Publications by authors named "Kathryn Field"

47 Publications

Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study.

PLoS Med 2021 May 3;18(5):e1003620. Epub 2021 May 3.

The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

Background: In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.

Methods And Findings: We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing.

Conclusions: We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM.

Trial Registration: ACTRN12612000345886.
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http://dx.doi.org/10.1371/journal.pmed.1003620DOI Listing
May 2021

Whole genome and biomarker analysis of patients with recurrent glioblastoma on bevacizumab: A subset analysis of the CABARET trial.

J Clin Neurosci 2019 Dec 30;70:157-163. Epub 2019 Sep 30.

Prince of Wales Clinical School, Cure Brain Cancer Biomarkers and Translational Research Group, University of New South Wales, Sydney, NSW, Australia.

The CABARET trial (ACTRN12610000915055) reported no difference in overall survival (OS) between patients with recurrent glioblastoma (GBM) randomized to either bevacizumab monotherapy or bevacizumab plus carboplatin. However, a subset of patients showed durable responses and prolonged survival, with recorded survival times of over 30 months in five of 122 patients (4%). Patient selection for bevacizumab therapy would be enhanced if a predictive biomarker of response or survival could be identified; this biomarker sub-study attempted to identify novel biomarkers. Patients who opted to participate in this sub-study and who had adequate biospecimens for analysis (n = 54) were retrospectively evaluated for the expression of a series of tumor proteins. Immunohistochemistry (IHC) was used to measure the expression of 19 proteins previously implicated in cancer treatment response to bevacizumab. MGMT promoter methylation was also assessed. Tumor DNA from five patients with outlying survival duration ('poor' and 'exceptional' survivors) was subjected to whole genome sequencing (WGS). No single protein expression level, including VEGF-A, predicted OS in the cohort. WGS of poor and exceptional survivors identified a gain in Chromosome 19 that was exclusive to the exceptional survivors. Validation of this finding requires examination of a larger independent cohort.
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http://dx.doi.org/10.1016/j.jocn.2019.08.044DOI Listing
December 2019

Diversification rates have no effect on the convergent evolution of foraging strategies in the most speciose genus of bats, Myotis.

Evolution 2019 11 24;73(11):2263-2280. Epub 2019 Oct 24.

Department of Evolution, Ecology and Organismal Biology, Ohio State University, Columbus, Ohio, 43210.

Adaptive radiations are defined as rapid diversification with phenotypic innovation led by colonization to new environments. Notably, adaptive radiations can occur in parallel when habitats with similar selective pressures are accessible promoting convergent adaptions. Although convergent evolution appears to be a common process, it is unclear what are the main drivers leading the reappearance of morphologies or ecological roles. We explore this question in Myotis bats, the only Chiropteran genus with a worldwide distribution. Three foraging strategies-gleaning, trawling, and aerial netting-repeatedly evolved in several regions of the world, each linked to characteristic morphologies recognized as ecomorphs. Phylogenomic, morphometric, and comparative approaches were adopted to investigate convergence of such foraging strategies and skull morphology as well as factors that explain diversification rates. Genomic and morphometric data were analyzed from ∼80% extant taxa. Results confirm that the ecomorphs evolved multiple times, with trawling evolving more often and foliage gleaning most recently. Skull morphology does not reflect common ancestry and evolves convergently with foraging strategy. Although diversification rates have been roughly constant across the genus, speciation rates are area-dependent and higher in taxa with temperate distributions. Results suggest that in this species-rich group of bats, first, stochastic processes have led divergence into multiple lineages. Then, natural selection in similar niches has promoted repeated adaptation of phenotypes and foraging strategies. Myotis bats are thus a remarkable case of ecomorphological convergence and an emerging model system for investigating the genomic basis of parallel adaptive radiation.
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http://dx.doi.org/10.1111/evo.13849DOI Listing
November 2019

Right versus left sided metastatic colorectal cancer: Teasing out clinicopathologic drivers of disparity in survival.

Asia Pac J Clin Oncol 2019 Jun 13;15(3):136-143. Epub 2019 Feb 13.

Footscray Hospital, Western Health, Footscray, Victoria, Australia.

Background: Metastatic colorectal cancer (mCRC) patients with a right-sided primary (RC) have an inferior survival to mCRC arising from a left-sided primary (LC). Previous analyses have suggested multiple factors contribute.

Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients. RC were defined as tumors proximal to the splenic flexure; LC were those at and distal to the splenic flexure and included rectal cancers. Patient, tumor, treatment, and survival data were analyzed stratified by side.

Results: Of 2306 patients enrolled from July 2009-March 2018, 747 (32%) had an RC. Patients with RC were older, more likely to be female and have a Charlson score ≥3. RC were more frequently BRAF mutated, deficient in mismatch repair, associated with peritoneal metastases, and less likely to receive chemotherapy. Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs. 10.8 months, hazard ratio [HR] for progression in RC 1.38, P < 0.001). Median overall survival for all RC patients was inferior (19.6 vs. 27.5 months, HR for death in RC 1.44, P < 0.001), and inferior within the treated (21 vs. 29.5 months, HR 1.52, P < 0.001) and untreated subgroups (5.9 vs. 10.3 months, HR 1.38, P = 0.009). Primary side remained a significant factor for overall survival in multivariate analysis.

