P14.29 The treatment of melanoma brain metastases with stereotactic radiosurgery concurrently with immune checkpoint inhibition is associated with improved extracranial disease control and overall survival compared to the overall metastatic melanoma cohort - a synergistic effect reaching beyond local control?

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii43-ii44
Author(s):  
P S Webb ◽  
M Zorman ◽  
R Watson ◽  
M Payne ◽  
N Coupe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Disease Control ◽  
Metastatic Melanoma ◽  
Local Control ◽  
Group Versus ◽  
Rank Test ◽  
Control Group ◽  
Extracranial Disease

Abstract BACKGROUND Melanoma brain metastases (MBM) are an increasingly common referral to the neuro-oncology MDT in the context of lengthening survivorship of metastatic melanoma (MM) patients in the immunotherapy era. Stereotactic radiosurgery (SRS) and immune checkpoint inhibition (ICI) are both effective in the management of MBM and, when combined, 12-month local control rates of >85% and overall survival (OS) >80% have been reported.[4,5] Recent local analysis of patients treated at our tertiary SRS referral centre has revealed even greater outcomes in this patient cohort. This study aimed to compare the outcomes of patients with MBM treated with concurrent SRS and ICI compared to the overall metastatic melanoma cohort, to elucidate whether the addition of SRS to ICI may improve disease control outside of the brain as well as within. MATERIAL AND METHODS A retrospective analysis of our local SRS database and an ARIA ePrescribing database search was performed to identify a cohort of patients treated with concurrent SRS and ICI for MBM, as well as a control cohort of MM patients who received ICI alone, over a 4 year period until February 2020. The primary endpoints were the extracranial progression free survival (PFS) and overall survival (OS) at 12 months. Secondary endpoints were the median PFS (mPFS) and OS (mOS). Kaplan-Meier curves and survival statistics were generated using SPSS v26. RESULTS A total of 34 MBM from 19 patients were identified in the SRS+ICI group and there were 200 patients in the control group. The minimum follow up was 12 months. The median patient age, duration of ICI and use of combination ICI favoured the SRS+ICI group. The number of sites of extracranial disease pre-ICI and overall anti-PD-1 usage was well matched. In the SRS+ICI group, there were no cases of extracranial progression and no deaths within 12 months. In the control group, the 12-month PFS and OS rates were 50.5% and 77.5% respectively. In terms of mPFS, this was not reached (estimated 37.6 months) in the SRS+ICI group, versus 13.4 months in the control group (log rank test, p=0.001). In terms of mOS, this was not reached in the SRS+ICI group, versus 55.8 months in the control group (log rank test, p=0.016). CONCLUSION We demonstrate improved extracranial disease control and survivorship amongst metastatic melanoma patients who develop brain metastases and are treated with concurrent SRS and ICI compared to those who do not. The outcomes of our control cohort are comparable to the 4-year follow up of the CheckMate 067 trial (n=945),[6] which strengthens the validity of the statistical comparisons made in this study. The improved extracranial disease control seen when SRS and ICI are combined in the treatment of MBM questions whether an abscopal effect may be at play, and therefore further accents the utility of SRS in MBM beyond that of local control alone. This could influence management in cases of borderline decisions for SRS.

Survival of melanoma patients with brain metastases treated with ipilimumab combined with stereotactic radiosurgery.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20019-e20019
Author(s):  
Karim Tazi ◽  
Cody Chiuzan ◽  
Keisuke Shirai
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Performance Status ◽  
Survival Rates ◽  
Stage Iv ◽  
Rank Test ◽  
Group A ◽  
Stage Iv Melanoma

e20019 Background: Historically, melanoma with brain metastases has a poor prognosis and is a major contributor to patient morbidity and mortality. Recently, the use of ipilimumab has improved overall survival in stage IV melanoma; however, the outcome of patients with brain metastases remains unclear. In this retrospective medical record review, we report the outcome of patients with stage IV melanoma with brain metastases treated with ipilimumab and brain stereotactic radiosurgery (SRS). Methods: All patients with metastatic melanoma treated with ipilimumab from April 2010 to March 2012 were identified and stratified by presence (A) or absence (B) of brain metastases. All patients with brain metastases received SRS. Performance status, dates of stage IV diagnosis, brain SRS and cycle 1 of ipilimumab administration were recorded. We used the Disease Specific Graded Prognostic Assessment (DS-GPA) to estimate the predicted survival. Overall survival was defined as time (months) from the date of the stage IV diagnosis and the time of ipilimumab administration to death or last follow-up. Survival curves were estimated using the Kaplan-Meier method, and compared using a two-tailed log-rank test. Results: Twelve of 30 patients treated with ipilimumab had brain metastases. Median age was 66 years. Median DS-GPA score was 3 (estimated mean survival of 8.7 months). Four patients (33%) in group A and 6 patients (33%) in group B died as of last follow-up. Median number of SRS treatment was 1 (1 to 4), and median total treated lesions were 3 (1-14). Median survivals from date of Stage IV for A and B were 29.1 and 32.9 months, respectively (p=0.67). The estimated 2 year survival rates from date of cycle 1 ipilimumab administration for A and B were 58% (95% CI: 32-100%) and 55% (95% CI: 32-93%), respectively. Ten out of 12 patients in group A maintained an ECOG PS of 0-1 as of last follow-up. Conclusions: Survival of patients with melanoma brain metastases treated with ipilimumab combined with SRS may be comparable to patients without brain metastases. Ipilimumab and SRS do not seem to adversely impact quality of life.

