NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma.

Background: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. Methods: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. Results: A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. Conclusions: Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations.

Physical activity and glioma: a case-control study with follow-up for survival.

PURPOSE: High-grade disease accounts for ~ 70% of all glioma, and has a high mortality rate. Few modifiable exposures are known to be related to glioma risk or mortality. METHODS: We examined associations between lifetime physical activity and physical activity at different ages (15-18 years, 19-29 years, 30-39 years, last 10 years) with the risk of glioma diagnosis, using data from a hospital-based family case-control study (495 cases; 371 controls). We followed up cases over a median of 25 months to examine whether physical activity was associated with all-cause mortality. Physical activity and potential confounders were assessed by self-administered questionnaire. We examined associations between physical activity (metabolic equivalent [MET]-h/wk) and glioma risk using unconditional logistic regression and with all-cause mortality in cases using Cox regression. RESULTS: We noted a reduced risk of glioma for the highest (≥ 47 MET-h/wk) versus lowest (< 24 METh/wk) category of physical activity for lifetime activity (OR = 0.58, 95% CI: 0.38-0.89) and at 15-18 years (OR = 0.57, 95% CI: 0.39-0.83). We did not observe any association between physical activity and all-cause mortality (HR for lifetime physical activity = 0.91, 95% CI: 0.64-1.29). CONCLUSION: Our findings are consistent with previous research that suggested physical activity during adolescence might be protective against glioma. Engaging in physical activity during adolescence has many health benefits; this health behavior may also offer protection against glioma.

Systems-Level Change to Alleviate Barriers to Cancer Clinical Trial Access for Adolescents and Young Adults in Australia.

Purpose: International data demonstrate association between clinical trial participation and reduced cancer mortality. Adolescents and young adults (AYA) have low clinical trial enrollment rates. We established a program to understand local barriers and develop targeted solutions that lead to greater AYA clinical trial participation. Methods: A steering committee (SC) with expertise in adult and pediatric oncology, research ethics, and consumer representation was formed. The SC mapped barriers related to AYA trial access and established working groups (WGs) around three themes. Results: The Regulatory Awareness WG identified a lack of understanding of processes that support protocol approval for clinical trials across the AYA age range. A guideline to raise awareness was developed. The Access WG identified challenges for young adults (18-25 years) to access a pediatric hospital to enroll in a pediatric trial. A procedure was developed to streamline applications for access. The first six applications using this procedure have been successful. The Availability WG identified lack of pediatric-adult oncology reciprocal relationships as a barrier to awareness of open trials, and future collaboration. An AYA Craft Group Framework was established to grow relationships within tumor streams across institutions; two craft groups are now operating locally. An additional achievement was a successful request to the Therapeutic Goods Administration for Australian adoption of the Food and Drug Administration Guidance on Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. Conclusion: This multipronged approach to improving AYA clinical trial access has relevance for other health environments. Our knowledge products are available as an online toolkit.

Perioperative clinical trials for glioma: Raising the bar.

Gliomas are a heterogeneous group of primary brain cancers with poor survival despite multimodality therapy that includes surgery, radiation and chemotherapy. Numerous clinical trials have investigated systemic therapies in glioma, but have largely been negative. Multiple factors have contributed to the lack of progress including tumour heterogeneity, the tumour micro-environment and presence of the blood-brain barrier, as well as extrinsic factors relating to trial design, such as the lack of a contemporaneous biopsy at the time of treatment. A number of strategies have been proposed to progress new agents into the clinic. Here, we review the progress of perioperative, including phase 0 and 'window of opportunity', studies and provide recommendations for trial design in the development of new agents for glioma. The incorporation of pre- and post-treatment biopsies in glioma early phase trials will provide valuable pharmacokinetic and pharmacodynamic data and also determine the target or biomarker effect, which will guide further development of new agents. Perioperative 'window of opportunity' studies must use drugs with a recommended-phase-2-dose, known safety profile and adequate blood-brain barrier penetration. Drugs shown to have on-target effects in perioperative trials can then be evaluated further in a larger cohort of patients in an adaptive trial to increase the efficiency of drug development.

Whole genome and biomarker analysis of patients with recurrent glioblastoma on bevacizumab: A subset analysis of the CABARET trial.

