Publications by authors named "Brooke E Wilson"

14 Publications

  • Page 1 of 1

Fragility index of trials supporting approval of anti-cancer drugs in common solid tumours.

Cancer Treat Rev 2021 Mar 16;94:102167. Epub 2021 Feb 16.

Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. Electronic address:

Background: The Fragility Indexquantifies the reliability of positive trials by estimating the number of events, which would change statistically significant results to non-significant results.

Methods: We identified randomized trials supporting drug approvals by the US FDA between 2009 and 2019 in lung, breast, prostate, and colon cancers and in melanoma. We reconstructed survival tablesand calculated the number of events, which would result in a non-significant result for the primary endpoint. The FI was then compared to the number of patients in each trial who withdrew consent or were lost to follow-up. Regression analyses were used to explore associations between RCT characteristics and FI and trials in which FI was lower or equal to number of participants who withdrew consent or were lost to follow-up.

Results: Among 81 RCTs, the median FI was 28. The median number of patients who withdrew consent or were lost to follow up was 27. FI was equal or lower than the number of patients who withdrew consent or were lost to follow-up in 47 trials (58%). There was a modest increase in FI over time (p = 0.02). Trials with overall survival as the primary endpoint (p = 0.006) and those in the palliative setting (p < 0.001) had lower FI. There was no association with trial sample size or duration of follow-up.

Findings: Statistical significance of RCTs in common solid tumours can be reversed often with a small number of additional events. Post-approval RCTs or real-world data analyses should be performed to ensure results of registration trials are robust.
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http://dx.doi.org/10.1016/j.ctrv.2021.102167DOI Listing
March 2021

Australia and New Zealand's responsibilities in improving oncology services in the Asia-Pacific: A call to action.

Asia Pac J Clin Oncol 2021 Feb 25. Epub 2021 Feb 25.

Collaboration for Cancer Outcomes, Research and Evaluation, Ingham Institute for Applied Medical Research, South West Clinical School, University of New South Wales, Kensington, New South Wales, Australia.

Aim: To review the expected increasing demand for cancer services among low and middle-income countries (LMICs) in the Asia-Pacific (APAC), and to describe ways in which Australia and New Zealand (ANZ) can provide support to improve cancer outcomes in our region.

Methods: We first review the current and projected incidence of cancer within the APAC between 2018 and 2040, and the estimated demand for chemotherapy, radiotherapy and surgery. We then explore potential ways in which ANZ can increase regional collaborations to improve cancer outcomes.

Results: We identify 6 ways that ANZ can collaborate with LMICs to improve cancer care in the APAC through the ANZ Regional Oncology Collaboration Strategy: Increasing education and institutional collaborations in the APAC region through in-country training, twinning partnerships, observerships and formalised training programs in order to increase cancer care quality and capacity. Promoting and assisting in the establishment and maintenance of population-based cancer registries in LMICs. Increasing research capacity in LMICs through collaboration and promoting high quality global oncology research within ANZ. Engaging and training Australian and New Zealand clinicians in global oncology, increasing awareness of this important career path, and increasing health policy engagement. Increasing web-based endeavours through virtual tumour boards, web-based advocacy platforms and web-based teaching programs. Continuing to leverage for funding through professional bodies, government, industry, not-for-profit organisations and local hospital funds.

Conclusion: We propose the creation of an Australian and New Zealand Interest Group to provide formalised and sustained collaboration between researchers, clinicians and stakeholders.
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http://dx.doi.org/10.1111/ajco.13544DOI Listing
February 2021

Global demand for cancer surgery and an estimate of the optimal surgical and anaesthesia workforce between 2018 and 2040: a population-based modelling study.

Lancet Oncol 2021 02 21;22(2):182-189. Epub 2021 Jan 21.

Collaboration for Cancer Outcomes Research and Evaluation, Ingham Institute of Applied Medical Research, South West Clinical School, University of New South Wales, Sydney, NSW, Australia.

