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Integration of high-dimensional tumor gene expression data with clinicopathological data can increase our understanding of disease diversity, enable retrospective patient stratification, and identify new potential biomarkers and therapeutic targets. Using a systems biology approach, we provide a holistic overview of gene co-expression networks in head and neck squamous cell carcinomas (HNSCC). Weighted gene co-expression network analysis of HNSCC RNA sequencing data from 519 patients from The Cancer Genome Atlas (TCGA) was used to determine correlates of 5-year survival, using regression tree-based optimal threshold calculations. Survival-associated gene sets were transformed to gene set scores that were assessed for correlation with clinicopathological data. We identified 8 gene co-expression modules for HNSCC tumors, each of which contained co-expressed genes associated significantly with 5-year survival. Survival-associated co-expression gene signatures correlated dominantly with tumor HPV and p16 status. Network analysis identified that survival was associated with signaling networks of infection, immunity, epithelial-mesenchymal transition (EMT), hypoxia, glycolysis, focal adhesion, extracellular matrix, MYC signaling, autophagy and transcriptional regulation. EMT-associated gene signatures were expressed dominantly in fibroblasts, and cancer-associated fibroblasts were inversely correlated with immune activity. Interestingly, a high Immune Suppression Score based on expression of 21 genes associated with immune inhibition and including immune checkpoints, cytokines and regulatory T cell factors, was also associated with increased survival probability, and was significantly higher in HPV+ HNSCC. Networks associated with HNSCC survival were further associated with survival in cervical cancer, melanoma and lung cancer. This study defines 5129 genes associated with HNSCC survival, organized into co-expressed networks, their correlation with clinicopathological dat

Background: While Australia ranks highly in terms of cancer survival internationally, disparities in outcomes exist within the nation. To address this issue, Optimal Care Pathways (OCPs) were developed as a standard of care. Key principles of care, timeframes, quality standards and support needs were described in a seven-step pathway for 18 cancers. This paper discusses the potential value of pathways for care delivery, contextualises Australia's pathway policy approach and describes implementation strategies and early evidence of OCP impact. Method(s): A literature review assessed international definitions and evidence of the utility of clinical care pathways. OCP implementation and evaluation approaches are described and case studies presented to demonstrate policy impact. Result(s): Australia's OCPs extend the traditional definition of care pathways by incorporating core principles and addressing the entire pathway from prevention to survivorship and end of life. In 2014-15, tumour-specific OCPs were developed drawing on the best-available evidence and stakeholder collaboration. After government endorsement, implementation tools and strategies were developed, with tailored roll-out in each of Australia's six states and two territories. Evaluation of implementation projects shows improved knowledge, awareness, and use of OCPs as tools for monitoring and improving performance. Population-based data confirm a positive relationship between care aligned with OCPs and cancer survival. Conclusion(s): OCPs are clinician- and consumer-built policy levers, supported by high-level government endorsement, to improve cancer outcomes for all Australians. Early findings suggest positive impacts on care quality and cancer survival. Low and high resource countries may consider similar pathway policies to improve cancer outcomes.Copyright © 2020 Elsevier Ltd

BACKGROUND: Cancer care involves many different healthcare providers. Delayed or inaccurate communication between specialists and general practitioners (GP) may negatively affect care. AIM: To describe the pattern and variation of communication between primary healthcare (PHC) services and hospitals and specialists in relation to the patient's cancer care. METHODS: A retrospective audit of clinical records of Indigenous Australians diagnosed with cancer during 2010-2016 identified through 10 PHC services in Queensland is described. Poisson regression was used to model the dichotomous outcome availability of hospital discharge summary versus not. RESULTS: A total of 138 patient records was audited; 115 of those patients visited the PHC service for cancer-related care after cancer diagnosis; 40.0% visited the service before a discharge summary was available, and 36.5% of the patients had no discharge summary in their medical notes. While most discharge summaries noted important information about the patient's cancer, 42.4% lacked details regarding the discharge medications regimen. CONCLUSIONS: Deficits in communication and information transfer between specialists and GP may adversely affect patient care. Indigenous Australians are a relatively disadvantaged group that experience poor health outcomes and relatively poor access to care. The low proportion of discharge summaries noting discharge medication regimen is of concern among Indigenous Australians with cancer who have high comorbidity burden and low health literacy. Our findings provide an insight into some of the factors associated with quality of cancer care, and may provide guidance for focus areas for further research and improvement efforts.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICI) in metastatic melanoma is well established. However, there are limited data regarding their efficacy in in-transit melanoma (ITM). This study assessed the efficacy of ICI in patients with ITM. METHODS: A retrospective review of patients with ITM commenced on an ICI between March 2013 and February 2018 at three tertiary centers in Australia. Patients were excluded if they had previous or synchronous distant metastases. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were based on a composite of radiological and clinical assessments. RESULTS: Fifty-four patients were included: 27 (50%) female; median age 75 (range 26-94); 12 (22%) stage IIIB, 40 (74%) stage IIIC and 2 (4%) stage IIID; 10 (19%) BRAF mutant. Forty (74%) received single-agent anti-PD-1 (pembrolizumab or nivolumab), 8 (15%) single agent anti-CTLA-4 (ipilimumab), 5 (9%) combination anti-PD-1/anti-CTLA-4 (ipilimumab and nivolumab or pembrolizumab) and 1 (2%) combination anti-PD-L1 (atezolizumab) and MEK inhibitor (cobimetinib). The median follow-up was 15 months (2-46).ORR to ICI was 54%: 14 (26%) complete responses; 15 (28%) partial responses; 9 (17%) stable disease; 16 (30%) progressive disease. Thirteen (46%) responders had only one ITM lesion. ORR was 58% for single-agent anti-PD-1, 38% for single-agent anti-CTLA4 and 40% for anti-PD-1/anti-CTLA-4. The median PFS was 11.7 months (6.6-not reached). 1-year and 2-year PFS were 48% and 39%, respectively,. Fourteen progressed locoregionally and 11 progressed distantly. The median OS was not reached. 1-year and 2-year OS were 85% and 63%, respectively. No clinicopathological features were associated with ORR. CONCLUSIONS AND RELEVANCE: ICI produce objective responses in ITM and should be considered in patients with unresectable ITM or disease recurrence.

