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The advent of systemic therapies with high intracranial efficacy in recent years is changing the therapeutic paradigm and renewing interest in the management of central nervous system (CNS) and leptomeningeal metastases from solid organ tumors. CNS metastases have traditionally heralded a dismal prognosis with median survival of 3-10 months, and were primarily treated with local therapeutic modalities, such as surgery or radiation therapy. Although these modalities still have a role in the management of CNS disease, newer agents, such as small molecule tyrosine kinase inhibitors and immune-checkpoint inhibitors, are now paving the way as an alternative therapeutic option for those with oligometastatic or low-volume intracranial disease, potentially eliminating or delaying the need for local treatment modalities in this setting. Herein, we summarize the systemic treatments with proven intracranial efficacy, currently approved for use in Australia for advanced mutation-driven non-small cell lung cancer, melanoma, and breast cancer, as well as novel agents in preclinical and clinical trial development.

Background: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest and important for accelerating future clinical trials. Methods: We established a novel xenograft model for cancer cachexia with a cachectic human PC3* cell line, which was responsive to anti-Fn14 mAb treatment. Using RNA-seq and secretomic analysis, genes differentially expressed in cachectic and non-cachectic tumors were identified and validated by digital droplet PCR (ddPCR). Correlation analysis was performed to investigate their impact on survival in cancer patients. Results: A total of 46 genes were highly expressed in cachectic PC3* tumors, which were downregulated by anti-Fn14 mAb treatment. High expression of the top 10 candidates was correlated with low survival and high cachexia risk in different cancer types. Elevated levels of LCN2 were observed in serum samples from cachectic patients compared with non-cachectic cancer patients. Conclusion: The top 10 candidates identified in this study are candidates as potential biomarkers for cancer cachexia. The diagnostic value of LCN2 in detecting cancer cachexia is confirmed in patient samples.

Objectives Gene rearrangements involving NTRK1, NTRK2, NTRK3, ROS1 and ALK have been identified in many types of cancer, including non-small cell lung cancer (NSCLC). Data in malignant pleural mesothelioma (MPM), lung neuroendocrine tumors (NETs) and small-cell lung cancer (SCLC) are lacking. Given the activity of NTRK, ROS-1 and ALK inhibitors in tumors harboring gene fusions, we sought to explore such rearrangements in these less common tumors in addition to NSCLC. Methods Archival tumor tissue from patients with MPM, lung NETs, SCLC and NSCLC were used to create tissue microarrays. Immunohistochemistry (IHC) was performed using a cocktail of antibodies against TRK, ROS1 and ALK. IHC positive samples underwent RNA sequencing using the ArcherDX FusionPlex CTL diagnostic assay. Clinical data were obtained through retrospective chart review. Results We performed IHC on 1116 samples: 335 MPMs, 522 NSCLCs, 105 SCLCs and 154 lung NETs. There were 23 IHC positive cases (2.1%) including eight MPMs (2.4%), eight NETs (5.2%), five SCLC (4.8%) and two NSCLC (0.4%). The following fusions were detected: one MPM with an NTRK ex10-TPM3 ex8, another MPM with an ALK ex20-EML4ex13, one lung intermediate-grade NET (atypical carcinoid) with an ALK ex20-EML4 ex6/intron6, and two NSCLCs with an ALK ex20-EML4 ex6/intron6 rearrangement. None of the patients received targeted treatment. Conclusions To our knowledge, we report for the first time NTRK and ALK rearrangements in a small subset of MPM. An ALK rearrangement was also detected in lung intermediate-grade NET (or atypical carcinoid). Our data suggest that IHC could be a useful screening test in such patients to ensure that all therapeutic strategies including targeted therapy are utilized.

Background: Activity-based funding (ABF) is a means of healthcare reimbursement, where hospitals are allocated funding based on the number and mix of clinical activity. The ABF model is based solely on Australian refined diagnosis-related group (AR-DRG) classifications of hospital encounters. Each AR-DRG is allocated a weighted activity unit (WAU) translating to cost value to determine ongoing funding allocations for each hospital annually. Aim: We explored cost consequences of AR-DRG coding variances within our Medical Oncology department over a 6-month period. Methods: All inpatient encounters for medical oncology from 1 January to 30 June 2014 were identified and paired with actual AR-DRG coding sheets submitted by the hospital coders. Inpatient charts were manually reviewed by a Medical Oncology Registrar to capture any changes or additional AR-DRGs, which were subsequently evaluated for total WAU value variance. Applying 1 WAU = $4676 as per the 2014 Queensland model, cost consequences were calculated. Results: A total of 116 encounters was identified for 72 patients. Of 116 patients, 95 (81%) had additional diagnoses captured, leading to an AR-DRG and WAU change in 26 encounters. The total reimbursement variance for this period was $143 404.07. Cost consequences resulted from: (i) use of abbreviations in clinical notes unable to be coded; and (ii) diagnoses not documented despite treatment delivered as per medication charts. Conclusion: Clinical note documentation ultimately determines the future funding of our healthcare system. Appropriate communication and education of medical staff and hospital coders are vital to ensure precise documentation and accurate AR-DRG coding for optimal and appropriate reimbursement in this funding model.

