ORCID Profile
0000-0002-6357-3899
Current Organisation
Liverpool Hospital
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Publisher: Elsevier BV
Date: 10-2018
Publisher: Wiley
Date: 12-2017
DOI: 10.1111/IMJ.13555
Abstract: Epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) is a subgroup of oncogene addicted lung cancer that predicts response to tyrosine kinase inhibitors (TKI). However, there is variability in response and survival outcomes in patients with EGFR mutation treated with TKI. To describe clinical characteristics, treatment patterns and factors influencing outcomes in patients with EGFR-mutated NSCLC in South Western Sydney Local Health District. Retrospective review of patients with EGFR-mutated NSCLC diagnosed between January 2010 and June 2016. A total of 85 EGFR-mutated NSCLC patients was identified 80 (94%) received first-line treatment with EGFR-TKI. The median follow-up was 10.7 months with a median duration of treatment of 9 months. On disease progression (n = 44), 37% had best supportive care only, 30% received chemotherapy, 23% participated in clinical trials, 7% continued on a first generation EGFR-TKI and 3% received afatinib. Overall response rate to first-line EGFR-TKI was 66%. Median progression-free survival (PFS) was 10.7 months (range 2.7-55.9 months) and median overall survival (OS) was 23 months (range 0.4-35.8 months). Multivariate Cox regression analysis showed that patients with lower disease burden (<4 sites) had longer PFS (hazard ratio (HR) 0.36, 95% confidence interval (CI) 0.18-0.72, P = 0.004) but not OS. Good performance status predicts longer OS (HR 0.33, CI 0.14-0.77, P = 0.01). Lower (<5) pre-treatment neutrophil-to-lymphocyte ratio (NLR) was associated with better PFS (HR 0.40, 95% CI 0.18-0.87, P = 0.02) and OS (HR 0.43, 95% CI 0.19-0.94, P = 0.04). There were no survival differences when patients were stratified by age, baseline albumin level and types of EGFR mutation. Results from this community-based cohort confirm known prognostic factors in patients with EGFR-mutated NSCLC receiving TKI and suggest the negative influence of a heightened host systemic inflammatory response on patient outcomes.
Publisher: Wiley
Date: 15-08-2019
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 09-2019
Analytical approaches and estimands to take account of missing patient-reported data in longitudinal studies
Publisher: Informa UK Limited
Date: 04-2019
DOI: 10.2147/PROM.S178963
Publisher: Springer Science and Business Media LLC
Date: 12-10-2018
Publisher: Springer Science and Business Media LLC
Date: 04-05-2018
DOI: 10.1007/S11764-018-0692-X
Abstract: Cognitive symptoms are common in cancer patients, with up to 70% reporting cognitive symptoms following chemotherapy. These symptoms can have a major impact on how an in idual functions in all aspects of their lives. This review evaluates self-reported cognitive function and its associations with neuropsychological tests and patient-reported outcomes in adult cancer patients who received chemotherapy treatment for a solid cancer. A search of multiple databases (Medline, Ovid at Nursing, PsycINFO, Allied and Complementary Medicine) from 1936 to 2017 was conducted, identifying 1563 unique articles, of which 101 met inclusion criteria. Of the 101 included studies, 48 (47%) were cross-sectional and 38 (38%) longitudinal in design, with 12 (12%) randomised controlled trials. A minority (26%) incorporated a healthy control arm in the study design, whilst the majority (79%) were in women with breast cancer. There was ersity in the assessment of self-reported cognitive symptoms. A total of 43 of 44 studies that sought an association between self-reported cognitive function and patient-reported outcomes found a moderate to strong association. Overall, 31 studies showed a lack of association between self-reported cognitive symptoms and neuropsychological results, whilst 14 studies reported a significant association between the two, but the association was often restricted to limited cognitive domains. The review found widespread heterogeneity in the assessment of self-reported cognitive symptoms and consistently absent or weak association with neuropsychological test scores. This research highlights the need for a standardised approach to measurement of self-reported cognitive symptoms in cancer patients.
Publisher: Wiley
Date: 2017
DOI: 10.1111/IMJ.13296
Abstract: Octogenarians represent a growing population reviewed in medical oncology clinics, yet there is a paucity of data on how chemotherapy is tolerated in this age group. To describe the use of palliative first-line chemotherapy in patients 80 years and over and factors associated with its use. We identified all new patients aged 80 years or older diagnosed with incurable advanced solid organ cancer and seen in one of three Sydney medical oncology outpatient clinics between January 2009 and December 2013. Patient, disease and treatment details were summarised and factors associated with chemotherapy use explored. Of 420 eligible patients, 100 (24%) started first-line chemotherapy. Younger age at diagnosis was the only factor associated with receiving chemotherapy (median 82.9 vs 84.1 years, P = 0.002). A total of 78% of patients had single-agent chemotherapy, and 41% received a full dose for the first cycle. During treatment, 54% experienced toxicity, necessitating dose reduction, delay or omission, and 32% were hospitalised. These events were associated with receipt of combination chemotherapy (OR 5.1 P = 0.04) and full-dose chemotherapy for cycle 1 (OR 3.5 P = 0.02). Radiological disease control was achieved in 60%. Chemotherapy was stopped because of progressive disease (48%), toxicity (37%) or completion of planned course (17%). A quarter of patients 80 years and older received first-line palliative chemotherapy. Despite most receiving a modified dose, one third were hospitalised during treatment. These findings highlight the need for careful clinical assessment and selection of older cancer patients for chemotherapy.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.LUNGCAN.2019.06.021
Abstract: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer. We recruited 28 patients with 103 serial blood s les. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood s les, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes. EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001). Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.
