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Objectives: Effective healthcare planning, resource allocation, and budgeting require accurate predictions of the number of patients needing treatment at specific cancer stages and treatment lines. The Predicting the Population Health Economic Impact of Current and New Cancer Treatments (PRIMCAT) for Colorectal Cancer (CRC) simulation model (PRIMCAT-CRC) was developed to meet this requirement for all CRC stages and relevant molecular profiles in Australia., Methods: Real-world data were used to estimate treatment utilization and time-to-event distributions. This populated a discrete-event simulation, projecting the number of patients receiving treatment across all disease stages and treatment lines for CRC and forecasting the number of patients likely to utilize future treatments. Illustrative analyses were undertaken, estimating treatments across disease stages and treatment lines over a 5-year period (2022-2026). We demonstrated the model's applicability through a case study introducing pembrolizumab as a first-line treatment for mismatch-repair-deficient stage IV., Results: Clinical registry data from 7163 patients informed the model. The model forecasts 15 738 incident and 2821 prevalent cases requiring treatment in 2022, rising to 15 921 and 2871, respectively, by 2026. Projections show that over 2022 to 2026, there will be a total of 116 752 treatments initiated, with 43% intended for stage IV disease. The introduction of pembrolizumab is projected for 706 patients annually, totaling 3530 individuals starting treatment with pembrolizumab over the forecasted period, without significantly altering downstream utilization of subsequent treatments., Conclusions: PRIMCAT-CRC is a versatile tool that can be used to estimate the eligible patient populations for novel cancer therapies, thereby reducing uncertainty for policymakers in decisions to publicly reimburse new treatments., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material., (Copyright © 2024. Published by Elsevier Inc.)

The Victorian Precision Oncology Summit, convened in 2023, was a joint initiative between the Victorian Comprehensive Cancer Centre Alliance (VCCC Alliance) and the Monash Partners Comprehensive Cancer Consortium (MPCCC) and was proposed to guide a coordinated state-wide conversation about how the oncology sector can overcome some of the current obstacles in achieving equity of access to clinical cancer genomics for Victorian patients. Themes that emerged from discussion groups at the Summit include standardisation, centralisation, funding, education and communication and insights across those themes are outlined in this manuscript. The event served as a large consultation piece for the development of a broader precision oncology roadmap, which explores equitable access to molecular testing for Victorian patients, currently in development by the VCCC Alliance and MPCCC in collaboration with other key Victorian and national stakeholders. While this symposium was a Victorian initiative, it is felt that the insights garnered from this consultation piece will be of interest to consumer groups, clinicians, researchers, educators, policy makers and other key stakeholders in other states of Australia as well as in other countries implementing comprehensive genomic profiling within complex health systems.

Purpose: There has been a significant rise in telehealth consultations across Australia since COVID-19 was declared a worldwide pandemic. We aimed to obtain patient feedback on telehealth, identify key strengths and weaknesses, and assess the feasibility of telehealth beyond the pandemic., Methods: A survey was developed to obtain patient feedback on telehealth. Patients attending medical oncology clinics at St George Hospital and Sutherland Hospital from April 1, 2020, to May 31, 2020, were identified. Patients who were reviewed via phone or videoconference were included in this study. Eligible patients were texted or emailed a survey link within a week of their telehealth consultation. Surveys were anonymous and completion of the survey implied informed consent. Patients who did not have a mobile number or e-mail were excluded from this study., Results: One thousand fifty-nine patients were reviewed during the study period, of whom 644 (60%) were reviewed via telehealth. The survey response rate was 36.3% (230 patients responded of 634 surveys sent). Ten telehealth patients did not have a mobile number or email and were excluded. Sixty-seven percent of telehealth consults were for active surveillance, 31% for prechemotherapy/treatment reviews, 1.6% for best supportive care, and 0.5% for new consults. Seventy percent of patients were satisfied that their medical needs were met via telehealth. Ninety percent wanted another telehealth consult, and 73% wanted telehealth to continue post resolution of the pandemic. Minimizing risk of exposure to COVID-19 and patient convenience were identified as key strengths of telehealth while absence of physical examination was the main disadvantage., Conclusion: Majority of the patients surveyed were satisfied that telehealth safely met their medical needs. There is a considerable demand for telehealth to continue beyond the pandemic.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial adverse effect of anticancer treatments. As such, the assessment of CIPN remains critically important in both research and clinic settings., Objective: To compare the validity of various patient-reported outcome measures (PROMs) with neurophysiological and sensory functional measures as the optimal method of CIPN assessment., Design, Setting, and Participants: This cohort study evaluated participants treated with neurotoxic chemotherapy across 2 cohorts using a dual-study design. Participants commencing treatment were assessed prospectively at beginning of neurotoxic treatment, midtreatment, and at the end of treatment. Participants who completed treatment up to 5 years prior were assessed cross-sectionally and completed a single assessment time point. Participants were recruited from oncology centers in Australia from August 2015 to November 2022. Data analysis occurred from February to November 2023., Exposures: Neurotoxic cancer treatment including taxanes, platinums, vinca-alkaloids, proteasome inhibitors, and thalidomide., Main Outcomes and Measures: CIPN was assessed via PROMs (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-CIPN20], Functional Assessment of Cancer Therapy/Gynecological Cancer Group Neurotoxicity Questionnaire (FACT/GOG-Ntx), and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE]), neurological and neurophysiological assessment (Total Neuropathy Score and sural and tibial compound nerve amplitudes), and sensory measures (Grating orientation, Von Frey monofilament, and 2-point discrimination tasks). Core measurement properties of CIPN outcome measures were evaluated. Convergent and known-groups validity was assessed cross-sectionally following treatment completion, and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between those who reported high and low levels of CIPN symptoms using linear regressions., Results: A total of 1033 participants (median [IQR] age, 61 [50-59] years; 676 female [65.4%]) were recruited to this study, incorporating 1623 assessments. PROMs demonstrated best ability to accurately assess CIPN (convergent validity), especially the PRO-CTCAE composite score (r = 0.85; P < .001) and EORTC-CIPN20 (r = 0.79; P < .001). PROMS also demonstrated the best ability to discriminate between CIPN severity (known-groups validity) and to detect changes at onset of CIPN development (responsiveness), especially for EORTC-CIPN20 (d = 0.67; 95% CI, 0.52-0.83), FACT/GOG-Ntx (d = 0.65; 95% CI, 0.49-0.81) and the PRO-CTCAE (d = 0.83; 95% CI, 0.64-1.02). Other measures did not achieve threshold for convergent validity (α < 0.7). Neurophysiological and sensory measures did not demonstrate acceptable responsiveness. In regression models, neurological, neurophysiological, and sensory outcome measures were significantly impaired in participants who reported high levels of CIPN symptoms compared with those who reported low levels of CIPN symptoms., Conclusions and Relevance: In this cohort study of 1033 cancer patients, PROMs were the only measures to satisfy all 3 core measurement property criteria (convergent validity, known-groups validity, and responsiveness). These findings suggest that adoption of PROMs in clinical practice can equip clinicians with valuable information in assessing CIPN morbidity.

Studies of patients with castrate-resistant prostate cancer at high risk of developing overt metastases but with no current evidence of evaluable disease on computed tomography or bone scan non-metastatic castrate-resistant prostrate cancer have demonstrated increased metastasis-free survival and overall survival following treatment with the next-generation oral anti-androgen apalutamide (in addition to therapies that aim to lower testosterone to castrate levels) or luteinizing hormone-releasing hormone antagonist or surgical castration. Patients receiving apalutamide can be managed by medical oncologists, radiation oncologists, or urologists, preferably as part of a multidisciplinary team. However, the importance of additional safety monitoring for significant adverse effects and drug interactions should not be underestimated. The toxicities of apalutamide are manageable with experience and should be managed proactively to minimize their impact on patients. Monitoring of patients for apalutamide-specific toxicities, including skin rash, hypothyroidism, and QT prolongation should be carried out regularly, particularly in the first few months following initiation. Monitoring should continue alongside monitoring for toxicities of androgen deprivation, including cardiovascular risk, hot flashes, weight gain, bone health, muscle wasting, and diabetic risk. This review is a practical guide to the use of apalutamide describing the management of patients including dosing and administration, toxicities, potential drug interactions, and safety monitoring requirements., (© 2024 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

As medical treatment increasingly focuses on improving health-related quality of life, patient-reported outcome measures (PROMs) are an essential component of clinical research. The National Gynae-Oncology Registry (NGOR) is an Australian clinical quality registry. A suitable PROM was required for the NGOR ovarian cancer module to complement clinical outcomes and provide insights into outcomes important to patients. Our narrative review aimed to identify existing ovarian cancer-specific PROMs and ascertain which tool would be most appropriate for implementation into the NGOR ovarian cancer module.A literature review of Cochrane Library, Embase, MEDLINE and PubMed databases was performed to identify existing ovarian cancer-specific PROM tools. A steering committee was convened to (1) determine the purpose of, and criteria for our required PROM; and (2) to review the available tools against the criteria and recommend the most appropriate one for implementation within the NGOR.The literature review yielded five tools: MOST, EORTC QLQ-OV28, FACIT-O, NFOSI-18 and QOL-OVCA. All were developed and validated for use in clinical trials, but none had been validated for use in clinical quality registry. Our expert steering committee pre-determined purpose of a PROM tool for use within the NGOR was to enable cross-service comparison and benchmarking to drive quality improvements. They identified that while there was no ideal, pre-existing, ovarian cancer-specific PROM tool for implementation into the NGOR, on the basis of its psychometric properties, its available translations, its length and its ability to be adapted, the EORTC tool is most fit-for-purpose for integration into the NGOR.This process enabled identification of the tool most appropriate to provide insights into how ovarian cancer treatments impact patients' quality of life and permit benchmarking across health services., (© 2024. The Author(s).)