The role of radiosurgery for multiple brain metastases

2000 ◽  
Vol 9 (2) ◽  
pp. 1-7 ◽  
Author(s):  
Kwan H. Cho ◽  
Walter A. Hall ◽  
Bruce J. Gerbi ◽  
Patrick D. Higgins
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Median Survival ◽  
Disease Status ◽  
Rank Test ◽  
Tumor Type ◽  
Multiple Brain Metastases ◽  
Extracranial Disease

Object The authors evaluated the role of stereotactic radiosurgery (SRS) in patients with multiple brain metastases by analyzing prognostic factors that predict survival. Methods Between March 1991 and January 1999, 83 patients with multiple brain metastases underwent SRS in which they used a 6 mV linear accelerator. The median radiation dose of 15 Gy (range 6–50 Gy) was delivered to the 40 to 90% (median 87%) isodose line encompassing the target. Actuarial overall survival was calculated from the date of SRS by using the Kaplan–Meier method. Univariate comparisons of survival between different groups were performed using a log-rank test. All 83 patients were included in the calculation of overall survival. Actuarial overall survival was 22% at 1 year and 13% at 2 years, and a median survival of 5.4 months (range, 0.3–28.8 months) was demonstrated. Variables that predicted survival were Karnofsky Performance Scale (KPS) score, extracranial disease status, and the number of intracranial metastases. Median survival in patients with a KPS score greater than as compared with less than 70 was 9.1 and 2.7 months, respectively (p = 0.002). Median survival when comparing absence and presence of extracranial disease was 9.9 and 4.1 months, respectively (p = 0.02). Median survival in patients harboring two, three, or four or more lesions was 6.6 months, 5.4 months, and 2.7 months, respectively (p = 0.02). In patients with a KPS score greater than or equal to 70 and with three or fewer lesions, median survival was 7 months or longer. In patients with four or more lesions median survival was 7.4 months for those with no extracranial disease and 2.4 months for those with extracranial disease. Other variables tested (sex, histological tumor type, previous resection, location of metastases, treatment modality, and tumor status) did not influence outcome. Conclusions The absence of extracranial disease, a KPS score greater than or equal to 70, and fewer number of metastases were shown to be significant predictors of longer survival. Stereotactic radiosurgery appears to be a reasonable therapeutic option in patients with up to three lesions when their KPS score is greater than or equal to 70, regardless of extracranial disease status. In those with four or more metastases, however, SRS should be limited to those with no extracranial disease.

Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery

2013 ◽  
Vol 119 (5) ◽  
pp. 1139-1144 ◽  
Author(s):  
Andrew M. Baschnagel ◽  
Kurt D. Meyer ◽  
Peter Y. Chen ◽  
Daniel J. Krauss ◽  
Rick E. Olson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Brain Metastases ◽  
Local Control ◽  
Tumor Volume ◽  
Continuous Variable ◽  
Total Tumor Volume ◽  
Extracranial Disease ◽  
Brain Failure ◽  
Distant Brain Failure

Object The aim of this study was to examine tumor volume as a prognostic factor for patients with brain metastases treated with Gamma Knife surgery (GKS). Methods Two hundred fifty patients with 1–14 brain metastases who had initially undergone GKS alone at a single institution were retrospectively reviewed. Patients who received upfront whole brain radiation therapy were excluded. Survival times were estimated using the Kaplan-Meier method. Univariate and multivariate analyses using Cox proportional hazard regression models were used to determine if various prognostic factors could predict overall survival, distant brain failure, and local control. Results Median overall survival was 7.1 months and the 1-year local control rate was 91.5%. Median time to distant brain failure was 8.0 months. On univariate analysis an increasing total tumor volume was significantly associated with worse survival (p = 0.031) whereas the number of brain metastases, analyzed as a continuous variable, was not (p = 0.082). After adjusting for age, Karnofsky Performance Scale score, and extracranial disease on multivariate analysis, total tumor volume was found to be a better predictor of overall survival (p = 0.046) than number of brain metastases analyzed as a continuous variable (p = 0.098). A total tumor volume cutoff value of ≥ 2 cm3 (p = 0.008) was a stronger predictor of overall survival than the number of brain metastases (p = 0.098). Larger tumor volume and extracranial disease, but not the number of brain metastases, were predictive of distant brain failure on multivariate analysis. Local tumor control at 1 year was 97% for lesions < 2 cm3 compared with 75% for lesions ≥ 2 cm3 (p < 0.001). Conclusions After adjusting for other factors, a total brain metastasis volume was a strong and independent predictor for overall survival, distant brain failure, and local control, even when considering the number of metastases.

