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Background: Technology has progressed from single gene panel to large-scale genomic sequencing. This is raising expectations from clinicians and patients alike. The utility and performance of this technology in a clinical setting needs to be evaluated., Aim: This pilot study investigated the feasibility of using exome-scale sequencing (ESS) to identify molecular drivers within cancers in real-time for Precision Oncology in the clinic., Methods: Between March 2014 and March 2015, the Victorian Comprehensive Cancer Centre Alliance explored the feasibility and utility of ESS in a pilot study. DNA extracted from the tumour specimens underwent both ESS and targeted 'hotspot' sequencing (TS). Blood was taken for germline analysis. A multi-disciplinary molecular tumour board determined the clinical relevance of identified mutations; in particular, whether they were 'actionable' and/or 'druggable'., Results: Of 23 patients screened, 15 (65%) met the tissue requirements for genomic analysis. TS and ESS were successful in all cases. ESS identified pathogenic somatic variants in 73% (11/15 cases) versus 53% (8/15 cases) using TS. Clinically focused ESS identified 63 variants, consisting of 30 somatic variants (including all 13 identified by TS) and 33 germline variants. Overall, there were 48 unique variants. ESS had a clinical impact in 53% (8/15 cases); 47% (7/15 cases) were referred to the familial cancer clinic, and 'druggable' targets were identified in 53% (8/15 cases)., Conclusion: ESS of tumour DNA impacted clinical decision-making in 53%, with 20% more pathogenic variants identified through ESS than TS. The identification of germline variants in 47% was an unexpected finding., (© 2018 Royal Australasian College of Physicians.)

Background: Advanced biliary tract cancers (BTCs) have a poor prognosis and limited treatment options. This exploratory phase II study aimed to evaluate the activity of the mTOR inhibitor everolimus in advanced BTC and explore prognostic biomarkers., Methods: Patients with advanced BTCs, who had not received chemotherapy for advanced disease, were enroled to receive everolimus (10 mg daily). The primary endpoint was disease control rate (DCR) at 12 weeks. Secondary endpoints included overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events. Activation status of the RAS and phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathways was assessed by DNA sequencing and immunohistochemistry on archival tumour tissue., Results: The study enroled 27 patients and the DCR at 12 weeks was 48%. Median PFS was 5.5 months (95% confidence interval (CI): 2.1-10.0 months) and median OS was 9.5 months (95% CI: 5.5-16.6 months). DCR at 12 weeks was significantly worse for gall bladder carcinoma compared to other anatomical sites, and there was a trend towards a worsened PFS and OS. Treatment was well tolerated. KRAS (12%) and PIK3CA mutations (12%) were uncommon. Immunohistochemical staining for PI3K/AKT/mTOR pathways did not significantly correlate with outcome., Conclusion: In unselected patients, everolimus demonstrated clinical activity as first-line monotherapy in advanced BTC.

Aims: In this retrospective analysis, we describe the efficacy and tolerability of weekly cisplatin 40 mg/m(2) used in concurrent chemoradiation of head and neck cancer at the Townsville Cancer Centre., Methods: Review of medical records of patients who received radical chemoradiotherapy for head and neck cancer at Townsville Cancer Centre from 2003 to 2009., Results: In all 102 patients were analysed, 62 of whom had definitive chemoradiation and the remainder adjuvant chemoradiotherapy. Median follow up was 20.1 months (range 5-86 months). Overall 68.6% of patients received 5 weeks or more of planned chemotherapy. Radiotherapy interruptions occurred in four (6.4%) patients. The rate of grade 3-4 adverse events was 51% including neutropenia (18.6%), mucositis (21.8%) and dysphagia (12.9%) and 30.7% of patients needed hospital admission to manage toxicities. For definitive and adjuvant groups, estimated 3-year survival was 64.5 and 71.5%, respectively, and estimated 3-year disease-specific survival rates were 70.3 and 81.6%, respectively. The 3-year overall survival for patients who received five or more cycles of chemotherapy was 75.2%, compared to 52.6% for those receiving fewer than five cycles (P = 0.018)., Conclusion: Despite this is being a small retrospective study, survival figures and toxicity profiles of low dose weekly cisplatin are comparable to historical controls using high-dose regimens, hence justifying our approach. In addition, radiotherapy interruptions are minimized and cisplatin is easy to administer in outpatient settings. Future three-arm studies could include this regimen as the basis of treatment combined with targeted therapies., (© 2011 Blackwell Publishing Asia Pty Ltd.)