Background: The growing demand for cancer surgery has placed a global strain on health systems. In-depth analyses of the global demand for cancer surgery and optimal workforce requirements are needed to plan service provision. We estimated the global demand for cancer surgery and the requirements for an optimal surgical and anaesthesia workforce, using benchmarks based on clinical guidelines.

Methods: Using models of benchmark surgical use based on clinical guidelines, we estimated the proportion of cancer cases with an indication for surgery across 183 countries, stratified by income group. These proportions were multiplied by age-adjusted national estimates of new cancer cases using GLOBOCAN 2018 data and then aggregated to obtain the estimated number of surgical procedures required globally. The numbers of cancer surgical procedures in 44 high-income countries were divided by the actual number of surgeons and anaesthetists in the respective countries to calculate cancer procedures per surgeon and anaesthetist ratios. Using the median (IQR) of these ratios as benchmarks, we developed a three-tiered optimal surgical and anaesthesia workforce matrix, and the predictions were extrapolated up to 2040.

Findings: Our model estimates that the number of cancer cases globally with an indication for surgery will increase by 5 million procedures (52%) between 2018 (9 065 000) and 2040 (13 821 000). The greatest relative increase in surgical demand will occur in 34 low-income countries, where we also observed the largest gaps in workforce requirements. To match the median benchmark for high-income countries, the surgical workforce in these countries would need to increase by almost four times and the anaesthesia workforce by nearly 5·5 times. The greatest increase in optimal workforce requirements from 2018 to 2040 will occur in low-income countries (from 28 000 surgeons to 58 000 surgeons; 107% increase), followed by lower-middle-income countries (from 166 000 surgeons to 277 000 surgeons; 67% increase).

Interpretation: The global demand for cancer surgery and the optimal workforce are predicted to increase over the next two decades and disproportionately affect low-income countries. These estimates provide an appropriate framework for planning the provision of surgical services for cancer worldwide.

Funding: University of New South Wales Scientia Scholarship and UK Research and Innovation Global Challenges Research Fund.
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http://dx.doi.org/10.1016/S1470-2045(20)30675-6DOI Listing
February 2021

The value of first-line chemotherapy and targeted therapy in the treatment of breast cancer.

Eur J Cancer Care (Engl) 2021 Jan 4;30(1):e13352. Epub 2020 Nov 4.

Collaboration for Cancer Outcomes Research and Evaluation (CCORE), Ingham Institute for Applied Medical Research, Sydney, NSW, Australia.

Objective: To investigate the value (survival benefit and cost) of first-line chemotherapy and targeted therapy in breast cancer at a population level.

Methods: Based on guideline recommendations, a model of optimal utilisation was constructed for first-line chemotherapy and targeted therapy in breast cancer, calculating the survival benefit and average cost of all regimens recommended for each treatment indication at 5 years and at 10 years.

Results: Survival benefits from chemotherapy and targeted therapy differ markedly depending on the treatment indications. The cost per life-year gained at 5 years is $38,044 for stages I and II, $33,749 for stage III and $ 151,668 for patients presenting with stage IV breast cancer. The cost per life-year gained at 10 years is $ 13,587 for early breast cancer. The most expensive chemotherapy indication in breast cancer is the treatment of metastatic HER2-positive breast cancer costing $330,978 per LYG for a survival benefit of 11% at 5 years falling to zero survival benefit at 10 years.

Conclusion: There are large differences in value between the different indications for first-course chemotherapy and targeted therapy in the treatment of breast cancer that should be considered when pricing cancer drugs.
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http://dx.doi.org/10.1111/ecc.13352DOI Listing
January 2021

Dual Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancer: Just a Gambit or Real CheckMate?

Cancer Cell 2020 10;38(4):438-440

Princess Margaret Cancer Centre, Division of Medical Oncology, University Health Network, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada. Electronic address:

In this issue of Cancer Cell, Sharma et al. report that ipilimumab and nivolumab combination achieved impressive response rates in patients with metastatic castration-resistant prostate cancer (mCRPC). But this regimen produced high rates of toxicity, treatment-related discontinuation, and death. Tolerability needs improvement for this combination to benefit more men with mCRPC.
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http://dx.doi.org/10.1016/j.ccell.2020.09.009DOI Listing
October 2020

The effect of antibiotics on clinical outcomes in immune-checkpoint blockade: a systematic review and meta-analysis of observational studies.

