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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.

Aim The neuro-oncology community in Australia is well positioned to collaborate internationally, with a motivated trials group, strong regulatory bodies and an attractive fiscal environment. We sought to identify gaps in the Australian neuro-oncology clinical trials landscape and describe strategies to increase international trial access in Australia. Methods We searched clinical trial registries to identify active adult primary brain cancer trials. We compared the participation rate and phase of these trials between tumour types and countries. A survey was distributed to the Cooperative Trials Group for Neuro-Oncology membership to identify barriers and solutions to effective international collaboration. Results Globally, 307 trials for adult primary brain cancers were identified. These included 50% pharmaceutical agents, 18% cellular therapies and 9% radiation therapy. Twelve adult primary brain cancer trials were actively recruiting in Australia at the time the survey was sent out. There were more early phase brain cancer trials (34%) compared with colorectal and breast cancer (21% and 24%, respectively). In Australia, 92% of brain cancer trials were involving pharmaceutical agents. The most commonly cited barrier was lack of funding for international trials (86%) and insufficient research time (75%). High ranking solutions included increasing the availability of funding for international trials and creating opportunities to develop personal relationships with collaborators. Accreditation of clinical research key performance indicators into practice (88%) and hospital accreditation (73%) also ranked highly. Conclusions Participation in international research in Australia could be improved by embedding clinical research targets into institutional funding, provision of funding for early phase studies and streamlining mutual ethics schemes.

The advent of immune checkpoint-inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study-withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12-16) of patients treated with PD(L)-1 inhibitors, 34% (95% CI 27-42) of patients treated with CTLA-4 inhibitors, 55% (95% CI 51-59) of patients on CPI combinations and 46% (95% CI 40-53) of patients on immunotherapy-chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future.

Background/aim This study was conducted retrospectively to evaluate rates of thrombocytopenia and their clinical impact during chemo-radiotherapy for glioblastomas and to elucidate associated clinical factors. Methods A total of 64 patients who received temozolomide chemotherapy at our institution was included; 35 patients received full-dose chemo-radiotherapy as per the STUPP protocol (Group A), and 9 patients received abbreviated radiotherapy with concurrent chemotherapy (Group B). Twenty patients received temozolomide alone with an intended 12 cycles of therapy for first relapse at least 6 months after completion of adjuvant chemotherapy (Group C). Results In Group A, 27 of 35 (77%) patients completed the chemo-radiotherapy phase; 14% had grade 3-4 thrombocytopenia leading to discontinuation. Of 27 patients, 16 (59%) completed adjuvant chemotherapy. There were no grade 3-4 thrombocytopenias, but 4% discontinued due to grade 2 thrombocytopenias. In Group B, four of nine (45%) patients completed the chemo-radiotherapy phase; 11% had grade 3-4 thrombocytopenias and discontinued treatment. Three of four (75%) patients completed adjuvant chemotherapy. Of these, 75% had grade 3-4 thrombocytopenias, but none discontinued. Finally, in Group C, 8 of 20 (40%) patients completed, with 10% discontinuing due to thrombocytopenias and the rest due to disease progression. In exploratory analyses, being female increased the risk of myelosuppresion, and there was a trend noticed in patients having a higher body surface area. Conclusion Our toxicity data were within range of the literature. We identified the group of patients that have increased thrombocytopenia risk. Larger pooled retrospective series and prospective studies are required.

Background Not-infrequently patients with head and neck cancer are also diagnosed with synchronous lung cancer or metachronous primary lung cancer, which complicates the treatment decisions and prognosis. Methods Patients were identified from a database of patients with head and neck cancer with second primary non-small cell lung cancer (NSCLC). Results Thirty-four eligible patients (15 with synchronous lung cancer and 19 with metachronous lung cancer) were identified. Thirteen of 15 patients with synchronous lung cancer received curative intent treatment for head and neck cancer first. Six of 15 patients were in complete remission, 5 of 15 patients had died, and 4 were alive with progressive disease. Median time between 2 diagnoses was 47 months in the metachronous lung cancer group. Twelve patients had died, 3 were alive with disease, and 4 were lost to follow-up. Median survival from the time of lung cancer diagnosis was 13 months with a trend to better survival with synchronous lung cancer (15 vs 11 months; p = .11). Conclusion Aggressive multidisciplinary management of second primary lung malignancies in patients with head and neck cancer can result in respectable long-term disease control particularly in patients with synchronous lung cancer. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

Background Little contemporary data are available regarding Australian patterns of care in adult medulloblastoma. It is unclear whether treatment, extrapolated from paediatric protocols despite known differences between the two groups, results in comparable efficacy. Aim To perform a retrospective review of patterns of care in adult medulloblastoma, especially with respect to adjuvant chemotherapy, in Australian patients. Methods All medulloblastoma patients aged 15 years or older at two neuro-oncology institutions were identified from January 1995–May 2011. Patients with supratentorial or peripheral tumours were excluded. Standardised data were extracted from each institution regarding symptoms, disease staging, treatments received, toxicities and survival outcomes. Results Seventeen eligible patients were identified. Median age was 37 years (range 20–67 years). All had good performance status (Eastern Cooperative Oncology Group 0–1). There were 11 standard-risk de novo patients, three high-risk de novo patients and three patients with recurrent disease. Median overall survival (OS) had not been reached for standard-risk patients with median follow up of 58 months. The median OS for high-risk de novo patients was 21 months, while the median OS was 15 months for patients with recurrent disease. Treatment was well tolerated, with haematological toxicities being most common. Conclusions Combined modality therapy (surgery followed by postoperative radiotherapy and adjuvant chemotherapy) was well tolerated and associated with good outcomes in standard-risk de novo patients. High-risk and recurrent disease patients do extremely poorly regardless of treatment and better treatment strategies are needed in these patients.

Monoclonal antibodies (mAbs) and tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR), which is often pathogenetically overexpressed or mutated in epithelial malignancies and glioma, have been modestly successful, with some approved for human use. MAb 806 was raised against de2-7EGFR (or EGFRvIII), a constitutively active mutation expressed in gliomas, but also recognizes a subset (