scholarly journals Brain radionecrosis in the present multiagent systemic therapy era: Time to redefine brain radiotherapy tolerance?

2020 ◽  
Vol 3 (2) ◽  
pp. 413 ◽  
Author(s):  
Anusheel Munshi
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.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 479-479
Author(s):  
Ajay Goud ◽  
Kara DeWalt ◽  
Courtney Carmichael ◽  
JoAnn Hsu ◽  
Manasvi Pinnamaneni ◽  
...  

479 Background: With improvements in systemic therapy for metastatic RCC (mRCC), an increased frequency of brain metastases (BM) has been observed, perhaps owing to the central nervous system (CNS) serving as a sanctuary site. The response of BM to VEGF-directed therapies has been poorly characterized. Methods: Patients (pts) with mRCC BM were identified from an institutional database. Selection of pts was further refined to pts who had received either VEGF-directed therapy during their diagnosis with BM or radiotherapy directed to their BM. Only those pts with brain MRI straddling systemic therapy and radiotherapy were selected for analysis. Imaging studies were anonymized and transmitted to an independent radiologist for review. Descriptive statistics were applied to characterize the change in sum of long axis dimensions (SLD) in two separate groups: (1) pts treated with VEGF-directed therapy and (2) pts treated with radiotherapy. Results: Of 276 pts with mRCC in our institutional database, 34 pts with BM were identified. Of these pts, 6 pts had serial MRI assessments at timepoints straddling receipt of VEGF-directed therapy. Pts had received sunitinib (n=2), sorafenib (n=2) or bevacizumab (n=2). A further 13 pts received radiotherapy with MRI imaging straddling delivery of either stereotactic radiation therapy (SRT) and whole brain radiotherapy (WBRT). Of these 19 patients, all patients had clear cell histology, and 13 patients were male. In pts receiving VEGF-directed agents, the average change in SLD of BM was -13.8%. In pts receiving radiotherapy, the average change in SLD was -6.5% (-13.0% in pts receiving SRT and +2.0% in pts receiving WBRT). Qualitatively, greater tumor necrosis and lesser rim enhancement was observed in post-treatment scans amongst pts receiving VEGF-directed agents. Conclusions: This pilot study suggested differences in CNS response with VEGF-directed therapy and radiotherapy. Multicenter collaborations are underway to validate these results in larger series.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi58-vi58
Author(s):  
Alan Nichol ◽  
Srinivas Raman ◽  
Benjamin Mou ◽  
Fred Hsu ◽  
Boris Valev ◽  
...  

Abstract BACKGROUND The clinical advantage of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in patients with brain metastases and poor prognosis is controversial. To investigate the feasibility of a phase III clinical trial in a population of patients with poor prognosis, we conducted a randomized feasibility study of WBRT versus SRS. METHODS Patients with Karnofsky performance status (KPS) ≥ 70, life expectancy of 3–6 months, based on both Diagnosis-Specific Graded Prognostic Assessments and attending oncologist opinion, and 1– 10 brain metastases with a diameter ≤ 4 cm were enrolled at six Canadian cancer centers. Patients were randomly assigned to WBRT (20 Gy in 5 fractions) or SRS (15 Gy in 1 fraction). The primary endpoint was the rate of accrual. A secondary endpoint was the ratio of screened subjects to accrued subjects. This trial is registered with ClinicalTrials.gov (NCT02220491). RESULTS Between January 2015 and November 2017, 210 were screened to enroll 22 patients (9.5 screened/participant) and 20 patients were randomized. The accrual rate was 0.63 patients / month. The most common reasons for exclusion were: estimated median survival outside 3–6 months (n = 40), baseline KPS below 70 (n = 28), and > 10 brain metastases (n = 28). The median survival was 7.0 months. The overall survival was 9.5 months (n = 11) for patients who had subsequent systemic therapy, compared to 3.7 months (n = 9) in patients who had none. In both arms, the cumulative incidence of retreatment with brain radiotherapy was 40%. CONCLUSIONS Accrual was slow and the median survival was longer than expected, but a randomized trial evaluating WBRT vs SRS in patients with poor prognosis would likely be feasible by enrolling only patients with no remaining systemic therapy options.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jana Schaule ◽  
Stephanie G. C. Kroeze ◽  
Oliver Blanck ◽  
Susanne Stera ◽  
Klaus H. Kahl ◽  
...  

Abstract Background Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). Methods This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS. Results One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0–40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03). Conclusion The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.


2020 ◽  
Vol 28 (11) ◽  
pp. 5363-5369 ◽  
Author(s):  
Jiheon Song ◽  
Rajiv Samant ◽  
Mohammad Jay ◽  
Hina Chaudry ◽  
Xin Yan Fan ◽  
...  

2006 ◽  
Vol 37 (10) ◽  
pp. 36-37
Author(s):  
NANCY WALSH
Keyword(s):  

1999 ◽  
Vol 56 (6) ◽  
pp. 330-333
Author(s):  
Dummer ◽  
Nestle ◽  
Hofbauer ◽  
Burg

Das metastasierende Melanom (MM) gehört zu den schwierig behandelbaren Malignomen, wobei Allgemeinzustand und Motivation des Patienten neben Zahl und Lokalisation der Metastasen das therapeutische Vorgehen bestimmen. Solitäre Metastasen in Lunge, ZNS, Weichteilen und Lymphknoten sollten primär chirurgisch entfernt werden. Multiple Metastasen, insbesondere abdominal, werden nur in Ausnahmefällen chirurgisch angegangen. Hier ist vielmehr ein systemische Chemoimmuntherapie angebracht. Aussichtsreiche Behandlungskonzepte beinhalten Interleukin-2, Interferon, und verschiedenen Zytostatika wie DTIC, Temozolamid, Vindesine oder Cisplatin. Bei ZNS- und Skelettfiliae ist die Radiotherapie einzusetzen. Durch diese Chemoimmuntherapien hat sich die Prognose des metastasierenden Melanoms bezüglich des Überlebens verbessert. Langfristig wird aber nur eine Kombination von zeitraubenden Multicenterstudien und experimentellen Ansätzen in der Lage sein, uns langsam an eine kurative Therapie heranzuführen.


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