Outcomes of patients with gallbladder cancer presenting with acute cholecystitis.

The main purpose of this study is to explore the outcomes of patients found to have gallbladder cancer during investigation and diagnosis of acute cholecystitis. The incidence of primary gallbladder cancer co-existing in acute cholecystitis is not well defined in the literature, with anecdotal reports suggesting that they experience worse outcomes than patients with gallbladder cancer found incidentally. METHODS: A retrospective review of all patients with gallbladder cancer managed at the Canberra Health Service between 1998 and May 2022 were identified and reviewed. RESULTS: A total of 65 patients were diagnosed with primary gallbladder cancer during the study period with a mean age of 70.4 years (SD 11.4, range 59-81.8 years) and a female preponderance (74% versus 26%) with a ratio of 2.8. Twenty (31%) patients presented with acute calculus cholecystitis and were found to have a primary gallbladder cancer. This group of patients were older and predominantly female, but the difference was not statistically significant. The overall 5-year survival in the cohort was 20% (stage 1 63%, stage 2 23%, stage 3 16%, and stage 4 0%). There was no statistically significant difference in survival between those who presented with acute cholecystitis vs other presentations. CONCLUSIONS: A third of the patients with gallbladder cancer presented with acute cholecystitis. There was no statistically significant difference in survival in those with bile spillage during cholecystectomy as well those presenting with acute cholecystitis.

Models for predicting venous thromboembolism in ambulatory patients with lung cancer: A systematic review and meta-analysis.

AIMS: The incidence of venous thromboembolism (VTE) in patients with lung cancer is relatively high, and risk stratification models are vital for the targeted application of thromboprophylaxis. We aimed to review VTE risk prediction models that have been developed in patients with lung cancer and evaluated their performance. METHODS AND RESULTS: Twenty-four eligible studies involving 123,493 patients were included. The pooled incidence of VTE within 12 months was 11 % (95 % CI 8 %-14 %). With the identified four VTE risk assessment tools, meta-analyses did not show a significant discriminatory capability of stratifying VTE risk for Khorana, PROTECHT and CONKO scores. The pooled sensitivity and specificity of the Khorana score were 24 % (95 % CI 11 %-44 %) and 84 % (95 % CI 73 %-91 %) at the 3-point cut-off, and 43 % (95 % CI 35 %-52 %) and 61 % (95 % CI 52 %-69 %) at the 2-point cut-off. However, a COMPASS-CAT score of ≥ 7 points indicated a significantly high VTE risk, with a RR of 4.68 (95 % CI 1.05-20.80). CONCLUSIONS: The Khorana score lacked discriminatory capability in identifying patients with lung cancer at high VTE risk, regardless of the cut-off value. The COMPASS-CAT score had better performance, but further validation is needed. The results indicate the need for robust VTE risk assessment tools specifically designed and validated for lung cancer patients. Future research should include relevant biomarkers as important predictors and consider the combined use of risk tools. PROSPERO registration number: CRD42021245907.

Response to COVID-19 vaccination in patients on cancer therapy: Analysis in a SARS-CoV-2-naïve population.

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.

A tailored approach to horizon scanning for cancer medicines.

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.

Hyperprogressive Disease (HPD) in Solid Tumours Receiving Immune Checkpoint Inhibitors in a Real-World Setting.

