Patient Priorities Concerning Treatment Decisions for Advanced Neuroendocrine Tumors Identified by Discrete Choice Experiments.

BACKGROUND: Patients with advanced neuroendocrine tumors (NETs) have multiple treatment options. Ideally, treatment decisions are shared between physician and patient; however, previous studies suggest that oncologists and patients place different value on treatment attributes such as adverse event (AE) rates. High-quality information on NET patient treatment preferences may facilitate patient-centered decision making by helping clinicians understand patient priorities. METHODS: This study used 2 discrete choice experiments (DCE) to elicit preferences of NET patients regarding advanced midgut and pancreatic NET (pNET) treatments. The DCEs used the "potentially all pairwise rankings of all possible alternatives" (PAPRIKA) method. The primary objective was to determine relative utility rankings for treatment attributes, including progression-free survival (PFS), treatment modality, and AE rates. Ranking of attribute profiles matching specific treatments was also determined. Levels for treatment attributes were obtained from randomized clinical trial data of NET treatments. RESULTS: One hundred and 10 participants completed the midgut NET DCE, and 132 completed the pNET DCE. Longer PFS was the highest ranked treatment attribute in 64.5% of participants in the midgut NET DCE, and in 59% in the pNET DCE. Approximately, 40% of participants in both scenarios prioritized lower AE rates or less invasive treatment modalities over PFS. Ranking of treatment profiles in the midgut NET scenario identified 60.9% of participants favoring peptide receptor radionuclide therapy (PRRT), and 30.0% somatostatin analogue dose escalation. CONCLUSION: NET patients have heterogeneous priorities when choosing between treatment options based on the results of 2 independent DCEs. These results highlight the importance of shared decision making for NET patients.

Attitudes towards COVID-19 vaccination in adults with haematological malignancies.

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-effects 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.

Differences in cancer clinical trial activity and trial characteristics at metropolitan and rural trial sites in Victoria, Australia.

OBJECTIVE: Cancer clinical trials (CCTs) provide access to emerging therapies and extra clinical care. We aimed to describe the volume and characteristics of CCTs available across Victoria, Australia, and identify factors associated with rural trial location. METHODS: Quantitative analysis of secondary data from Cancer Council Victoria's Clinical Trials Management Scheme dataset. DESIGN: A cross-sectional study design was used. SETTING: CCTs were available Victoria-wide in 2018. PARTICIPANTS: There were 1669 CCTs and 5909 CCT participants. MAIN OUTCOME MEASURES: Rural CCT location was assessed as a binary variable with categories of 'yes' (modified Monash [MM] categories 2-7) and 'no' (MM category 1). MM categories were determined from postcodes. The highest ('least rural') MM category was used for postcodes with multiple MM categories. RESULTS: Of 1669 CCTs, 168 (10.1%) were conducted in rural areas. Of 5909 CCT participants, 315 (5.3%) participated in rural CCTs. There were 526 CCTs (31.5%) with 1907 (32.3%) newly enrolled participants. Of 1892 newly enrolled participants with postcode data, 488 (25.8%) were rural residents. Of them, 368 (75.4%) participated in metropolitan CCTs. In a multivariable logistic regression analysis for all 1669 CCTs, odds of a rural rather than metropolitan CCT location were significantly (p-value <0.05) lower for early-phase than late-phase trials and non-solid than solid tumour trials but significantly (p-value <0.05) higher for non-industry than industry-sponsored trials. CONCLUSIONS: In Victoria, 10% of CCTs are at rural sites. Most rural-residing CCT participants travel to metropolitan sites, where there are more late-phase, non-solid-tumour and industry-sponsored trials. Approaches to increase the volume and variety of rural CCTs should be considered.

Workforce challenges across Victorian medical oncology services.

BACKGROUND: Cancer incidence is growing, with increasing treatment options and durations. This has led to an increase workload on the current oncology workforce. The global pandemic has increased this pressure further. AIMS: To determine the current medical oncology workforce in Victoria, current shortfalls and future anticipated shortfalls beyond the COVID-19 pandemic. METHODS: A self-reported, cross-sectional observational study of all current adult Victorian cancer services in June 2020 examining workforce, workload and early effects of the COVID-19 pandemic. RESULTS: The current average workload of 242 new patients per full-time equivalent consultant in medical oncology across Victoria. This is higher than optimal to deliver a safe and efficient cancer service. The significant variation in workforce between sites highlights the areas in need of most urgent resource allocation. Use of safe prescribing practises such as electronic chemotherapy prescribing are not universal but urgently needed. CONCLUSIONS: The medical oncology workforce in Victoria is inadequate to meet current and future demands. This needs to be addressed urgently to avoid an adverse impact on cancer measures and quality standards. Better, standardised data collection is needed to allow for ongoing measures of workforce activity. Novel workforce solutions will also need to be implemented in the short and medium term in the face of global workforce shortages.

The Disease Influenced Vaccine Acceptance Scale-Six (DIVAS-6): Validation of a Measure to Assess Disease-Related COVID-19 Vaccine Attitudes and Concerns.