The primary tumor side is emerging as a prognostic factor for patients with liver metastatic colorectal cancer (mCRC). In a combined analysis of data from 2 randomized studies, the addition of selective internal radiation therapy to first-line chemotherapy in patients with mCRC was associated with statistically and clinically significant overall survival gains for patients with a right-sided primary tumor. Background(s): The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone. Patients and Methods: Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side. Result(s): In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P =.810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P =.008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P =.264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P =.002). Conclusion(s): The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated

© 2018 by the authors. Amongst Indigenous Australians, “cancer” has negative connotations that detrimentally impact upon access to cancer care services. Barriers to accessing cancer services amongst Indigenous Australians are widely reported. In contrast, factors that facilitate this cohort to successfully navigate cancer care services (“enablers”) are scarcely reported in the literature. Through qualitative interviews, this article examines factors that assist Indigenous Australians to have positive cancer experiences. Semi-structured interviews were conducted with twelve adult Indigenous oncology patients recruited from a tertiary hospital in Queensland, Australia during 2012–2014. Data generated from the interviews were independently reviewed by two researchers via inductive thematic analytical processes. Discussions followed by consensus on themajor categories allowed conclusions to be drawn on potential enablers. Two major categories of enablers were identified by the researchers: resilience and communication. Individual’s intrinsic strength, their coping strategies, and receipt of support improved participant’s resilience and consequently supported a positive experience. Communication methods and an effective patient-provider relationship facilitated positive experiences for participants. Despite potential barriers to access of care for Indigenous cancer patients, participants in the study demonstrated that it was still possible to focus on the positive aspects of their cancer experiences. Many participants explained how cancer changed their outlook on life, often for the better, with many feeling empowered as they progressed through their cancer diagnosis and treatment processes.

© 2017, Springer-Verlag Berlin Heidelberg. Purpose: The purpose of this study was to explore Indigenous Australian cancer survivors’ perspectives of follow-up cancer care and management. Methods: This is a qualitative study employing individual interviews with 21 Indigenous cancer survivors (13 females, 8 males) recruited from a rural primary health service and large tertiary hospital in Brisbane, Queensland. Yarning methods were used to conduct semi-structured interviews. Yarning is a culturally appropriate, informal conversational process emphasising the importance of storytelling. Results: Findings describe a range of ways in which follow-up cancer care is experienced with four major categories elucidated, namely: links to tertiary health services, links to primary health services, communication between tertiary and primary health services, and lost in transition. Both positive and negative experiences were described; however, the importance of timely and informative discharge information, continuity of care, good communication between tertiary and primary health services, and strong therapeutic relationships were salient issues raised by participants. Conclusions: These findings highlight the importance of establishing strong therapeutic relationships between patients and tertiary and primary health professionals. Also important for survivorship is provision of discharge summaries or care plans at discharge for survivors and general practitioners as well as access to a range of allied health services. Alternative means for follow-up could be investigated for regional and rural survivors to facilitate convenient and cost-effective follow-up care. Finally, provision of responsive and flexible follow-up care to cater for the diverse range of needs and preferences of cancer survivors is required. A patient navigator available across the cancer continuum could go some way to addressing this.

