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In patients with glioblastoma, the addition of bevacizumab to radiotherapy and temozolomide induction therapy and the use of bevacizumab maintenance therapy did not influence overall survival. Freedom from progression was slightly increased but at the cost of increased toxic effects. Tumor progression in glioblastoma, the most common primary brain cancer, 1 , 2 is associated with deterioration in neurocognitive function, 3 , 4 decreased functional independence, 5 and a progressive decrease in health-related quality of life. 6 , 7 After surgical resection, the standard of care for patients with newly diagnosed glioblastoma and a good Karnofsky performance score (≥70, on a scale of 0 to 100, with higher numbers indicating better functioning) is concurrent radiotherapy and temozolomide, followed by adjuvant temozolomide. 8 – 11 The prognosis remains poor; no further improvements in outcomes have been documented since the introduction of radiotherapy–temozolomide therapy in 2005. Glioblastomas are characterized by overexpression . . .

The nearing completion of the Australian Bragg Centre for Proton Therapy and Research marks a transformative leap in cancer care in Australia. Highlighting the precision and potential of particle therapy in reducing long‐term side effects, particularly in paediatric and rare cancers, this editorial underscores Australia's commitment to integrating this innovative modality into national healthcare, despite challenges in accessibility and cost.

This letter critically evaluates the conclusions drawn by Li et al. (https://doi.org/10.1002/jmrs.773) in their comparison of proton beam therapy (PBT) and photon irradiation for paediatric and young adult patients. While acknowledging the complexities of treatment selection, the authors argue that PBT's benefits, particularly in reducing radiation exposure to organs at risk, should be given greater consideration. The letter calls for a comprehensive, nuanced approach to treatment decisions, emphasising long-term outcomes and the reduction of potential late effects.This letter critically evaluates the conclusions drawn by Li et al. (https://doi.org/10.1002/jmrs.773) in their comparison of proton beam therapy (PBT) and photon irradiation for paediatric and young adult patients. While acknowledging the complexities of treatment selection, the authors argue that PBT's benefits, particularly in reducing radiation exposure to organs at risk, should be given greater consideration. The letter calls for a comprehensive, nuanced approach to treatment decisions, emphasising long-term outcomes and the reduction of potential late effects.

Background We report a case of recurrent primary intraventricular synovial sarcoma of the brain with no extracranial primary, initially reported as a haemangiopericytoma. We believe this is the first reported case of primary intraventricular synovial sarcoma at this site. Case presentation A 27-year-old male presented to hospital with a new onset of seizures. Imaging revealed a left ventricular trigone mass with surrounding oedema. He underwent a left occipito-temporal craniotomy and resection with the histology reported as haemangiopericytoma. Resection was followed by adjuvant radiation treatment. Seven years later follow-up imaging revealed a 4 mm contrast enhancing lesion in the previous surgical bed. The patient underwent resection. Histological analysis of the recurrence revealed a spindle cell tumour with a SS18 gene rearrangement consistent with synovial sarcoma. Retrospective fluorescent in-situ hybridisation analysis of original histology also revealed a SS18 gene rearrangement consistent with a diagnosis of synovial sarcoma. Conclusion Synovial sarcoma should be included as part of the differential diagnosis for patients presenting with intraventricular spindle cell tumours in the brain.

Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy. The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. Cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted. ClinicalTrials.gov NCT01310855.

With the anticipated launch of the Australian Bragg Centre for Proton Therapy and Research (ABCPTR) in Adelaide, Australia, proton therapy will become a significant addition to existing cancer treatment options for Australians. The anticipated benefits will be particularly evident in rare cancers such as clival chordomas, a challenging tumour entity due to the anatomical relationship with critical structures, and proven radio‐resistance to conventional radiation therapy. The article synthesises key findings from major studies and evaluates the current evidence supporting various management strategies for clival chordomas. It also considers the influence of institutional volume and multidisciplinary team management on patient outcomes and outlines how high‐quality care can be effectively delivered within the Australian healthcare system, emphasising the potential impact of proton therapy on the treatment paradigm of clival chordomas in Australia. The article discusses the anticipated launch of the Australian Bragg Centre for Proton Therapy and Research (ABCPTR) in Adelaide, highlighting the potential benefits of proton therapy for rare cancers like clival chordomas. It synthesises key findings from major studies, evaluates management strategies for clival chordomas, considers the role of institutional volume and multidisciplinary teams in patient outcomes, and explores how high‐quality care can be delivered in the Australian healthcare system, emphasising the potential impact of proton therapy on clival chordoma treatment in Australia.

