ORCID Profile
0000-0002-2530-0523
Current Organisations
NHMRC Clinical Trials Centre
,
Chris O’Brien Lifehouse
,
The Kinghorn Cancer Centre
,
Royal Prince Alfred Hospital
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Publisher: Wiley
Date: 04-03-2020
DOI: 10.1002/CAM4.2948
Publisher: American Society of Clinical Oncology (ASCO)
Date: 04-2021
DOI: 10.1200/JCO.20.02232
Abstract: SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy with metastatic pancreatic ductal adenocarcinoma (PDAC). SEQUOIA, a randomized, global phase III study, compared FOLFOX with PEG + FOLFOX as second line in gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG + FOLFOX:FOLFOX) and stratified by prior gemcitabine and region. Eligible patients had only one prior gemcitabine-containing treatment. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), response evaluation per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1, and safety. Exploratory analyses included biomarkers related to immune activation. Between March 1, 2017, and September 9, 2019, 567 patients were randomly assigned PEG + FOLFOX (n = 283) or FOLFOX (n = 284). Most (94.7%) patients received prior gemcitabine plus nab paclitaxel. OS was similar comparing PEG + FOLFOX versus FOLFOX (median: 5.8 v 6.3 months hazard ratio = 1.045 95% CI, 0.863 to 1.265). Also, PFS (median 2.1 v 2.1 months hazard ratio = 0.981 95% CI, 0.808 to 1.190) and objective response rate (4.6% v 5.6%) were similar between the treatment arms. Most common (≥ 35%) treatment-emergent adverse events in PEG + FOLFOX versus FOLFOX were thrombocytopenia (55% v 20%), anemia (40% v 16%), fatigue (61% v 45%), neutropenia (39% v 28%), abdominal pain (37% v 29%), nausea (45% v 41%), neuropathy (37% v 38%), and decreased appetite (35% v 31%). Exploratory analyses revealed increases in total IL-18, interferon (IFN)-γ, and granzyme B and decreases in transforming growth factor (TGF)-β with the addition of PEG. PEG added to FOLFOX did not improve efficacy in advanced gemcitabine-refractory PDAC. Safety findings were consistent as previously observed from PEG with chemotherapy toxicity was manageable and tolerable. Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway.
Publisher: S. Karger AG
Date: 14-10-2020
DOI: 10.1159/000510446
Abstract: b i Background: /i /b Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. b i Methods: /i /b A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. b i Results: /i /b Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT ( i n /i = 67 72%) or dCRT ( i n /i = 26 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63% i /i = 0.001 HR 3.1 95% CI: 1.2–7.7) and DFS (0 vs. 41% i /i = 0.004 HR 3.6 95% CI: 1.4–8.9) on multivariable and IPTW sensitivity analyses. b i Conclusions: /i /b TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.
Publisher: BMJ
Date: 09-2022
DOI: 10.1136/BMJOPEN-2021-058107
Abstract: Glioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world setting to improve survival of people with GBM. Initial experimental arms are evaluating the effectiveness of interventions in newly diagnosed GBM (ndGBM). This study will compare maximal surgical resection followed by chemoradiotherapy plus adjuvant chemotherapy for 6 months with the addition of (1) ‘neoadjuvant’ chemotherapy beginning as soon as possible after surgery and/or (2) adjuvant chemotherapy continued until progression within the same study platform. MAGMA will establish a platform for open-label, multiarm, multicentre randomised controlled testing of treatments for GBM. The study began recruiting in September 2020 and recruitment to the initial two interventions in MAGMA is expected to continue until September 2023. Adults aged ≥18 years with ndGBM will be given the option of undergoing randomisation to each study intervention separately, thereby giving rise to a partial factorial design, with two separate randomisation time points, one for neoadjuvant therapy and one for extended therapy. Patients will have the option of being randomised at each time point or continuing on with standard treatment. The primary outcome for the study is overall survival from the date of initial surgery until death from any cause. Secondary outcomes include progression-free survival, time to first non-temozolomide treatment, overall survival from each treatment randomisation, clinically significant toxicity as measured by grade 3 or 4 adverse events and health-related quality-of-life measures. Tertiary outcomes are predictive rognostic biomarkers and health utilities and incremental cost-effectiveness ratio. The primary analysis of overall survival will be performed separately for each study intervention according to the intention to treat principle on all patients randomised to each study intervention. The study (Protocol version 2.0 dated 23 November 2020) was approved by a lead Human Research Ethics Committee (Sydney Local Health District: 2019/ETH13297). The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. ACTRN12620000048987.
