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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.

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.

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.