Conclusion: Our data from a real-world population confirms the poorer prognosis associated with RC. Primary tumor location remains significantly associated with overall survival even when adjusting for multiple factors, indicating the existence of further side-based differences that are as yet undefined.
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http://dx.doi.org/10.1111/ajco.13135DOI Listing
June 2019

Chemotherapy and biologic use in the routine management of metastatic colorectal cancer in Australia: is clinical practice following the evidence?

Intern Med J 2019 04;49(4):446-454

Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.

Background: Emerging evidence on the optimal use of chemotherapy and biologics in patients with metastatic colorectal cancer should impact management in routine care. Recent studies have demonstrated benefits for initial triplet chemotherapy (5-fluorouracil, oxaliplatin and irinotecan, FOLFOXIRI) and for initial treatment with an epidermal growth factor receptor inhibitor (EGFRi) in patients with a RAS wild-type tumour and a left-sided primary tumour.

Aim: To explore evolving pattern of metastatic colorectal cancer care over time in Australia.

Methods: We analysed data from the Treatment of Recurrent and Advanced Colorectal Cancer registry.

Results: From July 2009 to December 2017, 2552 metastatic colorectal cancer patients were entered into the Treatment of Recurrent and Advanced Colorectal Cancer registry. Of 1585 patients who initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI was given to 22 patients (1.4%), mostly young patients and those with potentially resectable disease. Along with first-line chemotherapy, 61% received bevacizumab, while 3.3% received an EGFRi, predominantly over the last 2 years. Within the KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to 37% in 2017. Across treatment sites, there was a wide variation in the utilisation of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear impact on survival outcomes from these regimens is not evident, potentially due to multiple confounders.

Conclusion: Doublet chemotherapy + bevacizumab remains the dominant initial strategy, with limited uptake of triplet chemotherapy and of EGFRi. Potential explanations include uncertainty about the significance of post hoc analyses for EGFRi and concerns regarding adverse events for both strategies.
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http://dx.doi.org/10.1111/imj.14115DOI Listing
April 2019

Stage-based Variation in the Effect of Primary Tumor Side on All Stages of Colorectal Cancer Recurrence and Survival.

Clin Colorectal Cancer 2018 09 26;17(3):e569-e577. Epub 2018 May 26.

Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Medical Oncology, Western Health, Footscray, VIC, Australia; Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia.

Background: Multiple studies have defined the prognostic and potential predictive significance of the primary tumor side in metastatic colorectal cancer (CRC). However, the currently available data for early-stage disease are limited and inconsistent.

Materials And Methods: We explored the clinicopathologic, treatment, and outcome data from a multisite Australian CRC registry from 2003 to 2016. Tumors at and distal to the splenic flexure were considered a left primary (LP).

Results: For the 6547 patients identified, the median age at diagnosis was 69 years, 55% were men, and most (63%) had a LP. Comparing the outcomes for right primary (RP) versus LP, time-to-recurrence was similar for stage I and III disease, but longer for those with a stage II RP (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.52-0.90; P < .01). Adjuvant chemotherapy provided a consistent benefit in stage III disease, regardless of the tumor side. Overall survival (OS) was similar for those with stage I and II disease between LP and RP patients; however, those with stage III RP disease had poorer OS (HR, 1.30; 95% CI, 1.04-1.62; P < .05) and cancer-specific survival (HR, 1.55; 95% CI, 1.19-2.03; P < .01). Patients with stage IV RP, whether de novo metastatic (HR, 1.15; 95% CI, 0.95-1.39) or relapsed post-early-stage disease (HR, 1.35; 95% CI, 1.11-1.65; P < .01), had poorer OS.

Conclusion: In early-stage CRC, the association of tumor side and effect on the time-to-recurrence and OS varies by stage. In stage III patients with an RP, poorer OS and cancer-specific survival outcomes are, in part, driven by inferior survival after recurrence, and tumor side did not influence adjuvant chemotherapy benefit.
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http://dx.doi.org/10.1016/j.clcc.2018.05.008DOI Listing
September 2018

The evolutionary pattern of mutations in glioblastoma reveals therapy-mediated selection.

Oncotarget 2018 Jan 15;9(8):7844-7858. Epub 2017 Dec 15.

School of Medicine, Deakin University, Geelong, Victoria, Australia.