Cancer Immunol Immunother 2020 Mar 21;69(3):343-354. Epub 2019 Dec 21.

Kinghorn Cancer Centre, St Vincent's Hospital Sydney, 370 Victoria Street, Darlinghurst, NSW, 2000, Australia.

Purpose: Pre-clinical and early clinical data suggests the microbiome plays an important role in oncogenesis and influences response to immune checkpoint blockade (ICB). The objective of this systematic review and meta-analysis was to determine whether antibiotics affect overall survival (OS) and progression free survival (PFS) in patients with solid malignancies treated with ICB.

Patients And Methods: A systematic search of EMBASE, MEDLINE and conference proceedings was conducted for observational studies examining the effect of antibiotics on ICB. A random effects study-level meta-analysis was performed with pooling of the hazards ratio (HR) for OS and PFS. Meta-regression was used to determine the impact of the timing of antibiotic exposure on OS.

Results: 766 studies were identified, and 18 studies met the inclusion criteria. Of the 2889 patients included, 826 (28.6%) were exposed to antibiotics. The most common malignancies were lung (59%), renal cell carcinoma (RCC) or urothelial carcinoma (16.3%) and melanoma (18.7%). OS was prolonged in those without antibiotic exposure (pooled HR 1.92, 95% CI 1.37-2.68, p < 0.001). The effect of antibiotics on OS was greater in studies defining antibiotic exposure as 42 days prior to initiation of ICB (HR 3.43, 95% CI 2.29-5.14, p < 0.0001). PFS was also longer in patients who did not receive antibiotics (pooled HR 1.65, 95% CI 1.3-2.1, p < 0.0001).

Conclusion: In patients receiving ICB, OS and PFS are longer in patients who are not exposed to antibiotics. Antibiotic use in the 42 days before starting ICB appears to be most detrimental to outcome.
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http://dx.doi.org/10.1007/s00262-019-02453-2DOI Listing
March 2020

Association between ribociclib and changes in creatinine in patients with hormone receptor positive metastatic breast cancer.

Intern Med J 2019 11;49(11):1438-1442

Department of Medical Oncology, Liverpool Hospital, Sydney, New South Wales, Australia.

Combination ribociclib and aromatase inhibitors are currently the preferred treatment in Australia for newly diagnosed hormone receptor positive metastatic breast cancer in the absence of visceral crisis. In our case series of 32 patients, 28% experienced grade 1 elevations in creatinine, a toxicity that was under-recognised in large phase III studies. Creatinine rise appears to be due to a reversible inhibition of renal efflux transporters rather than an acute kidney injury in the majority of cases.
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http://dx.doi.org/10.1111/imj.14629DOI Listing
November 2019

A critique of the fragility index.

Lancet Oncol 2019 10 30;20(10):e552. Epub 2019 Sep 30.

Division of Medical Oncology, Princess Margaret Cancer Centre and the University of Toronto, Toronto ON, M5G 2M9, Canada. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(19)30583-2DOI Listing
October 2019

Estimates of global chemotherapy demands and corresponding physician workforce requirements for 2018 and 2040: a population-based study.

Lancet Oncol 2019 06 8;20(6):769-780. Epub 2019 May 8.

University of New South Wales, Sydney, NSW, Australia; Collaboration for Cancer Outcomes, Research and Evaluation, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia.

Background: The incidence of cancer (excluding non-melanomatous skin cancers) is projected to rise from 17·0 million to 26·0 million between 2018 and 2040. A large proportion of these patients would be likely to derive benefit from chemotherapy, but no studies so far have quantified current and projected global chemotherapy demands. We aimed to estimate changes in national, regional, and global demands for first-course chemotherapy and the cancer physician workforce between 2018 and 2040 if all patients were treated according to best-practice evidence-based guidelines.

