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Background: Despite increasing evidence of benefit supporting CGP in personalizing cancer therapy, its widespread uptake remains limited. Barriers include low patient understanding, unmet patient expectations related to low utility, clinician concerns over cost-effectiveness, perceived value, and discomfort in management of complex genomic results. Methods: This prospective cross-institutional demonstration study was designed to evaluate implementation of CGP in the care of adult and paediatric advanced cancer pts, incorporating pt reported outcomes (PROMs), discrete choice experiment (DCE), ongoing process optimization and clinician evaluations. DNA sequencing of FFPE tumor and matched blood was completed with CGP (PMCC Comprehensive Cancer Panel; 391 genes) via central laboratory. A tumor board reported results weekly with emphasis on therapeutic relevance. Oncologists performed consent and results delivery. Pts completed pre-and post-test surveys, including validated and study-specific questions, DCE and if eligible, semi-structured interviews. Qualitative interviews were undertaken with study clinicians and laboratory staff to evaluate processes. Results: 86% (315) of 365 enrolled pts had successful CGP; of these 63% (199) had relevant therapeutic, diagnostic or germline results. 50 (16%) had treatment change at 6m, 49 (16%) had germline mutations. 293 (88% of adult pts) completed PROMs. 17 of 19 clinicians/laboratory staff approached consented to an interview. At consent pts cited multifaceted value in testing, showed good understanding of basic concepts, but most (69%) overestimated the likelihood of result-led change. Post-test pts remained consistently satisfied with accessing CGP; valuing research contribution, taking opportunities and information for family. 21% struggled with understanding results but there were low levels of decisional regret following participation (89% had nil/mild regret). Pt-elicited preferences (via DCE) indicated priority for high

Aims: Rare cancers (RCs) are difficult to research and consequently often lack evidence-based treatments. Identifying underlying genomic biomarkers may allow more rational selection of treatments or clinical trials. We report treatment and survival in RC patients (pts) following next-generation sequencing (NGS) in the NOMINATOR study (ACTRN12616001000493). Methods: Pts with rare histology, poor-prognosis solid-tumours, and limited treatment options underwent NGS (PMCC panel; 391 genes) of paired tumour:blood DNA. Virtual molecular tumour board review of clinical history, pathology and genomic results for actionability (OncoKB) provided treatment recommendations. Pts were followed for up to 2 years for impact on treatment and outcomes. Results: 121 pts were prospectively enrolled between July 2017 to Nov 2019 and 100 tumours successfully sequenced. 56 (56%) had potentially actionable results: 27 matched to a clinically validated drug; and 29 a biologically plausible treatment. As of August 2020, of 94 pt with advanced-stage disease (and excluding hormonal therapies), 13 started one or more lines of genomically-matched therapy; 57 an unmatched therapy; and 24 received no further treatment. Pts were more likely to access a matched therapy for approved indications (5/5) or with stronger evidence (OncoKB 2, 5/12). Drug access was provided by the government (PBS) (4), self-funded (3), pharma (3) or clinical trial (4). Median OS (mOS) from consent for pts receiving matched, unmatched, and no treatment was 20.9 (n = 13), 16.5 (57) and 20.1 (24) months, respectively. The corresponding mOS from advanced disease was 27.3, 31.0 and 33.8 months. 8 pts died prior to or within 28 days of NGS result availability. Conclusions: NGS in RCs was feasible and identified potentially actionable results in half of cases. OS was similar across treatment groups explored, although heterogeneity in RC type and prior treatments limit analysis. Earlier testing and impro

Background: Rare cancers (RCs) often lack proven treatments and consequently have poorer outcomes. Identification of molecular biomarkers can facilitate treatment selection and trials access for RC patients (pts) where histology-based trials are not feasible. We assessed the potential for next-generation sequencing (NGS) to impact RC care. Methods: Pts with a rare histology, poor-prognosis solid-tumor and no standard of care therapy underwent NGS genomic profiling of paired FFPE tumor and blood (PMCC comprehensive cancer panel; 391 genes). A virtual molecular tumour board (MTB) reviewed curated results regarding diagnosis, actionability (OncoKB) and treatment recommendations. Results: Between July 2017 and Nov 2019, 121 pt were prospectively enrolled across 4 Australian sites. 109 (91%) pts had a tumour with an incidence of < 1/100,000 person/years with 83 diverse RC histologies represented. 100 (83%) cases were successfully sequenced. The most commonly aberrant genes ( > 10%) were: TP53 (45%), CDKN2A/B, RB1, PTEN and NF1. 51 (51%) had at least one potentially actionable finding, with 27 matched to a clinically validated drug (OncoKB level 3 or better) [Table]. In 6 cases NGS resulted in a revised diagnosis (includes 4 with FDA approved therapy). Actionable germline mutations were detected in 3 individuals of which 2 were previously known. The majority of pts remain in follow-up, however, 8 died prior to or within 28 days of NGS result availability. Drug access remains a limitation with only 12 receiving therapy based on NGS/MTB guidance. Clinical trial information: ACTRN12616001000493. Conclusions: NGS in RCs is feasible with potential impact in half of cases. Earlier testing and improved off-label/trial drug access is necessary to increase the likelihood that RC patients may benefit from molecularly guided therapy.