The CABARET trial (ACTRN12610000915055) reported no difference in overall survival (OS) between patients with recurrent glioblastoma (GBM) randomized to either bevacizumab monotherapy or bevacizumab plus carboplatin. However, a subset of patients showed durable responses and prolonged survival, with recorded survival times of over 30 months in five of 122 patients (4%). Patient selection for bevacizumab therapy would be enhanced if a predictive biomarker of response or survival could be identified; this biomarker sub-study attempted to identify novel biomarkers. Patients who opted to participate in this sub-study and who had adequate biospecimens for analysis (n = 54) were retrospectively evaluated for the expression of a series of tumor proteins. Immunohistochemistry (IHC) was used to measure the expression of 19 proteins previously implicated in cancer treatment response to bevacizumab. MGMT promoter methylation was also assessed. Tumor DNA from five patients with outlying survival duration ('poor' and 'exceptional' survivors) was subjected to whole genome sequencing (WGS). No single protein expression level, including VEGF-A, predicted OS in the cohort. WGS of poor and exceptional survivors identified a gain in Chromosome 19 that was exclusive to the exceptional survivors. Validation of this finding requires examination of a larger independent cohort.

A Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2-Positive Metastatic Breast Cancer.

Venetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using a phase Ib 3 + 3 dose-escalation and expansion study design, 33 patients with ER and BCL2-positive metastatic disease (mean prior regimens, 2; range, 0-8) were treated with daily tamoxifen (20 mg) and venetoclax (200-800 mg). Apart from uncomplicated "on-target" lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase II dose (RP2D). In the expansion phase (18 patients), few high-grade treatment-related adverse events were observed. For 24 patients treated at the RP2D, the confirmed radiologic response rate was 54% and the clinical benefit rate was 75%. Treatment responses were preempted by metabolic responses (FDG-PET) at 4 weeks and correlated with serial changes in circulating tumor DNA. Radiologic responses (40%) and clinical benefit (70%) were observed in 10 patients with plasma-detected ESR1 mutations. SIGNIFICANCE: In the first clinical study to evaluate venetoclax in a solid tumor, we demonstrate that combining venetoclax with endocrine therapy has a tolerable safety profile and elicits notable activity in ER and BCL2-positive metastatic breast cancer. These findings support further investigation of combination therapy for patients with BCL2-positive tumors.See related commentary by Drago et al., p. 323.This article is highlighted in the In This Issue feature, p. 305.

The evolutionary pattern of mutations in glioblastoma reveals therapy-mediated selection.

Glioblastoma presents as a heterogeneous disease with poor prognosis despite the use of multimodal therapy. Analysis of genomic DNA changes between initial diagnosis and recurrence in response to standard treatment protocols would enhance understanding of disease progression and better inform new treatment strategies. A cohort of 21 patients with primary glioblastoma were examined between diagnosis and first recurrence. This study presented a rare opportunity to characterize molecular alterations in tumors observed in three patients who received no therapeutic intervention, other than surgery, offering a unique control. We focused this study by comparing the dynamic mutation profiles between the primary tumors and their matched recurrent counterparts. Molecular profiling of tumors was performed using multiplexed targeted deep sequencing of 409 well characterized cancer-associated genes, achieving a mean read depth of 1272 x. Three levels of evidence suggested an evolutionary pattern consistent with a response to therapy-mediated selection pressures exists in treated patients: 1) variant burden was reduced in recurrent tumors, 2) neutral evolutionary dynamics apparent in untreated tumors shifted toward a non-neutral mode of evolution in treated patients at recurrence, and 3) the recurrent tumor of one patient displayed an increased mutation rate attributable to a temozolomide-associated hypermutator phenotype. Our observations suggest that current treatment modalities are likely to fail in achieving long term remission with the majority of relapse samples containing distinct mutations when compared to primary diagnostic samples.

Precision oncology using a clinician-directed, tailored approach to molecular profiling.