Publisher: Wiley
Date: 15-09-2018
DOI: 10.1002/CNCR.31595
Abstract: To the authors' knowledge, outcomes and prognostic tools have yet to be clearly defined in patients with metastatic renal cell carcinoma (mRCC) who are treated with immuno-oncology (IO) checkpoint inhibitors (programmed death-ligand 1 [PD-L1] inhibitors). In the current study, the authors aimed to establish IO efficacy benchmarks in patients with mRCC and update patient outcomes in each International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class. A retrospective analysis was performed using the IMDC database with data from 38 centers. It included patients with mRCC who were treated with ≥1 line of IO. Overall response rates (ORRs), duration of treatment (DOT), and overall survival (OS) were calculated. Patients were stratified using IMDC prognostic factors. A total of 687 patients (90% with clear cell and 10% with non-clear cell) were included. The ORR was 27% in evaluable patients (461 patients). In patients treated with first-line nivolumab and ipilimumab (49 patients), the combination of PD-L1 inhibitor and vascular endothelial growth factor inhibitor (72 patients), and PD-L1 inhibitor (51 patients), the ORR was 31%, 39%, and 40%, respectively, and the median DOT was 8.3 months, 14.7 months, and 8.3 months, respectively. The ORR for second-line, third-line, and fourth-line nivolumab was 22%, 24%, and 26%, respectively. The median DOT was 5.7 months, 6.2 months, and 8.3 months, respectively, in the second-line, third-line, and fourth-line settings. When segregated into IMDC favorable-risk, intermediate-risk, and poor-risk groups, the median OS rates for the first-line, second-line, third-line, and fourth-line treatment settings were not reached (NR), NR, and NR, respectively (P = .163) NR, 26.7 months, and 7.4 months, respectively (P < 0. 0001) 36.1 months, 28.2 months, and 11.1 months, respectively (P = .016) and NR, NR, and 6.7 months, respectively (P = .047). The ORR was not found to deteriorate from the first-line to the fourth-line of IO therapy. In the second line through fourth line, the IMDC criteria appropriately stratified patients into favorable-risk, intermediate-risk, and poor-risk groups for OS.
Publisher: Wiley
Date: 12-01-2021
DOI: 10.1111/ANS.16537
Abstract: Human papilloma virus (HPV)‐associated oropharyngeal squamous cell carcinoma (OPSCC) continues to increase in incidence. Patients are younger, non‐smokers and most commonly present with a neck mass often with no other symptoms. This altered presentation compared with non‐HPV OPSCC may not be recognized by medical practitioners, leading to delayed diagnosis. Patients with histopathological confirmation of OPSCC and known HPV and/or P16 status who presented to our institution between 2012–2017 inclusive were included in the study. Demographic data, tumour characteristics and presenting symptoms were retrospectivxely obtained from both electronic‐ and paper‐based records. Descriptive statistics were used to report demographic data and the two s le t ‐test and Fisher's exact test were used to compare groups based on HPV status. Time to diagnosis was also reported. A total of 184 patients were included in the study. The majority of patients were male (85.4%) and HPV + (85.3%). The tonsillar complex (53.8%) and tongue base (42.4%) were the most common primary sites. HPV+ patients were less likely to smoke (17.8%) and they commonly presented with a neck mass (39.5% alone or with other symptoms 61.2%). Time to diagnosis in the HPV+ group was longer (15 weeks). Our review has highlighted the altered presentation of OPSCC due to the increased incidence of HPV infection. We showed a delayed time to diagnosis in HPV+ OPSCC compared with non‐HPV disease. This confirms the importance of focusing our efforts on educating medical practitioners and creating further awareness to facilitate early detection and treatment.