Background: The treatment of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Of particular interest are predictors of pathological complete response (pCR) that can guide personalized treatment. There are currently no clinical biomarkers which can accurately predict neoadjuvant therapy (NAT) response but body composition (BC) measures present as an emerging contender. The primary aim of the study was to determine if artificial intelligence (AI) derived body composition variables can predict pCR in patients with LARC., Methods: LARC patients who underwent NAT followed by surgery from 2012 to 2023 were identified from the Australian Comprehensive Cancer Outcomes and Research Database registry (ACCORD). A validated in-house pre-trained 3D AI model was used to measure body composition via computed tomography images of the entire Lumbar-3 vertebral level to produce a volumetric measurement of visceral fat (VF), subcutaneous fat (SCF) and skeletal muscle (SM). Multivariate analysis between patient body composition and histological outcomes was performed., Results: Of 214 LARC patients treated with NAT, 22.4% of patients achieved pCR. SM volume (P = 0.015) and age (P = 0.03) were positively associated with pCR in both male and female patients. SCF volume was associated with decreased likelihood of pCR (P = 0.059)., Conclusion: This is the first study in the literature utilizing AI-measured 3D Body composition in LARC patients to assess their impact on pathological response. SM volume and age were positive predictors of pCR disease in both male and female patients following NAT for LARC. Future studies investigating the impact of body composition on clinical outcomes and patients on other neoadjuvant regimens such as TNT are potential avenues for further research., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: The Royal Prince Alfred Hospital (RPAH) and Chris O'Brien Lifehouse (COBLH) established a formal Sarcoma of the Pelvic and Abdominal Retroperitoneum Collaboration (SPARC) in November 2020. An established multidisciplinary team (MDT) with the aims to centralise patient referrals and treatment, establish database and research, coordinate surgical resections is critical in improving patient outcomes and quality of life., Methods: A prospective database was established in October 2021. Clinical, pathological and radiological data points were recorded for all patients since the inception of SPARC. Quality of Life questionnaires were included and follow-up planned regularly for 5 years., Results: From November 2020 to Feb 2024, 294 new referrals were discussed at the MDT meeting. Majority were from the metropolitan area (182) followed by regional NSW (87), interstate (20) and five internationals. 141 operations were performed during this period compared to 119 operations from 2010 to November 2020 in RPAH. The inception of the SPARC program has resulted in exponential growth in operations, improving from the previous rate of 15 cases annually to 35. Liposarcomas followed by leiomyosarcomas are the most common types of sarcomas resected. The majority were extended resections (81.6%) and 22% were pelvic exenterations. Overall R0 rate is 54.6%, R1 38.3% and R2 1.4% (131 (92.9%) had R0/R1 resections. Overall complication rate is 35.5% with one in-hospital mortality., Conclusion: Success and expansion of a robust retroperitoneal sarcoma program requires a collaborative surgical approach, an MDT meeting, centralized referral process, and a research team in specialized tertiary institutions., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: Australia's National Bowel Cancer Screening Program consists of an immunohistochemical faecal occult blood test, targeting adults aged 50-74. Existing literature supports the principle of early detection of colorectal cancer (CRC) via national screening, but little is known about the association between colonoscopy or polypectomy rates and CRC stage over time. The aim of this study is to identify the longitudinal change to colonoscopy and polypectomy rates, and any stage shift associated with this screening program., Methods: A retrospective data-linkage study was performed using the Australian national health database (Medicare) to obtain colonoscopy and polypectomy rates between 1998 and 2017. A second prospective database of CRC resection specimens was analysed for this period. The cohort was divided based on time intervals related to the National Bowel Cancer Screening Program: pre-commencement 1998-2006 (Period A), immediately post-commencement 2007-2011 (Period B), and subsequent years 2012-2017 (Period C). Linear regression was used to test relation between annualized predictor and response variables., Results: Annual colonoscopy rates doubled, and polypectomy rates tripled during the study (P < 0.001). Annual colonoscopy rate correlated to a lower T-stage (P = 0.038) and lower N-stage (P = 0.026), and there was a 7% increase in early CRC (stage I-II) in Period C (P < 0.001). Across the study period there was also a significant increase in right-sided tumours, and concurrent MMR deficiency and BRAF mutation., Conclusion: Polypectomy and colonoscopy rates increased after the introduction of the National Bowel Cancer screening program. There was a clinically significant shift to earlier CRC stage which manifested 5 years after its implementation., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Introduction: Prognosis in oncology has improved with early diagnosis and novel therapies. However, critical illness continues to trigger clinical and ethical dilemmas for the treating oncology and intensive care unit (ICU) doctors., Objectives: The objective of this study was to investigate the perceptions of oncology and ICU doctors in managing critically ill cancer patients., Methods: A cross-sectional web-based survey exploring the management of a fictitious acutely deteriorating case vignette with solid-organ malignancy. The survey weblink was distributed between May and July 2022 to all Australian oncology and ICU doctors via newsletters to the members of the Medical Oncology Group of Australia, the Australian and New Zealand Intensive Care Society, and the College of Intensive Care Medicine inviting them to participate. The weblink was active till August 2022. The six domains included patient prognostication, advanced care plan, collaborative management, legal/ethical/moral challenges, ICU referral, and protocol-based ICU admission. The outcomes were reported as the level of agreement between oncology and ICU doctors for each domain/question., Results: 184 responses (64 oncology and 120 ICU doctors) were analysed. Most respondents were specialists (78.1% [n = 50] oncology, 78.3% [n = 94] ICU doctors). Oncology doctors more commonly reported managing cancer patients with poor prognosis than ICU doctors (p < 0.001). Oncology doctors less commonly referred such patients for ICU admission (29.7% [n = 19] vs. 80.8% [n = 97], p < 0.001; odds ratio [OR] = 0.07; 95% confidence interval [CI]: 0.03-0.16) and infrequently encountered patients with prior goals of care (GOC) in medical emergency team escalations (40.6% [n = 26] vs. 86.7% [n = 104]; p < 0.001; OR = 0.06; 95% CI: 0.02-0.15; p < 0.001). Oncology doctors were less likely to discuss GOC during medical emergency team calls or within 24 h of ICU admission. More oncology doctors than ICU doctors thought that training rotation in the corresponding speciality group was beneficial (56.3% [n = 36] vs. 31.7% [n = 38]; p = 0.012; OR = 2.07; 95% CI: 1.02-4.23; p = 0.045)., Conclusion: Oncology doctors were less likely to encounter acute patient deterioration or establish timely GOC for such patients. Oncology doctors believed that an ICU rotation during their training may have helped manage challenging situations., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC., Methods: SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included., Discussion: Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options., Trial Registration: The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673)., (© 2024. The Author(s).)

Background: Cancer patients have increased morbidity and mortality from COVID-19, but may respond poorly to vaccination. The Evaluation of COVID-19 Vaccination Efficacy and Rare Events in Solid Tumors (EVEREST) study, comparing seropositivity between cancer patients and healthy controls in a low SARS-CoV-2 community-transmission setting, allows determination of vaccine response with minimal interference from infection., Methods: Solid tumor patients from The Canberra Hospital, Canberra, Australia, and healthy controls who received COVID-19 vaccination between March 2021 and January 2022 were included. Blood samples were collected at baseline, pre-second vaccine dose and at 1, 3 (primary endpoint), and 6 months post-second dose. SARS-CoV-2 anti-spike-RBD (S-RBD) and anti-nucleocapsid IgG antibodies were measured., Results: Ninety-six solid tumor patients and 20 healthy controls were enrolled, with median age 62 years, and 60% were female. Participants received either AZD1222 (65%) or BNT162b2 (35%) COVID-19 vaccines. Seropositivity 3 months post vaccination was 87% (76/87) in patients and 100% (20/20) in controls (p = .12). Seropositivity was observed in 84% of patients on chemotherapy, 80% on immunotherapy, and 96% on targeted therapy (differences not satistically significant). Seropositivity in cancer patients increased from 40% (6/15) after first dose, to 95% (35/37) 1 month after second dose, then dropped to 87% (76/87) 3 months after second dose., Conclusion: Most patients and all controls became seropositive after two vaccine doses. Antibody concentrations and seropositivity showed a decrease between 1 and 3 months post vaccination, highlighting need for booster vaccinations. SARS-CoV-2 infection amplifies S-RBD antibody responses; however, cannot be adequately identified using nucleocapsid serology. This underlines the value of our COVID-naïve population in studying vaccine immunogenicity., (© 2024 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits., (© 2024. Crown.)