Glioblastoma presents as a heterogeneous disease with poor prognosis despite the use of multimodal therapy. Analysis of genomic DNA changes between initial diagnosis and recurrence in response to standard treatment protocols would enhance understanding of disease progression and better inform new treatment strategies. A cohort of 21 patients with primary glioblastoma were examined between diagnosis and first recurrence. This study presented a rare opportunity to characterize molecular alterations in tumors observed in three patients who received no therapeutic intervention, other than surgery, offering a unique control. We focused this study by comparing the dynamic mutation profiles between the primary tumors and their matched recurrent counterparts. Molecular profiling of tumors was performed using multiplexed targeted deep sequencing of 409 well characterized cancer-associated genes, achieving a mean read depth of 1272 x. Three levels of evidence suggested an evolutionary pattern consistent with a response to therapy-mediated selection pressures exists in treated patients: 1) variant burden was reduced in recurrent tumors, 2) neutral evolutionary dynamics apparent in untreated tumors shifted toward a non-neutral mode of evolution in treated patients at recurrence, and 3) the recurrent tumor of one patient displayed an increased mutation rate attributable to a temozolomide-associated hypermutator phenotype. Our observations suggest that current treatment modalities are likely to fail in achieving long term remission with the majority of relapse samples containing distinct mutations when compared to primary diagnostic samples.
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http://dx.doi.org/10.18632/oncotarget.23541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814263PMC
January 2018

The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas.

J Neurooncol 2018 Mar 7;137(1):181-189. Epub 2017 Dec 7.

Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.
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http://dx.doi.org/10.1007/s11060-017-2710-7DOI Listing
March 2018

Comparison between site and central radiological assessments for patients with recurrent glioblastoma on a clinical trial.

Asia Pac J Clin Oncol 2018 Oct 8;14(5):e359-e365. Epub 2017 Nov 8.

Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Aim: Assessment of magnetic resonance imaging (MRI) in glioblastoma can be challenging. For patients with recurrent glioblastoma managed on the CABARET trial, we compared disease status assessed at hospitals and subsequent blinded central expert radiological review.

Methods: MRI results and clinical status at specified time points were used for site and central assessment of disease status. Clinical status was determined by the site. Response Assessment in Neuro-Oncology (RANO) criteria were used for both assessments. Site and central assessments of progression-free survival (PFS) and response rates were compared. Inter-rater variability for central review progression dates was assessed.

Results: Central review resulted in shorter PFS in 45% of 89 evaluable patients (n = 40). Median PFS was 3.6 (central) versus 3.9 months (site) (hazard ratio 1.5, 95% confidence interval 1.3-1.8, P < 0.001). Responses were documented more frequently by sites (n = 16, 18%) than centrally (n = 11, 12%). Seven of 120 patients continued on trial without site-determined progression for more than 6 months beyond the central review determination of progression. Of scans reviewed by all three central reviewers, 33% were fully concordant for progression date.

Conclusion: While the difference between site and central PFS dates was statistically significant, the 0.3-month median difference is small. The variability within central review is consistent with previous studies, highlighting the challenges in MRI interpretation in this context. A small proportion of patients benefited from treatment well beyond the centrally determined progression date, reinforcing that clinical status together with radiology results are important determinants of whether a therapy is effective for an individual.
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http://dx.doi.org/10.1111/ajco.12806DOI Listing
October 2018

Continuing or ceasing bevacizumab beyond progression in recurrent glioblastoma: an exploratory randomized phase II trial.

Neurooncol Pract 2017 Sep 25;4(3):171-181. Epub 2017 May 25.

Prince of Wales Hospital, Barker Street, Randwick, Sydney, NSW 2031, Australia (E.J.H.); University of New South Wales, Sydney, NSW 2052, Australia (E.J.H.); Royal Melbourne Hospital, Grattan Street, Parkville 3050, Melbourne Victoria, Australia (K.M.F., M.A.R., P.P., C.G.); Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Grattan Street Parkville 3052, Victoria, Australia (K.M.F., M.A.R.); National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Sydney, NSW 2006, Australia (E.H.B., K.S., A.L., J.S.); Austin Hospital, 145 Studley Road, Heidelberg, Melbourne, Victoria 3084, Australia (L.C.); Sir Charles Gairdner Hospital, Nedlands, Perth 6009, Western Australia (A.K.N.); Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia (H.W.).

Background: In patients with recurrent glioblastoma, the benefit of bevacizumab beyond progression remains uncertain. We prospectively evaluated continuing or ceasing bevacizumab in patients who progressed while on bevacizumab.

Methods: CABARET, a phase II study, initially randomized patients to bevacizumab with or without carboplatin (Part 1). At progression, eligible patients underwent a second randomization to continue or cease bevacizumab (Part 2). They could also receive additional chemotherapy regimens (carboplatin, temozolomide, or etoposide) or supportive care.

Results: Of 120 patients treated in Part 1, 48 (80% of the anticipated 60-patient sample size) continued to Part 2. Despite randomization, there were some imbalances in patient characteristics. The best response was stable disease in 7 (30%) patients who continued bevacizumab and 2 (8%) patients who stopped receiving bevacizumab. There were no radiological responses. Median progression-free survival was 1.8 vs 2.0 months (bevacizumab vs no bevacizumab; hazard ratio [HR], 1.08; 95% CI, .59-1.96; = .81). Median overall survival was 3.4 vs 3.0 months (HR, .84; 95% CI, .47-1.50; = .56 and HR .70; 95% CI .38-1.29; = .25 after adjustment for baseline factors). Quality-of-life scores did not significantly differ between arms. While the maximum daily steroid dose was lower in the continuation arm, the difference was not statistically significant.