Publisher: Wiley
Date: 03-08-2023
DOI: 10.1111/IMJ.15561
Abstract: Geographic isolation and travel distance to specialist care is a known social determinant of health and contributes to poorer oncology survival outcomes. To compare survival and toxicity outcomes for patients travelling long distances ( km) for treatment on clinical trials with local patients ( km and 10–50 km). We performed a retrospective cohort study based at the Kinghorn Cancer Centre, a comprehensive cancer care centre in metropolitan Sydney. We included adult patients with advanced solid‐organ malignancies who were enrolled on therapeutic clinical trials between July 2015 and December 2017. Outcome measures included overall survival, progression‐free survival, rates of grade 3–4 toxicity and unplanned hospital admissions for the duration of the clinical trial. We included 173 patients, of whom 27% lived within 10 km, 29% lived between 10 and 50 km and 44% lived further than 50 km. We did not identify significant differences between survival or toxicity outcomes between patients travelling long distances and local patients. All patients should be considered for clinical trial referral based on clinical parameters and preference, regardless of geographic proximity. In the meantime, improving access to clinical trials for rural and regional patients continues to be a priority.
Publisher: Canadian Urological Association Journal
Date: 11-04-2017
DOI: 10.5489/CUAJ.4398
Abstract: Introduction: Clinical trial data has shown pazopanib to be noninferior in overall survival (OS) compared to sunitinib as first-line treatment for metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate outcomes and compare dose-modifying toxicities of mRCC patients treated with suntinib or pazopanib in the real-world setting.Methods: Data were collected on mRCC patients using the prospective Canadian Kidney Cancer Information System (CKCis) database from January 2011 to November 2015. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method.Results: We identified 670 patients treated with sunitinib (n=577) and pazopanib (n=93). There were no significant differences in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807). Patients treated with sunitinib had improved OS compared with pazopanib (median 31.7 vs. 20.6 months, p=0.028 adjusted hazard ratio [aHR] 0.60 95% confidence interval [CI] 0.38‒0.94). Time to treatment failure (TTF) was numerically, but not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130 aHR 0.87 95% CI 0.59‒1.28). Outcomes with in idualized dosing on sunitinib were unavailable for this analysis. Patients treated with sunitinib had a higher incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease patients treated with pazopanib had a higher incidence of hepatotoxicity.Conclusions: In Canadian patients with mRCC, treatment with sunitinib appears to be associated with an improved OS compared to pazopanib in the first-line setting. Patient selection factors and the contemporary practice of in idualized dosing with sunitinib may contribute to these real-world outcomes and warrant further investigation.
Publisher: MDPI AG
Date: 17-12-2022
DOI: 10.3390/CURRONCOL29120781
Abstract: The aim of this project was to determine research priorities, barriers, and enablers for adult primary brain tumour research in Australia and New Zealand. Consumers, health professionals, and researchers were invited to participate in a two-phase modified Delphi study. Phase 1 comprised an initial online survey (n = 91) and then focus groups (n = 29) which identified 60 key research topics, 26 barriers, and 32 enablers. Phase 2 comprised two online surveys to (1) reduce the list to 37 research priorities which achieved consensus ( % 2-point agreement) and had high mean importance ratings (n = 116 participants) and (2) determine the most important priorities, barriers, and enablers (n = 90 participants). The top ten ranked research priorities for the overall s le and sub-groups (consumers, health professionals, and researchers) were identified. Priorities focused on: tumour biology, pre-clinical research, clinical and translational research, and supportive care. Variations were seen between sub-groups. The top ten barriers to conducting brain tumour research related to funding and resources, accessibility and awareness of research, collaboration, and process. The top ten research enablers were funding and resources, collaboration, and workforce. The broad list of research priorities identified by this Delphi study, together with how consumers, health professionals, and researchers prioritised items differently, and provides an evidence-based research agenda for brain tumour research that is needed across a wide range of areas.
Publisher: Informa UK Limited
Date: 02-12-2014
DOI: 10.1586/14737140.2014.863468
Abstract: Despite therapeutic advances, the development of breast cancer brain metastases (BCBM) is still the harbinger of a dismal prognosis. Patient outcomes vary depending on factors, including tumor phenotype, extent of disease within and outside the brain, as well as patient performance status. Treatment includes surgery, radiation therapy and systemic therapy determined by patient and tumor characteristics. Despite these approaches, novel treatments are needed and there is growing interest in systemic therapies. However, the efficacy of pharmacologic agents is h ered by poor penetration of drugs across the blood-brain barrier. Therefore, there is a pressing need for a greater understanding of the natural history of BCBM to guide the development of further therapies. This review analyzes prognosis and treatment of BCBM by tumor phenotype and discusses ongoing research into new therapies.