Diverse factors and beliefs define treatment decisions of culturally and linguistically diverse patients. Recognizing, understanding and respecting these enable us to walk with them on their cancer journey, even if it may be the road less traveled.

Background/aim: Early phase clinical trials (EPCTs) assess the tolerability of novel anti-cancer therapeutics in patients with advanced malignancy. Patient selection is important given the modest clinical benefit and time commitments for trials. Prognostic scores have been developed to facilitate identification of high-risk patients. This study aimed to compare five prognostic scores to predict survival for patients on an EPCT., Patients and Methods: We performed a retrospective review of patients enrolled in EPCT at Liverpool Hospital, Sydney, from 2013 to 2023. Demographic, biochemical, and survival data were collected from electronic medical records. The score from five prognostic scoring systems (Royal Marsden hospital, MD Anderson Cancer centre, Gustave Roussy Immune, MD Anderson Immune Checkpoint Inhibitor and Princess Margaret Hospital Index) were calculated. Overall survival was measured using the Kaplan-Meier method and predictive discrimination was assessed using Harrell's c-index., Results: A total of 218 patients across 36 EPCTs were included. The median overall survival was 9.8 months with 22% of patients dying in less than 90 days. Seventeen to thirty-four percent of patients were categorised as high-risk. The MDACC score obtained the highest predictability for overall survival for the whole cohort (c-index=0.67, 95%CI=0.62-0.72) and the immunotherapy-based cohort (c-index= 0.65, 95%CI=0.59-0.71). However, all scores performed similarly with a significant overlap in the confidence intervals., Conclusion: Our retrospective audit confirms the utility of prognostic scores to predict survival in an Australian EPCT cohort, with similar predictive discrimination across various scoring systems. Integration of these prognostic tools into EPCT screening processes may optimise benefits and reduce risks associated with EPCTs., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Preoperative biopsy for retroperitoneal sarcoma (RPS) enables appropriate multidisciplinary treatment planning. A systematic review of literature from 1990 to June 2022 was conducted using the population, intervention, comparison and outcome model to evaluate the local recurrence and overall survival of preoperative biopsy compared to those that had not. Of 3192 studies screened, five retrospective cohort studies were identified. Three reported on biopsy needle tract seeding, with only one study reporting biopsy site recurrence of 2 %. Two found no significant difference in local recurrence and one found higher 5-year local recurrence rates in those who had not been biopsied. Three studies reported overall survival, including one with propensity matching, did not show a difference in overall survival. In conclusion, preoperative core needle biopsy of RPS is not associated with increased local recurrence or adverse survival outcomes., Competing Interests: Declaration of Competing Interest Stephanie Webster: Nil. Ana Cristina Vargas: Nil. Fiona Maclean: Nil. Jennifer Vu: Nil. Elissa Tong: Nil. David Coker: Nil. Iain Ward: Nil. Elizabeth Connolly: Nil. Deborah Di-Xin Zhou: Nil. Jasmine Mar: Nil. Smaro Lazarakis: Nil. David E Gyorki: Honorarium from BMS and Merck. Angela M Hong: Honorarium from Oncobeta and Telix., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A proportion of returned medications may potentially meet quality standards to be reused safely. In Australia, there is no regulatory guidance available to facilitate such medication reuse. This narrative review aimed to identify and review international literature describing medication reuse programs to provide insight into their implementation and potential barriers. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) -based guidelines, a literature search was conducted in Medline, Scopus, and Embase using key words such as 'medication' and 'reuse' to identify relevant articles. Two reviewers ascertained eligibility for inclusion. Inclusion criteria included English language and publication after 2010. From the articles selected, identified international medication reuse programs and relevant regulatory aspects were summarized. Details, both regulatory and operational, for the specific medication reuse programs, described in the selected articles was further explored via a grey literature search. Of the 1973 identified articles, 84 were assessed for eligibility and 17 were included in this review. Of these, 14 described scenarios where medication reuse is prohibited, 2 studies described programs allowing the reuse of medication and 1 study did not discuss whether reuse was prohibited or not. From these primary articles, secondary citations were identified, with eight from gray literature. Barriers to medication reuse included exposure to environmental extremes during storage, physical appearance, evidence of tampering, safety, and efficacy concerns for the returned medication. Programs that exist globally have overcome these barriers. Several programs that provide safe and effective reuse of medications were i© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com.dentified and described. The findings described in this review should be used to inform frameworks for legislative, regulatory, and professional practice change for medication reuse. Measures implemented in the UK's pandemic response to safely reuse medications in the nursing home and hospice settings and European medication donation programs should be further investigated. The concept of medication reuse is not novel and should be considered for the Australian setting., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: The association between frailty and short-term and long-term outcomes in patients receiving elective surgery for cancer remains unclear, particularly in those admitted to the ICU., Methods: In this multicentre retrospective cohort study, we included adults ≥16 yr old admitted to 158 ICUs in Australia from January 1, 2018 to March 31, 2022 after elective surgery for cancer. We investigated the association between frailty and survival time up to 4 yr (primary outcome), adjusting for a prespecified set of covariates. We analysed how this association changed in specific subgroups (age categories [<65, 65-80, ≥80 yr], and those who survived hospitalisation), and over time by splitting the survival information at monthly intervals., Results: We included 35,848 patients (median follow-up: 18.1 months [inter-quartile range: 8.3-31.1 months], 19,979 [56.1%] male, median age 69.0 yr [inter-quartile range: 58.8-76.0 yr]). Some 3502 (9.8%) patients were frail (defined as clinical frailty scale ≥5). Frailty was associated with lower survival (hazard ratio: 1.72, 95% confidence interval [CI]: 1.59-1.86 compared with clinical frailty scale ≤4); this was concordant across several sensitivity analyses. Frailty was most strongly associated with mortality early on in follow-up, up to 10 months (hazard ratio: 1.39, 95% CI: 1.03-1.86), but this association plateaued, and its predictive capacity subsequently diminished with time up until 4 yr (1.96, 95% CI: 0.73-5.28). Frailty was associated with similar effects when stratified based on age, and in those who survived hospitalisation., Conclusions: Frailty was associated with poorer outcomes after an ICU admission after elective surgery for cancer, particularly in the short term. However, its predictive capacity with time diminished, suggesting a potential need for longitudinal reassessment to ensure appropriate prognostication in this population., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Purpose: Mentorship has a positive influence on trainee skills and well-being. A 2022 Pilot Mentorship Program in New South Wales involving 40 participants revealed high burnout rates in Medical Oncology trainees. As part of an Australia-wide inaugural National Oncology Mentorship Program in 2023 (NOMP23), a national survey was undertaken to assess the prevalence of burnout, anxiety, depression, professional fulfilment, and drivers of distress in the Australian medical oncology workforce., Methods: NOMP23 is a 1-year prospective cohort study that recruited medical oncology trainees and consultants using e-mail correspondence between February and March 2023. Each participant completed a baseline survey which included the Maslach Burnout Index (MBI), Stanford Professional Fulfilment Index, and Patient Health Questionnaire-4 for anxiety and depression., Results: One hundred and twelve participants (56 mentors, 56 mentees) were enrolled in NOMP23, of which 86 (77%) completed the baseline survey. MBI results at baseline demonstrated that 77% of consultants and 82% of trainees experienced burnout in the past 12 months. Professional fulfilment was noted to be <5% in our cohort. Screening rates of anxiety and depression in trainees were 32% and 16%, respectively, compared with 7% and 2% for consultants. When assessing reasons for workplace stress, two thirds stated that heavy patient load contributed to stress, while almost three quarters attributed a heavy administrative load. Lack of supervision was a key stressor for trainees (39%), as was lack of support from the training college (58%)., Conclusion: Trainees and consultant medical oncologists demonstrate high rates of burnout and low professional fulfilment. The NOMP23 program has identified a number of key stress factors driving burnout and demonstrated concerning levels of anxiety and depression. Ongoing mentorship and other well-being initiatives are needed to address these issues.

Background and Objectives: The Primary Care Collaborative Cancer Clinical Trials Group (PC4) is funded by Cancer Australia to support the development of new cancer in primary care research. We undertook a research prioritisation exercise to identify cancer research priorities in Australian general practice., Method: We adapted the nominal group technique, including a literature search and stakeholder survey. An expert group from the Primary Care Collaborative Cancer Clinical Trials Group consolidated and ranked priorities. A second stakeholder survey reviewing the top 50 priorities informed a final prioritisation workshop., Results: Overall, 311 priorities were identified across the cancer continuum. Nearly one-third of priorities were related to cancer survivorship and included strategies to detect recurrence, behavioural interventions and tools to assess physical and psychosocial aspects of survivorship. Prevention/early detection comprised 43.4% of priorities. Palliative care produced the least priorities (9.6%). Cross cutting research priorities (15.1%) included quality and models of care., Discussion: This is the first study to identify cancer research priorities for general practice in Australia. It could be used to inform the development of targeted research and funding to improve the care and outcomes for Australians affected by cancer.