Publisher: Elsevier BV
Date: 08-2017
Publisher: Elsevier BV
Date: 2019
Publisher: Wiley
Date: 25-04-2022
DOI: 10.1111/JEP.13688
Abstract: Details of the development and implementation of integrated care pathways (ICPs) in the context of electronic collection of patient reported outcomes (ePROs) for cancer patients are largely lacking in the literature. This study describes what, why and how decisions were made to adapt and implement an ePROs ICP for patients with lung cancer. A consensus process was utilized, with the implementation advisory group including multidisciplinary representation from three participating hospitals, to identify local ch ions and adapt and incorporate the ePRO ICP into the local contexts. Engagement meetings were documented via meeting transcripts, and detailed notes from October 2019 to November 2020 were content‐analysed to identify decision‐making themes based on the Consolidated Framework for Implementation Research workflows and process maps were reviewed and modified to integrate ePROs. In total, 55 engagement activities were held (24 meetings, 20 workshops 11 educational sessions), with n = 96 staff from multiple disciplines participating in the ePROs implementation through advisory meetings, process mapping, change management and staff education. Decisions were made regarding eligible patient cohorts to include, the process for onboarding patients onto the ePRO system, and follow‐up and referral pathways. Rationales for decisions included alignment with existing workflows, utilizing available staff, minimizing staff and patient burden and maximizing patient engagement. Existing resources, staff input and technical and logistical reasons often guided the ICP decisions, highlighting the need for in‐depth engagement across all stakeholders for optimal implementation of ePRO ICPs. The ePRO implementation required substantial dialogue and systematic resolution to reach agreement on the final processes. Adapting the local ICP through rigorous engagement facilitated the successful implementation of ePROs as business‐as‐usual at all three cancer centres. Involving all relevant stakeholders is critical to the successful adaptation of ICPs before their introduction into routine care.
Publisher: Future Medicine Ltd
Date: 04-2017
Publisher: Wiley
Date: 27-01-2011
DOI: 10.1002/PON.1727
Abstract: There is little information about the accuracy of patient perceptions of their life expectancy. Here, we compare patient perceptions of their outlook and their oncologist's estimates of life expectancy to actual survival. The Unmet Needs Study recruited patients with metastatic cancer. Oncologists were asked to estimate patient survival as: (1) weeks (2) months (3) <1 year (4) 2 years. Patients were asked to estimate their outlook on a numerical scale from 1-7. Patient and oncologist estimates were compared with actual survival. Complete survival data were available for 50 patients: median age 63.5 years 48% male tumor types: 32% colorectal, 24% lung, 10% upper gastrointestinal cancer, 12% unknown primary and median survival 6.8 months. The oncologists were 32% accurate in predicting survival and overestimated survival 42% of the time (weighted kappa=0.34). The correlation between self-reported patient outlook and survival was modest (Spearman's rho=0.36, p=0.01). The median survival for categories of outlook of 1-3, 4-5, and 6-7 were 4.4, 5.4, and 14.8 months, respectively (p=0.01). Overseas-born patient was the only independent predictor for the oncologists' accurate estimates (p=0.01). Oncologists were relatively poor at predicting survival and tended to be optimistic in their prognostication. The probability of survival significantly decreased with worse self-reported patient outlook.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.CRITREVONC.2014.10.001
Abstract: There is increasing evidence for the use of circulating tumor cells (CTCs) as a "liquid biopsy" for early detection of lung cancer recurrence, prognosticating disease and monitoring treatment response. Further, CTC molecular analysis and interrogation of single cells hold significant potential in providing insights into tumor biology and the metastatic process. Ongoing research will likely see the translation of CTCs as a prognostic and predictive biomarker in both small cell, and non-small cell, lung cancer to routine clinical practice.
Publisher: Elsevier BV
Date: 11-2015
Abstract: We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.