Introduction: Hyperprogressive disease (HPD) is a state of accelerated tumor growth from cancer immunotherapy, associated with poor outcome. The reported incidence is 6% to 29% among studies using varying definitions of HPD, with no predictive biomarkers. Tumor infiltrating lymphocytes (TILs) are prognostic and predictive for immunotherapy benefit in various tumor types, but have only been tested for correlation with HPD in one study. Objectives: The objective of the study was to determine the prevalence of HPD in solid tumor patients treated with immune checkpoint inhibitor therapy in a real-world setting, and to assess clinicopathological features as potential biomarkers for HPD. Methods: We conducted a retrospective analysis of solid tumor patients treated with immune checkpoint inhibitors at a single institution. Imaging pre-immunotherapy and postimmunotherapy were assessed for HPD, and correlated against clinicopathological factors, including TILs and programmed death-ligand 1 (PD-L1) status through archival tumor assessment. HPD was defined per Matos et al as response evaluation criteria in solid tumors (RECIST) progressive disease, minimum increase in measurable lesions of 10 mm, plus increase of ≥40% in sum of target lesions compared with baseline and/or increase of ≥20% in sum of target lesions compared with baseline plus new lesions in at least 2 different organs. Results: HPD occurred in 11 of 87 patients (13%), and associated with inferior overall survival (median 5.5 months vs 18.3 months, P = .002). However, on multivariate analysis, only liver metastases (hazard ratio [HR] 4.66, 95% confidence interval [CI] 2.27-9.56, P < .001) and PD-L1 status (HR 0.53, 95% CI 0.30-0.95, P = .03) were significantly associated with survival. Presence of liver metastases correlated with occurence of HPD (P = .01). Age, sex, and monotherapy versus combination immunotherapy were not predictive for HPD. PD-L1 status and TILs were not associated with HPD. Conclusions: We found 13% HPD among solid tumor patients treated with immunotherapy, consistent with the range reported in prior series. Assessment for HPD is feasible outside of a clinical trials setting, using modified criteria that require comparison of 2 imaging studies. Liver metastases were associated with risk of HPD, while TILs and PD-L1 status were not predictive for HPD.

Identifying cancer-associated leukocyte profiles using high-resolution flow cytometry screening and machine learning.

Background: Machine learning (ML) is a valuable tool with the potential to aid clinical decision making. Adoption of ML to this end requires data that reliably correlates with the clinical outcome of interest; the advantage of ML is that it can model these correlations from complex multiparameter data sets that can be difficult to interpret conventionally. While currently available clinical data can be used in ML for this purpose, there exists the potential to discover new "biomarkers" that will enhance the effectiveness of ML in clinical decision making. Since the interaction of the immune system and cancer is a hallmark of tumor establishment and progression, one potential area for cancer biomarker discovery is through the investigation of cancer-related immune cell signatures. Hence, we hypothesize that blood immune cell signatures can act as a biomarker for cancer progression. Methods: To probe this, we have developed and tested a multiparameter cell-surface marker screening pipeline, using flow cytometry to obtain high-resolution systemic leukocyte population profiles that correlate with detection and characterization of several cancers in murine syngeneic tumor models. Results: We discovered a signature of several blood leukocyte subsets, the most notable of which were monocyte subsets, that could be used to train CATboost ML models to predict the presence and type of cancer present in the animals. Conclusions: Our findings highlight the potential utility of a screening approach to identify robust leukocyte biomarkers for cancer detection and characterization. This pipeline can easily be adapted to screen for cancer specific leukocyte markers from the blood of cancer patient.

CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4+ T cells.

As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency (PAD), analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene defects. CD57 marks dysfunctional T cells that have differentiated after antigenic stimulation. Indeed, while circulating CD57+ CD4+ T cells are normally rare, we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or blockade. We performed single-cell RNA-seq analysis of matched CD57+ CD4+ T cells from blood and tonsil samples. Circulating CD57+ CD4+ T cells (CD4cyt) exhibited a cytotoxic transcriptome similar to that of CD8+ effector cells, could kill B cells, and inhibited B-cell responses. CTLA4 restrained the formation of CD4cyt. While CD57 also marked an abundant subset of follicular helper T cells, which is consistent with their antigen-driven differentiation, this subset had a pre-exhaustion transcriptomic signature marked by TCF7, TOX, and ID3 expression and constitutive expression of CTLA4 and did not become cytotoxic even after CTLA4 inhibition. Thus, CD57+ CD4+ T-cell cytotoxicity and exhaustion phenotypes are compartmentalised between blood and germinal centers. CTLA4 is a key modifier of CD4+ T-cell cytotoxicity, and the pathological CD4cyt phenotype is accentuated by infection.

Building Capability and Capacity: The Establishment of an Oncology Unit in the Solomon Islands.