Return to work (RTW) is a marker of functional recovery for working-age cancer survivors. Identifying factors that impact on RTW in cancer survivors is an essential step to guide further research and interventions to support RTW. This systematic review aimed to identify nontreatment, non-cancer-related variables impacting RTW in Australian cancer survivors. A systematic search was conducted in EMBASE, PsycINFO, CINAHL, PubMed, and Google Scholar. Studies were eligible if they included: (1) adults living post diagnosis of malignancy; (2) quantitative data for nontreatment, non-cancer-related variables impacting RTW; (3) only Australian participants. Included studies were critically appraised, and relevant data extracted and synthesized narratively. Six studies were included in the review, published between 2008 and 2020. Studies were of variable quality and mixed methodologies. One study included malignancies of any type with the remainder focusing on survivors of colorectal cancer (n = 3), oropharyngeal cancer (n = 1), and glioblastoma multiforme (n = 1). Multiple factors were related to RTW in individual studies, including older age, presence of three or more comorbidities, fewer work hours pre-morbidly, lower body mass index, longer than recommended sleep duration, and not having private health insurance; however, there was limited consistency in findings between studies. Other variables examined included: occupation type, household income, healthy lifestyle behaviors, flexibility, and duration of employment with workplace; however, no significant associations with RTW were reported. Further research is required to gather compelling evidence on factors that influence RTW in Australian cancer survivors., (© 2023 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Background: Through the introduction of tumor agnostic therapies, people with metastatic cancer and their treating physicians are facing new treatment choices that have differing side effect and efficacy profiles from conventional chemotherapy., Objective: The present study undertakes a scoping review of research into the experiences of people with advanced or metastatic cancer across various solid tumor types with the goal of developing a tumor-agnostic conceptual model., Design: Automated queries on three internet search engines were performed to identify qualitative interview studies that focused on people with metastatic cancer. No limits were imposed for dates nor location of studies., Results: Of the 173 hits generated from the searches, 25 peer-reviewed papers were selected for the review with dates that ranged from 2007 to 2022. All papers originated from the USA, Europe, Australia, or Japan. Three major themes emerged that formed the basis for the tumor-agnostic conceptual model: symptoms, loss of autonomy, and adaptation/coping., Conclusions: The explication of the interplay between the physical and emotional symptoms experienced by those with advanced and metastatic cancer using a multi-tumor approach provides the potential to make generalizations about the needs of this population. An opportunity exists to potentially address these needs through matching patient needs and preferences with the characteristics of novel therapeutics., Implications for Cancer Survivors: In the era of tumor agnostic therapies, the elicitation of patient preferences across the spectrum of anatomical origins has the potential to enhance shared decision making in the setting of metastatic disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system., Methods: This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5-10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT)., Results: Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2-59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen's Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT., Conclusions: PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS., (© 2024. The Author(s).)

ASPiRATION is a national prospective observational cohort study assessing the feasibility, clinical and economic value of up-front tissue-based comprehensive genomic profiling (CGP) to identify actionable genomic alterations in participants with newly diagnosed metastatic non-squamous non-small-cell lung cancer in Australia. This study will enrol 1000 participants with tumor available for CGP and standard of care molecular testing ( EGFR / ALK/ROS1 ). Participants with actionable variants may receive novel targeted treatments through ASPiRATION-specific substudies, other trials/programs. Clinical outcome data will be collected for a minimum of 2 years. Study outcomes are descriptive, including the ability of CGP to identify additional actionable variants, leading to personalized treatment recommendations, and will describe the feasibility, efficiency, cost and utility of implementation of CGP nationally.

Background: The impact of RAS/BRAF mutation on primary response rates after total neoadjuvant therapy (TNT) in patients with advanced rectal cancer is unclear. The aim of this study was to assess complete response rates after TNT according to RAS/BRAF mutation status., Methods: A prospective observational study was performed in patients with rectal cancer who underwent TNT with curative intent at three South Australian hospitals between 2019 and 2023. Patients were classified according to their mutation status: mutant RAS/BRAF (mutRAS) or wild-type RAS/BRAF (wtRAS). The primary endpoint was overall complete response (oCR) rate, defined as the proportion of patients who achieved clinical complete response (cCR) and/or pathological complete response (pCR)., Results: Of the 150 patients eligible for inclusion, 80 patients with RAS/BRAF status available were identified. Of these, 43 (53.8%) patients were classified as mutRAS and 37 (46.3%) patients as wtRAS. Patients with mutRAS had significantly lower cCR and oCR rates after TNT than patients with wtRAS (14% vs. 37.8%, p = 0.014; 11.6% vs. 43.2%, p = 0.001, respectively). There was no significant difference in pCR rate between the groups. Of the 80 rectal cancer patients tested, 35 (43.8%) had metastatic disease (M1). There was no significant difference in complete M1 response rates between the groups (17.6% vs. 38.9%, p = 0.254)., Conclusion: RAS/BRAF mutations negatively impact primary tumor response rates after TNT in patients with advanced rectal cancer. Large-scale national studies are needed to determine whether RAS/BRAF status could be used to select optimal oncologic therapy in rectal cancer patients., (© 2023. Society of Surgical Oncology.)

Introduction: Consolidation durvalumab following platinum-based chemoradiotherapy (CRT) significantly improved overall survival for patients with unresectable stage III non-small cell lung cancer (NSCLC) in the PACIFIC trial. However, older patients were underrepresented in PACIFIC, and subsequent analyses suggested trends toward poorer survival and increased toxicity in patients aged ≥70 years old. We assessed the effectiveness and safety of consolidation durvalumab following CRT in older Australian patients with unresectable stage III NSCLC., Materials and Methods: This retrospective observational study was conducted across seven sites in Sydney, Australia between January 2018 and September 2021. All adult patients with unresectable stage III NSCLC who received platinum-based chemoradiotherapy followed by at least one cycle of consolidation durvalumab were included. Older patients were defined as being ≥70 years old., Results: Of 152 patients included in the analysis, 42.8% (n = 67) patients were 70 years or older. Median follow-up was 26.1 months. The two-year overall survival and median PFS was similar between older and younger patients. At two years, 74.8% (95% confidence interval [CI]: 65.4-84.2%) of patients <70 years old and 65.2% (95% CI: 53.4-77.0%) of older patients were alive (p = 0.07; hazard ratio [HR] 1.64, 95% CI: 0.95-2.81). Median progression-free survival (PFS) in patients <70 years was 30.3 months (95% CI: 22.2-38.4 months) compared with 26.7 months (95% CI: 12.8-40.6 months) in older patients (p = 0.22; HR 1.46, 95% CI: 0.80-2.65). Toxicity was also similar, with 11.5% of patients <70 years old and 18.5% of older patients experiencing grade 3-4 adverse events (AEs; p = 0.23); 16.1% and 24.6% of the patients, respectively, discontinued treatment due to toxicity (p = 0.19). Grade 3-4 AEs and treatment discontinuation were associated with Charlson Comorbidity Index >5 (p = 0.011) and chronic obstructive pulmonary disease diagnosis at presentation (p = 0.002), respectively., Discussion: Older Australian patients receiving consolidation durvalumab following CRT experienced comparable outcomes to their younger peers. Comorbidity burden may be more important determinants of treatment tolerance than chronological age., Competing Interests: Declaration of Competing Interest, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with PSA recurrence after radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) is unknown., Study Design: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open-label, multicentre, randomised Phase II trial., Endpoints: The primary endpoint is 3-year event-free survival, with events comprising one of PSA recurrence (PSA ≥0.2 ng/mL higher than baseline), radiological evidence of metastatic disease, or initiation of systemic or other salvage treatments. Secondary endpoints include patient-reported outcomes, treatment patterns, participant perceptions, and cost-effectiveness., Eligibility Criteria: Eligible participants have PSA recurrence of prostate cancer after radical prostatectomy, defined by serum PSA level of 0.2-0.5 ng/mL, deemed low risk according to modified European Association of Urology biochemical recurrence risk criteria (International Society for Urological Pathology Grade Group ≤2, PSA doubling time >12 months), with no definite/probable recurrent prostate cancer on PSMA-PET/CT., Patients and Methods: A total of 100 participants will be recruited from five Australian centres and randomised 1:1 to SRT or surveillance. Participants will undergo 6-monthly clinical evaluation for up to 36 months. Androgen-deprivation therapy is not permissible. Enrolment commenced May 2023., Trial Registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622001478707)., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction: Cancer is predominantly a disease of older adults, with an increasing number of cancer diagnoses in individuals aged 65 or older. Multiple geriatric factors have been shown to impact patient outcomes in cancer treatment. However, oncology specialists are not well adapted to incorporate geriatric assessment into practice due to a lack of resources and knowledge of the specialty.The primary aim of this study is to implement and evaluate a nurse-led, multidisciplinary model of care for older adults with cancer at two public tertiary hospitals in Melbourne, Australia., Methods and Analysis: This study will aim to assess 200 patients across 2 sites. Both sites will assess individuals with lung cancer; the second site will also include individuals with genitourinary, upper gastrointestinal and colorectal cancers.This process evaluation will use quantitative and qualitative methods to explore the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of the nurse-led, multidisciplinary model of care., Ethics and Dissemination: Ethical approval and local governance approvals have been obtained by Austin Health and Monash Health Human Research Ethics committees. Dissemination will occur via publications, conferences, social medical and local engagement with clinicians, consumers and managers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Up to 70% of people diagnosed with upper gastrointestinal (GI) tract or hepato-pancreato-biliary (HPB) cancers experience substantial reductions in quality of life (QoL), including high distress levels, pain, fatigue, sleep disturbances, weight loss and difficulty swallowing. With few advocacy groups and support systems for adults with upper GI or HPB cancers (i.e. pancreas, liver, stomach, bile duct and oesophageal) and their carers, online supportive care programs may represent an alternate cost-effective mechanism to support this patient group and carers. iCare is a self-directed, interactive, online program that provides information, resources, and psychological packages to patients and their carers from the treatment phase of their condition. The inception and development of iCare has been driven by consumers, advocacy groups, government and health professionals. The aims of this study are to determine the feasibility and acceptability of iCare, examine preliminary efficacy on health-related QoL and carer burden at 3- and 6-months post enrolment, and the potential cost-effectiveness of iCare, from health and societal perspectives, for both patients and carers., Methods and Analysis: A Phase II randomised controlled trial. Overall, 162 people with newly diagnosed upper GI or HPB cancers and 162 carers will be recruited via the Upper GI Cancer Registry, online advertisements, or hospital clinics. Patients and carers will be randomly allocated (1:1) to the iCare program or usual care. Participant assessments will be at enrolment, 3- and 6-months later. The primary outcomes are i) feasibility, measured by eligibility, recruitment, response and attrition rates, and ii) acceptability, measured by engagement with iCare (frequency of logins, time spent using iCare, and use of features over the intervention period). Secondary outcomes are patient changes in QoL and unmet needs, and carer burden, unmet needs and QoL. Linear mixed models will be fitted to obtain preliminary estimates of efficacy and variability for secondary outcomes. The economic analysis will include a cost-consequences analysis where all outcomes will be compared with costs., Discussion: iCare provides a potential model of supportive care to improve QoL, unmet needs and burden of disease among people living with upper GI or HPB cancers and their carers., Australian and New Zealand Clinical Trials Registry: ACTRN12623001185651. This protocol reflects Version #1 26 April 2023., (© 2024. The Author(s).)

