Recursive Partitioning Analysis of Systemic Therapy after Radiotherapy in Patients with Brain Metastases

2021 ◽  
pp. 1-6
Author(s):  
Carsten Nieder ◽  
Astrid Dalhaug ◽  
Ellinor Haukland
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Group Performance ◽  
Recursive Partitioning ◽  
Local Treatment ◽  
Eastern Cooperative Oncology Group ◽  
Recursive Partitioning Analysis ◽  
Endocrine Treatment ◽  
Brain Irradiation ◽  
Extracranial Disease

<b><i>Purpose:</i></b> The purpose of this study was to identify factors associated with the initiation or continuation of systemic treatment after brain irradiation. The outcome of interest was a utilization rate of at least 75%, given that active extracranial disease is common in patients with brain metastases. If left untreated, extracranial disease limits survival, regardless of successful local treatment of the brain metastases. In this context, systemic therapy has been shown to improve survival, e.g., after whole-brain radiotherapy. <b><i>Patients and Methods:</i></b> The study included 185 patients with active extracranial disease, 60% of whom received systemic therapy. <b><i>Results:</i></b> Survival from the start of brain irradiation was longest in patients who received additional immune checkpoint inhibitors, endocrine treatment, or anti-HER-2 drugs. After uni- and multivariate analyses, Eastern Cooperative Oncology Group performance status (PS) was selected as the first prediction criterion in the recursive partitioning analysis (RPA) decision tree analysis. RPA was successful for patients with PS 0–1, but patients with PS 2 had lower treatment utilization rates (maximum 60–70%, with a disease-dependent impact of age and LabBM score [blood test results]). The highest utilization rates were observed in (1) patients with PS 0 and (2) those with breast cancer, small-cell lung cancer, or lung adenocarcinoma with PS 1. <b><i>Conclusions:</i></b> These results inform the multidisciplinary discussion and treatment planning for the common scenario of simultaneous intra- and extracranial metastases.

New Era in the Management of Melanoma Brain Metastases

2018 ◽  
pp. 741-750 ◽  
Author(s):  
Hussein A. Tawbi ◽  
Celine Boutros ◽  
David Kok ◽  
Caroline Robert ◽  
Grant McArthur
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Single Agent ◽  
Local Treatment ◽  
New Era ◽  
Therapeutic Modalities ◽  
Melanoma Brain Metastases ◽  
Extracranial Disease ◽  
Induce Response ◽  
The Impact

The remarkable advances in the systemic therapy of metastatic melanoma have now extended the 1-year overall survival rate from 25% to nearing 85%. Systemic treatment in the form of BRAF-targeted therapy and immunotherapy is slowly but surely proving its efficacy in the treatment of metatstatic brain metastases (MBM). Single-agent BRAF inhibitors provide an intracranial response rate of 25% to 40%, whereas the combination of BRAFi/MEKi leads to responses in up to 58%. However, the durability of responses induced by BRAFi/MEKi seems to be even shorter than in extracranial disease. On the other hand, single-agent ipilimumab provides comparable clinical benefit in MBMs as it does in extracranial metastases. Single-agent PD-1 anitbodies induce response rates of approximately 20%, and those responses appear durable. Similarly the combination of CTLA-4+ PD-1 antibodies induces durable responses at an impressive rate of 55% and is safe to administer. Although the local treatment approaches with radiation and surgery remain important and are critically needed in the management of MBM, systemic therapy offers a new dimension that can augment the impact of those therapies and come at a potentially lower cost of neurocognitive impairment. Considerations for combining those modalities are direly needed, in addition to considering novel systemic combinations that target mechanisms specific to MBM. In this report, we will discuss the underlying biology of melanoma brain metastases, the clinical outcomes from recent clinical trials of targeted and immunotherapy, and their impact on clinical practice in the context of existing local therapeutic modalities.

scholarly journals Outcomes of changing systemic therapy in patients with relapsed breast cancer and 1 to 3 brain metastases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Omar Alhalabi ◽  
Zaid Soomro ◽  
Ryan Sun ◽  
Elshad Hasanov ◽  
Aya Albittar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Extracranial Disease ◽  
Initiation Of Therapy ◽  
The Impact

AbstractThe development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) following the diagnosis and management of oligometastatic (1–3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52–1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40–1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.

scholarly journals RADT-09. TYPE AND TIMING OF SYSTEMIC THERAPY USE PREDICT SURVIVAL IN PATIENTS WITH BRAIN METASTASES TREATED WITH RADIATION THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii183-ii183
Author(s):  
Kevin Fan ◽  
Nafisha Lalani ◽  
Nathalie Levasseur ◽  
Andra Krauze ◽  
Lovedeep Gondara ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Performance Status ◽  
Population Based ◽  
The Novel ◽  
Brain Radiotherapy ◽  
Prognostic Assessment ◽  
Baseline Variable ◽  
Extracranial Disease

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&lt; 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&lt; 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.

scholarly journals Does Graded Prognostic Assessment outperform Recursive Partitioning Analysis in patients with moderate prognosis brain metastases?

CNS Oncology ◽  
2016 ◽  
Vol 5 (2) ◽  
pp. 69-76 ◽  
Author(s):  
Neil C Estabrook ◽  
Stephen T Lutz ◽  
Cynthia S Johnson ◽  
Simon S Lo ◽  
Mark A Henderson
Keyword(s):  
Brain Metastases ◽  
Recursive Partitioning ◽  
Recursive Partitioning Analysis ◽  
Prognostic Assessment ◽  
Graded Prognostic Assessment

scholarly journals Factors influencing the outcome of stereotactic radiosurgery in patients with five or more brain metastases

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
E. Hamel-Perreault ◽  
D. Mathieu ◽  
L. Masson-Cote
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Nonsmall Cell Lung Cancer ◽  
Factors Influencing ◽  
Treatment Volume ◽  
Extracranial Disease

Background Stereotactic radiosurgery (srs) for patients with 5 or more brain metastases (bmets) is a matter of debate. We report our results with that approach and the factors influencing outcome.Methods In the 103 patients who underwent srs for the treatment of 5 or more bmets, primary histology was nonsmall- cell lung cancer (57% of patients). All patients were grouped by Karnofsky performance status and recursive partitioning analysis (rpa) classification. In our cohort, 72% of patients had uncontrolled extracranial disease, and 28% had stable or responding systemic disease. Previous irradiation for 1–4 bmets had been given to 56 patients (54%). The mean number of treated bmets was 7 (range: 5–19), and the median cumulative bmets volume was 2 cm3 (range: 0.06–28 cm3).Results Multivariate analyses showed that stable extracranial disease (p < 0.001) and rpa (p = 0.022) were independent prognostic factors for overall survival (os). Moreover, a cumulative treated bmets volume of less than 6 cm3 (adjusted hazard ratio: 2.54; p = 0.006; 95% confidence interval: 1.30 to 4.99) was associated with better os. The total number of bmets had no effect on survival (p = 0.206). No variable was found to be predictive of local control. The rpa was significant (p = 0.027) in terms of distant recurrence.Conclusions Our study suggests that srs is a reasonable option for the management of patients with 5 or more bmets, especially with a cumulative treatment volume of less than 6 cm3.

Brain metastases, survival and recursive partitioning analysis (RPA) our experience

2013 ◽  
Vol 18 ◽  
pp. S89
Author(s):  
J. Peña Vivas ◽  
C. Fuentes Sanchez ◽  
J. Martínez Cedres ◽  
S. Villamil Montufar ◽  
E. Garcia
Keyword(s):  
Brain Metastases ◽  
Recursive Partitioning ◽  
Recursive Partitioning Analysis
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