Conclusions: Patients who continued bevacizumab beyond disease progression did not have clear survival improvements, although the study was not powered to detect other than very large differences. While these data provide the only randomized evidence related to continuing bevacizumab beyond progression in recurrent glioblastoma, the small sample size precludes definitive conclusions and suggests this remains an open question.
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http://dx.doi.org/10.1093/nop/npw025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6655481PMC
September 2017

The role of early magnetic resonance imaging in predicting survival on bevacizumab for recurrent glioblastoma: Results from a prospective clinical trial (CABARET).

Cancer 2017 Sep 5;123(18):3576-3582. Epub 2017 Jul 5.

Royal North Shore Hospital, St Leonards, Sydney, New South Wales, Australia.

Background: Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival.

Methods: Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard.

Results: For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors.

Conclusions: In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30838DOI Listing
September 2017

Health-related quality of life outcomes from CABARET: a randomized phase 2 trial of carboplatin and bevacizumab in recurrent glioblastoma.

J Neurooncol 2017 Jul 22;133(3):623-631. Epub 2017 May 22.

Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia.

In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.
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http://dx.doi.org/10.1007/s11060-017-2479-8DOI Listing
July 2017

How accurate are medical oncologists' impressions of management of metastatic colorectal cancer in Australia?

Asia Pac J Clin Oncol 2018 Apr 16;14(2):e167-e174. Epub 2017 Mar 16.

Department of Medical Oncology, Western Hospital, Melbourne, Australia.

Aim: Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC.

Methods: Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice.

Results: Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals.

Conclusions: Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC.
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http://dx.doi.org/10.1111/ajco.12671DOI Listing
April 2018

Early perfusion MRI predicts survival outcome in patients with recurrent glioblastoma treated with bevacizumab and carboplatin.

J Neurooncol 2017 01 28;131(2):321-329. Epub 2016 Nov 28.

Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, 6th Floor, Clinical Sciences Building, Royal Parade, Parkville, VIC, 3050, Australia.

Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan-Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially load, correlated significantly with PFS and OS at both follow-up time-points. Patients with the greatest reduction in rCBV by 8-weeks of therapy had a significantly increased median OS (30 weeks; p = 0.013). PWI may be of significant clinical utility in managing patients with rGBM, particularly those treated with anti-angiogenic agents such as bevacizumab. These findings need to be confirmed prospectively in larger studies.
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http://dx.doi.org/10.1007/s11060-016-2300-0DOI Listing
January 2017

Impact of Primary Tumor Site on Bevacizumab Efficacy in Metastatic Colorectal Cancer.

Clin Colorectal Cancer 2016 Jun 13;15(2):e9-e15. Epub 2016 Feb 13.

Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia; Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.

Background: With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients. While the prognostic impact of primary tumor site on colorectal cancer (CRC) outcomes is established, emerging data suggest potential differences in response to biologic therapies. We studied the impact of tumor site on bevacizumab efficacy in patients with metastatic CRC.

Patients And Methods: We analyzed data of patients in an Australian prospective multicenter metastatic CRC (mCRC) registry who received first-line chemotherapy. Tumor site was defined as right colon, cecum to transverse; left colon, splenic flexure to rectosigmoid; and rectum. Kaplan-Meier and Cox models were used for survival analyses.

Results: Of 926 patients, 297 had right colon, 354 left colon, and 275 rectum primary disease. Median age was 68.6, 65.9, and 63.3 years, respectively (P = .001). Right colon disease was significantly associated with intraperitoneal spread (P < .0001), while left colon and rectum disease preferentially metastasized to the liver and lungs, respectively (P < .0001 in both settings). A total of 636 patients (68.7%) received bevacizumab. Progression-free survival was superior for bevacizumab-treated patients in all groups but appeared greatest in right colon disease (hazard ratio, 0.46; 95% confidence interval, 0.36-0.60; P ≤ .001). Overall survival was longest in patients with disease of the rectum, followed by left colon and right colon (median, 26.2, 23.6, and 18.2 months, respectively; P = .0004).

Conclusion: Tumor site appears to be prognostic in mCRC, with rectum and right colon disease associated with the best and worst outcomes, respectively. Patients who received bevacizumab in addition to chemotherapy had superior outcomes, with the effect appearing greatest in patients with right colon disease.
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http://dx.doi.org/10.1016/j.clcc.2016.02.007DOI Listing
June 2016

Primary Tumor Resection and Overall Survival in Patients With Metastatic Colorectal Cancer Treated With Palliative Intent.

Clin Colorectal Cancer 2016 09 29;15(3):e125-32. Epub 2015 Dec 29.

Department of Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; University of Melbourne, Parkville, VIC, Australia; Department of Medical Oncology, Western Health, Footscray, VIC, Australia.

