Assessment of artificial intelligence (AI) reporting methodology in glioma MRI studies using the Checklist for AI in Medical Imaging (CLAIM).

PURPOSE: The Checklist for Artificial Intelligence in Medical Imaging (CLAIM) is a recently released guideline designed for the optimal reporting methodology of artificial intelligence (AI) studies. Gliomas are the most common form of primary malignant brain tumour and numerous outcomes derived from AI algorithms such as grading, survival, treatment-related effects and molecular status have been reported. The aim of the study is to evaluate the AI reporting methodology for outcomes relating to gliomas in magnetic resonance imaging (MRI) using the CLAIM criteria. METHODS: A literature search was performed on three databases pertaining to AI augmentation of glioma MRI, published between the start of 2018 and the end of 2021 RESULTS: A total of 4308 articles were identified and 138 articles remained after screening. These articles were categorised into four main AI tasks: grading (n= 44), predicting molecular status (n= 50), predicting survival (n= 25) and distinguishing true tumour progression from treatment-related effects (n= 10). The average CLAIM score was 20/42 (range: 10-31). Studies most consistently reported the scientific background and clinical role of their AI approach. Areas of improvement were identified in the reporting of data collection, data management, ground truth and validation of AI performance. CONCLUSION: AI may be a means of producing high-accuracy results for certain tasks in glioma MRI; however, there remain issues with reporting quality. AI reporting guidelines may aid in a more reproducible and standardised approach to reporting and will aid in clinical integration.

Correlating MRI features with additional genetic markers and patient survival in histological grade 2-3 IDH-mutant astrocytomas.

PURPOSE: The increasing importance of molecular markers for classification and prognostication of diffuse gliomas has prompted the use of imaging features to predict genotype ("radiogenomics"). CDKN2A/B homozygous deletion has only recently been added to the diagnostic paradigm for IDH[isocitrate dehydrogenase]-mutant astrocytomas; thus, associated radiogenomic literature is sparse. There is also little data on whether different IDH mutations are associated with different imaging appearances. Furthermore, given that molecular status is now generally obtained routinely, the additional prognostic value of radiogenomic features is less clear. This study correlated MRI features with CDKN2A/B status, IDH mutation type and survival in histological grade 2-3 IDH-mutant brain astrocytomas. METHODS: Fifty-eight grade 2-3 IDH-mutant astrocytomas were identified, 50 with CDKN2A/B results. IDH mutations were stratified into IDH1-R132H and non-canonical mutations. Background and survival data were obtained. Two neuroradiologists independently assessed the following MRI features: T2-FLAIR mismatch (<25%, 25-50%, >50%), well-defined tumour margins, contrast-enhancement (absent, wispy, solid) and central necrosis. RESULTS: 8/50 tumours with CDKN2A/B results demonstrated homozygous deletion; slightly shorter survival was not significant (p=0.571). IDH1-R132H mutations were present in 50/58 (86%). No MRI features correlated with CDKN2A/B status or IDH mutation type. T2-FLAIR mismatch did not predict survival (p=0.977), but well-defined margins predicted longer survival (HR 0.36, p=0.008), while solid enhancement predicted shorter survival (HR 3.86, p=0.004). Both correlations remained significant on multivariate analysis. CONCLUSION: MRI features did not predict CDKN2A/B homozygous deletion, but provided additional positive and negative prognostic information which correlated more strongly with prognosis than CDKN2A/B status in our cohort.

Conventional MRI features can predict the molecular subtype of adult grade 2-3 intracranial diffuse gliomas.

