Northern Cancer Institute

Abstract BACKGROUND RT target volume delineation protocols for Glioblastoma(GBM) utilise uniform expansion around the surgical cavity/residual tumour, without consideration of adjacent sites at more risk for infiltration. However neuroanatomical subsites may have specific regions where tumour infiltration occurs, especially related to adjacent white matter tracts(WMT). This study categorises the infiltration/relapse pattern for three neuroanatomical sites as a means for developing future alternative target volume delineation protocols. METHODS Consecutive patients managed for GBM with EORTC-NCIC Protocol(60Gy) between 2008-2023 were identified. Tumours centred on anterior temporal(TempAnt), occipital(Occ) and posterior parietal(PostPar) lobes were initially selected for analysis. Based on assessment of T1-gadolinium-enhanced/T2-weighted MRI sequences adjacent sites of tumour infiltration and subsequent relapse was assessed. These sites were categorised into zones reflecting increasing extension of tumour away from initial involved gyrus, and scored in regards to proportional rate of involvement. Adjacent WMT involvement was recorded. Primary endpoint was relapse-free survival(RFS)and rate of distant relapse as defined by >20mm from surgical cavity/residual tumour. Involvement at relapse of each defined regional zone was assessed for the three neuroanatomical sites. RESULTS 497 patients were managed with median overall survival of 17.4 months(95%CI: 15.1-19.9 months). Fifteen neuroanatomical sites were used for categorisation of which 10% were AntTemp; 9% Occ and 11% PostPar. Infiltration pattern was consistent for each site, with predictable zones identified based on initial involved gyrus. For example with AntTemp the temporal stem/insular involvement was evident in 57% for T1gd and 94% for T2 signal; however hippocampal T2 signal seen in only 21% of patients. For Occ subsite the trigone of lateral ventricle was involved in 48%; varying for medial vs lateral based tumours. PostPar subsite had initial cingulate gyrus, splenium/parahippocampal involvement in 70% at diagnosis. Similarly at relapse the patterns were predictable with consistent zonal and adjacent WMT involvement. Median RFS for whole cohort was 11.9 months(95%CI: 10.6-13.3). In AntTemp 73% relapse sites involved external/extreme capsule or frontal lobe; and 87% had evidence of relapse involving WMT. For Occ lateral tumours commonly relapsed at trigone(69%vs50%) and anterior temporal region(46%vs15%); with medial tumours involving the splenium(40%vs11%). For PostPar distant relapse was evident in 53% with distal sites along Cingulum pathway. CONCLUSION GBM infiltration and relapse pathways occurred in predictable distribution around initial neuroanatomical site. RT potentially may be individualised for neuroanatomical subsite and non-isotropic target volume expansion.

SUMMARY RNAseq and DNAseq are fast, cost-effective and quantitative methods to dissect cancer cells. However, for each sample, they generate thousands of data points, and comparing patient samples multiplies the complexity. To handle these difficulties, we developed TumorMiner, a web-based tool for clinicians and basic researchers. Here we present our analyses and website for Small Cell Lung Cancer (SCLC). SCLC_TumorMiner includes 235 samples from untreated and relapse patients across the NCI, the University of Rochester, Tongji University and the University of Cologne (https://discover.nci.nih.gov/SclcTumorMinerCDB/). SCLC_TumorMiner allows the molecular classification of tumors based on the canonical NAPY classification and NMF, genomic network analyses exemplified by the Myc and Notch pathways, and the identification of risk-factors and predictive gene expression biomarkers for cell surface and intracellular targets such as DLL3, TROP2, SEZ6, CEA, TRPM5, SLFN11 and proapoptotic and multidrug resistance genes. The architecture of TumorMiner allows its extension to proteomic databases, and to other cancers and institutions worldwide to elucidate cancer pathways, achieve precision medicine and serve as a medical assistant software.

To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. Retrospective observational study; review of patient records in fifteen Australian institutions. All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival. A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths. In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials.

