Lucy Gately

Purpose: Evaluating fitness to drive among patients with brain tumours remains a challenge for clinicians. Due to difficulties in conducting prospective driving studies in this patient cohort, a Delphi study was performed to formulate new driving guidelines for patients with brain tumours. Methods: The survey questions, which were designed by utilising Australian driving guidelines and previous Delphi studies, established panelists’ expertise, and then used a 9-point Likert scale to formulate new driving guidelines. An expert group of panelists comprising medical oncologists, radiation oncologists, neurosurgeons, and neurologists were chosen based on membership to professional societies with validation in part one of the survey. Two rounds of anonymised surveys were performed using REDCap for data entry, and a novel automated methodology on R for data analysis. Results: 46 statements regarding fitness to drive were developed. Among the 37 surveys distributed, there were 26 responses (70.3% response rate) from round one, and 17 responses (65.4% response rate) for round two. Among the 46 statements, 19 (41.3%) achieved consensus. In addition to establishing a framework for assessing patients, there was notable consensus agreement for stable imaging required as part of evaluation and the need for continual reassessment. Conclusion: Despite clinicians being aware of driving guidelines, determining fitness to drive among patients with brain tumours remains a challenge. This Delphi study identified consensus agreement for the need for stable imaging, and continually reassessing fitness to drive. These novel findings could be translated into future driving guidelines and consensus statements can be integrated into clinical practice.

Background: Grade-2 gliomas (G2-glioma) are uncommon. In 2016, RTOG9802 established the addition of chemotherapy after radiation (CRT) as a new standard of care for patients with high-risk G2-glioma, defined as subtotal resection or age ≥40 yrs. Here, we report current practices using real-world data. Methods: Patients diagnosed with G2-glioma from 1 January 2016 to 31 December 2022 were identified in BRAIN, a prospective clinical registry collecting data on patients with brain tumours. High- and low-risk were defined as per RTOG9802. Two time periods, January 2016–December 2019 (TP1) and January 2020–December 2022 (TP2), were defined. Survival was estimated using the Kaplan–Meier method. Results: 224 patients were identified. Overall, 38 (17%) were low-risk, with 35 (91%) observed without further treatment. A total of 186 (83%) were high-risk, with 96 (52%) observed, 63 (34%) receiving CRT, and 19 (10%) receiving radiation. Over time, CRT use increased (TP1 vs. TP2: 22% vs. 36%, p = 0.004), and the rate of biopsy (TP1 vs. TP2: 35% vs. 20%, p = 0.02) and radiotherapy alone (TP1 vs. TP2: 14% vs. 4%, p = 0.01) decreased. Median progression-free survival (PFS) was significantly longer in high-risk patients who received CRT (NR) over observation (39 months) (HR 0.49, p = 0.007). In high-risk patients who were observed, 59 (61%) were progression-free at 12 months and 10 (10%) at 5 years. OS data remains immature. Conclusions: Congruent with RTOG9802, real-world BRAIN data shows CRT is associated with improved PFS compared to observation in high-risk G2-glioma. Whilst CRT use has increased over time, observation after surgery remains the most common strategy, with some high-risk patients achieving clinically meaningful PFS. Validated biomarkers are urgently required to better inform patient management.

PURPOSE: Real-world data (RWD) collected on patients treated as part of routine clinical care form the basis of cancer clinical registries. Capturing accurate death data can be challenging, with inaccurate survival data potentially compromising the integrity of registry-based research. Here, we explore the utility of data linkage (DL) to state-based registries to enhance the capture of survival outcomes. METHODS: We identified consecutive adult patients with brain tumors treated in the state of Victoria from the Brain Tumour Registry Australia: Innovation and Translation (BRAIN) database, who had no recorded date of death and no follow-up within the last 6 months. Full name and date of birth were used to match patients in the BRAIN registry with those in the Victorian Births, Deaths and Marriages (BDM) registry. Overall survival (OS) outcomes were compared pre- and post-DL. RESULTS: Of the 7,346 clinical registry patients, 5,462 (74%) had no date of death and no follow-up recorded within the last 6 months. Of the 5,462 patients, 1,588 (29%) were matched with a date of death in BDM. Factors associated with an increased number of matches were poor prognosis tumors, older age, and social disadvantage. OS was significantly overestimated pre-DL compared with post-DL for the entire cohort (pre- v post-DL: hazard ratio, 1.43; P < .001; median, 29.9 months v 16.7 months) and for most individual tumor types. This finding was present independent of the tumor prognosis. CONCLUSION: As revealed by linkage with BDM, a high proportion of patients in a brain cancer clinical registry had missing death data, contributed to by informative censoring, inflating OS calculations. DL to pertinent registries on an ongoing basis should be considered to ensure accurate reporting of survival data and interpretation of RWD outcomes.

Purpose The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. Methods Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. Results Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0–1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. Conclusion In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

Purpose The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. Methods GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data.Journal instruction requires a city for affiliations; however, these was missing in affiliations [1, 2, 11,15, 16, 18,20, 22, 23, 24, 25, 27, 30, 31, 32, 33, 34]. Please verify if the provided city is correct and amend if necessary.Completed Results 205 patients were recruited: 159 in GEINO14-01 (2014–2018) and 46 in EX-TEM (2019–2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation.As keywords are mandatory for this journal, please provide 3-6 keywordsglioblastoma; temozolomide; survival Conclusion For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data.