PURPOSE: Molecular biomarkers are important for classifying intracranial gliomas, prompting research into correlating imaging with genotype ("radiogenomics"). A limitation of the existing radiogenomics literature is the paucity of studies specifically characterizing grade 2-3 gliomas into the three key molecular subtypes. Our study investigated the accuracy of multiple different conventional MRI features for genotype prediction. METHODS: Grade 2-3 gliomas diagnosed between 2007 and 2013 were identified. Two neuroradiologists independently assessed nine conventional MRI features. Features with better inter-observer agreement (κ ≥ 0.6) proceeded to consensus assessment. MRI features were correlated with genotype, classified as IDH-mutant and 1p/19q-codeleted (IDHmut/1p19qcodel), IDH-mutant and 1p/19q-intact (IDHmut/1p19qint), or IDH-wildtype (IDHwt). For IDHwt tumors, additional molecular markers of glioblastoma were noted. RESULTS: One hundred nineteen patients were included. T2-FLAIR mismatch (stratified as > 50%, 25-50%, or < 25%) was the most predictive feature across genotypes (p < 0.001). All 30 tumors with > 50% mismatch were IDHmut/1p19qint, and all seven with 25-50% mismatch. Well-defined margins correlated with IDHmut/1p19qint status on univariate analysis (p < 0.001), but this related to correlation with T2-FLAIR mismatch; there was no longer an association when considering only tumors with < 25% mismatch (p = 0.386). Enhancement (p = 0.001), necrosis (p = 0.002), and hemorrhage (p = 0.027) correlated with IDHwt status (especially "molecular glioblastoma"). Calcification correlated with IDHmut/1p19qcodel status (p = 0.003). A simple, step-wise algorithm incorporating these features, when present, correctly predicted genotype with a positive predictive value 91.8%. CONCLUSION: T2-FLAIR mismatch strongly predicts IDHmut/1p19qint even with a lower threshold of ≥ 25% mismatch and outweighs other features. Secondary features include enhancement, necrosis and hemorrhage (predicting IDHwt, especially "molecular glioblastoma"), and calcification (predicting IDHmut/1p19qcodel).

Conventional MRI features of adult diffuse glioma molecular subtypes: a systematic review.

PURPOSE: Molecular parameters have become integral to glioma diagnosis. Much of radiogenomics research has focused on the use of advanced MRI techniques, but conventional MRI sequences remain the mainstay of clinical assessments. The aim of this research was to synthesize the current published data on the accuracy of standard clinical MRI for diffuse glioma genotyping, specifically targeting IDH and 1p19q status. METHODS: A systematic search was performed in September 2019 using PubMed and the Cochrane Library, identifying studies on the diagnostic value of T1 pre-/post-contrast, T2, FLAIR, T2*/SWI and/or 3-directional diffusion-weighted imaging sequences for the prediction of IDH and/or 1p19q status in WHO grade II-IV diffuse astrocytic and oligodendroglial tumours as defined in the WHO 2016 Classification of CNS Tumours. RESULTS: Forty-four studies including a total of 5286 patients fulfilled the inclusion criteria. Correlations between key glioma molecular markers, namely IDH and 1p19q, and distinctive MRI findings have been established, including tumour location, signal composition (including the T2-FLAIR mismatch sign) and apparent diffusion coefficient values. CONCLUSION: Consistent trends have emerged indicating that conventional MRI is valuable for glioma genotyping, particularly in presumed lower grade glioma. However, due to limited interobserver testing, the reproducibility of qualitatively assessed visual features remains an area of uncertainty.

The role of 2-hydroxyglutarate magnetic resonance spectroscopy for the determination of isocitrate dehydrogenase status in lower grade gliomas versus glioblastoma: a systematic review and meta-analysis of diagnostic test accuracy.

