ORCID Profile
0000-0001-5692-1317
Current Organisation
Fiona Stanley Hospital
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Publisher: Wiley
Date: 07-12-2019
Publisher: Impact Journals, LLC
Date: 04-01-2019
Publisher: Springer Science and Business Media LLC
Date: 13-09-2014
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529724.V1
Abstract: AbstractPurpose: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment. Experimental Design: Plasma circulating tumor DNA (ctDNA) was quantified in 125 s les collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- ( i n /i = 32) or second-line ( i n /i = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy ( i n /i = 66). An external validation cohort included 128 patients commencing ICI therapies in the first- ( i N /i = 77) or second-line ( i N /i = 51) settings. Results: In the discovery cohort, low ctDNA (≤20 copies/mL) prior to commencing therapy predicted longer progression-free survival (PFS) in patients treated with first-line ICIs [HR, 0.20 95% confidence interval (CI) 0.07–0.53 i P /i 0.0001], but not in the second-line setting. An independent cohort validated that ctDNA is predictive of PFS in the first-line setting (HR, 0.42 95% CI, 0.22–0.83 i P /i = 0.006), but not in the second-line ICI setting. Moreover, ctDNA prior to commencing ICI treatment was not predictive of PFS for patients pretreated with BRAF/MEK inhibitors in either the discovery or validation cohorts. Reduced PFS and overall survival were observed in patients with high ctDNA receiving anti–PD-1 monotherapy, relative to those treated with combination anti–CTLA-4/anti–PD-1 inhibitors. Conclusions: Pretreatment ctDNA is a reliable indicator of patient outcome in the first-line ICI treatment setting, but not in the second-line ICI setting, especially in patients pretreated with BRAF/MEK inhibitors. Preliminary evidence indicated that treatment-naïve patients with high ctDNA may preferentially benefit from combined ICIs. /
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.FERTNSTERT.2014.07.737
Abstract: To develop a simple, convenient, and stable storage method for semen before DNA fragmentation testing. Experimental cross-sectional study. Fertility clinic. 164 male partners of infertile couples. Comparison of sperm DNA fragmentation levels (DFLs) using fresh, snap-frozen and air-dried semen, with air-dried s les stored at different temperatures and time periods to assess DNA stability. DFL determined by Halosperm G2 kit. Results are expressed as mean ± standard error of the mean. The DFLs from fresh and air-dried semen gave comparable results (1.08% ± 0.65%), and from snap-frozen and fresh s les a statistically significant difference (5.5% ± 1.09%). Air-dried semen stored at room temperature for 7 days had a statistically significantly higher DFL compared with semen stored overnight (46.29% ± 9.12%). S les stored at 4°C for 7 days or 1 day showed no statistically significant difference (0.83% ± 0.82%). DFLs from s les stored for either 1 or 30 days at 4°C showed a statistically significant difference (19.59% ± 5.72%) those stored at -22°C showed no statistically significant difference (0.68% ± 0.53%). Air-drying semen is a simple and stable storage method for up to 1 month at -22°C before DNA fragmentation testing.
Publisher: MDPI AG
Date: 16-12-2020
Abstract: In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma s les from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors (76%, p = 0.0149). Decreasing ctDNA levels within 12 weeks of treatment was strongly concordant with treatment response (Cohen’s k = 0.798, p 0.001) and predictive of longer progression free survival. Notably, a slower kinetic of ctDNA decline was observed in patients treated with immunotherapy compared to those on BRAF/MEK inhibitors. Whole exome sequencing of ctDNA was also conducted in 9 patients commencing anti-PD-1 therapy to derive tumour mutational burden (TMB) and neoepitope load measurements. The results showed a trend of high TMB and neoepitope load in responders compared to non-responders. Overall, our data suggest that changes in ctDNA can serve as an early indicator of outcomes in metastatic melanoma patients treated with systemic therapies and therefore may serve as a tool to guide treatment decisions.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JMOLDX.2017.11.009
Abstract: The identification of somatic mutations is crucial for guiding therapeutic decisions about personalized melanoma treatment. However, genetic analysis of tumors is usually performed on limited and often low-quality DNA from tumors with low tumor cellularity and high tumor heterogeneity. Different mutation-detection platforms exist, with varying analytical sensitivities. Here we evaluated the detection of common mutations in BRAF, NRAS, and TERT promoter in 40 melanoma FFPE tissues using Droplet Digital (dd)PCR, and compared the results to the detection rates obtained by Sanger sequencing and pyrosequencing. The cellularity of tumors analyzed ranged from 5% to 50% (n = 28) and 50% to 90% (n = 12). Overall, droplet digital (dd)PCR was more sensitive, detecting mutations in 12.5% and 23% of tumors deemed as wild-type by pyrosequencing and Sanger sequencing, respectively. The increased sensitivity of ddPCR was more apparent among tumors with <50% tumor cellularity. Implementation of ddPCR-based assays may facilitate analysis of early-stage tumors and support research into improving outcomes in melanoma patients.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22477679.V1