Publisher: Wiley
Date: 15-05-2018
DOI: 10.1002/CAM4.1493
Abstract: Several systems (tumor‐node‐metastasis [ TNM ], Barcelona Clinic Liver Cancer [ BCLC ], Okuda, Cancer of the Liver Italian Program [ CLIP ], and albumin–bilirubin grade [ ALBI ]) were developed to estimate the prognosis of patients with hepatocellular carcinoma ( HCC ) mostly prior to the prevalent use of sorafenib. We aimed to compare the prognostic and discriminatory power of these models in predicting survival for HCC patients treated with sorafenib and to identify independent prognostic factors for survival in this population. Patients who received sorafenib for the treatment of HCC between 1 January 2008 and 30 June 2015 in the provinces of British Columbia and Alberta, and two large cancer centers in Toronto, Ontario, were included. Survival was assessed using the Kaplan–Meier method. Multivariate Cox regression was used to identify predictors of survival. The models were compared with respect to homogeneity, discriminatory ability, monotonicity of gradients, time‐dependent area under the curve, and Akaike information criterion. A total of 681 patients were included. 80% were males, 86% had Child–Pugh class A, and 37% of patients were East Asians. The most common etiology for liver disease was hepatitis B (34%) and C (31%). In all model comparisons, CLIP performed better while BCLC and TNM 7 performed less favorably but the differences were small. The utility of each system in allocating patients into different prognostic groups varied, for ex le, TNM poorly differentiated patients in advanced stages (8.7 months (m) (95% CI 6.5–11.5) versus 8.4 m (95% CI 7.0–9.6) for stages III and IV , respectively) while ALBI had excellent discrimination of early grades (15.6 m [95% CI 13.0–18.4] versus 8.3 m [95% CI 7.0–9.2] for grades 1 and 2, respectively). On multivariate analysis, hepatitis C, alcoholism, and prior hepatic resection were independently prognostic of better survival ( P 0.01). In conclusion, none of the prognostic systems was optimal in predicting survival in sorafenib‐treated patients with HCC . Etiology of liver disease should be considered in future models and clinical trial designs.
Publisher: Oxford University Press (OUP)
Date: 31-08-2021
DOI: 10.1093/NOP/NPAB055
Abstract: The goal of a clinical quality registry is to deliver immediate gains in survival and quality of life by delivering timely feedback to practitioners, thereby ensuring every patient receives the best existing treatment. We are developing an Australian Brain Cancer Registry (ABCR) to identify, describe, and measure the impact of the variation and gaps in brain cancer care from the time of diagnosis to the end of life. To determine a set of clinical quality indicators (CQIs) for the ABCR, a database and internet search were used to identify relevant guidelines, which were then assessed for quality using the AGREE II Global Rating Scale. Potential indicators were extracted from 21 clinical guidelines, ranked using a modified Delphi process completed in 2 rounds by a panel of experts and other stakeholders, and refined by a multidisciplinary Working Group. Nineteen key quality reporting domains were chosen, specified by 57 CQIs detailing the specific inclusion and outcome characteristics to be reported. The selected CQIs will form the basis for the ABCR, provide a framework for achievable data collection, and specify best practices for patients and health care providers, with a view to improving care for brain cancer patients. To our knowledge, the systematic and comprehensive approach we have taken is a world first in selecting the reporting specifications for a brain cancer clinical registry.
Publisher: Elsevier BV
Date: 08-2020
Publisher: MDPI AG
Date: 12-2018
DOI: 10.3747/CO.25.4208
Abstract: Background: We aimed to assess current treatment patterns and outcomes in elderly patients with localized gastric and esophageal (GE) cancers. Methods: This retrospective analysis considered patients 75 years of age or older with ge cancers treated during 2012–2014. Patient demographics and tumour characteristics were collected. Overall survival (OS) and disease-free survival were assessed by univariable and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors affecting treatment choices. Results: The 110 patients in the study cohort had a median age of 81 years (range: 75–99 years). Primary disease sites were esophageal (55%) and gastric (45%). Treatment received included radiation therapy alone (29%), surgery alone (26%), surgery plus perioperative therapy (14%), chemoradiation alone (10%), and supportive care alone (14%). In multivariable analyses, surgery (hazard ratio: 0.48 95% confidence interval: 0.26 to 0.90 p = 0.02) was the only independent predictor for improved os. Patients with a good Eastern Cooperative Oncology Group performance status (p = 0.008), gastric disease site (p = 0.02), and adenocarcinoma histology (p = 0.01) were more likely to undergo surgery. Conclusions: At our institution, few patients 75 years of age and older received multimodality therapy for localized ge cancers. Outcomes were better for patients who underwent surgery than for those who did not. To ensure optimal treatment selection, comprehensive geriatric assessment should be considered for patients 75 years of age and older with localized GE cancers.