scholarly journals Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

2015 ◽  
Vol 123 (2) ◽  
pp. 395-401 ◽  
Author(s):  
David Ly ◽  
Hilary P. Bagshaw ◽  
Christopher J. Anker ◽  
Jonathan D. Tward ◽  
Kenneth F. Grossmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Braf Inhibitor ◽  
Local Control Rate ◽  
Inhibitor Therapy ◽  
Braf Inhibitors ◽  
Whole Brain Radiation

OBJECT BRAF inhibitors improve progression-free and overall survival in patients with metastatic melanoma. Brain metastases are common, and stereotactic radiosurgery (SRS) has been used, resulting in excellent local control. Because BRAF inhibitors are associated with intracranial responses, the authors hypothesized that BRAF inhibitors would improve local control in patients with melanoma who are receiving SRS for brain metastases. METHODS The authors retrospectively identified patients with metastatic melanoma who had been tested for BRAF mutation and treated with SRS for brain metastases. Patients with previous resection, multiple brain metastases, or multiple courses of SRS were eligible. SRS was delivered in a single fraction to a median dose of 2000 cGy. Patients with a BRAF mutation were treated with a BRAF inhibitor on the basis of physician preference. RESULTS The authors identified 52 patients who were treated in 82 treatment sessions for 185 brain metastases and 13 tumor beds. At a median follow-up of 10.5 months, the 1-year local control rate was 69.2%. At 1 year, the local control rate for brain metastases in patients with BRAF mutation with BRAF treatment was 85.0%, and the local control rate for brain metastases in those without BRAF treatment was 51.5% (p = 0.0077). The rates of distant brain failure, freedom from whole-brain radiation, and overall survival were not different on the basis of BRAF mutation status or inhibitor therapy. The number of new intratumoral hemorrhages after SRS was increased significantly in patients with BRAF treatment. CONCLUSIONS Treatment with BRAF inhibitors was associated with improved local control after SRS in patients with melanoma and brain metastases. An increased number of intratumoral hemorrhages was associated with BRAF inhibitor therapy.

scholarly journals Ipilimumab and Stereotactic Radiosurgery with CyberKnife® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1857
Author(s):  
Valentina Borzillo ◽  
Rossella Di Franco ◽  
Diana Giannarelli ◽  
Fabrizio Cammarota ◽  
Esmeralda Scipilliti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Local Control ◽  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Melanoma Brain Metastases ◽  
One Year ◽  
The Impact

The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.

Regression of cardiac amyloid deposits with novel therapeutics: reaching new frontiers in cardiac ATTR amyloidosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Amyloidosis ◽  
T1 Mapping ◽  
Group Versus ◽  
Control Group ◽  
Cardiac Amyloid ◽  
Attr Amyloidosis ◽  
Amyloid Load ◽  
The Impact

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p&lt;0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p&lt;0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

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.

Resection and surgically targeted radiation therapy for locally recurrent GBM.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2054-2054
Author(s):  
David Brachman ◽  
Peter Nakaji ◽  
Kris Smith ◽  
Theresa Thomas ◽  
Christopher Dardis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Local Control ◽  
Local Treatment ◽  
Post Hoc Analysis ◽  
Locally Recurrent ◽  
Targeted Radiation Therapy ◽  
Post Hoc ◽  
Recurrent Gbm

