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Cytokines influence the biological behaviour of prostate cancer (PC) and may influence patient outcome and serve as useful prognostic biomarkers. The aim of the present study was to evaluate cytokine expression levels in prostatic needle biopsy specimens and the association with clinicopathological characteristics of patients with PC. A total of 18 patients with PC who underwent transrectal ultrasound (TRUS) guided prostate biopsy were included in the clinical study. These patients were naïve to radiotherapy (RT) or androgen deprivation therapy prior to TRUS biopsy and clinical follow up data was collected. Cytokine expression levels were analysed by using immunohistochemistry and Spearman's correlation test was used to determine the correlation between cytokine expression and clinicopathological characteristics. Expression levels of pro-inflammatory TNF-α and IL-6 decreased as Gleason score (GS) increased; however, a statistically significant difference was not detected. A statically significant correlation was observed between needle biopsy specimen and pre-RT plasma sample expression levels of pro-inflammatory TNF-α and IL-6 (P=0.01 and P=0.05, respectively) and anti-inflammatory TGF-β1 (P=0.05). However, further studies are needed to confirm these results using a larger sample size to confirm the prognostic value of pro-inflammatory TNF-α and IL-6 and anti-inflammatory TGF-β1 in patients with PC.

BackgroundMetastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials.MethodsMedical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed.Results23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1–2 immune-related adverse events.ConclusionICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.

Background: Radiotherapy (RT) alone or in combination with androgen deprivation therapy (ADT) is most common non-operative treatments for localised prostate cancer (PC). Some circulatory cytokines are believed to play an important role in RT resistance and lead to tumour progression, invasion, and angiogenesis. The aim of this study is to assess the influence of ADT and RT on the expression of circulatory cytokines levels in plasma at different time points. Methods: Between Nov 2015 and Aug 2016, 18 patients with localized PC were selected for this clinical study. All patients had received neoadjuvant ADT using a leuteinizing hormone-releasing hormone (LH-RH) analogs prior to RT. Peripheral blood samples were collected prior to ADT, before RT, at the end of RT and 3 months after the completion of RT. Blood plasma samples were monitored for the pro-inflammatory and profibrotic cytokines TNF-α, TGF-β1, IL-6, and IL-8, using enzyme-linked immunosorbent assay (ELISA) procedures. Results: The concentration of TGF-β1 rose while IL-6 levels declined in post-ADT samples when compared pre-ADT. Levels of TGF-β1 increased in post-RT blood plasma compared to pre-RT blood plasma. Those changes were not statically significant. Three months post-RT completion, TGF-β1 levels decreased and IL-6 and IL-8 levels increased. Although levels of TGF-β1, IL-6 and IL-8 were found to be altered 3 months post-RT completion, only changes in IL-8 levels were found to be statistically significant (P=0.05). Conclusions: In conclusion the changes in cytokines levels have been found after ADT and RT, which strengthen the finding of other clinical studies. Accept that small numbers of samples made difficult to attain significant results. Large clinical studies will be required to validate these findings and hopefully become useful biomarkers in the clinical setting to predict patient outcome and success of treatment received.

Background and purpose: Quality indicators (QIs) have been developed for many aspects of prostate cancer care, but are under-developed with regard to radiotherapy treatment. We aimed to develop a valid, relevant and feasible set of core QIs to measure quality of radiotherapy care in men with prostate cancer. Materials and methods: We used a RAND-modified Delphi process to select QIs that were regarded as both important and feasible measures of quality radiotherapy care. This involved two phases: (1) a literature review to identify a list of proposed QIs; and (2) a QI selection process by an expert panel (n = 12) conducted in a series of three rounds: two online questionnaires’ and one face-to-face meeting. The RAND criterion identified variation in ratings and determined the level of agreement after each round of voting. Results: A total of 144 candidate QIs, which included measures from pre-treatment to post-treatment and survivorship care were identified. After three rounds of voting, the panel approved a comprehensive set of 17 QIs, with most assessing a process of care (n = 16, 94.1%) and the remaining assessing a health outcome. Conclusion: This study developed a core set of 17 QIs which will be used to report from the Prostate Cancer Outcomes Registry-Australia & New Zealand, to monitor the quality of radiotherapy care prostate cancer patients receive. Refereed/Peer-reviewed