PURPOSE: To describe the establishment of an oncology unit at the National Referral Hospital (NRH) in the Solomon Islands, a low-income nation in the South Pacific. METHODS: A scoping visit was carried out in 2016 to assist in the development of coordinated cancer services and to establish a medical oncology unit at the NRH at the request of the Medical Superintendent. This was followed by an observership visit to Canberra by an NRH doctor training in oncology in 2017. After a request from the Solomon Islands Ministry of Health, the Australian Government Department of Foreign Affairs and Trade (DFAT) arranged an in-country multidisciplinary mission under the Royal Australasian College of Surgeons/Royal Australasian College of Physicians Pacific Islands Program to help in the commissioning of the NRH Medical Oncology Unit in September 2018. Staff training and education sessions were held. The team, with the assistance of an Australian Volunteers International Pharmacist, has helped the NRH staff to develop localized Solomon Islands Oncology Guidelines. Donated equipment and supplies have helped with the initial establishment of the service. A second DFAT Oncology mission visit was made in 2019 followed by two NRH oncology nurses visiting Canberra on observership later that year and support of the Solomon's doctor to pursue postgraduate education in cancer sciences. Ongoing mentorship and support has been maintained. RESULTS: The island nation now has a sustainable oncology unit delivering chemotherapy treatments and management of patients with cancer. CONCLUSION: A collaborative multidisciplinary team approach by professionals from the high-income country working with colleagues from the low-income nation with coordination of different stakeholders was the key to this successful initiative in improving cancer care.

Clinical predictors of survival in real world practice in stage IV melanoma.

BACKGROUND AND AIM: While studies continually identify new clinical prognostic factors in stage IV melanoma, the introduction of targeted and immunotherapies have revolutionised the prognosis of advanced melanoma since 2011. The study aims to investigate the prognostic significance of past and newly identified clinical factors in a contemporary cohort. METHODS: A retrospective analysis of The Canberra Hospital melanoma database identified 161 patients with Stage IV melanoma between 2011 and 2017. Survival was analysed by demographics and clinical factors with chi-square tests to determine significance. Logistic binary regression was performed to test the independence of the clinical factors on predicting the survival outcome. RESULTS: Overall, the 3-month, 6-month, 9-month, and 12-month stage IV melanoma survival rate of our cohort was 79%, 67%, 55%, and 45%, respectively. Age, sex, and BRAF mutation status were found to have no impact on survival, whereas M1d category of the American Joint Committee on Cancer (AJCC) staging (8th edition), neutrophil-lymphocyte ratio (NLR) >3, elevated serum LDH, more than three metastatic sites, brain metastases, poorer Eastern cooperative oncology group (ECOG) status were associated with poorer survival. Binary logistic regression test identified AJCC staging, NLR (cutoff score 3), LDH, and brain metastases as independent prognostic factors. CONCLUSION: Most clinical factors investigated in this study were found to have a statistically significant impact on survival, with AJCC (8th edition) staging M1a-M1d, NLR (cutoff score 3), LDH, and brain metastases identified as independent prognostic factors in stage IV melanoma from a contemporary cohort treated with targeted therapies and immunotherapies.

A Phase 1 Proof of Concept Study Evaluating the Addition of an LSD1 Inhibitor to Nab-Paclitaxel in Advanced or Metastatic Breast Cancer (EPI-PRIMED).

Objective: Lysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and cancer progression. The purpose of this study was to investigate the safety of combination, nab-paclitaxel and phenelzine, an irreversible LSD1 inhibitor in patients with metastatic breast cancer (mBC). Methods: Eligible patients with mBC were treated with nab-paclitaxel (100mg/m2) weekly for 3 weeks with one week break in a 28-day cycle. Dose escalation of phenelzine followed the Cumulative Cohort Design and phenelzine treatment commenced from day 2 of first cycle. Eleven patients were screened, and eligible patients were enrolled in cohorts with the dose of phenelzine ranging from 45mg to 90mg. Results: The Optimum Biological Dose was established at 60mg of phenelzine daily in combination with nab-paclitaxel and considered as the recommended phase 2 dose. Most (95%) of adverse events were grade 1 or 2 with two grade 3 events being diarrhea and neutropenia at 45mg and 60mg phenelzine respectively, with no unexpected toxicity/deaths. Commonly reported toxicities were fatigue (n=4,50%), dizziness (n=6,75%), neutropenia (n=3,37.5%), peripheral neuropathy (n=3,37.5%), diarrhea (n=2,25%), and hallucination (n=2,25%). After a median follow up of 113 weeks, all patients showed disease progression on trial with 4 patients being alive at the time of data cut off, including one patient with triple negative breast cancer. Median progression-free survival was 34 weeks. Significant inhibition of LSD1 and suppression of mesenchymal markers in circulating tumor cells were noted. Conclusion: Phenelzine in combination with nab-paclitaxel was well tolerated, without any unexpected toxicities in patients with mBC and demonstrated evidence of antitumor activity. For the first time, this proof-of-concept study showed in-vivo inhibition of LSD1 suppressed mesenchymal markers, which are known to facilitate generation of cancer stem cells with metastatic potential. Clinical Trial Registration: ClinicalTrials.Gov NCT03505528, UTN of U1111-1197-5518.