Sullivan, Richard MBChB; Russo, Marc MBBS; Taylor, Nathan MBBS; Santarelli, Danielle PhD Author Information

Nurses represent the largest sector of the healthcare workforce, and it is established that they are faced with ongoing physical and mental demands that leave many continuously stressed. In turn, this chronic stress may affect cardiac autonomic activity, which can be non‐invasively evaluated using heart rate variability (HRV). The association between neurocognitive parameters during acute stress situations and HRV has not been previously explored in nurses compared to non‐nurses and such, our study aimed to assess these differences. Neurocognitive data were obtained using the Mini‐Mental State Examination and Cognistat psychometric questionnaires. ECG‐derived HRV parameters were acquired during the Trier Social Stress Test. Between‐group differences were found in domain‐specific cognitive performance for the similarities (p = .03), and judgment (p = .002) domains and in the following HRV parameters: SDNNbaseline, (p = .004), LFpreparation (p = .002), SDNNpreparation (p = .002), HFpreparation (p = .02), and TPpreparation (p = .003). Negative correlations were found between HF power and domain‐specific cognitive performance in nurses. In contrast, both negative and positive correlations were found between HRV and domain‐specific cognitive performance in the non‐nurse group. The current findings highlight the prospective use of autonomic HRV markers in relation to cognitive performance while building a relationship between autonomic dysfunction and cognition.

TPS8586 Background: Standard first line treatment for unresectable malignant pleural mesothelioma (MPM) is platinum-based chemotherapy with pemetrexed. Two recent, single-arm, phase 2 trials (DREAM1 and PrE05052) combining the PD-L1 inhibitor durvalumab and standard first line cisplatin and pemetrexed (CP) exceeded pre-specified criteria for proceeding to phase 3. DREAM3R aims to determine the effectiveness of adding durvalumab to first line CP chemotherapy in advanced MPM. Methods: Treatment-naïve patients with advanced MPM will be randomised (2:1) to EITHER durvalumab 1500 mg every 3 weeks plus doublet chemotherapy (cisplatin 75 mg/m2 and pemetrexed 500 mg/m2) every 3 weeks for 4-6 cycles, followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target sample size is 480 patients (320 durvalumab, 160 control) recruited over 27 months, with follow up for an additional 24 months. This provides over 85% power if the true hazard ratio for overall survival is 0.70, with 2-sided alpha of 0.05, assuming a median survival of 15 months in the control group. Key inclusion criteria: MPM of any histological subtype; measurable disease as per RECIST 1.1 modified for mesothelioma (mRECIST 1.1) without prior radiotherapy to these sites; ECOG PS 0-1; and, adequate hematologic, renal, and liver function tests. Key exclusion criteria: prior systemic anticancer treatment for MPM; diagnosis based only on cytology or fine needle aspiration biopsy; contraindication to immunotherapy; and conditions requiring immunosuppressives or corticosteroids. Stratification: Age (18-70 years vs. > 70), sex, histology (epithelioid vs. non-epithelioid), and region (USA vs. ANZ). The primary endpoint is overall survival. Secondary endpoints include progression-free survival; objective tumour response (by mRECIST 1.1 and iRECIST); adverse events; health-related quality of life; and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DREAM and PrE0505 studies, PD-L1 expression, tumour mutation burden, nuanced genomic characteristics, and HLA subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma. Clinical trial information: NCT04334759. and ACTRN 12620001199909.

The rapid rise in cancer incidence within the world's poorest nations highlights the need for equitable access to evidence-based cancer care. It has been previously demonstrated that radiotherapy is a cost-effective and necessary tool in cancer treatment. However, globally there is a growing divide between demand and supply of radiotherapy services. In low- and middle-income countries, this resource gap is particularly problematic. By region, the Asia-Pacific has been demonstrated to have the highest absolute deficit in radiotherapy services. Radiation oncologists in Australia and New Zealand are geographically well positioned to assist departments within the Asia-Pacific to help to reduce these inequities. The Asia-Pacific Radiation Oncology Special Interest Group (APROSIG) aims to support oncology professionals in the Asia-Pacific to develop safe and sustainable cancer services. Members have already contributed to multiple projects throughout the region, supported by grants and departmental funding. However, the backbone of support comes from volunteers sharing their time and expertise. The Australasian oncological community has the skills and knowledge to help not only those within our borders but also beyond. Such efforts provide the potential to develop valuable clinical, educational, research and leadership experiences whilst establishing networking opportunities throughout the most populated regions of the world. More options for growth and work in global health must be investigated, encouraging future trainees to consider a role within the global cancer community. Without prompt and continued action, the resource deficit is likely to grow and the inequity in accessing radiotherapy and other cancer services further magnified.