Publisher: Elsevier BV
Date: 05-2023
Publisher: Wiley
Date: 07-05-2020
DOI: 10.1002/CAM4.3116
Publisher: BMJ
Date: 04-04-2022
Abstract: Measurement of Response Evaluation Criteria In Solid Tumors (RECIST) relies on reproducible unidimensional tumor measurements. This study assessed intraobserver and interobserver variability of target lesion selection and measurement, according to RECIST version 1.1 in patients with ovarian cancer. Eight international radiologists independently viewed 47 images demonstrating malignant lesions in patients with ovarian cancer and selected and measured lesions according to RECIST V.1.1 criteria. Thirteen images were viewed twice. Interobserver variability of selection and measurement were calculated for all images. Intraobserver variability of selection and measurement were calculated for images viewed twice. Lesions were classified according to their anatomical site as pulmonary, hepatic, pelvic mass, peritoneal, lymph nodal, or other. Lesion selection variability was assessed by calculating the reproducibility rate. Lesion measurement variability was assessed with the intra-class correlation coefficient. From 47 images, 82 distinct lesions were identified. For lesion selection, the interobserver and intraobserver reproducibility rates were high, at 0.91 and 0.93, respectively. Interobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass and other lesions. Intraobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass, hepatic, nodal, and other lesions. Selection reproducibility was lowest for peritoneal lesions (interobserver reproducibility rate 0.76 and intraobserver reproducibility rate 0.69). For lesion measurement, the overall interobserver and intraobserver intraclass correlation coefficients showed very good concordance of 0.84 and 0.94, respectively. Interobserver intraclass correlation coefficient showed very good concordance for hepatic, pulmonary, peritoneal, and other lesions, and ranged from 0.84 to 0.97, but only moderate concordance for lymph node lesions (0.58). Intraobserver intraclass correlation coefficient showed very good concordance for all lesions, ranging from 0.82 to 0.99. In total, 85% of total measurement variability resulted from interobserver measurement difference. Our study showed that while selection and measurement concordance were high, there was significant interobserver and intraobserver variability. Most resulted from interobserver variability. Compared with other lesions, peritoneal lesions had the lowest selection reproducibility, and lymph node lesions had the lowest measurement concordance. These factors need consideration to improve response assessment, especially as progression free survival remains the most common endpoint in phase III trials.
Publisher: AME Publishing Company
Date: 04-2020
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.CURRPROBLCANCER.2017.10.007
Abstract: Hepatocellular carcinoma is a common malignancy which usually emerges on a background of chronic liver disease. Unfortunately, with contemporary management, patients with advanced hepatocellular carcinoma have few treatment options, and prognosis is poor. The emergence of immunotherapy has afforded new therapeutic opportunities. This article reviews the clinical evidence for immunotherapy in advanced hepatocellular carcinoma and presents ideas for future drug development.
Publisher: MDPI AG
Date: 16-02-2022
Abstract: Gliomas are the most common malignant primary brain tumor in adults. Despite advances in multimodality therapy, incorporating surgery, radiotherapy, systemic therapy, tumor treating fields and supportive care, patient outcomes remain poor, especially in glioblastoma where median survival has remained static at around 15 months, for decades. Low-grade gliomas typically harbor isocitrate dehydrogenase (IDH) mutations, grow more slowly and confer a better prognosis than glioblastoma. However, nearly all gliomas eventually recur and progress in a way similar to glioblastoma. One of the novel therapies being developed in this area are poly(ADP-Ribose) polymerase (PARP) inhibitors. PARP inhibitors belong to a class of drugs that target DNA damage repair pathways. This leads to synthetic lethality of cancer cells with coexisting homologous recombination deficiency. PARP inhibitors may also potentiate the cytotoxic effects of radiotherapy and chemotherapy, and prime the tumor microenvironment for immunotherapy. In this review, we examine the rationale and clinical evidence for PARP inhibitors in glioma and suggest therapeutic opportunities.