The Management of Unresectable, Advanced Gastrointestinal Stromal Tumours.

Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal tract mesenchymal tumours. Tyrosine kinase inhibitors (TKIs) have transformed the management of advanced GIST. Imatinib was the first TKI to gain approval as management for patients with advanced GIST, establishing a new standard of care. Since then, as a result of several trials including the GRID and INVICTUS studies, we now have five lines of approved targeted therapy, including imatinib, sunitinib, regorafenib, ripretinib and avapritinib for the treatment of unresectable, advanced GISTs. In this review, the Australasian Gastrointestinal Trials Group (AGITG) provide an overview of the key trials that have changed clinical practice, discuss the molecular drivers of GISTs, the importance of molecular testing and directing therapy according to molecular targets, as well as future strategies in the management of advanced GISTs.

Selective Targeting of Protein Kinase C (PKC)-θ Nuclear Translocation Reduces Mesenchymal Gene Signatures and Reinvigorates Dysfunctional CD8+ T Cells in Immunotherapy-Resistant and Metastatic Cancers.

Protein kinase C (PKC)-θ is a serine/threonine kinase with both cytoplasmic and nuclear functions. Nuclear chromatin-associated PKC-θ (nPKC-θ) is increasingly recognized to be pathogenic in cancer, whereas its cytoplasmic signaling is restricted to normal T-cell function. Here we show that nPKC-θ is enriched in circulating tumor cells (CTCs) in patients with triple-negative breast cancer (TNBC) brain metastases and immunotherapy-resistant metastatic melanoma and is associated with poor survival in immunotherapy-resistant disease. To target nPKC-θ, we designed a novel PKC-θ peptide inhibitor (nPKC-θi2) that selectively inhibits nPKC-θ nuclear translocation but not PKC-θ signaling in healthy T cells. Targeting nPKC-θ reduced mesenchymal cancer stem cell signatures in immunotherapy-resistant CTCs and TNBC xenografts. PKC-θ was also enriched in the nuclei of CD8+ T cells isolated from stage IV immunotherapy-resistant metastatic cancer patients. We show for the first time that nPKC-θ complexes with ZEB1, a key repressive transcription factor in epithelial-to-mesenchymal transition (EMT), in immunotherapy-resistant dysfunctional PD1+/CD8+ T cells. nPKC-θi2 inhibited the ZEB1/PKC-θ repressive complex to induce cytokine production in CD8+ T cells isolated from patients with immunotherapy-resistant disease. These data establish for the first time that nPKC-θ mediates immunotherapy resistance via its activity in CTCs and dysfunctional CD8+ T cells. Disrupting nPKC-θ but retaining its cytoplasmic function may offer a means to target metastases in combination with chemotherapy or immunotherapy.

Prediction models for venous thromboembolism in ambulatory adults with pancreatic and gastro-oesophageal cancer: protocol for systematic review and meta-analysis.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication of cancer. Pancreatic and gastro-oesophageal cancers are among malignancies that have the highest rates of VTE occurrence. VTE can increase cancer-related morbidity and mortality and disrupt cancer treatment. The risk of VTE can be managed with measures such as using anticoagulant drugs, although the risk of bleeding may be an impeding factor. Therefore, a VTE risk assessment should be performed before the start of anticoagulation in individual patients. Several prediction models have been published, but most of them have low sensitivity and unknown clinical applicability in pancreatic or gastro-oesphageal cancers. We intend to do this systematic review to identify all applicable published predictive models and compare their performance in those types of cancer. METHODS AND ANALYSIS: All studies in which a prediction model for VTE have been developed, validated or compared using adult ambulatory patients with pancreatic or gastro-oesphageal cancers will be identified and the reported predictive performance indicators will be extracted. Full text peer-reviewed journal articles of observational or experimental studies published in English will be included. Five databases (Medline, EMBASE, Web of Science, CINAHL and Cochrane) will be searched. Two reviewers will independently undertake each of the phases of screening, data extraction and risk of bias assessment. The quality of the selected studies will be assessed using Prediction model Risk Of Bias Assessment Tool. The results from the review will be used for a narrative information synthesis, and if the same models have been validated in multiple studies, meta-analyses will be done to pool the predictive performance measures. ETHICS AND DISSEMINATION: There is no need for ethics approval because the review will use previously peer-reviewed articles. The results will be published. PROSPERO REGISTRATION NUMBER: CRD42021253887.