Summary Background A short course of radiotherapy is commonly prescribed for palliative relief of malignant dysphagia in patients with incurable oesophageal cancer. We compared chemoradiotherapy with radiotherapy alone for dysphagia relief in the palliative setting. Methods This multicentre randomised controlled trial included patients with advanced or metastatic oesophageal cancer who were randomly assigned (1:1) through a computer-generated adaptive biased coin design to either palliative chemoradiotherapy or radiotherapy alone for treatment of malignant dysphagia at 22 hospitals in Australia, Canada, New Zealand, and the UK. Eligible patients had biopsy-proven oesophageal cancer that was unsuitable for curative treatment, symptomatic dysphagia, Eastern Cooperative Oncology Group performance status 0–2, and adequate haematological and renal function. Patients were stratified by hospital, dysphagia score (Mellow scale 1–4), and presence of metastases. The radiotherapy dose was 35 Gy in 15 fractions over 3 weeks for patients in Australia and New Zealand and 30 Gy in ten fractions over 2 weeks for patients in Canada and the UK. Chemotherapy consisted of one cycle of intravenous cisplatin (either 80 mg/m 2 on day 1 or 20 mg/m 2 per day on days 1–4 of radiotherapy at clinician's discretion) and intravenous fluorouracil 800 mg/m 2 per day on days 1–4 of radiotherapy in week 1. Patients were assessed weekly during treatment. The primary endpoint was dysphagia relief (defined as ≥1 point reduction on the Mellow scale at 9 weeks and maintained 4 weeks later), and key secondary endpoints were dysphagia progression-free survival (defined as a worsening of at least 1 point on the Mellow scale from baseline or best response) and overall survival. These endpoints were analysed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00193882. This trial is closed. Findings Between July 7, 2003, and March 21, 2012, 111 patients were randomly assigned to chemoradiotherapy and 109 patients to radiotherapy. One patient in the chemoradiotherapy group was omitted from analysis because of ineligibility. 50 (45%, 95% CI 36–55) patients in the chemoradiotherapy group and 38 (35%, 26–44) in the radiotherapy group obtained dysphagia relief (difference 10·6%, 95% CI −2 to 23; p=0·13). Median dysphagia progression-free survival was 4·1 months (95% CI 3·5–4·8) versus 3·4 months (3·1–4·3) in the chemoradiotherapy and radiotherapy groups, respectively (p=0·58), and median overall survival was 6·9 months (95% CI 5·1–8·3) versus 6·7 months (4·9–8·0), respectively (p=0·88). Of the 211 patients who commenced radiotherapy, grade 3–4 acute toxicity occurred in 38 (36%) patients in the chemoradiotherapy group and in 17 (16%) patients in the radiotherapy group (p=0·0017). Anaemia, thrombocytopenia, neutropenia, oesophagitis, diarrhoea, nausea and vomiting, and mucositis were significantly worse in patients who had chemoradiotherapy than in patients who had radiotherapy. Interpretation Palliative chemoradiotherapy showed a modest, but not statistically significant, increase in dysphagia relief compared with radiotherapy alone, with minimal improvement in dysphagia progression-free survival and overall survival with chemoradiotherapy but at a cost of increased toxicity. A short course of radiotherapy alone should be considered a safe and well tolerated treatment for malignant dysphagia in the palliative setting. Funding National Health and Medical Research Council, Canadian Cancer Society Research Institute, Canadian Cancer Trials Group, Trans Tasman Radiation Oncology Group, and Cancer Australia.

AIMS In the Northern Territory (NT) of Australia, Indigenous women have a lower incidence of breast cancer, but a higher mortality than Non-indigenous women. The aim of this study was to describe and compare breast cancer pathological features related to stage and biological aggression between the two groups. METHODS Subjects were identified by extract from the NT Cancer Registry in two separate cohorts, cohort 1 (1991-2000) and cohort 2 (2001-2010). Data from cohort 1 included age, stage, tumor grade and estrogen receptor status (ER) and treatment completion. Additional pathological variables including tumor size, HER2 status, lymphovascular invasion and derived tumor phenotype were available for cohort 2. Bivariate P values for categoric variables were calculated using Fisher's exact tests. The Wilcoxon rank-sum test was used to compare cohort 2. Logistic regression was used to calculate odds ratios. RESULTS There were 359 (44 indigenous) eligible women in cohort 1 and 526 (100 indigenous) for cohort 2. In cohort 1, in both cohorts, indigenous women were more likely to present at an advanced stage, but there was no difference in ER status or tumor grade. When derived phenotypes were compared, indigenous women were less likely to have better prognosis luminal A tumors, and more likely to have HER2-enriched tumors. CONCLUSION This two decade long comparison of the pathological features of breast cancer between indigenous and nonindigenous women of the NT has confirmed that Indigenous women not only present at a later stage than NI women but are also afflicted by poorer prognosis tumors, particularly HER2 enriched.