Background: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP)., Methods: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years)., Results: Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP., Conclusion: Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Louise Nott reports consulting fees for advisory boards with BMS, Roche, Pfier, Servier, Ipsen, AstraZeneca and Novartis. Louise Nott reports speaker honorarium with MSD, Amgen, MS and Celgene. Louise Nott reports support for attending educational meetings with MSD and Novartis. There are no other interests declared by the authors which may be considered as potential competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Despite people with haematological malignancies being particularly vulnerable to severe COVID-19 infection and complications, vaccine hesitancy may be a barrier to optimal vaccination. This study explored attitudes towards COVID-19 vaccination in people with haematological malignancies., Methods: People with haematological malignancies at nine Australian health services were surveyed between June and October 2021. Sociodemographic and clinical characteristics were collected. Attitudes towards COVID-19 vaccination were explored using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale, and the Disease Influenced Vaccine Acceptance Scale-Six. Open-ended comments were qualitatively analysed., Results: A total of 869 people with haematological malignancies (mean age 64.2 years, 43.6% female) participated. Most participants (85.3%) reported that they had received at least one COVID-19 vaccine dose. Participants who were younger, spoke English as a non-dominant language, and had a shorter time since diagnosis were less likely to be vaccinated. Those who were female or spoke English as their non-dominant language reported greater vaccine side-effect concerns. Younger participants reported greater concerns about the vaccine impacting their treatment., Conclusion: People with haematological malignancies reported high vaccine uptake; however, targeted education for specific participant groups may address vaccine hesitancy concerns, given the need for COVID-19 vaccine boosters., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [ 177 Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]fluoro-2-deoxy-D-glucose (2-[ 18 F]FDG) PET-CT., Methods: TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[ 18 F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [ 177 Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m 2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete., Findings: 291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [ 177 Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [ 177 Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [ 177 Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [ 177 Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference -0·5 months [95% CI -3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1)., Interpretation: These results support the use of [ 177 Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[ 18 F]FDG-discordant disease., Funding: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It's a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman's Ride., Competing Interests: Declaration of interests MSH reports research grant support (to their institution) from Novartis (including AAA and Endocyte), Australian Nuclear Science and Technology Organization (ANSTO), Bayer, Isotopia, and MIM; and consulting fees for lectures or advisory boards from Astellas and AstraZeneca in the past 2 years, and from Janssen, MSD, and Mundipharma in the past 5 years. LE reports personal fees from AstraZenca, Janssen, and Astellas, outside the submitted work. SS reports grants from AAA, AstraZeneca, MSD, and Genetech to their institution; and personal fees from AstraZeneca, MSD, Bristol Myers Squibb, and AstraZeneca to their institution, outside the submitted work. DAP reports personal fees from Ipsen and Eisai, outside the submitted work. RJF reports institution funding and consulting fees from AIQ Solutions, outside of the submitted work; and committee involvement in the Australasian Radiopharmaceutical Trials Network (unpaid). CG donated personal fees from Astellas, Janssen, AstraZeneca, Bristol Myers Squibb, EMD Serono, Ipsen, Astellas, and MSD, direct and complete, to a third party not-for-profit. AMS reports trial or research funding from EMD Serono, ITM, AVID, Medimmune, Telix, Adalta, Fusion, Antengene, Earli, Curis, and Cyclotek; grants from the Australian National Health and Medical Research Council (NHMRC) and Medical Research Future Fund (MRFF), including an NHMRC Investigator Grant; and board and advisory committee involvement for the Australian and New Zealand Society of Nuclear Medicine and Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group (unpaid); all outside the submitted work. EMK reports personal fees from Astellas Pharma, Janssen, Pfizer, Ipsen, and Roche, all outside the submitted work; and is supported by a Prostate Cancer Foundation Young Investigator Award and University of British Columbia Killam Postdoctoral Fellowship. AAA reports grants or personal fees from Janssen, Astellas, Novartis, Merck Serono, Tolmar, Amgen, Pfizer, Bayer, Telix Pharmaceuticals, Bristol Myers Squibb, Sanofi, Noxopharm, AstraZeneca, Ipsen, MSD, Aculeus Therapeutics, and Daiichi Sankyo; and grants from Astellas (investigator), Merck Serono (investigator), AstraZeneca (investigator), Bristol Myers Squibb (institutional), AstraZeneca (institutional), Aptevo Therapeutics (institutional), GlaxoSmithKline (institutional), Pfizer (institutional), MedImmune (institutional), Astellas (institutional), Synthorx (institutional), Bionomics (institutional), Sanofi Aventis (institutional), Novartis (institutional), Ipsen (institutional), Exelixis (institutional), MSD (institutional), Janssen (institutional), Eli Lilly (institutional), Gilead Sciences (institutional), Merck Serono (institutional), and Hinova (institutional), all outside the submitted work. MRS reports grants to his institution from the NHMRC, Cancer Australia, Astellas, Amgen, AstraZeneca, Bayer, Bionomics, Bristol Myers Squibb, Celgene, Medivation, MSD, Pfizer, Roche, Sanofi, and Tilray, all outside the submitted work. IDD reports grants from the NHMRC, during the conduct of the study; and institutional payments to support prostate cancer trials from Pfizer, the ANZUP Cancer Trials Group, Bayer, Astellas, Janssen, Movember Foundation, and MSD, outside the submitted work. IDD is also unremunerated Chair of the ANZUP Cancer Trials Group, and is supported in part by an NHMRC Investigator Grant (grant number 2016274). AMJ reports consulting or advisory roles (to their institution) from Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, Eisai, Bayer, and Astellas Pharma; and research funding (to their institution) from Bristol Myers Squibb, Janssen Oncology, MSD, Mayne Pharma, Genentech, Bayer, Lilly, Pfizer, and AstraZeneca. AI reports personal fees for a consulting role for Curium Pharma and payment to their institution for a consulting role from Ambrx Pharma, all outside the submitted work. AJW reports a consulting role for and travel support from Bayer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose of Review: The treatment of stage III N2 non-small cell lung cancer (NSCLC) remains debated. There is an absence of a universally agreed definition of resectability for this heterogeneous group and a lack of trial data., Recent Findings: We reviewed and compared current international guidelines and evidence surrounding management of stage III N2 NSCLC. The Irish and Australian guidelines advise subcategorising N2 disease into N2a (may be resectable) and N2b (never resectable). On the contrary, American and British guidelines avoid subcategorising N2 disease, emphasising importance of local MDT decisions. It is suggested that evidence for resection of stage III tumours is relatively weak, but that stage IIIA should generally be considered for resection, and stage IIIB is not recommended for resection. For resectable disease, surgery may be combined with neoadjuvant chemoimmunotherapy, or adjuvant chemotherapy followed by immunotherapy and radiotherapy in selected patients. There is some evidence that technically resectable disease can be treated solely with radiotherapy with similar outcomes to resection. In the event of unresectable disease, chemoradiotherapy has been the traditional management option. However, recent studies with chemoradiotherapy alongside immunotherapy appear promising. There are many factors that influence the treatment pathway offered to patients with stage III N2 NSCLC, including patient factors, team expertise, and local resources. Therefore, the role of MDTs in defining resectability and formulating an individualised treatment plan is crucial., (© 2024. Crown.)