PURPOSE: Magnetic resonance spectroscopy (MRS) provides a non-invasive means of determining isocitrate dehydrogenase (IDH) status. Determination of 2-hydroxyglutarate (2-HG) presence through MRS is a means of determining IDH status; however, differences may be seen by grade. The goal of this paper is to perform a diagnostic test accuracy (DTA) meta-analysis on 2-HG MRS for IDH status in both lower-grade glioma (LGG) and glioblastoma (GBM) in preoperative patients. METHODS: A systematic review and meta-analysis were performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Diagnostic Test Accuracy guidelines. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2. The search was up to date as of 09/02/2021. Nine English-language journal articles were included. RESULTS: The meta-analysis found a pooled sensitivity of 93% (95% CI 58-99%) and specificity of 84% (95% CI 51-96%) for LGG (n= 181). For GBM (n= 77), the pooled sensitivity was 84% (95% CI 25.0-99%) and the specificity was 97% (95% CI 43-100%). CONCLUSION: 2-HG MRS shows promise as a non-invasive means of determining IDH status, with specificity higher for GBM and sensitivity higher for LGG. The wide confidence intervals are notable, however, in particular related to the small number of IDH-mutant GBM studied. Diagnostic heterogeneity was particularly present for LGG, and the hierarchical summary receiver operator curves showed poor predictive accuracy in both groups. For more conclusive results, diagnostic test accuracy statistics need to be quantified with larger studies and more deliberate study design.

FDG PET/CT for tumoral and systemic immune response monitoring of advanced melanoma during first-line combination ipilimumab and nivolumab treatment.

PURPOSE: We aimed to investigate the role of FDG-PET/CT in monitoring of response and immune-related adverse events (irAEs) following first-line combination-immune checkpoint inhibitor (combination-ICI) therapy for advanced melanoma. METHODS: We retrospectively reviewed outcomes in patients who had (1) first-line nivolumab plus ipilimumab; (2) pre- and post-treatment FDG-PET/CT scans (pre-FDG-PET/CT and post-FDG-PET/CT) within 2 and 4 months of starting ICI, respectively; and (3) at least one lesion assessable by PET response criteria in solid tumors (PERCIST). Extracranial response was monitored by 3 monthly FDG-PET/CT. Whole-body metabolic tumor volume (wbMTV) was measured pre- and post-treatment and correlated with outcome. FDG-PET/CT manifestations of irAE were defined as new increased non-tumoral uptake on post-FDG-PET/CT and were correlated with clinical presentation. RESULTS: Thirty-one consecutive patients, median age 60 years (range, 30-78), were identified from 2016 to 2018. The median number of combination-ICI cycles to the first post-FDG-PET/CT response assessment was 3 (interquartile range (IQR), 2-4). The best-overall responses were complete metabolic response (CMR) in 25 (80%), partial metabolic response (PMR) in 3 (10%), and progressive metabolic disease (PMD) in 3 (10%) patients. Patients with PMD had significantly higher pre-treatment wbMTV (p = 0.009). At a median follow-up of 21.5 months, 26 (84%) patients were alive with median progression-free and overall survival not reached. Secondary progression occurred in 9/31 (29%) patients at a median of 8.2 months (IQR, 6.9-15.5), of those majority (78%) was detected by FDG-PET/CT. Of 36 findings on post-FDG-PET/CT suggestive of irAE, 29 (80%) had clinical confirmation. In 3 (7%), the FDG-PET/CT findings preceded clinical presentation. The most common FDG-PET/CT detectable irAEs were endocrinopathies (36%) and enterocolitis (35%). CONCLUSION: FDG-PET/CT response evaluation predicts the long-term outcome of patients treated with first-line combination-ICIs. Long-term treatment response monitoring for detection of extracranial secondary progression is feasible by FDG-PET/CT. Beyond response assessment, FDG-PET/CT frequently detects clinically relevant irAEs, which may involve multiple systems contemporaneously or at various time-points and may precede clinical diagnosis.

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma.

For the reference citation '[57]' in the second paragraph of the Results section of the original article there was no corresponding entry in the References section. It should have referred to the below mentioned article by Ebrahimkhani et al. (2018).

Serum microRNA is a biomarker for post-operative monitoring in glioma.