Background: Tumour molecular profiling is an important component of precision oncology. The genomic rearrangements identified in tumours now contribute important information to facilitate accurate diagnosis, prognosis and increasingly can guide therapeutic decisions. iPREDICT (iPR) is a national precision medicine study, offering targeted next generation sequencing (NGS) to adult and paediatric patients with high-risk solid tumours with the aim of identifying actionable variants to guide treatment decisions. Aims: This prospective study was designed to assess patient perception, feasibility and clinical impact of a personalised medicine approach utilising NGS for patients with advanced cancer. Methods: iPREDICT was conducted across seven hospitals utilising NGS (PMCC Comprehensive Cancer Panel; 391 genes). A molecular tumour board was established to evaluate results and treatment recommendations. A detailed evaluation of the testing process, result delivery and patient and trial staff perception was conducted though validated and study-specific surveys, discrete choice experiments and semi-structured interviews. Results: Between April 2017 and September 2018, 315 patients with advanced cancer were enrolled across seven sites and underwent tumour and matched germline NGS. 84% (265) had successful tests. Of patients with successful tests, 208 potentially actionable findings were detected in 144 (55%). 41 (15%) went on to receive a change in treatment; six6 (2%) avoided therapy thought not to be beneficial, nine (3%) received new access to funded therapy, 17 (6%) enrolled on targeted trials and nine (3%) patients commenced off-label therapy. Germline mutations were detected in 46 (17%). A formal evaluation of patient choice and perception of the testing process have provided important insights into health care implementation. Conclusions: Our findings confirm feasibility of molecular profiling in high-risk solid tumours in the Austra

Melanomas are derived from melanocytes – highly specialized pigment-producing cells residing in the basal layers of the skin. The majority of melanomas continue to produce melanin, presenting a potential disease specific biomarker, so far largely unexplored. This thesis begins by examining how melanin might be exploited as a melanoma specific target for molecular based imaging. The novel fluorinated, melanin-binding radiopharmaceutical, MEL050, is tested as a PET-tracer in ten patients with advanced melanoma. We establish MEL050 safety, and detail metabolism, radiopharmacokinetics and normal biodistribution. Diagnostic parameters are compared with a gold-standard of FDG PET/CT. Excellent specificity of 100% but more variable sensitivity is demonstrated. Overall sensitivity was 47%. In a subset of five patients who underwent resection of all known disease sites, histological assessment of tumour melanin correlated with MEL050 PET signal: 100% for melanotic tumours but 0% for amelanotic tumours. These findings suggested a high frequency of amelanotic metastases – an aspect of melanoma not well detailed in the literature. In order to validate melanin as a suitable target for melanoma imaging, but also to determine if changes in its expression may reflect clinically meaningful differences in underlying biology, we next examined melanoma melanin in two distinct clinical cohorts. In the first, amelanosis was evaluated in tumours from 253 patients with primary melanoma. 20% were macroscopically amelanotic. These tumours had a higher Breslow thickness (p < 0.001), were more likely to be ulcerated (p = 0.002), have increased mitoses (p < 0.001) and be BRAF wild-type (p < 0.001). In a multivariate survival analysis, amelanosis was associated with worse disease free survival (HR 2.3, p = 0.031) and disease specific survival (HR 2.5, p = 0.033). The second cohort examined patients with more advanced melanoma. 142 patients with stage IIIa melanoma had sentinel node tumours exami

Traditional approaches to joint control required accurate modelling of the system dynamic of the plant in question. Fuzzy Associative Memory (FAM) control schemes allow adequate control without a model of the system to be controlled. This paper presents a FAM based joint controller implemented on a humanoid robot. An empirically tuned PI velocity control loop is augmented with this feed forward FAM, with considerable reduction in joint position error achieved online and with minimal additional computational overhead.

The GuRoo is a 1.2 m tall, 23 degree of freedom humanoid constructed at the University of Queensland for research into humanoid robotics. The key challenge being addressed by the GuRoo project is the development of appropriate learning strategies for control and coordination of the robot's many joints. The development of learning strategies is seen as a way to side-step the inherent intricacy of modeling a multi-DOF biped robot. This paper outlines the approach taken to generate an appropriate control scheme for the joints of the GuRoo. The paper demonstrates the determination of local feedback control parameters using a genetic algorithm. The feedback loop is then augmented by a predictive modulator that learns a form of feed-forward control to overcome the irregular loads experienced at each joint during the gait cycle. The predictive modulator is based on the CMAC architecture. Results from tests on the GuRoo platform show that both systems provide improvements in stability and tracking of joint control.

This paper describes experiments conducted in order to simultaneously tune 15 joints of a humanoid robot. Two Genetic Algorithm (GA) based tuning methods were developed and compared against a hand-tuned solution. The system was tuned in order to minimise tracking error while at the same time achieve smooth joint motion. Joint smoothness is crucial for the accurate calculation of online ZMP estimation, a prerequisite for a closedloop dynamically stable humanoid walking gait. Results in both simulation and on a real robot are presented, demonstrating the superior smoothness performance of the GA based methods.

This paper describes a process for evolving a stable humanoid walking gait that is based around parameterised loci of motion. The parameters of the loci are chosen by an evolutionary process based on the criteria that the robot's ZMP (zero moment point) follows a desirable path. The paper illustrates the evolution of a straight line walking gait. The gait has been tested on a 1.2 m tall humanoid robot (GuRoo). The results, apart form illustrating a successful walk, illustrate the effectiveness of the ZMP path criterion in not only ensuring a stable walk, but also in achieving efficient use of the actuators.