Background: In primary localised resectable retroperitoneal sarcoma (RPS), loco-regional and distant relapse occur frequently despite optimal surgical management. The role of chemotherapy in improving outcomes is unclear., Methods: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether neoadjuvant or adjuvant chemotherapy improve outcomes in adults with primary localised resectable RPS. Medline, Embase and Cochrane Central were queried for publications from 1946 to June 2022 that evaluated recurrence free survival, overall survival, and post operative complications. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed., Results: Twenty three studies were identified; one meta-analysis of retrospective studies and 22 retrospective studies including three with propensity matched cohorts. Most studies did not analyse outcomes by histology, detail treatment regimens, provide baseline characteristics or selection criteria for those receiving chemotherapy. Evidence of selection bias was illustrated in several studies. Newcastle-Ottawa quality of retrospective cohort studies was good for 12 studies and poor for 10 studies. All studies were assessed as Level III-2 evidence by the Australian NHMRC hierarchy. Overall, the addition of neoadjuvant or adjuvant chemotherapy to surgery was not associated with improvement in local recurrence, metastasis free survival, disease free survival or overall survival in primary localised resectable RPS. There is some evidence of an association of chemotherapy with worse overall survival. One single centre study showed that neoadjuvant chemotherapy was not associated with increased post operative complications compared to surgery alone in primary localised resectable RPS., Conclusions: There is currently no evidence that demonstrates the addition of chemotherapy to surgery improves outcomes in adult patients with primary localised resectable RPS. Available evidence is limited by its retrospective nature and high likelihood of selection bias with chemotherapy generally administered to patients at higher risk of recurrence and many patients not receiving care in high volume sarcoma centres. Randomised trials are required to conclusively determine the role of chemotherapy in primary localised resectable RPS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joanna Connor: Honorarium for advisory board for Pfizer; David Gyorki: Honorarium for BMS and Merck; Angela Hong: Honorarium for advisory board for Oncobeta and Provectus. The other authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments). Similar assay accuracy is achieved in a prospective study of third-line or later mCRC treatment, AGITG FORECAST-1 (n = 30 patients). "Resistant" predictions are associated with inferior progression-free survival; misclassification rates are similar by regimen. Liver metastases are the optimal site for sampling, with testing achievable within 7 weeks for 68.8% cases. Our findings indicate that PDTO drug panel testing can provide predictive information for multifarious standard-of-care therapies for mCRC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