PURPOSE: A circulating biomarker has potential to provide more accurate information for glioma progression post treatment, however no such biomarker is currently available. We aimed to discover a microRNA serum biomarker for longitudinal monitoring of glioma patients. METHODS: A prospectively collected cohort of 91 glioma patients and 17 healthy controls underwent pre and post-operative serum miRNA profiling using Nanostring®. Differentially expressed miRNAs were discovered using a machine learning random forest analysis. Candidate miRNAs were then assessed by droplet digital PCR in 11 patients with multiple follow up samples and compared to tumor volume based on magnetic resonance imaging. RESULTS: A 9-gene miRNA signature was identified that could distinguish between glioma and healthy controls with 99.8% accuracy. Two miRNAs miR-223 and miR-320e, best demonstrated dynamic changes that correlated closely with tumor volume in LGG and GBM respectively. Importantly, miRNA levels did not increase in two cases of pseudo-progression, indicating the potential utility of this test in guiding treatment decisions. CONCLUSIONS: We identified a highly accurate 9-miRNA signature associated with glioma serum. Additionally, we observed dynamic changes in specific miRNAs correlating with tumor volume over long-term follow up. These results support a large prospective validation study of serum miRNA biomarkers in glioma.

The incidence and significance of multicentric noncontrast-enhancing lesions distant from a histologically-proven glioblastoma.

Improvements in imaging are increasing the detection of multiple lesions in the setting of glioblastoma. Occasionally distant non-enhancing lesions may be identified which have the appearances of a multicentric low-grade glioma. We aimed to determine the incidence, prognostic significance and diagnostic value of this appearance in new glioblastoma patients. Pre-operative MRIs of patients with a new diagnosis of glioblastoma were reviewed to identify multicentric non-enhancing lesions, defined as areas of FLAIR hyperintensity and mass effect, without post-contrast enhancement, separate from the histologically-proven glioblastoma. Patient survival was compared to glioblastoma patients without these appearances, and follow-up imaging was reviewed. Nine of 151 patients (6 %) had multicentric non-enhancing lesions. Their median survival of 183 days was significantly worse than the 278 days for patients without multicentric nonenhancing lesions (p = 0.025). Follow-up MRIs were performed in four patients. In one patient, there were several additional lesions, one of which developed evidence of necrosis within 22 days of presentation. In the other three patients, the multicentric lesions developed enhancement and evidence of necrosis within 1 year, and became confluent on FLAIR with the dominant lesion. The appearance of a multicentric non-enhancing lesion is an uncommon finding in glioblastoma, but a poor prognostic feature. These lesions progress faster than expected for a low-grade glioma and are thus likely to represent more advanced lesions than their appearances suggest. Confluence with the dominant lesion developing with time suggests that the tumor is more extensive than appreciated on imaging.

MRI-based deep learning techniques for the prediction of isocitrate dehydrogenase and 1p/19q status in grade 2-4 adult gliomas.

Molecular biomarkers are becoming increasingly important in the classification of intracranial gliomas. While tissue sampling remains the gold standard, there is growing interest in the use of deep learning (DL) techniques to predict these markers. This narrative review with a systematic approach identifies and synthesises the current published data on DL techniques using conventional MRI sequences for predicting isocitrate dehydrogenase (IDH) and 1p/19q-codeletion status in World Health Organisation grade 2-4 gliomas. Three databases were searched for relevant studies. In all, 13 studies met the inclusion criteria after exclusions. Key results, limitations and discrepancies between studies were synthesised. High accuracy has been reported in some studies, but the existing literature has several limitations, including generally small cohort sizes, a paucity of studies with independent testing cohorts and a lack of studies assessing IDH and 1p/19q together. While DL shows promise as a non-invasive means of predicting glioma genotype, addressing these limitations in future research will be important for facilitating clinical translation.

Prospective comparison of volumetric post-contrast T1-Sampling Perfection with Application optimized Contrasts by using different flip angle Evolutions and Magnetization-Prepared Rapid Acquisition with Gradient Echo in patients with metastatic melanoma.