Publisher: Frontiers Media SA
Date: 18-11-2020
Publisher: MDPI AG
Date: 13-07-2020
DOI: 10.3390/IJMS21144954
Abstract: Extracellular vesicles (EVs) play key roles in glioblastoma (GBM astrocytoma grade IV) biology and are novel sources of biomarkers. EVs released from GBM tumors can cross the blood-brain-barrier into the periphery carrying GBM molecules, including small non-coding RNA (sncRNA). Biomarkers cargoed in circulating EVs have shown great promise for assessing the molecular state of brain tumors in situ. Neurosurgical aspirate fluids captured during tumor resections are a rich source of GBM-EVs isolated directly from tumor microenvironments. Using density gradient ultracentrifugation, EVs were purified from cavitron ultrasonic surgical aspirate (CUSA) washings from GBM (n = 12) and astrocytoma II-III (GII-III, n = 5) surgeries. The sncRNA contents of surgically captured EVs were profiled using the Illumina® NextSeqTM 500 NGS System. Differential expression analysis identified 27 miRNA and 10 piRNA species in GBM relative to GII-III CUSA-EVs. Resolved CUSA-EV sncRNAs could discriminate serum-EV sncRNA profiles from GBM and GII-III patients and healthy controls and 14 miRNAs (including miR-486-3p and miR-106b-3p) and cancer-associated piRNAs (piR_016658, _016659, _020829 and _204090) were also significantly expressed in serum-EVs. Circulating EV markers that correlate with histological, neuroradiographic and clinical parameters will provide objective measures of tumor activity and improve the accuracy of GBM tumor surveillance.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.SOC.2017.05.006
Abstract: Hepatocellular carcinoma is a common malignancy that typically occurs in the setting of comorbid liver disease. Optimal management is challenging, especially given the assortment of available treatment modalities. This article reviews the randomized clinical trials that have formed the basis of contemporary hepatocellular carcinoma management.
Publisher: MDPI AG
Date: 03-07-2020
DOI: 10.3390/IJMS21134754
Abstract: Improving outcomes for diffuse glioma patients requires methods that can accurately and sensitively monitor tumour activity and treatment response. Extracellular vesicles (EV) are membranous nanoparticles that can traverse the blood–brain-barrier, carrying oncogenic molecules into the circulation. Measuring clinically relevant glioma biomarkers cargoed in circulating EVs could revolutionise how glioma patients are managed. Despite their suitability for biomarker discovery, the co-isolation of highly abundant complex blood proteins has hindered comprehensive proteomic studies of circulating-EVs. Plasma-EVs isolated from pre-operative glioma grade II–IV patients (n = 41) and controls (n = 11) were sequenced by Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) and data extraction was performed by aligning against a custom 8662-protein library. Overall, 4054 proteins were measured in plasma-EVs. Differentially expressed proteins and putative circulating-EV markers were identified (adj. p-value 0.05), including those reported in previous in-vitro and ex-vivo glioma-EV studies. Principal component analysis showed that plasma-EV protein profiles clustered according to glioma histological-subtype and grade, and plasma-EVs res led from patients with recurrent tumour progression grouped with more aggressive glioma s les. The extensive plasma-EV proteome profiles achieved here highlight the potential for SWATH-MS to define circulating-EV biomarkers for objective blood-based measurements of glioma activity that could serve as ideal surrogate endpoints to assess tumour progression and allow more dynamic, patient-centred treatment protocols.
Publisher: Future Medicine Ltd
Date: 2018
Abstract: High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been investigated, including targeted therapies, immunotherapeutics and tumor-treating fields. This review summarizes the key findings from this research, and presents a perspective on future opportunities to advance the field.