Prostate cancer (PC) is a common cancer (excluding non-melanoma skin cancer) in men in many parts of the world, although incidence and mortality rates vary significantly by population. In current medical practice, prognostic markers for PC include the presenting serum prostate-specific antigen (PSA) level, tumour Gleason score (GS) and clinical tumour stage. However, existing pre-treatment factors cannot be used to predict acute radiotherapy (RT)-induced toxicity. Therefore, new protein biomarkers are required in RT oncology to improve decision-making, treatment and therapy monitoring for PC patients. The aim of this systematic review is to the update potential research to address the difference in cytokine expression and their association with RT-induced toxicity and clinical outcomes. Studies were collected after searching three electronic databases: PubMed, Medline, and Google Scholar. An additional search was carried out through cross-check on a bibliography of selected articles. After the selection process made by two of the authors, 19 articles met the inclusion criteria and were included in the systematic review. Results from previous studies identified elevated levels of cytokines have been reported in several types of cancers and have sometimes correlated with disease progression or prognosis. Elevated levels of cytokine were noticed after immediate exposure to RT and their association with RT-induced acute/late toxicity of PC patients. Moreover, above studies also identified overexpression of cytokines on tumour biopsies and correlation with shortening cancer-specific survival and biochemical recurrence. Thus, altered levels of cytokine might be predictive biomarkers for RT-induced and clinical outcomes of PC patients.

340 Background: In advanced oesophageal cancer (OC), 90% of patients have dysphagia as a principal symptom. The randomised TROG 03.01 trial reported no significant overall survival or dysphagia relief difference between 15 fractions (#) radiotherapy alone (RT) or RT plus chemotherapy (CRT) Future studies may consider RT hypofractionation, different chemotherapy, esophageal stenting, and best supportive care. Comparing costs and outcomes, economic evaluation often informs public funding decisions in countries such as Australia and the UK. The objective of this analysis was to derive baseline cost and outcome for further studies. Methods: Given equal outcomes (non-inferiority) between treatment arms, cost-minimisation analysis (CMA) was used to evaluate cost-effectiveness, cost a deciding factor if no other benefit was predicted. We explored 15 and 10 # courses used in TROG 03.01 and alternatives, 1 or 5 # Study design and uncertainty analyses were provided. Sub-analysis assessed salvage therapy for local and systemic progression. The EQ-5D (and SF-12) was used to determine utility values to estimate Quality-Adjusted Life years (QALYs) for evaluation. Results: From a health system perspective, costs and outcomes of RT were estimated at $4,700 AUD (15 # course). If, compared with RT alone, an alternative option is more costly but more effective, then a cost-utility analysis (CUA) is preferred economic evaluation. Intervention and in/outpatient costs, initial phase and post treatment were considered for stent insertion and alternative chemotherapy regimens. Alternatively, autocontoured CT planning and machine learning were modelled to reduce RT planning cost (est. $650/p). Total cost for 5 # is $3200 could be further reduced through process efficiency savings using CMA approach. Conclusions: The value of palliative approaches in common malignancies is difficult to assess. This study uses economic analysis to guide paying authority decisions. RT can be simplified from the TROG 03.01 approach to lessen cost and simplify treatment. The clinical efficiency of 1 or 5 # should be evaluated.