Purpose: SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer. Patients and Methods: Chemotherapy-naive patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm. Result(s): Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267).Median PFS at any site was 10.2 v 10.7months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95%CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4%in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8%v 78.7% in control v SIRT; P = .042). Grade >= 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT. Conclusion(s): The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liveronly metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies.Copyright © 2016 by American Society of Clinical Oncology.

Background: Liver metastases are the dominant site of disease in mCRC and the dominant cause of death. The SIRFLOX study was designed to assess the efficacy and safety of combining FOLFOX chemotherapy (+/- bevacizumab) with SIRT using yttrium-90 (Y-90) resin microspheres as first-line treatment of patients with liver metastases from mCRC. Method(s): SIRFLOX was an international, multi-centre, open-label, RCT in chemotherapy-naive patients with non-resectable, liver-only or liver-dominant (liver plus lung and/or lymph node metastases) mCRC. Arm A: mFOLFOX6 (+/- bevacizumab, at investigator discretion) was compared to arm B: mFOLFOX6 + SIRT (SIR-Spheres; Sirtex) administered once with cycle 1 (+/- bevacizumab, at investigator discretion) until disease progression. The primary endpoint was Progression-Free Survival (PFS) using RECIST v1.0 by independent central imaging review in the intention-to-treat (ITT) cohort. PFS in the liver, as defined by Cumulative Incidence of Liver Progression (Liver CIP), was assessed by Competing Risk analysis. Stratification variables included presence of extra-hepatic metastases (liver-only vs. liver-dominant), degree of liver involvement (<=25% vs. >25%), and ITT with bevacizumab (with vs. no bevacizumab). Result(s): From October 2006 to April 2013, 530 patients were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases; 292 (55%) were stratified to receive bevacizumab. Median follow-up was 36.1 months. The median overall PFS was 10.2 vs. 10.7 months in arms Avs. B, respectively (hazard ratio [HR]: 0.93; 95% CI 0.77-1.12; p = 0.429) by Kaplan-Meier analysis. The median Liver PFS was 12.6 vs. 20.5 months in arm Avs. B (HR: 0.69; 95% CI 0.55-0.90; p = 0.002). Median Liver PFS was 12.4 vs. 21.1 months in arm Avs. B (HR: 0.64; 95% CI 0.48-0.86; p = 0.003) for patients with liver-only metastases, and 12.6 vs. 16.7 months (HR: 0.77, 95% CI 0.54-1.09; p = 0.147) for those with liver and extra-hepatic metastases. M

Background: The SIRFLOX study assessed the efficacy and safety of combining FOLFOX chemotherapy (+/- bev) with SIRT as first-line treatment of patients with CRC liver metastases. Planned sub-analyses analyses included +/- extra-hepatic metastases, +/- bev and site of first progression. Method(s): SIRFLOX was an international, multi-centre, open-label, RCT in chemotherapy-naive patients with non-resectable, liver-only or liverdominant mCRC. Arm A: mFOLFOX6 +/- bev vs. arm B: mFOLFOX6 +/- bev +SIRT using yttrium-90 resin microspheres (SIR-Spheres; Sirtex) administered once with cycle 1. The primary endpoint was overall PFS using RECIST v1.0. Stratification variables included +/- extra-hepatic metastases, and +/- bev. Liver PFS was assessed by Competing Risk analysis. First progression was judged by independent reader blinded to study arm. Result(s): 530 patients were randomised (A, n = 263; B, n = 267), 212 (40%) had EHD; 292 (55%) received bev. Median follow-up was 36.1 months. Median overall PFS was 10.2 vs. 10.7 months in A vs. B, respectively (p = 0.428). Median liver PFS was 12.6 vs. 20.5 months in A vs. B (p = 0.002). Median Liver PFS was 12.4 vs. 21.1 months in A vs. B (p = 0.003) for patients with liver-only metastases, and 12.6 vs. 16.7 months (p = 0.147) for those with liver and extra-hepatic metastases. Median Liver PFS was 10.6 vs. 18.9 months in A vs. B (p = 0.028) for patients with ITT -bev, and 12.7 vs. 21.0 months (p = 0.018) for those with ITT +bev. The site of first progression was more frequently the liver (+/- other sites) in A [164/ 178, 92.1%] vs. B [120/166, 72.3%] (p < 0.001). All-causality grade >=3 adverse events occurred in 73.3% vs. 85.4% (NS) of patients in A vs. B. Conclusion(s): In first-line treatment of patients with non-resectable CRC liver metastases, adding SIRT to FOLFOX-based chemotherapy failed to improve overall PFS. The addition of SIRT significantly extended median liver PFS and reduced the frequency that first disease progres