This cost analysis, from a societal perspective, compared the cost difference of a networked teletrial model (NTTM) with four regional hubs versus conventional trial operation at a single metropolitan specialist centre. The Australian phase 3 cancer interventional randomised controlled trial included 152 of 328 regional participants (patient enrolment 2018-2021; 6-month primary end point). The NTTM significantly reduced (AU$2155 per patient) patient travel cost and time and lost productivity., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Introduction: The COVID-19 pandemic caused rapid implementation of telehealth for melanoma follow-up care in Australia. This study explores Australian melanoma patients and clinicians' level of satisfaction with telehealth., Methods: A cross-sectional study was conducted across three specialist melanoma centres in Sydney, Australia. Melanoma patients (all stages) and clinicians completed mixed methods surveys seeking socio-demographic and clinical information and questionnaires to assess satisfaction with telehealth. Additionally, patients completed measures of quality of life, fear of cancer recurrence and trust in their oncologist. Patients and clinicians provided open-ended responses to qualitative questions about their perceptions of telehealth., Results: One hundred and fifteen patients and 13 clinicians responded to surveys. Telephone was used by 109 (95%) patients and 11 (85%) clinicians. Fifty-seven (50%) patients and nine (69%) clinicians preferred face-to-face consultations, 38 (33%) patients and 3 (23%) clinicians preferred a combination of face-to-face and telehealth consultations. Five (4%) patients and nil clinicians preferred telehealth consultations. Patients diagnosed with early-stage melanoma, using telehealth for the first time, who have lower trust in their oncologist, and having higher care delivery, communication and supportive care concerns were likely to report lower satisfaction with telehealth. Open-ended responses were consistent between patients and clinicians, who reported safety, convenience and improved access to care as major benefits, while identifying personal, interpersonal, clinical and system-related disadvantages., Discussion: While telehealth has been widely implemented during COVID-19, the benefits identified by patients and clinicians may extend past the pandemic. Telehealth may be considered for use in conjunction with face-to-face consultations to provide melanoma follow-up care., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Recent advances in cancer therapeutics have improved outcomes, resulting in increasing candidacy of patients with metastatic cancer being admitted to intensive care units (ICUs). A large proportion of patients also have frailty, predisposing them to poor outcomes, yet the literature reporting on this is scarce. We aimed to assess the impact of frailty on survival in patients with metastatic cancer admitted to the ICU., Methods: In this retrospective registry-based cohort study, we used data from the Australia and New Zealand Intensive Care Society Adult Patient (age ≥16 years) database to identify patients with advanced (solid and haematological cancer) and a documented Clinical Frailty scale (CFS) admitted to 166 Australian ICUs. Patients without metastatic cancer were excluded. We analysed the effect of frailty (CFS 5-8) on long-term survival, and how this effect changed in specific subgroups (cancer subtypes, age [<65 years or ≥65 years], and those who survived hospitalisation). Because estimates tend to cluster within centres and vary between them, we used Cox proportional hazards regression models with robust sandwich variance estimators to assess the effect of frailty on survival time up to 4 years after ICU admission between groups., Findings: Between Jan 1, 2018, and March 31, 2022, 30 026 patients were eligible, and after exclusions 21 174 patients were included in the analysis; of these, 6806 (32·1%) had frailty, and 11 662 (55·1%) were male, 9489 (44·8%) were female, and 23 (0·1%) were intersex or self-reported indeterminate sex. The overall survival was lower for patients with frailty at 4 years compared with patients without frailty (29·5% vs 10·9%; p<0·0001). Frailty was associated with shorter 4-year survival times (adjusted hazard ratio 1·52 [95% CI 1·43-1·60]), and this effect was seen across all cancer subtypes. Frailty was associated with shorter survival times in patients younger than 65 years (1·66 [1·51-1·83]) and aged 65 years or older (1·40 [1·38-1·56]), but its effects were larger in patients younger than 65 years (p interaction <0·0001). Frailty was also associated with shorter survival times in patients who survived hospitalisation (1·49 [1·40-1·59])., Interpretation: In patients with metastatic cancer admitted to the ICU, frailty was associated with poorer long-term survival. Patients with frailty might benefit from a goal-concordant time-limited trial in the ICU and will need suitable post-intensive care supportive management., Funding: None., Competing Interests: Declaration of interests MA reports travel expenses and advisory board fees from Pfizer and MSD and has been a member of a steering committee for the CP-MGA271 trial (MacroGenics). RRL reports a Dean's Research Development award from National University of Singapore, Singapore. RS reports research grants from Paxman Coolers, MSD, and Natera; consulting fees from Bristol Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, GSK, Diethelm Keller Siber Hegner, and Astellas; honoraria from MSD, Eli Lilly, Bristol Myers Squibb, Roche, Taiho, AstraZeneca, Diethelm Keller Siber Hegner, and Ipsen; travel expenses from Roche, AstraZeneca, Taiho, Eisai, and Diethelm Keller Siber Hegner; and patents support from Paxman and Auristone. DP chairs the ANZICS Centre for Outcomes and Resource Evaluation Clinical Quality Registry (the data custodian for the present study); is a Vice-President and Board Member of ANZICS; and has been a clinical lead for Safer Care Victoria Critical Care network. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Horizon scanning (HS) is the systematic identification of emerging therapies to inform policy and decision-makers. We developed an agile and tailored HS methodology that combined multi-criteria decision analysis weighting and Delphi rounds. As secondary objectives, we aimed to identify new medicines in melanoma, non-small cell lung cancer and colorectal cancer most likely to impact the Australian government's pharmaceutical budget by 2025 and to compare clinician and consumer priorities in cancer medicine reimbursement., Method: Three cancer-specific clinician panels (total n = 27) and a consumer panel (n = 7) were formed. Six prioritisation criteria were developed with consumer input. Criteria weightings were elicited using the Analytic Hierarchy Process (AHP). Candidate medicines were identified and filtered from a primary database and validated against secondary and tertiary sources. Clinician panels participated in a three-round Delphi survey to identify and score the top five medicines in each cancer type., Results: The AHP and Delphi process was completed in eight weeks. Prioritisation criteria focused on toxicity, quality of life (QoL), cost savings, strength of evidence, survival, and unmet need. In both curative and non-curative settings, consumers prioritised toxicity and QoL over survival gains, whereas clinicians prioritised survival. HS results project the ongoing prevalence of high-cost medicines. Since completion in October 2021, the HS has identified 70 % of relevant medicines submitted for Pharmaceutical Benefit Advisory Committee assessment and 60% of the medicines that received a positive recommendation., Conclusion: Tested in the Australian context, our method appears to be an efficient and flexible approach to HS that can be tailored to address specific disease types by using elicited weights to prioritise according to incremental value from both a consumer and clinical perspective., Policy Summary: Since HS is of global interest, our example provides a reproducible blueprint for adaptation to other healthcare settings that integrates consumer input and priorities., Competing Interests: Declaration of Competing Interest MA has received financial support to attend conferences and meetings by AstraZeneca and serves on the advisory board for Pfizer and Bristol Myers Squibb. PAA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Canofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune. He has received research funding grants from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. He has received travel support from Pfizer. SA has served uncompensated on the boards of Health Issues Centre, Australia, Victorian Agency for Health Information, and Safer Care Victoria. MPB has received honoraria from BNS Australia, USD Oncology, and Novartis. He holds an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, and Cartherics for which his institution receives reimbursements. His institution has also received reimbursement for research support from Bristol Myers Squibb, Merck Sharp & Dohme, Pharmaust, Zucero Therapeutics, and CStone Pharmaceuticals. MB has received compensation and research support as an advisor and consultant to Pierre Fabre, MSD, GSK, Servier, and AstraZeneca. MI is on the advisory boards of Pfizer, Roche, Takeda, BeiGene, Amgen, Merck, and MSD and has received honoraria from Pfizer, Roche, Takeda, Novartis, as well as research funding from Pfizer. TJ reports consulting fees from AstraZeneca and MSD, and advisory boards and committees for AstraZeneca, Amgen, Bristol Myers Squibb, Merck & Co., MSD, Gilead, Puma, Pfizer Inc., Roche AG, Specialised Therapeutics, and Takeda Pharmaceutical, outside the submitted work. SK reports honoraria to institution from Astra Zeneca, Roche, Pfizer, Bristol Myers Squibb, MSD and Takeda; consulting fees from AstraZeneca, Pfizer, MSD, Novartis, Roche, Takeda, Amgen; and research funding to institution from Astra Zeneca. MK reports institutional grants from Nordic Farma, Merck-Serono, Pierre Fabre, Servier, Bayer, Bristol Myers Squibb, Merck, and Roche; and consulting fees and honoraria paid to institution from Pierre Fabre and Servier. BTL has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly. He has received research grants to his institution from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly. He has received academic travel support from Amgen, Jiangsu Hengrui Medicine and MORE Health. He is an inventor on two institutional patents at MSK (US62/685,057, US62/514,661) and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. BTL is supported by the Memorial Sloan Kettering Cancer Centre Support Grant P30 CA008748 and Research Project Grant R01CA249666 from the National Institutes of Health. GVL is consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, OncoSec, PHMR Ltd, Pierre Fabre, Provectus, Qbiotics, Regeneron. JML receives research support from Ipsen Pharmaceuticals, Novartis and Amgen, and reports consulting fees and/or honoraria from Amgen, Ipsen, Taiho, Novartis, SAGA Diagnostics and Natera. BM is on the advisory boards of Amgen, MSD, Bristol Myers Squibb, Beigene and AstraZeneca. GAM has received research support from Bristol Myers Squibb and as Principal Investigator his institution has received reimbursement of trial costs from Roche-Genentech. TMM reports consulting fees and participation on advisory boards for Bristol Myers Squibb, MSD, Merck, AstraZeneca, Novartis, GSK, Eisai, and honoraria from AstraZeneca. TMM has received support to attend meetings from Bristol Myers Squibb and AstraZeneca. LN has received institutional consulting fees from Bristol Myers Squibb, Pfizer, and Merck Sharp & Dohme, and reports support to attend a research meeting from AstraZeneca. NP has served on advisory boards or received personal honoraria from Boehringer Ingelheim, MSD, Merck, Bristol-Myers Squib, Astra Zeneca, Takeda, Pfizer, Roche, Novartis, Ipsen and Bayer and has received research funding to his institution from Bayer, Pfizer and Roche. TMP has received research support from Roche and Pfizer, and holds a consulting or advisory role for Merck, Bristol Myers Squibb, Novartis, Sanofi/Regeneron, and Pfizer. SP is compensated consultant to Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, EQRx, GSK, Guardant Health, Incyte, Janssen, Lilly, Merck Serono, MSD, Novartis, Roche, Takeda, Pfizer, Seattle Genetics, Turning Point Therapeutics, declares expert testimony to Roche and Merck Serono, and travel support from Janssen and Roche.BJS is on the Advisory Boards/Honoraria for Pfizer, Novartis, Roche, AstraZeneca, Merck, Bristol Myers Squibb, Eli Lilly, Amgen, BeiGene, Janssen, Takeda. JAS has received support for conference attendance from MSD (virtual registration ASCO). JT has received consulting fees or honoraria from Haystack Oncology, Servier, Pierre Fabre, MSD, Merck Serono, Amgen, Novartis, Seres and AstraZeneca. JT is on the advisory boards of Beigene, Daiichi Sankyo, Gilead, Illumina, Novartis, BMS, and MSD. WX has received research support from Merck, honoraria from MSD, Merck and AstraZeneca, and support for attending meetings from MSD (virtual registration ASCO) and Eli Lilly (virtual registration SABCS). WX is on the advisory boards of MSD, Merck and Novartis, and holds unpaid positions as Chair of the Melanoma and Skin Cancer trials group and Australasian Merkel Cell Carcinoma interest group.DY has received institutional payments for his role on advisory boards for AstraZeneca, Servier, Specialised Therapeutics, MSD and BayerJZ serves in an advisory/consultancy role for Merck Sharp & Dohme, Specialised Therapeutics, CEND, Deciphera, Revolution Medicine, FivePHusion, Genorbio, 1Global, Novotech, Alloplex Biotherapeutics, NOUS Consulting, and Oncology Republic; owns stock in Biomarin, Ophthea, Amarin, Concert Pharmaceuticals, Frequency Therapeutics, Gilead, Madrigal Pharmaceuticals, UniQure, Zogenix, Orphazyme, Moderna Therapeutics, TWST, Novavax, and Teladoc; has received honoraria from Gilead Sciences, MSD Oncology, and Viatris; and his institution has received research funding from Bristol-Myers Squibb, AstraZeneca, Pfizer, IQvia, Mylan, Ipsen, Eisai, Medtronic, MSD Oncology and Servier; and has received travel, accommodations, expenses from ICON Group, MSD Oncology, and PRAXIS., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: International guidelines advocate for active surveillance as the preferred treatment strategy for patients with stage 1 testicular cancer after orchidectomy although a personalized discussion is required., Materials and Methods: We conducted an analysis of individuals registered in iTestis, Australia's testicular cancer registry, to describe the patterns of relapse and outcomes of patients treated in Australia where the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Surveillance Recommendations are widely adopted., Results: A total of 650 individuals diagnosed between 2000 and 2020 were included, 63% (411 of 650) seminoma and 37% (239 of 650) nonseminoma. The median age was 34 years (range 14-74). 26% (106 of 411) with seminoma and 15% (36 of 239) nonseminoma received adjuvant chemotherapy. After a median follow-up of 43 months (range 0-267) postorchidectomy, relapse occurred in 10% (43 of 411) of seminoma and 18% (43 of 239) of nonseminoma. The two-year relapse-free survival was 92% (95% CI, 89 to 95) and 82% (95% CI, 78 to 87) in seminoma and nonseminoma, respectively. All relapses (86 of 86) were detected at a routine surveillance visit; 98% (85 of 86) were asymptomatic and detected solely through imaging (62 of 86, 72%), tumor markers (6 of 86, 7%), or a combination (17 of 86, 20%). The most common relapse site was isolated retroperitoneal lymphadenopathy (53 of 86, 62%). No nonpulmonary visceral metastases occurred. At relapse, 98% (84 of 86) had International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis; 2 of 86 intermediate prognosis (both nonseminoma). No deaths occurred., Conclusion: In our cohort of stage 1 testicular cancer, where national surveillance recommendations have been widely adopted, recurrences were detected at routine surveillance visits and, almost exclusively, asymptomatic with IGCCCG good-prognosis disease. This provides reassurance that active surveillance is safe.

Background: Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1-5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs., Methods: Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy., Results: The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity., Conclusion: Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease., (© 2023. The Author(s).)

Purpose: The O-(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation., Methods: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBR max ), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBR max /TBR mean ) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD])., Results: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBR max , and TBR mean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement., Conclusion: The FIG study credentialing program has increased expertise across study sites. TBR max and TBR mean were robust, with considerable variability in BTV delineation and image interpretation observed., (© 2023. The Author(s).)