Managing patients with advanced soft tissue sarcoma: Evolving landscape from an Australian perspective.

AIM: Despite lack of advances in the first-line systemic therapy, the overall survival (OS) has continued to improve in patients with advanced soft tissue sarcoma (STS) with the recent estimation of median OS at 20 months. Several systemic therapy options are available now for the second-line and beyond, with more treatment tailored to histology and molecular subtype. The aim of this retrospective study was to characterize current patterns of care in managing patients with advanced STS (aSTS) in Australia. METHODS: Sarcoma databases from 7 Australian sarcoma services were accessed to identify patients diagnosed with locally advanced inoperable and/or metastatic STS between January 1, 2010 and December 31, 2015. Baseline clinicopathological factors and initial treatment patterns were descriptively analyzed. For the Victorian cohort where treatment of aSTS and follow-up details were available, further exploratory analysis was conducted to determine the impact of patient and tumor characteristics and the use of palliative-intent treatment OS. RESULTS: Of 2261 cases of STS, 671 were deemed as aSTS. Two thirds were relapsed disease with a mean 1.9 years from initial diagnosis. Median age at diagnosis of aSTS was 59 years (18-95 years) and 56.3% was male. Histology classification revealed four main subtypes: undifferentiated pleomorphic sarcoma (UPS) (23.1%), leiomyosarcoma (18.2%), liposarcoma (12.8%), synovial sarcoma (8.2%), and other comprising 14 STS subtypes. For the Victorian cohort (N = 361), approximately 80% of patients accessed palliative-intent treatment of various modalities. Nearly 40% of patients underwent tumor-debulking surgery or metastasectomy, of which lung wedge resection was the most common (N = 83, 47.7%). A total of 438 palliative-intent radiotherapy treatments were delivered to 259 patients (71.7%), with the majority in the form of external beam radiotherapy. Palliative-intent systemic therapy was delivered to 51.5% of patients (N = 186), mostly (73%). Anthracycline-based therapy was the most commonly delivered therapy (N = 135, 72.6%). Approximately half of the patients in each line of therapy failed to proceed to the subsequent line of systemic therapy with 29.4% receiving three or more lines of therapy (N = 55). A total of 18.3% of patient (N = 34) participated in clinical trials or accessed off-label drugs. The median OS for the Victoria cohort was 15.4 months (95% confidence interval: 12.1, 18.2). The UPS histology subtype was associated with poorer OS, whereas receiving any modality of palliative-intent treatment conferred survival benefit. CONCLUSION: In Australia, aSTS is managed with diverse treatment approaches comprising various therapy modalities. Further work is planned in describing healthcare resource utilization and estimating costs by this patient cohort.

Patient demographics and management landscape of metastatic colorectal cancer in the third-line setting: Real-world data in an australian population.

BACKGROUND: Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden. AIMS: This analysis aims to explore real-world treatment landscape of metastatic colorectal cancer in the third-line setting. METHODS: We retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression. RESULTS: Out of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third-line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)-oxaliplatin combination was the most common choice (51%), followed by FP-irinotecan (15%), trifluridine/tipiracil (11%), mono-chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP-doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP-doublet (18%), mono-chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4-41.2), and median time on third-line treatment was 3 months (range 0.1-40). CONCLUSIONS: In real-world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients.

Australia and New Zealand's responsibilities in improving oncology services in the Asia-Pacific: A call to action.