Methods: Data for the incidence of 29 types of cancer in 183 countries in 2018, and projections of incidence in 2040, were obtained from GLOBOCAN 2018. Optimal chemotherapy utilisation from evidence-based guidelines was applied to these incidence data to generate the number of new patients requiring first-course chemotherapy in 2018 and 2040. We then estimated the corresponding cancer physician workforce required to deliver this chemotherapy (on the basis of physicians seeing 150 new patients requiring chemotherapy per year). We did sensitivity analyses to investigate how cancer stage at presentation affected chemotherapy demands. We also did sensitivity analyses to explore changes to workforce requirements if each physician was seeing 100 new patients requiring chemotherapy per year or 300 new patients requiring chemotherapy per year.

Findings: Between 2018 and 2040, the number of patients requiring first-course chemotherapy annually will increase from 9·8 million to 15·0 million, a relative increase of 53%. The estimated proportion of patients needing chemotherapy who reside in low-income or middle-income countries was 63% (6 162 240 of 9 782 783) in 2018, and will be 67% (10 071 049 of 14 984 560) in 2040. The most common indications for chemotherapy worldwide in 2040 will be lung cancer (accounting for 2 455 137 [16·4%] of 14 984 560 cases eligible for chemotherapy), breast cancer (1 898 740 [12·7%]), and colorectal cancer (1 678 153 [11·1%]). We estimated that, in 2018, 65 000 cancer physicians were required worldwide to deliver optimal chemotherapy-a figure that we estimate will rise to 100 000 by 2040 (with estimates ranging from from 50 000 to 150 000, depending on workload).

Interpretation: Strategic investments in chemotherapy service provision and cancer physicians are needed to meet the projected increased demand for chemotherapy in 2040.

Funding: None.
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http://dx.doi.org/10.1016/S1470-2045(19)30163-9DOI Listing
June 2019

Lung transplantation for non-small cell lung cancer and multifocal bronchioalveolar cell carcinoma.

Lancet Oncol 2018 07 29;19(7):e351-e358. Epub 2018 Jun 29.

The Lung Transplant Unit, St Vincent's Hospital, Sydney, NSW, Australia.

Lung transplantation for primary bronchogenic cancer could lead to increased survival and improved quality of life for patients who have malignant disease, for which other therapies might be inappropriate. This Review examines the development of experience and outcomes for this indication and explores the limitations that are inherent in lung transplantation for malignant disease. Bronchogenic malignancy is a rare indication for lung transplantation constituting only 0·13% of all lung transplants in the USA from 1987 to 2010 and is only indicated for early-stage disease when conventional surgical techniques are contraindicated by poor lung function in which an unacceptably high risk of short-term mortality is expected. Outcomes can be extrapolated from the experience of finding an unexpected malignancy in an explanted lung for which approximately 30% of recipients, dependent on stage, succumb from distant metastatic disease in the first few years after transplant, after which long-term survival is similar to transplantation for other conditions. Care must be taken for lung transplantation for multifocal bronchoalveolar cell carcinoma to ensure that the donor lung is not contaminated with residual bronchoalveolar cell carcinoma cells in the upper airways during surgical implantation. The rarity of lung transplantation for cancer, and the absence of head-to-head trials comparing lung transplantation with conventional cancer care, limit the conclusions that can be drawn about lung transplantation for this indication. Furthermore, the ethical balance of how to allocate a scarce resource, such as a donor lung, remains an unresolved dilemma given the uncertainties regarding long-term survival. Conversely, individual patients might have substantial increases in survival and quality of life equivalent or superior to conventional cancer treatment methods.
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http://dx.doi.org/10.1016/S1470-2045(18)30297-3DOI Listing
July 2018

Ecological effects of cefepime use during antibiotic cycling on the Gram-negative enteric flora of ICU patients.

Intensive Care Med Exp 2018 Jul 27;6(1):19. Epub 2018 Jul 27.

Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW, Australia.