Abstract: Tables S1-S8 and Figures S1-S4
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529769.V1
Abstract: AbstractPurpose: Brain involvement occurs in the majority of patients with metastatic melanoma. The potential of circulating tumor DNA (ctDNA) for surveillance and monitoring systemic therapy response in patients with melanoma brain metastases merits investigation. Experimental Design: This study examined circulating i BRAF, NRAS /i , and i c-KIT /i mutations in patients with melanoma with active brain metastases receiving PD-1 inhibitor–based therapy. Intracranial and extracranial disease volumes were measured using the sum of product of diameters, and response assessment performed using RECIST. Longitudinal plasma s les were analyzed for ctDNA over the first 12 weeks of treatment (threshold 2.5 copies/mL plasma). Results: Of a total of 72 patients, 13 patients had intracranial metastases only and 59 patients had concurrent intracranial and extracranial metastases. ctDNA detectability was 0% and 64%, respectively, and detectability was associated with extracranial disease volume ( i P /i 0.01). Undetectable ctDNA on-therapy was associated with extracranial response ( i P /i 0.01) but not intracranial response. The median overall survival in patients with undetectable ( i n /i = 34) versus detectable ( i n /i = 38) ctDNA at baseline was 39.2 versus 10.6 months [HR, 0.51 95% confidence interval (CI), 0.28–0.94 i P /i = 0.03] and on-therapy was 39.2 versus 9.2 months (HR, 0.32 95% CI, 0.16–0.63 i P /i 0.01). Conclusions: ctDNA remains a strong prognostic biomarker in patients with melanoma with brain metastases, especially in patients with concurrent extracranial disease. However, ctDNA was not able to detect or monitor intracranial disease activity, and we recommend against using ctDNA as a sole test during surveillance and therapeutic monitoring in patients with melanoma. /
Publisher: American Association for Cancer Research (AACR)
Date: 08-2020
DOI: 10.1158/1078-0432.CCR-19-3926
Abstract: Brain involvement occurs in the majority of patients with metastatic melanoma. The potential of circulating tumor DNA (ctDNA) for surveillance and monitoring systemic therapy response in patients with melanoma brain metastases merits investigation. This study examined circulating BRAF, NRAS, and c-KIT mutations in patients with melanoma with active brain metastases receiving PD-1 inhibitor–based therapy. Intracranial and extracranial disease volumes were measured using the sum of product of diameters, and response assessment performed using RECIST. Longitudinal plasma s les were analyzed for ctDNA over the first 12 weeks of treatment (threshold 2.5 copies/mL plasma). Of a total of 72 patients, 13 patients had intracranial metastases only and 59 patients had concurrent intracranial and extracranial metastases. ctDNA detectability was 0% and 64%, respectively, and detectability was associated with extracranial disease volume (P & 0.01). Undetectable ctDNA on-therapy was associated with extracranial response (P & 0.01) but not intracranial response. The median overall survival in patients with undetectable (n = 34) versus detectable (n = 38) ctDNA at baseline was 39.2 versus 10.6 months [HR, 0.51 95% confidence interval (CI), 0.28–0.94 P = 0.03] and on-therapy was 39.2 versus 9.2 months (HR, 0.32 95% CI, 0.16–0.63 P & 0.01). ctDNA remains a strong prognostic biomarker in patients with melanoma with brain metastases, especially in patients with concurrent extracranial disease. However, ctDNA was not able to detect or monitor intracranial disease activity, and we recommend against using ctDNA as a sole test during surveillance and therapeutic monitoring in patients with melanoma.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529724
Abstract: AbstractPurpose: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment. Experimental Design: Plasma circulating tumor DNA (ctDNA) was quantified in 125 s les collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- ( i n /i = 32) or second-line ( i n /i = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy ( i n /i = 66). An external validation cohort included 128 patients commencing ICI therapies in the first- ( i N /i = 77) or second-line ( i N /i = 51) settings. Results: In the discovery cohort, low ctDNA (≤20 copies/mL) prior to commencing therapy predicted longer progression-free survival (PFS) in patients treated with first-line ICIs [HR, 0.20 95% confidence interval (CI) 0.07–0.53 i P /i 0.0001], but not in the second-line setting. An independent cohort validated that ctDNA is predictive of PFS in the first-line setting (HR, 0.42 95% CI, 0.22–0.83 i P /i = 0.006), but not in the second-line ICI setting. Moreover, ctDNA prior to commencing ICI treatment was not predictive of PFS for patients pretreated with BRAF/MEK inhibitors in either the discovery or validation cohorts. Reduced PFS and overall survival were observed in patients with high ctDNA receiving anti–PD-1 monotherapy, relative to those treated with combination anti–CTLA-4/anti–PD-1 inhibitors. Conclusions: Pretreatment ctDNA is a reliable indicator of patient outcome in the first-line ICI treatment setting, but not in the second-line ICI setting, especially in patients pretreated with BRAF/MEK inhibitors. Preliminary evidence indicated that treatment-naïve patients with high ctDNA may preferentially benefit from combined ICIs. /