AIM: To review the expected increasing demand for cancer services among low and middle-income countries (LMICs) in the Asia-Pacific (APAC), and to describe ways in which Australia and New Zealand (ANZ) can provide support to improve cancer outcomes in our region. METHODS: We first review the current and projected incidence of cancer within the APAC between 2018 and 2040, and the estimated demand for chemotherapy, radiotherapy and surgery. We then explore potential ways in which ANZ can increase regional collaborations to improve cancer outcomes. RESULTS: We identify 6 ways that ANZ can collaborate with LMICs to improve cancer care in the APAC through the ANZ Regional Oncology Collaboration Strategy: Increasing education and institutional collaborations in the APAC region through in-country training, twinning partnerships, observerships and formalised training programs in order to increase cancer care quality and capacity. Promoting and assisting in the establishment and maintenance of population-based cancer registries in LMICs. Increasing research capacity in LMICs through collaboration and promoting high quality global oncology research within ANZ. Engaging and training Australian and New Zealand clinicians in global oncology, increasing awareness of this important career path, and increasing health policy engagement. Increasing web-based endeavours through virtual tumour boards, web-based advocacy platforms and web-based teaching programs. Continuing to leverage for funding through professional bodies, government, industry, not-for-profit organisations and local hospital funds. CONCLUSION: We propose the creation of an Australian and New Zealand Interest Group to provide formalised and sustained collaboration between researchers, clinicians and stakeholders.

Identifying women at risk of weight gain after a breast cancer diagnosis: Results from a cohort of Australian women.

ISSUES ADDRESSED: This study aimed to identify risk factors associated with weight gain post a diagnosis of breast cancer in a cohort of Australian women. METHODS: In this retrospective clinical audit, objectively measured weight, age and menopause status, treatment type/s, grade, stage, oestrogen receptor and progesterone receptor (PR) status were extracted for 73 breast cancer patients from an ongoing breast cancer treatment quality assurance project. Weight gain or loss was classified as a body mass increase or decrease of ≥5% of weight at diagnosis. RESULTS: When compared to weight at diagnosis, 57% of patients maintained, 22% gained, and 21% lost weight at 24 months post-diagnosis. Factors associated with weight gain were a diagnosis of grade II (P < .001) or grade III (P < .001) compared to grade I breast cancer, and refusal of radiotherapy (P < .001). Factors associated with weight loss were being postmenopausal compared to premenopausal (P = .033), PR positive compared to PR negative (P < .001), refusal of chemotherapy (P < .001) and radiotherapy recommended (P < .001). CONCLUSIONS: The maintenance of weight in a majority of women in this cohort is a novel finding. Early identification of women at risk of weight gain post a breast cancer diagnosis can assist health professionals identify, and therefore assisting patients in the prevention and management of weight gain and associated sequela. Investigating the weight-related communications between a patient and specialist, their access to allied health professionals and social support may assist in understanding the overall positive changes in this cohort.

Models for predicting venous thromboembolism in ambulatory patients with lung cancer: a systematic review protocol.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients with cancer and has a determining role in the disease prognosis. The risk is significantly increased with certain types of cancer, such as lung cancer. Partly due to difficulties in managing haemorrhage in outpatient settings, anticoagulant prophylaxis is only recommended for ambulatory patients at high risk of VTE. This requires a precise VTE risk assessment in individual patients. Although VTE risk assessment models have been developed and updated in recent years, there are conflicting reports on the effectiveness of such risk prediction models in patient management. The aim of this systematic review is to gain a better understanding of the available VTE risk assessment tools for ambulatory patients with lung cancer and compare their predictive performance. METHODS AND ANALYSIS: A systematic review will be conducted using MEDLINE, Cochrane Library, CINAHL, Scopus and Web of Science databases from inception to 30 September 2021, to identify all reports published in English describing VTE risk prediction models which have included adult ambulatory patients with primary lung cancer for model development and/or validation. Two independent reviewers will conduct article screening, study selection, data extraction and quality assessment of the primary studies. Any disagreements will be referred to a third researcher to resolve. The included studies will be assessed for risk of bias and applicability. The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies will be used for data extraction and appraisal. Data from similar studies will be used for meta-analysis to determine the incidence of VTE and the performance of the risk models. ETHICS AND DISSEMINATION: Ethics approval is not required. We will disseminate the results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021245907.