ORCID Profile
0000-0002-2219-2459
Current Organisations
Illawarra Shoalhaven Local Health District
,
NHMRC Clinical Trials Centre
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Future Medicine Ltd
Date: 05-2022
Abstract: Immune checkpoint inhibitors have been incorporated into the treatment of various malignancies. An increasing body of literature is reporting rare but potentially fatal adverse events associated with these agents. In this case series, the authors report the clinical features and outcomes of seven patients who received immune checkpoint inhibitors for different solid organ malignancies and developed a tetrad of immune-related myocarditis, myositis, myasthenia gravis and transaminitis. Herein the authors review the literature and describe the current diagnostic and management approach for this overlapping syndrome. The authors' series highlights the importance of a high index of clinical suspicion, prompt comprehensive investigations, early multidisciplinary team involvement and initiation of immunosuppressive therapy when immune-related adverse events are suspected.
Publisher: BMJ
Date: 21-08-2013
Publisher: Springer Science and Business Media LLC
Date: 18-08-2021
DOI: 10.1186/S12885-021-08644-4
Abstract: Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a “lighter” treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population. MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS / BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies. MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer. Australia New Zealand Clinical Trials Registry: ACTRN12618000233224 , prospectively registered 14 February 2018.
Publisher: MDPI AG
Date: 09-03-2022
Abstract: Angiogenesis inhibitors have been adopted into the standard armamentarium of therapies for advanced-stage renal cell carcinomas (RCC), but more recently, combination regimens with immune checkpoint inhibitors have demonstrated better outcomes. Despite this, the majority of affected patients still eventually experience progressive disease due to therapeutic resistance mechanisms, and there remains a need to develop novel therapeutic strategies. This article will review the synergistic mechanisms behind angiogenesis and immunomodulation in the tumor microenvironment and discuss the pre-clinical and clinical evidence for both clear-cell and non-clear-cell RCC, exploring opportunities for future growth in this exciting area of drug development.
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.JGO.2019.05.013
Abstract: There is uncertainty whether older patients derive a similar benefit from immune checkpoint inhibitors (ICI) as younger patients. We performed a meta-analysis of ICI trials in advanced cancers to better estimate treatment benefit in the older population. We performed an electronic search for randomized trials of ICI, either as monotherapy or in combination with other agents. Hazard ratios (HR) for subgroups defined by different age cut-offs were extracted. Pooled overall survival (OS) treatment estimates were calculated using the inverse variance weighted method. In nineteen trials comparing ICI monotherapy versus non-ICI treatment, there was no significant treatment-age interaction (age ≥ 65 years: N = 6064, HR 0.73 age < 65 years: N = 7250, HR 0.79 P-interaction = 0.27). Findings were similar at older age cut-offs of 70 years (age ≥ 70 years: N = 433, HR = 0.93 age < 70 years: N = 169, HR = 0.95 P-interaction = 0.91) and 75 years (age ≥ 75 years: N = 139, HR = 0.75 age < 75 years: N = 1133, HR = 0.61 P-interaction = 0.72) respectively, and for trials of ICI combination therapy. ICI therapy improves OS in both younger and older patients with advanced cancers, and the magnitude of improvement does not depend on age. Patient selection for ICI therapy should be done based on performance status and adequate organ function independently of age.
Publisher: Wiley
Date: 30-01-2022
DOI: 10.1111/AJCO.13745
Abstract: Patients with early‐onset colorectal cancer (EO‐CRC) have unique characteristics. Contemporary data on the pathological and molecular features, and survival of EO‐CRC are limited in the Australian context. To determine the demographic, histopathological and molecular characteristics of adults with EO‐CRC, and their survival. We conducted a retrospective study of adults aged 18–49 years with EO‐CRC who were referred to the Illawarra Shoalhaven Local Health District, South Eastern Sydney Local Health District and Royal North Shore Hospital in New South Wales, Australia, between 2014 and 2018. Of 257 patients included, 94 (37%) patients presented with de novo metastatic CRC, 80% patients had near‐average risk family history and 89% had a symptomatic presentation. In 159 patients with nonmetastatic disease at diagnosis, stage III disease (OR 3.88 [95% CI: 1.13–13.3] p = .03) and the presence of perineural invasion (PNI) (OR 6.63 [95% CI: 2.21–19.84] p = .001) were risk factors associated with the development of metastatic disease. Among 94 patients with de novo metastatic disease, 43 (43%) and 12 (14%) patients harbored a KRAS or BRAF V600E mutation, respectively. The median overall survival was 29.6 months (95% CI: 20.4–38.7). BRAF mutation was associated with inferior survival (HR 3.00 [95% CI: 1.30–6.94] p = .01). The prevalence of KRAS and BRAF mutations in our cohort is similar to the overseas experience. Stage III disease at diagnosis, presence of PNI and BRAF mutation are adverse prognostic indicators. A better understanding of the molecular landscape is needed for this patient cohort, so as to better tailor prevention strategies, screening and treatment pathways.
No related grants have been discovered for Derrick Siu.