Background: The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC.

Patients And Methods: Consecutive patients from the Australian 'Treatment of Recurrent and Advanced Colorectal Cancer' registry were examined from June 2009 to March 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between multiple patient or clinical variables and OS. Patients with metachronous mCRC were excluded from the analyses.

Results: A total of 690 patients de novo and 373 metachronous mCRC patients treated with palliative intent were identified. The median follow-up period was 30 months. The median age of de novo patients was 66 years; 57% were male; 77% had an Eastern Cooperative Oncology Group performance status of 0 to 1; and 76% had a colon primary. A total of 216 de novo mCRC patients treated with palliative intent underwent PTR at diagnosis and were more likely to have a colon primary (odds ratio [OR], 15.4), a lower carcinoembryonic antigen level (OR, 2.08), and peritoneal involvement (OR, 2.58; P < .001). On multivariate analysis, PTR at diagnosis in de novo patients was not associated with significantly improved OS (hazard ratio [HR], 0.82; 99% confidence interval [CI], 0.62-1.09; P = .068). PTR at diagnosis did not correlate with outcome in de novo patients with a colon primary (HR, 0.74; 99% CI, 0.54-1.01; P = .014) or a rectal primary (HR, 0.81; 99% CI, 0.27-2.44; P = .621).

Conclusion: For de novo mCRC patients treated with palliative intent, PTR at diagnosis does not significantly improve OS when adjusting for known major prognostic factors. The outcomes of randomized trials examining the survival impact of PTR are awaited.
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http://dx.doi.org/10.1016/j.clcc.2015.12.010DOI Listing
September 2016

Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia.

J Geriatr Oncol 2015 Sep 17;6(5):387-94. Epub 2015 Jul 17.

Department of Medical Oncology, The Canberra Hospital, Canberra, Australia; ANU Medical School, Australian National University, Acton, Australia. Electronic address:

Objectives: The elderly accounts for a large proportion of patients with metastatic colorectal cancer (mCRC). This study reviews patterns of care and outcomes for elderly patients with mCRC in the community setting.

Materials And Methods: Elderly patients (≥ 65 years) with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry were identified. Treatment, bevacizumab-related adverse events, and overall survival (OS) were analysed by age cohorts, comparing those aged 65-74 vs. 75-84 vs. ≥ 85 years and correlated with potential prognostic factors. Factors affecting chemotherapy and bevacizumab administration were analysed using logistic regression analysis.

Results: Of 1439 patients, 363, 352, and 106 were aged 65-74, 75-84, and ≥ 85 years, respectively. 584 (71%) patients received first-line chemotherapy, with chemotherapy use declining with advancing age (84%, 69%, and 34% in 65-74-, 75-84- and ≥ 85-year-olds, respectively). Seven (10%) patients aged ≥ 85 years were not treated with chemotherapy on the basis of age alone. Only 10 of 36 very elderly patients who received chemotherapy also received bevacizumab. Factors affecting bevacizumab administration included age, treatment location, and comorbidities. There was no impact of age on bevacizumab-related adverse events. Resection of metastatic disease occurred in 173 (21%) patients overall, with rates declining with age (26% vs. 21% vs. 6%).

Conclusion: Chemotherapy usage and resection of metastatic disease decline with advancing age. A minority of patients are not treated with systemic therapy due to advanced age alone. Our cohort suggests underutilisation of bevacizumab in older patients, but where given, toxicity rates did not increase with age.
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http://dx.doi.org/10.1016/j.jgo.2015.06.001DOI Listing
September 2015

Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma.

Neuro Oncol 2015 Nov 30;17(11):1504-13. Epub 2015 Jun 30.

Royal Melbourne Hospital, Parkville, Australia (K.M.F, P.M.P, M.A.R.), National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (J.S., C.S.B.B., E.H.B, K.S., A.L.); Sir Charles Gairdner Hospital, Nedlands, Australia (A.K.N); School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia (A.K.N); Austin Health, Heidelberg, Australia (L.C., G.F.); Royal North Shore Hospital, St Leonards, Australia (H.W.); Prince of Wales Hospital, Randwick, Australia (E.J.H); University of New South Wales, Sydney, Australia (E.J.H); Monash Medical Centre, Clayton, Australia (R.F.); Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia (P.M.P., M.A.R., G.F.).

Background: The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy.

Methods: This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS).

Results: One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately.

Conclusions: Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies.

Clinical Trials Registration Nr: ACTRN12610000915055.
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http://dx.doi.org/10.1093/neuonc/nov104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648304PMC
November 2015

Impact of Diabetes Status and Medication on Presentation, Treatment, and Outcome of Stage II Colon Cancer Patients.

J Cancer Epidemiol 2015 5;2015:189132. Epub 2015 May 5.

Royal Melbourne Hospital, Melbourne, VIC 3050, Australia ; Western Hospital, Footscray, VIC 3011, Australia ; BioGrid Australia, Melbourne, VIC 3050, Australia.