Background: Adrenocortical carcinoma is a rare malignancy, with poor prognosis and limited treatment options for patients with advanced disease. Chemotherapy is the current standard first-line treatment, providing only a modest survival benefit. There is only limited treatment experience with immunotherapy using single-agent anti-PD-1/PD-L1 therapy. To date no clinical trials have been reported using combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade in this patient population. Methods: CA209-538 is a prospective multicentre clinical trial in patients with advanced rare cancers. Participants received the anti-PD-1 antibody nivolumab (3 mg/kg IV) and the anti-CTLA-4 antibody ipilimumab (1 mg/kg IV) every three weeks for four doses, followed by nivolumab (3 mg/kg IV) every two weeks and continued for up to 96 weeks, until disease progression or unacceptable toxicity. Response was assessed every 12 weeks by RECIST version 1.1. Primary endpoint was clinical benefit rate (complete response, partial response, stable disease at 12 weeks). Results: Six patients with adrenocortical carcinoma were enrolled and received treatment. Two patients (33%) have an ongoing partial response (10 and 25 months +) and two patients (33%) stable disease leading to a disease control rate of 66%. Both responders had tumors with a microsatellite instable phenotype. One patient rapidly progressed shortly after enrollment into the trial and did not undergo restaging. Immunotherapy-related toxicity was reported in all patients, with four patients (67%) experiencing grade 3/4 hepatitis leading to discontinuation of treatment. Conclusions: This is the first treatment experience using ipilimumab and nivolumab combination immunotherapy in patients with advanced adrenocortical carcinoma. Durable responses have been observed in a subset of patients suggesting that this treatment regimen should be further investigated in this patient population.

Immune checkpoint inhibitors (ICIs) have become pivotal in the treatment of lung cancer. An increasing number of immune‐related adverse events (irAEs) have been recognized with their use. To our knowledge, this is the first published case of sarcoid‐like pulmonary lymphadenopathy associated with durvalumab, a monoclonal antibody against programmed death ligand‐1 (PD‐L1). A 76‐year‐old woman received adjuvant durvalumab for Stage IIA pT2aN1M0 (American Joint Committee on Cancer, Seventh edition) poorly differentiated lung adenocarcinoma. After three cycles, a sarcoid‐like granulomatous reaction was identified in mediastinal and hilar lymph nodes. Although the lymphadenopathy remained stable in size with the ongoing treatment, progressive intracranial metastases were identified after a further three cycles of durvalumab. Sarcoid‐like inflammation with the formation of non‐caseating granulomas in the absence of systemic sarcoidosis is an irAE which may mimic disease progression. Although a subset of patients who experience this reaction may have a favourable response to checkpoint inhibition, progression of disease may occur contemporaneously., Immune checkpoint inhibitors, such as durvalumab, are associated with a variety of unique immune‐related adverse events. In this case, sarcoid‐like mediastinal and hilar lymphadenopathy developed with the use of adjuvant durvalumab for the treatment of lung adenocarcinoma.

Introduction: The Queensland Remote Chemotherapy Supervision (QReCS) model enables rural nurses to administer chemotherapy in smaller rural towns under supervision by health professionals from larger centers using telehealth. Its implementation began in North Queensland, Australia (population, 650,000), in 2014 between two regional cancer centers (Townsville and Cairns as primary sites) and six rural sites (125 to 1,000 kilometers from primary sites). Our study examined the implementation processes, feasibility, and safety of this model. Methods: Details of implementation and patients’ clinical details for the period of 2014 to 2016 for descriptive analysis were extracted from telechemotherapy project notes and oncology information systems of North Queensland, respectively. Results: After a successful pilot study in Townsville Cancer Centre, statewide rural and cancer networks of Queensland Health, in collaboration with clinicians and managers across the state of Queensland, developed the QReCS model and a guide for operationalizing it. QReCS was implemented at six sites from 2014 to 2016. Main enablers across North Queensland included collaboration among clinicians and managers, availability of common electronic medical records, funding from Queensland Health, and installation of telehealth infrastructure by statewide telehealth services. Main barriers included turnover of senior management and nursing staff at two rural towns. Sixty-two patients received 327 cycles of low- to medium-risk chemotherapy agents. Rates of treatment delays, adverse events, and hospital admissions were similar to those in face-to-face care. Conclusion: Implementation of the QReCS model across a large geographic region is feasible with acceptable safety profiles. Leadership by and collaboration among clinicians and managers, adequacy of resources and common governance are key enablers.

e20045 Background: In the pre-PET era, weight loss is a harbinger of occult metastatic disease in patients with stage III NSCLC. Identifying the relationship between weight loss and pattern of relapse (POR), may enable stratification of patients into prognostic groups associated with increased risk of relapse. We sought to identify if weight loss remains a negative independent prognostic factor after FDG-PET staging. Methods: A retrospective audit (using web-based and electronic databases) was conducted in all patients with stage III NSCLC treated with definitive CRT between 01/07/2013 and 30/06/2018 at the Royal Brisbane and Women’s Hospital and The Prince Charles Hospital, Queensland, Australia. A descriptive analysis was applied to describe the primary end-point of PFS and secondary end-points of OS and POR, in relation to the percentage of pre-treatment weight loss (0-10% vs > 10-20% vs > 20%). A subset analysis looked at other prognostic factors identified in NSCLC to account for potential confounders. Results: Of the 127 patients (mean age 65 years, mean weight 76kg, 57% male, 42% current smokers) who commenced treatment during the study period, 24% lost > 10% and 3% lost > 20% weight. Median TTP for the entire cohort was 9 months. Based on multivariable modelling, risk of PD or death was 45% higher with > 10% loss of body weight (p = 0.004), and risk of death was 36% higher with > 10% of body weight (p = 0.05). Of the 54% that died during follow-up, 31 had distant PD, 18 had locoregional PD, 6 had local PD, and 10 had no PD. Males were at increased risk of PD. Conclusions: A prognostic link continues to be identified between significant (> 10%) weight loss and risk of progressive disease or death in stage III NSCLC treated with definitive CRT despite pre-treatment FDG-PET. These findings identify a sub-group of patients where weight loss could still be a surrogate for micro-metastases not detected on PET, or other adverse prognostic markers. Other treatment strategies or improved diagnostic strategies are warranted.