Publisher: Springer Science and Business Media LLC
Date: 22-10-2019
DOI: 10.1007/S00262-019-02416-7
Abstract: Blockade of the PD-1/PD-L1 pathway with targeted monoclonal antibodies has demonstrated encouraging anti-tumour activity in multiple cancer types. We present the case of a patient with BRAF-negative stage IVC anaplastic thyroid cancer (ATC) treated with the anti-PD-1 monoclonal antibody, pembrolizumab, following radiographic progression on chemoradiation. Blood s les were collected prior to and at four time points during treatment with pembrolizumab. Mass cytometry was used to determine expression of relevant biomarkers by peripheral blood mononuclear cells. Faecal s les were collected at baseline and 4 weeks following treatment initiation taxonomic profiling using 16S ribosomal RNA (rRNA) gene sequencing was performed. Following treatment, a marked expansion in CD20
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.JTHO.2016.11.2236
Abstract: Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors (TKIs) used for treatment of advanced EGFR-mutated NSCLC. Estimating differences in toxicity between these EGFR TKIs is important for personalizing treatment. We performed a meta-analysis of randomized trials that compared EGFR TKI therapy against chemotherapy or placebo. We extracted data from the EGFR TKI arm for indirect comparisons to estimate the relative risk for toxic death, grade 3 to 4 (G3/4) adverse events (AEs), and discontinuation of treatment because of AE for each EGFR TKI. Sixteen trials included 2535 patients with mutated or wild-type EGFR. Toxic deaths were rare (1.7%), with pneumonitis being most frequent cause and no significant differences between EGFR TKIs. Overall, 40% of patients experienced G3/4 AEs. The risk for G3/4 AEs was lower with gefitinib (29.1%) than with erlotinib (54.1%) or afatinib (42.1%) (p < 0.01). Discontinuation of treatment because of AEs occurred in 7.7% of patients, with no significant differences between EGFR TKIs. Diarrhea (in 53.3% of cases) and rash (in 66.5%) were the most frequent AEs. The risk for rash was higher with afatinib (84.8%) than with erlotinib (62.0%) or gefitinib (62.0%) (p < 0.01). The risk for diarrhea was higher with afatinib (91.7%) than with erlotinib (42.4%) or gefitinib (44.4%) (p < 0.01). The risk for increased liver enzyme levels was higher with gefitinib (61.7%) than with erlotinib (17.8%) or afatinib (20.1%) (p < 0.01). A risk-benefit contour was used to assess the trade-off between efficacy and toxicity for different EGFR TKIs. EGFR TKIs are well tolerated, with less than 10% of patients discontinuing treatment because of AEs. The profile of and risk for toxicities vary between EGFR TKIs and can be used to inform the selection of treatment.
Publisher: Wiley
Date: 08-06-2018
DOI: 10.1002/PON.4777
Abstract: Patient reported outcomes (PROs) are important in oncology research however, missing data can pose a threat to the validity of results. Psycho-oncology researchers should be aware of the statistical options for handling missing data robustly. One rarely used set of methods, which includes extensions for handling missing data, is generalized estimating equations (GEEs). Our objective was to demonstrate use of GEEs to analyze PROs with missing data in randomized trials with assessments at fixed time points. We introduce GEEs and show, with a worked ex le, how to use GEEs that account for missing data: inverse probability weighted GEEs and multiple imputation with GEE. We use data from an RCT evaluating a web-based brain training for cancer survivors reporting cognitive symptoms after chemotherapy treatment. The primary outcome for this demonstration is the binary outcome of cognitive impairment. Several methods are used, and results are compared. We demonstrate that estimates can vary depending on the choice of analytical approach, with odds ratios for no cognitive impairment ranging from 2.04 to 5.74. While most of these estimates were statistically significant (P < 0.05), a few were not. Researchers using PROs should use statistical methods that handle missing data in a way as to result in unbiased estimates. GEE extensions are analytic options for handling dropouts in longitudinal RCTs, particularly if the outcome is not continuous.
Publisher: OMICS Publishing Group
Date: 2018
Publisher: Massachusetts Medical Society
Date: 31-05-2018
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-01-2017
Abstract: Cognitive impairment is reported frequently by cancer survivors. There are no proven treatments. We evaluated a cognitive rehabilitation program (Insight) and compared it with standard care in cancer survivors self-reporting cognitive symptoms. We recruited adult cancer survivors with a primary malignancy (excluding central nervous system malignancies) who had completed three or more cycles of adjuvant chemotherapy in the previous 6 to 60 months and reported persistent cognitive symptoms. All participants received a 30-minute telephone consultation and were then randomly assigned to the 15-week, home-based intervention or to standard care. Primary outcome was self-reported cognitive function (Functional Assessment of Cancer Therapy Cognitive Function [FACT-COG] perceived cognitive impairment [PCI] subscale): difference between groups after intervention (T2) and 6 months later (T3). A total of 242 participants were randomly assigned: median age, 53 years 95% female. The primary outcome of difference in FACT-COG PCI was significant, with less PCI in the intervention group at T2 ( P .001). This difference was sustained at T3 ( P .001). At T2, there was a significant difference in all FACT-COG subscales, favoring the intervention. Neuropsychological results were not significantly different between the groups at T2 or T3. There were significantly lower levels of anxiety/depression and fatigue in the intervention group at T2. There were significant improvements in stress in the intervention group at both time points. There was no significant difference in quality of life between the groups at T2, but the intervention group had better quality of life at T3. The intervention, Insight, led to improvements in cognitive symptoms compared with standard care. To our knowledge, this is the first large randomized controlled trial showing an improvement in self-reported cognitive function in cancer survivors, indicating that this intervention is a feasible treatment.
No related grants have been discovered for Victoria Bray.