AIM: Precision oncology involves molecularly matching patients to targeted agents usually in early drug development (EDD) programs. Molecular profiling (MP) identifies actionable targets. Comprehensive commercial MP platforms are costly and in resource limited environments, a more practical approach to MP is necessary to support EDD and precision oncology. We adopted a clinician-directed, tailored approach to MP to enrol patients onto molecularly targeted trials. We report the feasibility of this approach. METHODS: All patients referred to the Royal Melbourne Hospital (RMH) EDD between September 2013 and September 2015 were identified in a prospective database. Key captured data included clinicopathological data, MP platform ordered (if any), molecular targets identified and subsequent enrolment onto clinical trials. EDD-clinician decisions to order MP and the platform utilized was guided by patient consultation, tumor type, trial availability and requirement for molecular information. RESULTS: We identified 377 patients referred to RMH EDD. A total of 216 (57%) had MP ordered. The remainder had known actionable targets (19%), or were inappropriate for clinical trials (24%). In those undergoing MP, 187 genetic aberrations were found in 113 patients with 98 considered actionable targets in 86 patients. Ninety-eight (25%) patients were enrolled onto a clinical trial, including 40 (11%) receiving molecularly matched treatments. Median progression-free survival was improved in patients enrolled onto molecularly matched trials compared to those on unmatched trials (3.6 months vs 1.9 months, HR 0.58 [0.38-0.89], P  =  0.013). CONCLUSION: A clinician-directed, tailored approach to the use of MP is feasible, resulting in 11% of patients enrolled onto molecularly matched trials.

Comparison between site and central radiological assessments for patients with recurrent glioblastoma on a clinical trial.

AIM: Assessment of magnetic resonance imaging (MRI) in glioblastoma can be challenging. For patients with recurrent glioblastoma managed on the CABARET trial, we compared disease status assessed at hospitals and subsequent blinded central expert radiological review. METHODS: MRI results and clinical status at specified time points were used for site and central assessment of disease status. Clinical status was determined by the site. Response Assessment in Neuro-Oncology (RANO) criteria were used for both assessments. Site and central assessments of progression-free survival (PFS) and response rates were compared. Inter-rater variability for central review progression dates was assessed. RESULTS: Central review resulted in shorter PFS in 45% of 89 evaluable patients (n = 40). Median PFS was 3.6 (central) versus 3.9 months (site) (hazard ratio 1.5, 95% confidence interval 1.3-1.8, P < 0.001). Responses were documented more frequently by sites (n = 16, 18%) than centrally (n = 11, 12%). Seven of 120 patients continued on trial without site-determined progression for more than 6 months beyond the central review determination of progression. Of scans reviewed by all three central reviewers, 33% were fully concordant for progression date. CONCLUSION: While the difference between site and central PFS dates was statistically significant, the 0.3-month median difference is small. The variability within central review is consistent with previous studies, highlighting the challenges in MRI interpretation in this context. A small proportion of patients benefited from treatment well beyond the centrally determined progression date, reinforcing that clinical status together with radiology results are important determinants of whether a therapy is effective for an individual.

The role of early magnetic resonance imaging in predicting survival on bevacizumab for recurrent glioblastoma: Results from a prospective clinical trial (CABARET).

BACKGROUND: Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. METHODS: Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. RESULTS: For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. CONCLUSIONS: In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society.

Health-related quality of life outcomes from CABARET: a randomized phase 2 trial of carboplatin and bevacizumab in recurrent glioblastoma.

In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.

Early perfusion MRI predicts survival outcome in patients with recurrent glioblastoma treated with bevacizumab and carboplatin.

Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan-Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially load, correlated significantly with PFS and OS at both follow-up time-points. Patients with the greatest reduction in rCBVload by 8-weeks of therapy had a significantly increased median OS (30 weeks; p = 0.013). PWI may be of significant clinical utility in managing patients with rGBM, particularly those treated with anti-angiogenic agents such as bevacizumab. These findings need to be confirmed prospectively in larger studies.

Continuing or ceasing bevacizumab beyond progression in recurrent glioblastoma: an exploratory randomized phase II trial.