This study examines the impact of cefepime and APP-β (antipseudomonal penicillin/ β-lactamase inhibitor combinations) on Gram-negative bacterial colonization and resistance in two Australian ICUs. While resistance did not cumulatively increase, cefepime (but not APP-β treatment) was associated with acquisition of antibiotic resistant Enterobacteriaceae, consistent with an ecological effect. Analysis of the resident gut E. coli population in a subset of patients showed an increase in markers of horizontal gene transfer after cefepime exposure that helps explain the increase in APP-β resistance and reminds us that unmeasured impacts on the microbiome are key outcome determinants that need to be fully explored.
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http://dx.doi.org/10.1186/s40635-018-0185-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063807PMC
July 2018

Appendicectomy at a children's hospital: what has changed over a decade?

ANZ J Surg 2012 Sep 20;82(9):639-43. Epub 2012 Aug 20.

Douglas Cohen Department of Paediatric Surgery, The Children's Hospital at Westmead, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

Background: Appendicectomy remains the most common abdominal emergency procedure performed by surgeons. We reviewed appendicectomies for the calendar years 1999 and 2009 to assess any changes in the referral, presentation and management at a tertiary paediatric institution.

Methods: We performed a retrospective chart review on all appendicectomies at our institution in 1999 and 2009. Patients were identified using the International Classification of Diseases 9 and 10 Australian Modification codes. A P-value of <0.05 was considered significant.

Results: The number of emergency appendicectomies more than doubled from 126 to 296 between 1999 and 2009. The rate of laparoscopic appendicectomy increased from <1% in 1999 to 70.3% in 2009. Overall, the mean patient age increased from 8.6 years in 1999 to 9.68 in 2009 (P = 0.005). There was an increase in the proportion (19.8% versus 39.5%, P < 0.001) and age (5.3 versus 8.8, P < 0.0001) of patients referred via inter-hospital transfers between the two time periods. In 2009, laparoscopic surgery required on average 13.6 min longer than open surgery. This increase in surgical duration was offset by a decrease in the length of stay (5.0 ± 0.7 versus 3.5 ± 0.3, P < 0.0001).

Conclusions: Our institution has experienced an extraordinary rise in the number of appendicectomies performed, which cannot be explained by an increase in the local paediatric population alone. There appears to have been dramatic shift in the surgical care of children to our tertiary paediatric centre. The majority of appendicectomies in 2009 were laparoscopic, with a reduced length of stay despite longer operative times.
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http://dx.doi.org/10.1111/j.1445-2197.2012.06168.xDOI Listing
September 2012

Delayed diagnosis of anorectal malformations: are current guidelines sufficient?

J Paediatr Child Health 2010 May 22;46(5):268-72. Epub 2010 Mar 22.

Department of Academic Surgery, The Children's Hospital at Westmead, The University of Sydney, New South Wales, Australia.

Aim: To determine the frequency and presenting features of infants with delayed diagnosis of anorectal malformations (ARM) referred to an Australian tertiary paediatric institution.

Methods: Infants referred to our institution with a final diagnosis of ARM were retrospectively reviewed between 2001 and 2009. The first cohort consisted of patients that were referred between November 2001 and November 2006 with the diagnosis of an ARM that had been delayed for more than 48 h. The second cohort was those referred between December 2006 and May 2009 with whom the diagnosis of ARM had not been made within 24 h of birth.

Results: Nineteen infants were referred with delayed diagnosis of an ARM over the 7.5 years of the study. Of 44 patients referred to our institution between December 2006 and May 2009, diagnosis of an ARM was delayed more than 24 h in 14 (32%). There was no difference in gender, birth weight, prematurity, type of malformation or presence of associated anomalies between those with timely and delayed diagnosis of their ARM. A significantly greater proportion of those with a delayed diagnosis presented with obstructive symptoms (86% vs. 27%, P < 0.001), including abdominal distension (57%) and delayed passage of meconium or stool (29%). Despite undergoing neonatal examination, the diagnosis of ARM was missed in 12 patients overall.

Conclusion: Delayed diagnosis of an ARM appears to be common, occurring in approximately 32% of patients referred to our institution over the last 2.5 years. Current guidelines appear insufficient to ensure prompt diagnosis of ARM.
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http://dx.doi.org/10.1111/j.1440-1754.2009.01683.xDOI Listing
May 2010