INTRODUCTION: Volumetric turbo spin echo (3D-TSE) T1-weighted imaging techniques such as T1-SPACE (Sampling Perfection with Application optimized Contrasts by using different flip angle Evolutions) improve detection of intracranial metastases (IM) compared to volumetric magnetisation-prepared gradient recalled echo techniques such as MPRAGE (Magnetization-Prepared Rapid Acquisition with Gradient Echo). However, incomplete vascular suppression can produce false positives when using 3D-TSE. Research into 3D-TSE has generally targeted patients with known or suspected IM, but the clinical implications of false positives are greater in patients with lower likelihood of IM. This study examined additional findings identified by T1-SPACE in patients with metastatic melanoma, targeting patients with a lower incidence of IM. METHODS: Patients with metastatic melanoma and an upcoming brain MRI booking were identified prospectively. Consent for adding post-contrast T1-SPACE to the MRI protocol (which included MPRAGE) was obtained. Imaging was initially assessed without T1-SPACE. Subsequently, T1-SPACE images were examined and additional findings identified were recorded, including their correlation with MPRAGE. RESULTS: One hundred examinations were performed, 24 having evidence of active IM. T1-SPACE allowed identification of additional lesions in five patients, including two with small solitary IM not identified when first assessing MPRAGE. In 18 examinations, T1-SPACE identified additional equivocal findings, confidently attributed to artefact (most commonly normal vessels) following correlation with MPRAGE. CONCLUSION: T1-SPACE improves detection of small lesions in patients without known IM, changing patient management. False positives are common but can be clarified with MPRAGE. Combining T1-SPACE and MPRAGE allows both sensitivity and specificity to be optimised.

Radiogenomics of adult intracranial gliomas after the 2021 World Health Organisation classification: a review of changes, challenges and opportunities.

The classification of diffuse gliomas has undergone substantial changes over the last decade, starting with the 2016 World Health Organisation (WHO) classification, which introduced the importance of molecular markers for glioma diagnosis, in particular, isocitrate dehydrogenase (IDH) status and 1p/19-codeletion. This has spurred research into the correlation of imaging features with the key molecular markers, known as "radiogenomics" or "imaging genomics". Radiogenomics has a variety of possible benefits, including supplementing immunohistochemistry to refine the histological diagnosis and overcoming some of the limitations of the histological assessment. The recent 2021 WHO classification has introduced a variety of changes and continues the trend of increasing the importance of molecular markers in the diagnosis. Key changes include a formal distinction between adult- and paediatric-type diffuse gliomas, the addition of new diagnostic entities, refinements to the nomenclature for IDH-mutant (IDHmut) and IDH-wildtype (IDHwt) gliomas, a shift to grading within tumour types, and the addition of molecular markers as a determinant of tumour grade in addition to phenotype. These changes provide both challenges and opportunities for the field of radiogenomics, which are discussed in this review. This includes implications for the interpretation of research performed prior to the 2021 classification, based on the shift to first classifying gliomas based on genotype ahead of grade, as well as opportunities for future research and priorities for clinical integration.

Investigating the role of delayed contrast magnetic resonance imaging (MRI) to differentiate radiation necrosis from tumour recurrence in brain metastases after stereotactic radiosurgery.