BACKGROUND: In patients with recurrent glioblastoma, the benefit of bevacizumab beyond progression remains uncertain. We prospectively evaluated continuing or ceasing bevacizumab in patients who progressed while on bevacizumab. METHODS: CABARET, a phase II study, initially randomized patients to bevacizumab with or without carboplatin (Part 1). At progression, eligible patients underwent a second randomization to continue or cease bevacizumab (Part 2). They could also receive additional chemotherapy regimens (carboplatin, temozolomide, or etoposide) or supportive care. RESULTS: Of 120 patients treated in Part 1, 48 (80% of the anticipated 60-patient sample size) continued to Part 2. Despite randomization, there were some imbalances in patient characteristics. The best response was stable disease in 7 (30%) patients who continued bevacizumab and 2 (8%) patients who stopped receiving bevacizumab. There were no radiological responses. Median progression-free survival was 1.8 vs 2.0 months (bevacizumab vs no bevacizumab; hazard ratio [HR], 1.08; 95% CI, .59-1.96; P = .81). Median overall survival was 3.4 vs 3.0 months (HR, .84; 95% CI, .47-1.50; P = .56 and HR .70; 95% CI .38-1.29; P = .25 after adjustment for baseline factors). Quality-of-life scores did not significantly differ between arms. While the maximum daily steroid dose was lower in the continuation arm, the difference was not statistically significant. CONCLUSIONS: Patients who continued bevacizumab beyond disease progression did not have clear survival improvements, although the study was not powered to detect other than very large differences. While these data provide the only randomized evidence related to continuing bevacizumab beyond progression in recurrent glioblastoma, the small sample size precludes definitive conclusions and suggests this remains an open question.

Recurrent glioblastoma: Current patterns of care in an Australian population.

This retrospective population-based survey examined current patterns of care for patients with recurrent glioblastoma (rGBM) who had previously undergone surgery and post-operative therapy at original diagnosis. The patients were identified from the Victorian Cancer Registry (VCR) from 2006 to 2008. Patient demographics, tumour characteristics and oncological management were extracted using a standardised survey by the treating clinicians/VCR staff and results analysed by the VCR. Kaplan-Meier estimates of overall survival (OS) at diagnosis and progression were calculated. A total of 95 patients (48%) received treatment for first recurrence; craniotomy and post-operative treatment (38), craniotomy only (34) and non-surgical treatment (23). Patients receiving treatment at first progression had a higher median OS than those who did not (7 versus 3 months, p<0.0001). All patients progressed after treatment for first progression with 43 patients (45%) receiving treatment at second progression. To our knowledge this is the first population-based pattern of care survey of treatment for rGBM in an era where post-operative "Stupp" chemo-radiation is standard. First and second line therapy for rGBM is common and associated with significant benefit. Treatment generally includes re-resection and/or systemic therapy.

Glioblastoma multiforme in the very elderly.

Glioblastoma is the most malignant and most common primary brain tumour and is treated with resection followed by post-operative radiotherapy and chemotherapy. However, a significant amount of patients are older than 80 years, and such an approach may not be appropriate. Data on patients aged 80 or older with glioblastoma from two hospitals was collected using the CNS Tumour Database on the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD) system operated by BioGrid. Between 2008 and July 2011, 40 patients aged 80 years or older were diagnosed with glioblastoma. The median ECOG PS was 2 and the ASA score was 3. All 40 patients underwent surgery and 33% had a gross total resection. Only six patients (15%) had either post-operative radiotherapy or chemotherapy. The overall median survival was 4 months (range 0-18 months) and 28% of patients lived between 6 and 24 months. This is the largest reported cohort of very elderly patients with glioblastoma. Patients tolerated surgery but few went on to receive post-operative radiotherapy or chemotherapy. This patient population requires special attention and in particular would benefit from participation in suitable clinical trials to determine the best care regime.

First in human nanotechnology doxorubicin delivery system to target epidermal growth factor receptors in recurrent glioblastoma.