2054 Background: Recurrent GBM (rGBM) is a diffuse disease, and resection (R) alone does not provide durable local control (LC) or prolong overall survival (OS). Hypothesizing R plus immediate radiation (RT) may achieve durable LC and secondarily improve OS by permitting time for subsequent potentially effective but biologically slower treatments to have an impact, we prospectively evaluated R combined with a novel surgically targeted radiation therapy (STaRT) device utilizing Cs-131 embedded in bioresorbable collagen tiles. Methods: From 2/13-2/18 patients (pts) with locally recurrent GBM were treated on a prospective single arm trial (ClinicalTrials.gov, NCT#03088579) of maximum safe resection and immediate RT (GammaTile, GT Medical Technologies, Tempe AZ). Upon resection the at-risk areas of the surgical bed were lined with the GammaTile (GT) device, delivering 60-80 Gy at 5 mm. Follow up treatments were not specified but captured; no pt. underwent additional local therapy without progression, and no pt. was lost to follow up. We present study specified endpoints of local control (LC), overall survival (OS), and adverse events (AE), and a post hoc, hypothesis-generating analysis of outcomes by receipt of systemic (Sys) therapy. Results: 28 locally recurrent GBM were treated, 20 at first progression (range 1-3). Median age was 58 years (yrs.) (range 21-80), KPS 80 (60-100), female: male ratio 10:18 (36/64%). MGMT was methylated in 11%, unmethylated in 18%, and unknown in 71%. For all pts., median OS was 10.7 months (mo.) (range.1-42.3), and radiographic LC was 8.8 mo. (range.01-34.5). LC (defined as < 15 mm from surgical bed) was maintained in 50% of pts., and no first failure was local. 12 mo. OS was 75% for pts. < 50 yrs. vs. 43% for > 50 yrs. (HR.46, p =.009). MGMT, KPS, and sex were non-predictive. After R+GT, 17 pts. received > 1 cycle of systemic therapy (Sys), either as adjuvant or salvage, alone or in combination . Sys was bevacizumab (BEV) in 15 pts., temozolomide (TMZ) in 12, and lomustine (CCNU) in 8 (N > 17 as some pts. received > 1 Sys). Post hoc analysis disclosed a 15.1 mo. OS for pts. receiving > 1 cycle of Sys (Sys+, N = 17) vs. 6.5 mo. for no Sys (Sys-, N = 11) (hazard ratio (HR).38, p =.017)). LC was 11.4 mo. for Sys+ and 2.1 mo. for Sys- (HR.44; p =.16)). Median OS (mo.) for BEV+ vs. BEV- was 16.7/4.5 (HR.38, p =.017), for TMZ+ vs. TMZ- 17.5/6.7 (HR.40, p =.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR.61, p =.25), respectively. Three attributed AE occurred, 1 dehiscence requiring surgery and 2 radiation brain effects, medically treated. 4 unrelated deaths occurred < 60 days post-op, all in the Sys- cohort, impacting their opportunity for subsequent treatment. Conclusions: In this study local treatment alone was insufficient to achieve prolonged OS. Post hoc analysis suggests R+GT coupled with Sys may have potential to impact OS in rGBM patients. GT was FDA cleared in 2020 for use in newly diagnosed malignant and all recurrent intracranial neoplasms. Clinical trial information: NCT#03088579.

scholarly journals Nonclonal chromosomal alterations and poor survival in cytopenic patients without hematological malignancies

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Osamu Imataki ◽  
Hiroyuki Kubo ◽  
Akihiro Takeuchi ◽  
Makiko Uemura ◽  
Norimitsu Kadowaki
Keyword(s):  
Single Cell ◽  
Chromosomal Aberration ◽  
Hematological Malignancies ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Aspiration ◽  
Normal Karyotype ◽  
Rank Test ◽  
Control Group ◽  
Chromosomal Alterations

Abstract Background Clonal chromosomal alterations (CCAs) reflect recurrent genetic changes derived from a single evolving clone, whereas nonclonal chromosomal alterations (NCCAs) comprise a single or nonrecurrent chromosomal abnormality. CCAs and NCCAs in hematopoietic cells have been partially investigated in cytopenic patients without hematological malignancies. Methods This single-center retrospective study included 253 consecutive patients who underwent bone marrow aspiration to determine the cause of cytopenia between 2012 and 2015. Patients with hematological malignancies were excluded. CCA was defined as a chromosomal aberration detected in more than two cells, and NCCA was defined as a chromosomal aberration detected in a single cell. Results The median age of the patients was 66 years. There were 135 patients without hematological malignancies (median age, 64 years; 69 females); of these, 27 patients (median age, 69 years; 8 females) harbored chromosomal abnormalities. CCAs were detected in 14 patients; the most common CCA was −Y in eight patients, followed by inv.(9) in three patients and mar1+, inv. (12), and t (19;21) in one patient each. NCCAs were detected in 13 patients; the most frequent NCCA was +Y in four patients, followed by del (20), + 8, inv. (2), − 8, and add (6) in one patient each. Moreover, nonclonal translocation abnormalities, including t (9;14), t (14;16), and t (13;21), were observed in three patients. One patient had a complex karyotype in a single cell. The remaining 106 patients with normal karyotypes comprised the control group (median age, 65 years; range, 1–92 years; 56 females). Further, follow-up analysis revealed that the overall survival of the NCCA group was worse than that of the CCA and the normal karyotype groups (P < 0.0001; log-rank test). The survival of the NCCA-harboring cytopenic patients was worse than that of the CCA-harboring cytopenic patients without hematological malignancies, suggesting that follow-up should be considered for both CCA- and NCCA-harboring cytopenic patients.

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