Diabetes is a risk factor for colorectal cancer and several reports suggest worse cancer-specific outcomes in diabetes patients. Recent studies in multiple tumour types indicate metformin may positively impact on cancer-specific and overall survival. A population-based series of stage II colorectal cancer patients treated and followed from 2000 to 2013 were analysed for baseline characteristics, treatment, and outcomes. 1116 patients with stage II colon cancer were identified, 55.5% were male and median age was 70.9 years (range 20.5-101.2). The diabetes patients (21.6%, n = 241) were older than nondiabetes patients (median 74.0 versus 69.6, p = 0.0001). There was no impact of diabetes on cancer presentation or pathology. Diabetes patients were less likely to receive adjuvant treatment (13.7 versus 24.8%, p = 0.002) but were equally likely to complete treatment (69.7 versus 67.7%, p = 1.00). Diabetes did not significantly impact cancer recurrence (HR = 1.07, 95% CI 0.71-1.63) or overall survival (HR = 1.23, 95% CI 0.88-1.72), adjusted for age. Diabetes medication did not impact cancer recurrence or survival. Cancer presentation and outcomes in diabetes patients are comparable to those of nondiabetes patients in those with stage II colon cancer. The effect of metformin merits further evaluation in patients with colon cancer.
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http://dx.doi.org/10.1155/2015/189132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436511PMC
June 2015

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab.

World J Gastroenterol 2015 May;21(17):5352-8

Aflah Roohullah, Lorraine Chantrill, Macarthur Cancer Therapy Centre, Campbelltown, NSW 2560, Australia.

Aim: To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.

Methods: We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.

Results: Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups.

Conclusion: Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.
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http://dx.doi.org/10.3748/wjg.v21.i17.5352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419077PMC
May 2015

Primary Tumor Resection in Patients With Metastatic Colorectal Cancer Is Associated With Reversal of Systemic Inflammation and Improved Survival.

Clin Colorectal Cancer 2015 Sep 7;14(3):185-91. Epub 2015 Mar 7.

Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Australia; University of Melbourne, Melbourne, Australia; Department of Oncology, Western Health, Footscray, Australia; BioGrid Australia, Melbourne, Australia.

Background: The true survival benefit of noncurative primary tumor resection in patients with de novo metastatic colorectal cancer (mCRC) remains uncertain. The present study examined the effect of primary tumor resection on systemic inflammation and survival in patients with mCRC.

Materials And Methods: Consecutive patients with de novo mCRC who had undergone primary tumor resection were identified from a prospective database. Patients were excluded if they had undergone resection of metastases, had undergone delayed primary resection, or if blood samples were unavailable. The neutrophil/lymphocyte ratio (NLR) was used as a biomarker of systemic inflammation. Overall survival (OS) was compared between patient groups according to the pre- and postprimary resection NLR. The associations between the reversal of an elevated NLR and primary tumor bulk or performance status were explored.

Results: A total of 145 eligible patients were identified from the database, with a median age of 70 years. The baseline NLR was elevated (> 5) in 65 patients, 36 (55%) of whom had a low NLR after surgery. The reversal of an elevated NLR was associated with significantly improved OS (hazard ratio, 0.53; P = .017). A similar benefit was seen after excluding patients undergoing emergency primary resection. NLR reversal was more frequent in patients with larger primary tumors or good performance status.

Conclusion: The present study is the first to demonstrate a relationship between the reversal of a systemic inflammatory response and the improved survival after primary resection in those with mCRC. A greater effect was seen in patients with large primary tumors. If validated, these observations could guide clinical decision-making in patients with mCRC at presentation.
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http://dx.doi.org/10.1016/j.clcc.2015.02.004DOI Listing
September 2015

Novel quality indicators for metastatic colorectal cancer management identify significant variations in these measures across treatment centers in Australia.

Asia Pac J Clin Oncol 2015 Sep 14;11(3):262-71. Epub 2015 Apr 14.

The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.

Aims: Defining multidisciplinary quality of care indicators (QCIs) for metastatic colorectal cancer (mCRC) could improve understanding of variations in routine practice care. This may identify areas of below-average performance, which could then be addressed by clinicians to improve the quality of care delivered. This study aimed to define a panel of QCIs in mCRC and, based on these QCIs, to evaluate quality of care across multiple Australian sites.

Methods: A panel of clinicians with expertise in colorectal cancer defined evidence-based or best practice-based QCIs relevant to the routine multidisciplinary management of mCRC patients through structured consensus discussion. Related data were extracted from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry, a prospectively maintained database recording comprehensive details on consecutive mCRC patients across multiple Australian hospitals. Variations in QCIs across sites were explored.

Results: Of 13 QCIs defined, data related to 10 were reliably extracted from TRACC. Analysis of data on 1276 patients across 10 sites demonstrated low rates of screening for hereditary nonpolyposis colorectal cancer in young patients and significant variation in surveillance-detected recurrences, lung resection rates and palliative chemotherapy use. Exploratory analyses suggested correlation between liver resection rates and survival.