Background: Real-world data (RWD) is increasingly being embraced as an invaluable source of information to address clinical and policy-relevant questions that are unlikely to ever be answered by clinical trials. However, the largely unrealised potential of RWD is the value to be gained by supporting prospective studies and translational research. Here we describe the design and implementation of an Australian brain cancer registry, BRAIN, which is pursuing these opportunities. Methods: BRAIN was designed by a panel of clinicians in conjunction with BIOGRID to capture comprehensive clinical data on patients diagnosed with brain tumours from diagnosis through treatment to recurrence or death. Extensive internal and external testing was undertaken, followed by implementation at multiple sites across Victoria and Tasmania. Results: Between February 2021 and December 2021, a total of 350 new patients from 10 sites, including one private and two regional, were entered into BRAIN. Additionally, BRAIN supports the world’s first registry trial in neuro-oncology, EX-TEM, addressing the optimal duration of post-radiation temozolomide; and BioBRAIN, a dedicated brain tumour translational program providing a pipeline for biospecimen collection matched with linked clinical data. Conclusions: Here we report on the first data collection effort in brain tumours for Australia, which we believe to be unique worldwide given the number of sites and patients involved and the extent to which the registry resource is being leveraged to support clinical and translational research. Further directions such as passive data flow and data linkages, use of artificial intelligence and inclusion of patient-entered data are being explored.

Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70 years (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. The study endpoint was prostate cancer, including metastatic or non-metastatic disease, confirmed by an expert panel. After excluding participants with a history of prostate cancer at enrolment, we used a multivariable Cox proportional hazards model to assess the association between the PRS and incident prostate cancer risk, adjusting for covariates. Additionally, we examined the distribution of Gleason grade groups by PRS group to determine if a higher PRS was associated with higher grade disease. We tested for interaction between the PRS and aspirin treatment. Logistic regression was used to independently assess the association of the PRS with prevalent (pre-trial) prostate cancer, reported in medical histories. During a median follow-up time of 4.6 years, 218 of the 5701 participants (3.8%) were diagnosed with prostate cancer. The PRS predicted incident risk with a hazard ratio (HR) of 1.52 per standard deviation (SD) (95% confidence interval (CI) 1.33–1.74, p < 0.001). Men in the top quintile of the PRS distribution had an almost three times higher risk of prostate cancer than men in the lowest quintile (HR = 2.99 (95% CI 1.90–4.27), p < 0.001). However, a higher PRS was not associated with a higher Gleason grade groups. We found no interaction between aspirin treatment and the PRS for prostate cancer risk. The PRS was also associated with prevalent prostate cancer (odds ratio = 1.80 per SD (95% CI 1.65–1.96), p < 0.001).While a PRS for prostate cancer is strongly associated with incident risk in men aged ≥70 years, the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease.

248 Background: Quality indicators (QI) are essential to monitor the efficacy of cancer care and to guide quality improvement, however many are derived from ‘expert consensus’ and are not validated against outcomes. Moreover, the majority of oncological QI are defined in the surgical setting, with only a paucity of QI for the treatment of metastatic disease. We aimed to define and validate novel QI for metastatic colorectal cancer (mCRC) based on therapeutic approaches associated with a proven survival benefit. Methods: Data was analysed from TRACC, a multisite Australian registry collecting prospective demographic, tumour, treatment and outcome data for mCRC. We identified all patients diagnosed across 11 hospitals and explored variation by site with regards to patient and tumour characteristics, first-line chemotherapy administration and resection of oligometastatic disease. Log-rank testing and Kaplan-Meier curves compare overall survival (OS) between sites, and Pearson correlation was used to assess associations with each QI. Results: We examined data from 3132 patients diagnosed with mCRC between July 2009 – April 2021. Median age was 66 years (range 62 – 71 years by site), ECOG 0-1 81% (range 69 – 96% by site), and Charlson Comorbidity Index ≤2 43% (33 – 59% by site). Multivariate analysis confirmed association of known adverse prognostic factors with inferior OS (poor ECOG, right sided primary, KRAS or BRAF mutation, all p 2 = 0.851), rate of liver resection (9.8 – 23.2% by site) was moderately correlated (R² = 0.523), and rates of active treatment with first-line chemotherapy (63 - 90% by site) were weakly correlated (R² = 0.209). Other proposed QI such as rates of lung metastases resection or chemotherapy administration in the elderly showed significant variation by site, but did not correlate with survival. Conclusions: There is significant variation in OS for patients with mCRC in these Australian hospitals, with major differences in treatment approaches. Treatment strategies known to improve survival outcomes, such as triplet FOLFOXIRI chemotherapy and resection of liver metastases, may be potential QI to benchmark and track quality improvement over time. Further analysis will determine the impact of baseline patient populations between sites, and to correlate these QI with other quality measures.