Publisher: American Association for Cancer Research (AACR)
Date: 13-11-2020
DOI: 10.1158/1078-0432.CCR-20-2251
Abstract: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment. Plasma circulating tumor DNA (ctDNA) was quantified in 125 s les collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- (n = 32) or second-line (n = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy (n = 66). An external validation cohort included 128 patients commencing ICI therapies in the first- (N = 77) or second-line (N = 51) settings. In the discovery cohort, low ctDNA (≤20 copies/mL) prior to commencing therapy predicted longer progression-free survival (PFS) in patients treated with first-line ICIs [HR, 0.20 95% confidence interval (CI) 0.07–0.53 P & 0.0001], but not in the second-line setting. An independent cohort validated that ctDNA is predictive of PFS in the first-line setting (HR, 0.42 95% CI, 0.22–0.83 P = 0.006), but not in the second-line ICI setting. Moreover, ctDNA prior to commencing ICI treatment was not predictive of PFS for patients pretreated with BRAF/MEK inhibitors in either the discovery or validation cohorts. Reduced PFS and overall survival were observed in patients with high ctDNA receiving anti–PD-1 monotherapy, relative to those treated with combination anti–CTLA-4/anti–PD-1 inhibitors. Pretreatment ctDNA is a reliable indicator of patient outcome in the first-line ICI treatment setting, but not in the second-line ICI setting, especially in patients pretreated with BRAF/MEK inhibitors. Preliminary evidence indicated that treatment-naïve patients with high ctDNA may preferentially benefit from combined ICIs.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529769
Abstract: AbstractPurpose: Brain involvement occurs in the majority of patients with metastatic melanoma. The potential of circulating tumor DNA (ctDNA) for surveillance and monitoring systemic therapy response in patients with melanoma brain metastases merits investigation. Experimental Design: This study examined circulating i BRAF, NRAS /i , and i c-KIT /i mutations in patients with melanoma with active brain metastases receiving PD-1 inhibitor–based therapy. Intracranial and extracranial disease volumes were measured using the sum of product of diameters, and response assessment performed using RECIST. Longitudinal plasma s les were analyzed for ctDNA over the first 12 weeks of treatment (threshold 2.5 copies/mL plasma). Results: Of a total of 72 patients, 13 patients had intracranial metastases only and 59 patients had concurrent intracranial and extracranial metastases. ctDNA detectability was 0% and 64%, respectively, and detectability was associated with extracranial disease volume ( i P /i 0.01). Undetectable ctDNA on-therapy was associated with extracranial response ( i P /i 0.01) but not intracranial response. The median overall survival in patients with undetectable ( i n /i = 34) versus detectable ( i n /i = 38) ctDNA at baseline was 39.2 versus 10.6 months [HR, 0.51 95% confidence interval (CI), 0.28–0.94 i P /i = 0.03] and on-therapy was 39.2 versus 9.2 months (HR, 0.32 95% CI, 0.16–0.63 i P /i 0.01). Conclusions: ctDNA remains a strong prognostic biomarker in patients with melanoma with brain metastases, especially in patients with concurrent extracranial disease. However, ctDNA was not able to detect or monitor intracranial disease activity, and we recommend against using ctDNA as a sole test during surveillance and therapeutic monitoring in patients with melanoma. /
Publisher: Springer Science and Business Media LLC
Date: 09-07-2018
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22477832.V1
Abstract: Supplementary Figure 1. Flow chart of patient selection. Supplementary Figure 2. Flowchart of patients with disease response assessment available (n = 57).
Publisher: OMICS Publishing Group
Date: 2015
Publisher: Impact Journals, LLC
Date: 18-08-2017
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22477679
Abstract: Tables S1-S8 and Figures S1-S4
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22477832
Abstract: Supplementary Figure 1. Flow chart of patient selection. Supplementary Figure 2. Flowchart of patients with disease response assessment available (n = 57).
Publisher: Springer Science and Business Media LLC
Date: 14-11-2016
No related grants have been discovered for Ashleigh McEvoy.