INTRODUCTION: The incidence of radionecrosis (RN) after stereotactic radiosurgery (SRS) to brain metastases is increasing. An overlap in the conventional MRI appearances of RN and tumour recurrence (TR) is diagnostically challenging. Delayed contrast MRI compares contrast enhancement over two time periods to create treatment response assessment maps (TRAMs). We aim to assess the utility of TRAMs in brain metastases patients. METHODS: Delayed contrast MRI scans were performed on ten brain metastases patients, previously treated with SRS, who developed equivocal lesion(s) on routine MRI follow-up. T1-weighted images were obtained five minutes and 60-75 min after contrast injection, followed by Brain Lab software analysis to create TRAMs. TRAMs patterns were then compared with the patient's clinical status, subsequent imaging, and histology results. RESULTS: We identified three regions on TRAMs: central, peripheral, and surrounding. Each region could be described either as contrast accumulation (red colour and representing non-tumour tissue) or contrast clearance (blue colour and representing tumour tissue). Our analysis demonstrated similarities in the TRAMs pattern between TR and RN, though to varying degrees. CONCLUSION: In conclusion, the TRAMs appearances of RN and TR overlap. Our findings suggest that the previously-described correlation between contrast clearance and TR is at least partially attributable to more solid initial enhancement, rather than convincingly a difference in the underlying tissue properties, and the additional diagnostic value of TRAMs may be limited. Thus, further research on TRAMs is necessary prior to incorporating it into routine clinical management after SRS for brain metastases.

Prospective Comparison of T1-SPACE and MPRAGE for the Identification of Intrinsic T1 Hyperintensity in Patients with Intracranial Melanoma Metastases.

BACKGROUND AND PURPOSE: Volumetric TSE (3D-TSE) techniques are increasingly replacing volumetric magnetization-prepared gradient recalled-echo (3D-GRE) sequences due to improved metastasis detection. In addition to providing a baseline for assessing postcontrast enhancement, precontrast T1WI also identifies intrinsic T1 hyperintensity, for example, reflecting melanin or blood products. The ability of precontrast 3D-TSE to demonstrate intrinsic T1 hyperintensity is not clear from the literature; thus, this study compares precontrast 3D-TSE and 3D-GRE sequences for identifying intrinsic T1 hyperintensity in patients with metastatic melanoma. MATERIALS AND METHODS: Patients with metastatic melanoma and previously reported intrinsic T1 hyperintensity were identified. MRIs were performed at 3T including both 3D-GRE (MPRAGE) and 3D-TSE T1 sampling perfection with application-optimized contrasts by using different flip angle evolution (T1-SPACE) sequences precontrast. Axial 1-mm slices of both T1WI sequences were independently reviewed by 2 neuroradiologists, comparing the conspicuity of each lesion between the 2 sequences according to a 5-point scale and assessing whether the intrinsic T1 hyperintensity was attributable to melanin, blood products, or both. RESULTS: Twenty examinations were performed, with a total of 214 lesions demonstrating intrinsic T1 hyperintensity. Both readers found that intrinsic T1 hyperintensity was less conspicuous with T1-SPACE compared with MPRAGE for most lesions assessed (81.8%, averaged across both readers), including for lesions with intrinsic T1 hyperintensity attributable to melanin and blood products. Intrinsic T1 hyperintensity was rarely more conspicuous on T1-SPACE (1.4%). CONCLUSIONS: Precontrast intrinsic T1 hyperintensity is more conspicuous with MPRAGE than T1-SPACE. In patients with metastatic melanoma, 3D-GRE should be preferred as the precontrast T1WI sequence when both 3D-TSE and 3D-GRE are performed postcontrast and when not administering IV contrast.

Radiogenomics Provides Insights into Gliomas Demonstrating Single-Arm 1p or 19q Deletion.