Objectives: To assess the influence of geographic remoteness on health care utilization at end of life (EOL) by people with advanced cancer in a geographically diverse Australian local health district, using two objective measures of rurality and travel-time estimations to health care facilities. Methods: This retrospective cohort study examined the association between rurality (using the Modified Monash Model) and travel-time estimation, and demographic and clinical factors, with the receipt of >1 inpatient and outpatient health service in the last year of life in multivariate models. The study cohort comprised of 3546 patients with cancer, aged ≥18 years, who died in a public hospital between 2015 and 2019. Results: Compared with decedents from metropolitan areas, decedents from some rural areas had higher rates of emergency department visits (small rural towns: aRR 1.29, 95% CI: 1.07-1.57) and ICU admissions (large rural towns: aRR 1.32, 95% CI: 1.03-1.69), but lower rates of acute hospital admissions (large rural towns: aRR 0.83, 95% CI: 0.76-0.90), inpatient palliative care (PC) (regional centers: aRR 0.85, 95% CI: 0.75-0.97), and inpatient radiotherapy (lowest in small rural towns: aRR 0.07, 95% CI: 0.03-0.18). Decedents from rural and regional centers had lower rates of outpatient chemotherapy and radiotherapy use, yet higher rates of outpatient cancer service utilization ( p  < 0.05). Shorter travel times (10-<30 minutes) were associated with higher rates of inpatient specialist PC (aRR 1.48, 95% CI: 1.09-1.98). Conclusions: Reporting on a series of inpatient and outpatient services used in the last year of life, measures of rurality and travel-time estimates can be useful tools to estimate geographic variation in EOL cancer care provision, with significant gaps uncovered in inpatient PC and outpatient service utilization in rural areas. Policies aimed at redistributing EOL resources in rural and regional communities to reduce travel times to health care facilities could help to reduce regional disparities and ensure equitable access to EOL care services.

Background: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia., Aims: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland., Methods: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions., Results: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD)., Conclusion: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Next generation sequencing (NGS) is increasingly used in standard clinical practice to identify patients with potentially actionable mutations. Stratification of NGS mutation tiers is currently based on the European Society of Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT[E]) Tier I-V & X. Allele frequency is also increasingly recognised as an important prognostic tool in advanced cancer. The aim of this study was to determine the genomic mutations in metastatic colorectal cancer (CRC) in an Australian multicultural population and their influence on survival outcomes., Methods: Next generation sequencing with the 50-gene panel Oncomine Precision Assay™ was used on 180 CRC tissue samples obtained across six Sydney hospitals between June 2021 and March 2022., Results: From 180 samples, 147 (82%) had at least one gene mutation identified with 68 (38%) having two or more concurrent mutations. Tier I variants included RAS wild-type [EI] in 73 (41%) and BRAF V600E [EIA] in 27 (15%). Non-tier I variants include 2 (1%) ERBB2 amplification [EIIB], 26 (15%) PIK3CA hotspot mutations [EIIIA] and 9 (5%) MET focal amplifications [EIIIA]. NGS testing revealed an additional 22% of cases with Tier II & III mutations. 43% of patients also presented with potentially actionable Tier III & IV mutations. Patients with concurrent TP53 and RAS mutations had significantly reduced overall survival (6.1 months versus 21.1 months, p <0.01). High KRAS allele frequency, as defined by those with over 20% variant allele frequency (VAF), also demonstrated reduced overall survival (12.1 months versus 42.9 months, p = 0.04)., Conclusions: In addition to identifying patients with genomic alterations suitable for clinically proven standard of care therapeutic options, the 50 gene NGS panel has significant potential in identifying potentially actionable non-tier 1 mutations and therefore may become future standard clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nindra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The use of immune checkpoint inhibitors has altered therapeutic paradigms in NSCLC. However, they may cause immune-related toxicities, including acute kidney injury (irAKI), especially when combined with nephrotoxic agents. We investigated the incidence, management and outcomes of AKI in Australian NSCLC patients., Methods: Medical records from a cancer centre registry were reviewed. AKI was defined and graded on absolute creatinine rise, or rise above baseline. Fishers exact test compared proportions. The Kaplan-Meier method estimated survival, and multiple logistic regression tested for risk factors., Results: Of 449 patients who underwent immunotherapy from 2013 to 2021, the median age was 65 years and 61% were male. Metastatic disease was present in 68% at diagnosis, the remainder had stage Ia-III disease; 70% had adenocarcinoma; and 17% had EGFR mutations. AKI was identified in 65 patients (14.5%) of which 19 were irAKI (4.2%). Within irAKI patients, eleven (58%) had other immune-related adverse events. Median time to irAKI onset was 4 months (IQR 4-6). Seventeen (89%) patients had AKI stage 1 or 2; two had stage 3. Eleven patients developed chronic kidney disease; none required renal replacement therapy. Kidney biopsies demonstrated acute interstitial nephritis (n = 3), acute tubular necrosis (n = 1) and anti-phospholipase A2 receptor negative membranous glomerulonephritis (n = 1). Five patients were rechallenged with immunotherapy; two had recurrent irAKI. The median overall survival for those with irAKI was not reached versus 12 months with no irAKI (HR 0.35, 95 %CI 0.20-0.60, p = 0.01). Risk factors for irAKI included having an additional, non-renal irAE (OR 6.21, 95 %CI 2.35-17.26, p ≤ 0.01); immunotherapy combined with other cancer therapies (OR 5.62, 95 %CI 2.08-16.20, p ≤ 0.01); and ECOG performance status > 1 (OR 4.39 (95 %CI 1.11-14.90, p = 0.02) CONCLUSIONS: The incidence of irAKI was similar to the published literature. Renal recovery was poor, however survival was not compromised. Improved diagnostic and therapeutic strategies for irAKI would benefit this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: Response to the substantial and long-term impacts that a cancer diagnosis and treatment has on the growing population of cancer survivors, requires priority-driven, impactful research. This study aimed to map Australian cancer survivorship research activities to identify gaps and opportunities for improvement and compare activities against identified survivorship research priorities., Methods: An online survey was completed by Australian researchers regarding their cancer survivorship research, and the barriers they identified to conducting such research. Current research activity was compared to recently established Australian survivorship research priorities., Results: Overall, 178 participants completed the online survey. The majority of the research undertaken utilized survey or qualitative designs and focused on breast cancer, adult populations, and those in early survivorship (<5 years post-treatment). Barriers to conducting survivorship research included funding, collaboration and networking, mentoring, and time constraints. There was moderate alignment with existing research priorities. Investigating models of care and health service delivery were the most frequently researched priorities. Research priorities that were less commonly investigated included patient navigation, patient-reported outcomes, multimorbidity, fear of cancer recurrence, and economic issues., Conclusion: This study provides the first snapshot of Australian survivorship research activity. Comparison to established priorities demonstrates health services research is receiving attention and highlights areas for potential pursuits, such as rare cancers or multimorbidity. Findings indicate the need for improved funding and infrastructure to support researchers in advancing the survivorship research agenda., (© 2023 John Wiley & Sons Australia, Ltd.)

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible., (© 2023 UICC.)

Background: Pain is a common, debilitating, and feared symptom, including among cancer survivors. However, large-scale population-based evidence on pain and its impact in cancer survivors is limited. We quantified the prevalence of pain in community-dwelling people with and without cancer, and its relation to physical functioning, psychological distress, and quality of life (QoL)., Methods: Questionnaire data from participants in the 45 and Up Study (Wave 2, n = 122,398, 2012-2015, mean age = 60.8 years), an Australian population-based cohort study, were linked to cancer registration data to ascertain prior cancer diagnoses. Modified Poisson regression estimated age- and sex-adjusted prevalence ratios (PRs) for bodily pain and pain sufficient to interfere with daily activities (high-impact pain) in people with versus without cancer, for 13 cancer types, overall and according to clinical, personal, and health characteristics. The relation of high-impact pain to physical and mental health outcomes was quantified in people with and without cancer., Results: Overall, 34.9% (5,436/15,570) of cancer survivors and 31.3% (32,471/103,604) of participants without cancer reported bodily pain (PR = 1.07 [95% CI = 1.05-1.10]), and 15.9% (2,468/15,550) versus 13.1% (13,573/103,623), respectively, reported high-impact pain (PR = 1.13 [1.09-1.18]). Pain was greater with more recent cancer diagnosis, more advanced disease, and recent cancer treatment. High-impact pain varied by cancer type; compared to cancer-free participants, PRs were: 2.23 (1.71-2.90) for multiple myeloma; 1.87 (1.53-2.29) for lung cancer; 1.06 (0.98-1.16) for breast cancer; 1.05 (0.94-1.17) for colorectal cancer; 1.04 (0.96-1.13) for prostate cancer; and 1.02 (0.92-1.12) for melanoma. Regardless of cancer diagnosis, high-impact pain was strongly related to impaired physical functioning, psychological distress, and reduced QoL., Conclusions: Pain is common, interfering with daily life in around one-in-eight older community-dwelling participants. Pain was elevated overall in cancer survivors, particularly for certain cancer types, around diagnosis and treatment, and with advanced disease. However, pain was comparable to population levels for many common cancers, including breast, prostate and colorectal cancer, and melanoma., (© 2023. BioMed Central Ltd., part of Springer Nature.)