Conclusions: We have defined a novel set of mCRC QCIs and have demonstrated wide variation in the quality of care of mCRC across multiple Australian sites. With further validation to confirm a direct correlation between QCI and patient outcomes, these QCIs could be applied to improve the quality of care received by all mCRC patients.
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http://dx.doi.org/10.1111/ajco.12355DOI Listing
September 2015

The rapidly escalating cost of treating colorectal cancer in Australia.

Asia Pac J Clin Oncol 2016 Mar 13;12(1):33-40. Epub 2015 Apr 13.

Royal Melbourne Hospital, Parkville, Australia.

Aims: Considerable progress in cancer treatment is leading to better outcomes, but the cost of therapy is placing increasing pressure on the health system. Understanding the real-world cost of therapies for each stage will become increasingly important in informing treatment selection and health policy.

Methods: To explore the cost of treating colorectal cancer in the modern era, data were entered onto a prospective database at four hospitals. We estimated the impact of bevacizumab by using data from July 2009, and projected the likely impact of the recent listing of cetuximab. The utility of these data for estimating the cost-effectiveness of treatment was explored.

Results: Cancer stage and age at diagnosis were major determinants of treatment received and the associated cost. The cost of early stage disease has not substantially changed whereas therapies such as oxaliplatin and irinotecan were significant contributors to substantial increases in stage IV disease, now $71,156 per patient. Bevacizumab has added at least $10,247 per patient and we estimate that cetuximab will add a further $12,022. An exploratory analysis of the cost-effectiveness of oxaliplatin for adjuvant therapy of stage III colon cancer suggests that this is well within the accepted range.

Conclusion: These data suggest that recent progress in the treatment of later stages of colorectal cancer is being achieved at significant financial cost. The increased costs of managing later stages of disease make an investment in prevention and early detection ever more attractive.
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http://dx.doi.org/10.1111/ajco.12350DOI Listing
March 2016

The Importance of Efficacy: Using the Extended Parallel Process Model to Examine Factors Related to Preschool-Age Children Enrolled in Medicaid Receiving Preventive Dental Visits.

Health Educ Behav 2015 Dec 10;42(6):805-13. Epub 2015 Apr 10.

University of Iowa, Iowa City, IA, USA.

Early preventive dental visits are vital to the oral health of children. Yet many children, especially preschool-age children enrolled in Medicaid, do not receive early visits. This study attempts to uncover factors that can be used to encourage parents to seek preventive dental care for preschool-age children enrolled in Medicaid. The extended parallel process model was used as a theoretical framework for this research. This model suggests that people will act if the perceived threat (severity and susceptibility) is high enough and if efficacy levels (self-efficacy and response efficacy) are likewise high. Following Witte's method of categorizing people's perceptions and emotions into one of four categories based on levels of threat and efficacy, this article describes four groups (high threat/high efficacy, high threat/low efficacy, low threat/high efficacy, and low threat/low efficacy) of parents and how they compare to each other. Using logistic regression to model if a child had a preventive visit, results indicate that parents with low threat/high efficacy and parents with high threat/high efficacy had approximately 2.5 times the odds of having a child with a preventive oral health visit compared to parents with low threat/low efficacy, when controlling for perceived oral health status, health literacy, and child's age. The importance of efficacy needs to be incorporated in interventions aimed at increasing preventive dental visits for young children.
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http://dx.doi.org/10.1177/1090198115580575DOI Listing
December 2015

Geriatric assessment of older patients with cancer in Australia--a multicentre audit.

J Geriatr Oncol 2015 May 23;6(3):185-93. Epub 2015 Mar 23.

Border Medical Oncology, Suite 1, 69 Nordsvan Drive, Wodonga, VIC 3690, Australia. Electronic address:

Objective: The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics.

Material And Methods: This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010.

Results: Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM.

Conclusion: This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians.
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http://dx.doi.org/10.1016/j.jgo.2015.03.001DOI Listing
May 2015

Bevacizumab and glioblastoma: scientific review, newly reported updates, and ongoing controversies.

Cancer 2015 Apr 26;121(7):997-1007. Epub 2014 Sep 26.

Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Anti-angiogenic therapy for glioblastoma has been in the spotlight for several years, as researchers and clinicians strive to find agents with meaningful efficacy against glioblastoma. Bevacizumab in particular, in the second half of the last decade, became the most significant breakthrough in anti-glioblastoma therapy since temozolomide. Optimism for bevacizumab has been somewhat challenged given recent clinical trials that have raised questions regarding its clinical effectiveness, the optimal timing of its use and the validity of endpoints, among other issues. In addition, uncertainty has recently arisen regarding the effects of bevacizumab on quality of life and neurocognitive function, two key clinical endpoints of unquestionable significance among glioblastoma patients. In this review, we highlight these controversies and other recent work related to bevacizumab for glioblastoma.
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http://dx.doi.org/10.1002/cncr.28935DOI Listing
April 2015

Translation of clinical trial outcomes to metastatic colorectal cancer patients in community practice.

