Systemic Therapy for Brain Metastases: Melanoma

2020 ◽  
pp. 235-244
Author(s):  
Sarah Weiss ◽  
Harriet Kluger
2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii183-ii183
Author(s):  
Kevin Fan ◽  
Nafisha Lalani ◽  
Nathalie Levasseur ◽  
Andra Krauze ◽  
Lovedeep Gondara ◽  
...  

Abstract PURPOSE We aimed to investigate whether systemic therapy (ST) use around the time of brain radiotherapy (RT) predicts overall survival for patients with brain metastases (BM). We also aimed to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) in a population-based cohort. METHODS We used provincial RT and pharmacy databases to retrospectively review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016. We used a randomly selected subset with complete baseline data to develop a multivariate analysis (MVA)-based nomogram including ST use to predict survival after RT and to validate the DS-GPA. RESULTS In our 3095-patient cohort, the median overall survival (OS) of the 999 recipients of ST after RT was 5.0 months (CI 4.1-6.0) longer than the OS of the 2096 non-recipients of ST after RT (p< 0.0001): targeted therapy (HR 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55) and cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79). The OS of patients who discontinued ST after RT was 0.9 months (CI 0.3-1.4) shorter than the OS of those who did not receive ST before nor after RT (p< 0.0001). A MVA in the 200-patient subset demonstrated that the traditional baseline variables: cancer diagnosis, age, performance status, presence of extracranial disease, and number of BMs predicted survival, as did the novel variables: ST use before RT and ST use after RT. The MVA-based nomogram had a bootstrap-corrected Harrell’s Concordance Index of 0.70. In the 179 patients within this subset with DS-GPA-compatible diagnoses, the DS-GPA overestimated OS by 6.3 months (CI 5.3- 9.8) (p= 0.0006). CONCLUSIONS The type and timing of ST use around RT predict survival for patients with BMs. A novel baseline variable “ST planned after RT” should be prospectively collected to validate these findings in other cohorts.


2021 ◽  
Vol 22 (12) ◽  
Author(s):  
Alessia Pellerino ◽  
Francesco Bruno ◽  
Roberta Rudà ◽  
Riccardo Soffietti

2020 ◽  
pp. 1421-1454
Author(s):  
Kim Margolin ◽  
Michael Davies ◽  
Harriet Kluger ◽  
Hussein Tawbi

Author(s):  
John B. Fiveash ◽  
Anatoly Nikolaev ◽  
Robert M. Conry

2021 ◽  
pp. 1-11
Author(s):  
Dennis London ◽  
Dev N. Patel ◽  
Bernadine Donahue ◽  
Ralph E. Navarro ◽  
Jason Gurewitz ◽  
...  

OBJECTIVE Patients with non–small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33–3.81, p = 2.5 × 10−3; HR 2.51, 95% CI 1.45–4.34, p = 9.8 × 10−4, respectively). CONCLUSIONS The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.


2015 ◽  
Vol 26 (5) ◽  
pp. 579-581 ◽  
Author(s):  
Elisabeth S. Bergen ◽  
Anna S. Berghoff ◽  
Margaretha Rudas ◽  
Matthias Preusser ◽  
Rupert Bartsch

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i31-i31
Author(s):  
Dhiego Bastos ◽  
Ganesh Rao ◽  
Isabella Glitza ◽  
Jonathan Loree ◽  
Jeffrey S Weinberg2 ◽  
...  

Abstract BACKGROUND: LITT has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS. Objectives: Evaluate the predictive factors associated with local recurrence after LITT. METHODS: Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence. RESULTS: 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence and 31 radiation necrosis). Freedom from local recurrence at 6 months was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 months. Incompletely ablated lesions had a shorter median time for local recurrence (p< 0.001). Larger lesions (>6cc) had shorter time for local recurrence (p=0.03). Dural based lesions showed a shorter time to local recurrence (p=0.01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (p=0.01). Patients receiving systemic therapy after LITT had longer time to local recurrence (p=0.01). In multivariate Cox-regression model the HR for incomplete ablated lesions was 4.88 (p< 0.001), 3.12 (p=0.03) for recurrent tumors, and 2.56 (p=0.02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%. CONCLUSIONS: Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.


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