitioning analysis OT - SRS = stereotactic radiosurgery OT - SSRS = staged stereotactic radiosurgery OT - TTP = time to local progression OT - WBRT = whole-brain radiation therapy OT - hypo-FSRS = hypofractionated stereotactic radiosurgery OT - hypofractionated radiosurgery OT - large brain metastasis OT - local control OT - oncology OT - radiation necrosis OT - radiosurgery OT - stereotactic radiosurgery EDAT- 2017/09/25 06:00 MHDA- 2019/10/11 06:00 CRDT- 2017/09/23 06:00 PHST- 2017/09/25 06:00 [pubmed] PHST- 2019/10/11 06:00 [medline] PHST- 2017/09/23 06:00 [entrez] AID - 2017.3.JNS162532 [pii] AID - 10.3171/2017.3.JNS162532 [doi] PST - ppublish SO - J Neurosurg. 2018 Aug;129(2):366-382. doi: 10.3171/2017.3.JNS162532. Epub 2017 Sep 22.