BACKGROUND AND PURPOSE: IDH-mutant gliomas are further divided on the basis of 1p/19q status: oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and astrocytoma, IDH-mutant (without codeletion). Occasionally, testing may reveal single-arm 1p or 19q deletion (unideletion), which remains within the diagnosis of astrocytoma. Molecular assessment has some limitations, however, raising the possibility that some unideleted tumors could actually be codeleted. This study assessed whether unideleted tumors had MR imaging features and survival more consistent with astrocytomas or oligodendrogliomas. MATERIALS AND METHODS: One hundred twenty-one IDH-mutant grade 2-3 gliomas with 1p/19q results were identified. Two neuroradiologists assessed the T2-FLAIR mismatch sign and calcifications, as differentiators of astrocytomas and oligodendrogliomas. MR imaging features and survival were compared among the unideleted tumors, codeleted tumors, and those without 1p or 19q deletion. RESULTS: The cohort comprised 65 tumors without 1p or 19q deletion, 12 unideleted tumors, and 44 codeleted. The proportion of unideleted tumors demonstrating the T2-FLAIR mismatch sign (33%) was similar to that in tumors without deletion (49%; P = .39), but significantly higher than codeleted tumors (0%; P = .001). Calcifications were less frequent in unideleted tumors (0%) than in codeleted tumors (25%), but this difference did not reach statistical significance (P = .097). The median survival of patients with unideleted tumors was 7.8 years, which was similar to that in tumors without deletion (8.5 years; P = .72) but significantly shorter than that in codeleted tumors (not reaching median survival after 12 years; P = .013). CONCLUSIONS: IDH-mutant gliomas with single-arm 1p or 19q deletion have MR imaging appearance and survival that are similar to those of astrocytomas without 1p or 19q deletion and significantly different from those of 1p/19q-codeleted oligodendrogliomas.

Radiation necrosis and therapeutic outcomes in patients treated with linear accelerator-based hypofractionated stereotactic radiosurgery for intact intracranial metastases.

INTRODUCTION: Balancing disease control and treatment-related toxicities can be challenging when treating higher-risk brain metastases (BMs) that are larger in size or eloquent anatomical locations. Hypofractionated stereotactic radiosurgery (hfSRS) is expected to offer superior or equal efficacy with lower toxicity profile compared with single-fraction SRS (sfSRS). We report the efficacy and toxicity profiles of hfSRS in a consecutive cohort of patients to support this predicted benefit from hfSRS for high-risk BMs. METHODS: We retrospectively analysed 185 consecutive individual lesions from 152 patients with intact BMs treated with hfSRS between 1 July 2016 and 31 October 2019 and followed up to 30 April 2022 with serial brain magnetic resonance imaging (MRI). The primary endpoint was the event of radiation necrosis (RN). Local control (LC) rate and distant brain failure (DBF) were reported as secondary outcomes. Kaplan-Meier method was used to report the cumulative incidence of RN and overall survival and the incidence of DBF. Potential risk factors for RN were assessed using univariable Cox regression analysis. RESULTS: The median follow-up was 38.0 months, and the median survival post-SRS was 9.5 months. The cumulative incidence rate of RN was 13.2% (95% CI: 7.0-24.7%), and 18.1% of patients with confirmed RN were symptomatic. Higher mean dose delivered to planning target volume (PTV) (HR 1.22, 95% CI: 1.05-1.42, P = 0.01), higher mean BED10 (biological equivalent dose assuming a tissue α / ß ratio of 10) (HR 1.12, 95% CI: 1.04-1.2, P < 0.001), and higher mean BED2 (HR 1.02, 95% CI: 1-1.04, P = 0.04) delivered to the lesion was associated with increased risk of RN. LC rate was 86% and the cumulative incidence of DBF was 36% with a median onset of 28.4 months. CONCLUSIONS: Our results support the predicted radiobiological benefit of the use of hfSRS in high-risk BMs to limit treatment-related toxicity with low risk for symptomatic RN comparable with lower risk population receiving sfSRS while achieving satisfactory local disease control.

Favourable outcomes with an initial active surveillance strategy for asymptomatic radiation-induced meningiomas in long-term survivors of paediatric and young adult malignancies.

