scholarly journals Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy

2022 ◽  
Vol 11 ◽  
Author(s):  
Aidan M. Burke ◽  
Michael Carrasquilla ◽  
Walter C. Jean ◽  
Brian T. Collins ◽  
Amjad N. Anaizi ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Outcomes ◽  
Tumor Volume ◽  
Cytotoxic T Lymphocyte ◽  
Increased Risk ◽  
Historical Series ◽  
Melanoma Brain Metastases ◽  
Median Volume ◽  
Cell Death Protein

Purpose/ObjectivesClinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes.Materials and MethodsPatients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated.ResultsTwenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated.ConclusionsIn our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery ◽  
2018 ◽  
Vol 85 (2) ◽  
pp. 257-263 ◽  
Author(s):  
Ryan T Hughes ◽  
Emory R McTyre ◽  
Michael LeCompte ◽  
Christina K Cramer ◽  
Michael T Munley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Outcomes ◽  
Whole Brain Radiotherapy ◽  
Cox Proportional Hazards ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Increased Risk

Abstract BACKGROUND The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial. OBJECTIVE To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group. METHODS A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox proportional hazards. RESULTS Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respectively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume parameters predicted for death, neurologic death or toxicity. CONCLUSION SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

scholarly journals (OA15) Clinical Outcomes of Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immunotherapy

2018 ◽  
Vol 101 (2) ◽  
pp. e7 ◽  
Author(s):  
Aidan M. Burke ◽  
Michael Carrasquilla ◽  
Eshetu Tefera ◽  
Walter C. Jean ◽  
Brian T. Collins ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Outcomes ◽  
Melanoma Brain Metastases

scholarly journals Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

2018 ◽  
Vol 129 (2) ◽  
pp. 366-382 ◽  
Author(s):  
Lilyana Angelov ◽  
Alireza M. Mohammadi ◽  
Elizabeth E. Bennett ◽  
Mahmoud Abbassy ◽  
Paul Elson ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Binary Data ◽  
Tumor Volume ◽  
Demographic Data ◽  
Maximum Diameter ◽  
Local Progression ◽  
Imaging Results ◽  
Increased Risk

OBJECTIVEStereotactic 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.METHODSFifty-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.RESULTSAmong 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 cm3 (range 2.4–31.3 cm3) and 7.0 cm3 (range 1.0–29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1–23.1 cm3). 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.CONCLUSIONS2-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.

scholarly journals Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity

2018 ◽  
Vol 139 (2) ◽  
pp. 421-429 ◽  
Author(s):  
Kevin Diao ◽  
Shelly X. Bian ◽  
David M. Routman ◽  
Cheng Yu ◽  
Jason C. Ye ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Outcomes ◽  
Melanoma Brain Metastases

Hemorrhagic and Cystic Brain Metastases Are Associated With an Increased Risk of Leptomeningeal Dissemination After Surgical Resection and Adjuvant Stereotactic Radiosurgery

Neurosurgery ◽  
2018 ◽  
Vol 85 (5) ◽  
pp. 632-641 ◽  
Author(s):  
Robert H Press ◽  
Chao Zhang ◽  
Mudit Chowdhary ◽  
Roshan S Prabhu ◽  
Matthew J Ferris ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Cumulative Incidence ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Competing Risk ◽  
Leptomeningeal Dissemination ◽  
Increased Risk

Abstract BACKGROUND Brain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection. OBJECTIVE To investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD. METHODS One hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method. RESULTS Median imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, P = .015), cystic features (HR 2.34, P = .013), breast histology (HR 3.23, P = .016), and number of brain metastases >1 (HR 2.09, P = .032) were independently associated with increased risk of LMD. CONCLUSION Hemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk.

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