Publisher: Mary Ann Liebert Inc
Date: 10-2018
Abstract: We aimed to evaluate the effectiveness of an adult-based adolescent and young adult (AYA) cancer program by assessing patient satisfaction and whether programming offers added incremental benefit beyond primary oncology providers (POP) to address their needs. A modified validated survey was used to ask two questions: (1) rate on a 10-point Likert scale their level of satisfaction with the information provided to them by their POP and (2) did the AYA consult provide added value on top of their POP. Young people at PM were recruited over two separate time points spaced 1 year apart. Descriptive statistics was used to report demographics and survey responses. Differences in demographics between cohorts 1 and 2 were compared using Student's t-tests. Participants were an average of 31 years (range 15-39) of age (Cohort 1 = 137 Cohort 2 = 130) and were dominated by diagnoses of leukemia, lymphoma, and breast cancer. More patients had a consultation with the AYA program in 2016 (Cohort 2 = 55/130, 42%) compared to 2015 (Cohort 1 = 34/137, 25%, p = 0.026). Mean satisfaction scores (±SD) with information provided by POP in AYA domains in both cohorts combined were highest among (1) cancer information (8.09 ± 2.22), (2) social supports (7.45 ± 2.52), and (3) school/work (7.42 ± 2.88). When evaluating the incremental benefit of the AYA-dedicated team, statistically significant added value was perceived in 5/10 domains, including school/work (p < 0.001), social supports (p < 0.001), physical appearance (p = 0.009), sexual health (p = 0.01), and fertility (p < 0.001). Participants were satisfied with the information provided by their POP and still declared incremental added benefit of the AYA program. Cancer centers should continue to advocate for AYA focused programming with ongoing evaluation.
Publisher: MDPI AG
Date: 28-01-2020
Abstract: Aggressive pituitary tumors account for up to 10% of pituitary tumors and are characterized by resistance to medical treatment and multiple recurrences despite standard therapies, including surgery, radiotherapy, and chemotherapy. They are associated with increased morbidity and mortality, particularly pituitary carcinomas, which have mortality rates of up to 66% at 1 year after diagnosis. Novel targeted therapies under investigation include mammalian target of rapamycin (mTOR), tyrosine kinase, and vascular endothelial growth factor (VEGF) inhibitors. More recently, immune checkpoint inhibitors have been proposed as a potential treatment option for pituitary tumors. An increased understanding of the molecular pathogenesis of aggressive pituitary tumors is required to identify potential biomarkers and therapeutic targets. This review discusses novel approaches to the management of aggressive pituitary tumors and the role of molecular profiling.
Publisher: American Association for Cancer Research (AACR)
Date: 06-2019
DOI: 10.1158/1078-0432.CCR-18-3205
Abstract: Isocitrate dehydrogenase (IDH) mutations are common in low-grade gliomas and the IDH mutation status is now integrated into the WHO classification of gliomas. IDH mutations lead to preferential accumulation of the R- relative to the S-enantiomer of 2-hydroxyglutarate (2-HG). We investigated the utility of tissue total 2-HG, R-2-HG, and the R-2-HG/S-2-HG ratio (rRS) as diagnostic and prognostic biomarkers for IDH mutations in gliomas. Experimental Design: Glioma tissue and blood s les from 87 patients were analyzed with HPLC-MS/MS coupled with a CHIROBIOTIC column to quantify both enantiomers of 2-HG. ROC analysis was conducted to evaluate the sensitivity and specificity of 2-HG, R-2-HG, and rRS. The feasibility of real-time determination of IDH status was evaluated in 11 patients intraoperatively. The prognostic value of rRS was evaluated using the Kaplan–Meier method. The rRS in glioma tissues clearly distinguished patients with IDH-mutant versus wild-type tumors (P & 0.001). Sensitivity and specificity using an rRS cut-off value of 32.26 were 97% and 100%, respectively. None of total 2-HG, R-2-HG, or rRS was elevated in serum s les. Among patients with IDH-mutant tumors, tissue rRS stratifies overall survival. The duration of tissue analysis is approximately 60 minutes. Our study demonstrates that rRS is a reliable biomarker of IDH mutation status. This technique can be used to determine IDH mutation status intraoperatively, and to guide treatment decisions based on IDH mutation status in real time. Finally, rRS values may provide additional prognostic information and further validation is required.
Publisher: Wiley
Date: 11-06-2020
DOI: 10.1002/CAM4.3228
No related grants have been discovered for Hao-Wen Sim.