PURPOSE: Radiation-induced meningiomas (RIM) are the most common secondary neoplasm post cranial radiotherapy, yet optimal surveillance and treatment strategies remain contentious. Herein, we report the clinical outcomes and radiological growth rate of RIM, diagnosed in a cohort of survivors undergoing MRI screening, with the objective of informing clinical guidelines and practice. MATERIALS AND METHODS: Long-term survivors of paediatric or young-adult malignancies, diagnosed with RIM between 1990 and 2015, were identified. Absolute (AGR) and relative (RGR) volumetric growth rates were calculated. Rapid growth was defined as AGR > 2 cm3/year or AGR > 1 cm3/year and RGR ≥ 30% RESULTS: Fifty-two patients (87 RIM) were included. Median age at first RIM diagnosis was 33.9 (range,13.8-54.1) years. Seventy-seven (88%) RIM were asymptomatic at detection. Median follow-up time from first RIM detection was 11 (range, 0.6-28) years. Median absolute and relative volumetric growth rates were 0.05 (IQR 0.01-0.11) cm3 and 26 (IQR 7-79) % per year, respectively. Two (3.3%) RIM demonstrated rapid growth. Active surveillance was adopted for 67 (77%) RIM in 40 patients. Neurological sequelae due to RIM progression were reported in 5% of patients on active surveillance. Surgery was performed for 33 RIM (30 patients): 18 (54.5%) at diagnosis and 15 (45.5%) after active surveillance. Histopathology was WHO Grade 1 (85.2%), 2 (11.1%), 3 (3.7%). Following resection, 10-year local recurrence rate was 12%. During follow-up, 19 (37%) survivors developed multiple RIM. CONCLUSIONS: Asymptomatic RIM are typically low-grade tumours which exhibit slow growth. Active surveillance appears to be a safe initial strategy for asymptomatic RIM, associated with a low rate of neurological morbidity.

Imaging for assessment of cancer treatment response to immune checkpoint inhibitors can be complementary in identifying hypophysitis.

Introduction: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. Methods: This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. Results: There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. Conclusion: Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.

[18F]-fluoroethyl-L-tyrosine (FET) in glioblastoma (FIG) TROG 18.06 study: protocol for a prospective, multicentre PET/CT trial.

INTRODUCTION: Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication. METHODS AND ANALYSIS: The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival. ETHICS AND DISSEMINATION: The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12619001735145.

Correlation of MRI signal characteristics of intracranial melanoma metastases with BRAF mutation status.

BRAF V600 mutations (BRAF mut ) are associated with more pigmentation in primary melanomas, but data on melanin content of metastases are limited. This study compares signal characteristics of BRAF mut and BRAF-wildtype (BRAF wt ) intracranial melanoma metastases (IMM). MRI brain examinations at first diagnosis of IMM were identified, all performed at 3-Tesla including 1 mm volumetric pre- and postcontrast T1-weighted imaging and susceptibility-weighted imaging (SWI). Individual metastases were assessed by a neuroradiologist, stratified by size (≥10 mm, 'larger', vs. 2-9 mm, 'small'; up to 10 per group); presence of intrinsic T1-hyperintensity (T1H) and, if present, whether confidently attributable to melanin as opposed to haemorrhage; evidence of haemorrhage; presence of central necrosis. A total of 267 IMM in 73 patients were assessed (87 larger IMM, 180 small). The proportion of larger IMM was similar in both groups (31% BRAF mut and 36% BRAF wt ). In small IMM, MRI evidence of melanin was more common in BRAF mut patients (42% vs. 26%; P = 0.038). Haemorrhage was more common in larger IMM (51%, vs. 20% of small IMM; P < 0.0001), but did not differ based on BRAF status. Central necrosis was more common in larger IMM (44% vs. 7%; P < 0.0001) and in BRAF mut IMM (23% vs. 11%; P = 0.011). In the BRAF mut cohort, central necrosis was more common in patients without previous anti-BRAF therapy (33% vs. 7%; P = 0.0001). T1H attributable to melanin is only slightly more common in BRAF mut IMM than BRAF wt . Higher rates of central necrosis in BRAF mut patients without previous anti-BRAF therapy suggest that anti-BRAF therapy may affect the patterns of IMM growth.