Background. MicroRNAs (miRNAs) have been found to play an important role in the development and outcomes for multiple human cancers. Their role as a prognostic biomarker in non-small-cell lung cancer (NSCLC) remains unclear. This meta-analysis aims to clarify the role of various miRNAs in the survival of NSCLC patients. Materials and Methods. All studies were identified through medical database search engines. A meta-analysis was conducted to assess the correlation between miRNAs expressions and overall survival among those NSCLC studies. Relevant data were extracted from each eligible study regarding baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and P value, which were utilized to calculate a pooled effect size. Result. Thirty-two studies were included in the meta-analysis. Using a random effect model, the combined HR and 95% CI for overall survival (OS) was calculated as 1.59 (1.39–1.82), predicting a poor overall survival. Five miRNAs (miR-21, miR-155, miR-let-7, miR-148a, and miR-148b) were found to be of significance for predicting OS in at least two studies, hence, selected for subgroup analysis. Subgroup analysis disclosed that elevated levels of miR-21 and miR-155 in both cancer tissue and blood samples were associated with worse OS. Compared to American studies (I-squared: P value: 0.94), Asian and European studies exhibited greater heterogeneity in miRNA expression and relationship to OS (I-squared, P values were approximately 78.85%, let-7 were associated with poor prognosis in NSCLC. Conclusion. miR-21, miR-155, miR-148a, miR-148b, and miR-let-7 are consistently up- or downregulated in NSCLC and are associated with poor OS. These miRNAs show potential as useful prognostic biomarkers in the diagnosis, treatment, and follow-up of NSCLC.

9540 Background: mMCC is a rare, highly aggressive neuroendocrine cancer with a poor prognosis. ICIs have favourable efficacy and safety in clinical trials. We outline single centre experience utilising ICIs in mMCC. Methods: Medical records of patients (pts) with mMCC treated with ICIs from Aug 2015 to Dec 2018 at Peter MacCallum Cancer Centre in Australia were retrospectively analysed. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples were performed. Baseline tumor volumes and responses were assessed with FDG-PET scans using the Hicks criteria. Results: 23 pts with mMCC were treated with ICIs. Pt characteristics are summarised in Table. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 7 pts. Objective responses (OR) were observed in 14 pts (61%); 10 (44%) complete metabolic responses (CMR) and 4 (17%) partial metabolic responses (PMR). Median time to response was 9 weeks (range 4 to 11) and 12-month progression-free survival (PFS) rate was 32%. Increased OR were seen in pts aged less than 75 (OR 8/10, 80% vs 46%), no prior history of chemotherapy (OR 10/14, 71% vs 44%), pts with an immune-related adverse event (irAE) (OR 6/6, 100% vs 47%) and in MCPyV negative pts (OR 9/11, 82% vs 50%). Pts with a CMR had lower mean-tumor volume on baseline FDG-PET scan (CMR: 35.7mL, no CMR: 187.8mL, p value 0.05). 10 pts received radiation (RT) during ICI: 4 pts started RT concurrently (OR 75%, CMR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. 6 pts (26%) had a Grade 1-2 irAE. Conclusions: ICIs showed efficacy and safety consistent with trial data. Younger age, negative MCPyV status, no prior chemotherapy, lower baseline FDG-PET tumor volume and irAEs are potentially associated with better responses. [Table: see text]

Background: The development, monitoring, and reporting of indicator measures that describe standard of care provide the gold standard for assessing quality of care and patient outcomes. Although indicator measures have been reported, little evidence of their use in measuring and benchmarking performance is available. A standard set, defining numerator, denominator, and risk adjustments, will enable global benchmarking of quality of care. Objective: To develop a set of indicators to enable assessment and reporting of quality of care for men with localised prostate cancer (PCa). Design, setting, and participants: Candidate indicators were identified from the literature. An international panel was invited to participate in a modified Delphi process. Teleconferences were held before and after each voting round to provide instruction and to review results. Outcome measurements and statistical analysis: Panellists were asked to rate each proposed indicator on a Likert scale of 1–9 in a two-round iterative process. Calculations required to report on the endorsed indicators were evaluated and modified to reflect the data capture of the Prostate Cancer Outcomes Registry–Australia and New Zealand (PCOR-ANZ). Results and limitations: A total of 97 candidate indicators were identified, of which 12 were endorsed. The set includes indicators covering pre-, intra-, and post-treatment of PCa care, within the limits of the data captured by PCOR-ANZ. Conclusions: The 12 endorsed quality measures enable international benchmarking on the quality of care of men with localised PCa. Reporting on these indicators enhances safety and efficacy of treatment, reduces variation in care, and can improve patient outcomes. Patient summary: PCa has the highest incidence of all cancers in men. Early diagnosis and relatively high survival rates mean issues of quality of care and best possible health outcomes for patients are important. This paper identifies 12 important measurable quality indicators in PCa care. This paper identifies 12 important measurable quality indicators in prostate cancer care. These measures provide a global standard for registries to benchmark quality of care of men with localised prostate cancer Refereed/Peer-reviewed