Glioblastoma is an aggressive form of central nervous system tumor. Recurrence rates following primary therapy are high, and few second-line treatment options provide durable clinical benefit. Aberrations of the epidermal growth factor receptor ( ) gene are observed in up to 57% of glioblastoma cases and EGFR overexpression has been identified in approximately 60% of primary glioblastomas. In preclinical studies, afatinib, a second-generation ErbB blocker, inhibited cell proliferation in cells harboring mutations commonly found in glioblastoma. In two previous Phase I/II studies of afatinib plus temozolomide in patients with glioblastoma, limited efficacy was observed; however, there was notable benefit in patients with the variant III ( mutation, amplification, and those with loss of phosphatase and tensin homolog (PTEN). This case series report details treatment histories of three long-term responders from these trials. Next-generation sequencing of tumor samples identified alterations in a number of cancer-related genes, including mutations in, and amplification of, . Tumor samples from all three patients shared favorable prognostic factors, eg O -methylguanine-DNA methyl-transferase ( ) gene promoter methylation; however, negative prognostic factors were also observed, suggesting that these shared genetic features did not completely account for the favorable responses. The genetic profile of the tumor from Patient 1 showed clear differences from the other two tumors: lack of involvement of aberrations but with a mutation occurring in . Preclinical studies showed that single-agent afatinib and temozolomide both separately inhibit the growth of tumors with a C-terminal EGFR truncation, thus providing further rationale for combining these two agents in the treatment of glioblastomas harboring EGFR aberrations. These findings suggest that afatinib may provide treatment benefit in patients with glioblastomas that harbor ErbB family aberrations and, potentially, other genetic aberrations. Further studies are needed to establish which patients with newly diagnosed/recurrent glioblastomas may potentially benefit from treatment with afatinib.

Purpose 32 P-chromic phosphate colloid treatments of astrocytoma and craniopharyngioma cystic brain tumours in paediatric patients are conventionally based on a sphere model under the assumption of uniform uptake. The aims of this study were to determine the distribution of the absorbed dose delivered by 32 P on a patient-specific basis and to evaluate the accuracy with which this can be predicted from a pretherapy administration of 99m Tc-Sn colloid. Methods Three patients were treated with 32 P-chromic phosphate colloid following 99m Tc-Sn colloid administrations. Convolution dosimetry was performed using pretherapy and posttherapy sequential SPECT imaging, and verified with EGSnrc Monte Carlo radiation transport simulations. Mean absorbed doses to the cyst wall and dose–volume histograms were also calculated and compared with those obtained by the sphere model approach. Results Highly nonuniform uptake distributions of both the 99m Tc and 32 P colloids were observed and characterized by dose–volume histograms to the cyst wall. Mean absorbed doses delivered to the cyst wall, obtained with the convolution method, were on average 21 % (SD 18 %) and 50 % (SD 30 %) lower than those predicted by the 99m Tc distribution and the uniform assumption of the sphere model, respectively. Conclusion Absorbed doses delivered to the cyst wall by 32 P are more accurately predicted from image-based patient-specific convolution dosimetry than from simple sphere models. These results indicate the necessity to perform personalized treatment planning and verification for intracavitary irradiation of cystic brain tumours treated with radiocolloids. Patient-specific dosimetry can be used to guide the frequency and levels of repeated administrations and would facilitate data collection and comparison to support the multicentre trials necessary to progress this therapy.

Glioblastoma has a poor prognosis accompanied by debilitating neurological symptoms and impaired quality of life. Effective treatment strategies are needed, beyond the current standard of care (SOC), to improve outcomes. Glioblastomas are highly vascularized with elevated levels of VEGF, representing an appropriate target for selective therapies. The role of the anti-VEGF agent bevacizumab in newly diagnosed and recurrent glioblastoma is not fully clear at this time. Although bevacizumab has demonstrated improvements in progression-free survival in newly diagnosed and recurrent glioblastoma, there remain challenges in assessing disease progression after antiangiogenic treatment. The bevacizumab mechanism of action suggests a rationale for continuing bevacizumab treatment through multiple lines of therapy, strengthened by longer progression-free and overall survival observed with bevacizumab continuation beyond progression in a Phase III study in metastatic colorectal cancer and in pooled analyses of Phase II trials in glioblastoma. A novel study (randomized, double-blind, Phase IIIb; TAMIGA [MO28347]) aims to evaluate whether continuing bevacizumab plus lomustine (as second-line therapy) and SOC (third line and beyond) improves survival compared with placebo plus lomustine and then placebo plus SOC in patients with glioblastoma who progressed after first-line bevacizumab plus SOC.

Since the inception of phase I clinical trials in cancer, patients with symptomatic brain metastases have commonly been excluded from participation because of a poor outlook. However, patients with asymptomatic brain metastases pose an increasingly frequent challenge for clinicians: more sensitive brain imaging can identify clinically silent brain metastases; frequency of detection might have increased because of changes in the natural history of many tumour types as a result of more effective systemic treatment; and routine brain imaging as a screening procedure before entry into a clinical trial can show lesions which are of questionable clinical importance, but which frequently preclude trial enrolment. Evidence suggests that delaying whole-brain radiotherapy until symptomatic progression has no adverse effect on prognosis. Safety and efficacy data are accumulating for targeted agents to treat brain metastases. We think that a subset of patients with asymptomatic brain metastases might be appropriately entered into phase I trials, and we present our approach for their stratification. As a consequence, patients might have increased access to experimental treatments and thus effective interventions for brain metastases might be developed more promptly.