Asia Pac J Clin Oncol 2014 Dec 17;10(4):361-7. Epub 2014 Aug 17.

Western Hospital, Royal Melbourne Hospital and University of Melbourne, Melbourne, Victoria, Australia; Royal Melbourne Hospital, Royal Melbourne Hospital and University of Melbourne, Melbourne, Victoria, Australia.

Aim: As multiple new agents have been added to the treatment options for patients with metastatic colorectal cancer, survival outcomes in clinical trials have continued to improve. Similarly, improved outcomes in routine clinical care would be anticipated, but have yet to be demonstrated. Here, we aim to explore whether survival gains demonstrated in clinical trials are reproducible in routine practice, and whether factors beyond new therapies may be contributing to improved outcomes.

Methods: Comparison of comprehensive treatment and outcome data for consecutive patients diagnosed in 2003-2006 versus 2007-2010 at four specialist hospitals in Australia.

Results: Data were available on 965 patients; median age 66.1 years (range 19-93), 572 (59%) were male. For the latter time period, there was an increase in patients receiving any treatment (74% vs 66%, P = 0.014), initial combination chemotherapy (57% vs 44%, P < 0.001) and bevacizumab (15% vs 2%, P < 0.001). There was no change in the percentage undergoing resection of distant metastatic disease. For the latter time period, overall survival was improved (median 24.8 vs 17.4 months, P < 0.001), including patients not receiving any active treatment (11.9 vs 6.4 months, P = 0.014).

Conclusion: Survival outcomes in routine clinical care for patients with metastatic colorectal cancer have markedly improved in recent years following the introduction of multiple new active therapies. The improved outcome of untreated patients suggests earlier diagnosis and improved supportive care may also be contributing to survival gains.
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http://dx.doi.org/10.1111/ajco.12260DOI Listing
December 2014

Comparison between poor and long-term survivors with glioblastoma: review of an Australian dataset.

Asia Pac J Clin Oncol 2014 Jun 22;10(2):153-61. Epub 2013 May 22.

Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Aims: Despite the largely poor prognosis for patients with glioblastoma, 5-year survival approaches 10%. In many circumstances the reasons for discrepant outcomes remain unknown. This retrospective cohort study compared clinical and socio-demographic variables between long-term and poor survivors with glioblastoma.

Methods: Data from patients with glioblastoma diagnosed from 1998-2010 were accessed from two institutions. The cohort was divided into poor (<6 months), average (6-24 months) and long-term (>24 months) survivors. Clinical and socio-demographic variables were compared.

Results: In total 529 patients were included; 221 (42%) were poor, 260 (49%) average and 48 (9%) long-term survivors. Those surviving >24 months were younger and significantly more likely to be in a higher socioeconomic status group; be of a better performance status; have a frontal lobe tumor; have a craniotomy (rather than a biopsy); have a macroscopic resection; have two or more operations; and participate in a clinical trial. Country of birth, regional versus city residence and public versus private hospital treatment were not associated with differential survival outcomes. An ordered logistic regression analysis showed that age, performance status, extent of resection and clinical trial participation were independently associated with survival.

Conclusion: Reassuringly, no statistically significant socio-demographic differences exist when comparing long-term and poor survivors with glioblastoma. Patients surviving more than 2 years were significantly more likely to have participated in a clinical trial. This research could contribute towards informing further research on prognostic variables for patients with glioblastoma.
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http://dx.doi.org/10.1111/ajco.12076DOI Listing
June 2014

Clinical trial participation and outcome for patients with glioblastoma: multivariate analysis from a comprehensive dataset.

J Clin Neurosci 2013 Jun 29;20(6):783-9. Epub 2013 Apr 29.

Department of Medical Oncology, Royal Melbourne Hospital, Victoria, Australia.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Although multiple clinical and tumor-related variables affect survival outcomes, the effect of clinical trial participation has not been explored. The aim of this study was to determine whether clinical trial participation improves outcome for patients with GBM. Data from patients with GBM were accessed from a dataset collected over 12 years (1998-2010) at two institutions. Univariable and multivariate logistic regression analyses were performed to look for relationships between clinical trial participation, other baseline clinical and sociodemographic variables and overall survival (OS). In total, 542 patients were identified and included in the analysis; median age was 62 years. Sixty-one patients (11%) were enrolled in a clinical trial. Clinical trial enrollment was associated with improved median survival (14.5 months compared to 6.3 months, p < 0.001) and this difference remained significant in multivariate analysis (hazard ratio 0.67, p = 0.046). Age, poor performance status and operation type were also independent predictors for OS in multivariate analysis. Disease site, socioeconomic status and co-morbidity did not affect survival outcome. This is the first study in patients with GBM to suggest a survival benefit from clinical trial participation, independent of age and performance status; while also confirming the importance of other previously reported prognostic factors. This should encourage clinicians to offer trial therapies to patients with GBM and encourage patients to participate in available studies.
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http://dx.doi.org/10.1016/j.jocn.2012.09.013DOI Listing
June 2013