There are limited treatment options for patients with recurrent glioblastoma (GBM). The EnGeneIC delivery vehicle (EDV) is a novel nanocellular (minicell) compound which packages theoretically effective concentrations of chemotherapeutic drugs that are designed to target tumors via minicell-surface attached bispecific proteins (EnGeneIC, Lane Cove West, NSW, Australia). Epidermal growth factor receptor (EGFR) is overexpressed in 40-50% of patients with GBM and is a promising target for new therapeutics. (V)EDVDox contains doxorubicin (Dox) within the minicells and targets EGFR through Vectibix (V; Amgen Biologicals, Thousand Oaks, CA, USA). We conducted a first in human Phase I study of (V)EDVDox in adults with recurrent GBM expressing EGFR on immunohistochemistry, following standard therapy including radiation and temozolomide, to establish a safe maximum tolerated dose and determine a recommended Phase II dose (RPTD). (V)EDVDox was administered weekly in an 8week cycle, with dose escalation in successive cohorts of patients using a standard 3+3 design. In total, 14 patients were treated at three dose levels, and the RPTD was identified as 5×10(9)(V)EDVDox. Overall (V)EDVDox was well tolerated, with no dose limiting toxicity and no withdrawals from the study due to adverse events. The most common adverse events were nausea, fever, and chills or rigors, experienced in seven, five and five patients, respectively. Transient uncomplicated hypophosphatemia was seen in seven patients and was not dose-related. Our results demonstrate that (V)EDVDox, up to a dose of 5×10(9)(V)EDVDox weekly, is well tolerated in patients with recurrent GBM.

Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma.

BACKGROUND: The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy. METHODS: This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS). RESULTS: One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately. CONCLUSIONS: Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies. CLINICAL TRIALS REGISTRATION NR: ACTRN12610000915055.

Management of glioblastoma in Victoria, Australia (2006-2008).

We describe the management of patients with newly diagnosed glioblastoma multiforme (GBM) in a population-based cohort and compare this to a previously studied cohort. We performed a retrospective cohort study of patients diagnosed with GBM from 2006-2008 in Victoria, Australia. Patients were identified from the population-based Victorian Cancer Registry and their treating doctors surveyed by questionnaire. Outcomes were then compared to a study of GBM patients who were diagnosed between 1998 and 2000 using an identical methodology. We reviewed 351 eligible patients. There were slightly more males (62%) and a minority had multifocal disease (13%). Total macroscopic resection, partial resection or biopsy only was performed in 32%, 37% and 24% of patients, respectively. The majority of patients were referred to a radiation oncologist and medical oncologist postoperatively. A total of 56% of patients were treated with postoperative radiotherapy with concurrent and sequential temozolomide and had a median survival of 14.4 months. This was significantly better than patients treated with postoperative radiotherapy alone in the current or earlier cohorts (2006-2008: median survival 6.2 months, p<0.0001 versus 1998-2000: 8.9 months, p<0.0001). This study demonstrates that postoperative chemoradiation has become the standard of care in this Victorian population with an associated improvement in median survival.

Symptomatic cardiac metastasis responding to pazopanib in a patient with renal cell carcinoma.

We report a case of an 82-year-old man with renal cell carcinoma who developed a cardiac metastasis within the interventricular septum. He had been under watchful waiting for indolent metastatic renal cell carcinoma for many years before developing symptoms consistent with heart failure. At this time, a 44 mm interventricular septal mass, consistent with a cardiac metastasis, was identified as the cause of his symptoms. Pazopanib was initiated which led to both a clinical and radiological response.

Ependymoma in adults: Local experience with an uncommon tumour.

This study reviews our tertiary hospital experience in an adult population of ependymoma patients. Ependymomas are uncommon tumours of the central nervous system (CNS) and the literature provides little information to guide management and predict prognosis. The prospectively maintained Australian Comprehensive Cancer Outcomes and Research Database of CNS tumours was searched for patients diagnosed with ependymomas at the Royal Melbourne Hospital between January 2008 and December 2013. A total of 39 adult patients with ependymoma were identified, including 13 with spinal myxopapillary ependymoma. The mean age at diagnosis was 44 years. All patients underwent surgical resection, 67% of whom had a gross macroscopic resection. Postoperative adjuvant radiotherapy was administered to 11 patients (30%), two (5%) died from progressive disease and seven (18%) developed recurrent disease. Our findings are consistent with the existing literature for patient demographics and the approach to treatment, whilst our clinical outcomes appear more favourable. This study provides the basis for further and necessary research, including determination of the molecular characterisation of these tumours and the identification of prognostic and predictive biomarkers and treatment targets.