Patients with underlying comorbidities are particularly vulnerable to poor outcomes from SARS-CoV-2 infection. Despite the context-specific nature of vaccine hesitancy, there are currently no scales that incorporate disease or treatment-related hesitancy factors. We developed a six-item scale assessing disease-related COVID-19 vaccine attitudes and concerns (The Disease Influenced COVID-19 Vaccine Acceptance Scale-Six: DIVAS-6). A survey incorporating the DIVAS-6 was completed by 4683 participants with severe and/or chronic illness (3560 cancer; 842 diabetes; 281 multiple sclerosis (MS)). The survey included the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale, demographic, disease-related, and vaccination status questions. The six items loaded onto two factors (disease complacency and vaccine vulnerability) using exploratory factor analysis and exploratory structural equation modeling. The two factors were internally consistent. Measurement invariance analysis showed the two factors displayed psychometric equivalence across the patient groups. Each factor significantly correlated with the two Oxford COVID-19 Vaccine scales, showing convergent validity. The summary score showed acceptable ability to discriminate vaccination status across diseases, with the total sample providing good-to-excellent discriminative ability. The DIVAS-6 has two factors measuring COVID-19 vaccine attitudes and concerns relating to potential complications of SARS-CoV-2 infection due to underlying disease (disease complacency) and vaccine-related impact on disease progression and treatment (vaccine vulnerability). This is the first validated scale to measure disease-related COVID-19 vaccine concerns and has been validated in people with cancer, diabetes, and MS. It is quick to administer and should assist with guiding information delivery about COVID-19 vaccination in medically vulnerable populations.

Atherosclerotic Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. METHOD: A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. RESULTS: Over a median follow-up of 3.4 years (2.8-4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79-8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87-9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. CONCLUSIONS: History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment.

Protocol for SARS-CoV-2 post-vaccine surveillance study in Australian adults and children with cancer: an observational study of safety and serological and immunological response to SARS-CoV-2 vaccination (SerOzNET).

BACKGROUND: Cancer is associated with excess morbidity and mortality from coronavirus disease 2019 (COVID-19) following infection by the novel pandemic coronavirus SARS-CoV-2. Vaccinations against SARS-CoV-2 have been rapidly developed and proved highly effective in reducing the incidence of severe COVID-19 in clinical trials of healthy populations. However, patients with cancer were excluded from pivotal clinical trials. Early data suggest that vaccine response is less robust in patients with immunosuppressive conditions or treatments, while toxicity and acceptability of COVID-19 vaccines in the cancer population is unknown. Unanswered questions remain about the impact of various cancer characteristics (such as treatment modality and degree of immunosuppression) on serological response to and safety of COVID-19 vaccinations. Furthermore, as the virus and disease manifestations evolve, ongoing data is required to address the impact of new variants. METHODS: SerOzNET is a prospective observational study of adults and children with cancer undergoing routine SARS-CoV-2 vaccination in Australia. Peripheral blood will be collected and processed at five timepoints (one pre-vaccination and four post-vaccination) for analysis of serologic responses to vaccine and exploration of T-cell immune correlates. Cohorts include: solid organ cancer (SOC) or haematological malignancy (HM) patients currently receiving (1) chemotherapy, (2) immune checkpoint inhibitors (3) hormonal or targeted therapy; (4) patients who completed chemotherapy within 6-12 months of vaccination; (5) HM patients with conditions associated with hypogammaglobulinaemia or immunocompromise; (6) SOC or HM patients with allergy to PEG or polysorbate 80. Data from healthy controls already enrolled on several parallel studies with comparable time points will be used for comparison. For children, patients with current or prior cancer who have not received recent systemic therapy will act as controls. Standardised scales for quality-of-life assessment, patient-reported toxicity and vaccine hesitancy will be obtained. DISCUSSION: The SerOzNET study was commenced in June 2021 to prospectively study immune correlates of vaccination in specific cancer cohorts. The high proportion of the Australian population naïve to COVID-19 infection and vaccination at study commencement has allowed a unique window of opportunity to study vaccine-related immunity. Quality of life and patient-reported adverse events have not yet been reported in detail post-vaccination for cancer patients. Trial registration This trial is registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001004853. Submitted for registration 25 June 2021. Registered 30 July 2021 (Retrospectively registered). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382281&isReview=true.

MONARCC: a randomised phase II study of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first-line therapy for RAS and BRAF wildtype metastatic colorectal cancer: a study by the Australasian Gastrointestinal Trials Group (AGITG).

BACKGROUND: Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a "lighter" treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population. METHODS/DESIGN: MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS/BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies. DISCUSSION: MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12618000233224 , prospectively registered 14 February 2018.

Oral paclitaxel with encequidar compared to intravenous paclitaxel in patients with advanced cancer: A randomised crossover pharmacokinetic study.

AIMS: Paclitaxel is a widely used anti-neoplastic agent but has low oral bioavailability due to gut extrusion by P-glycoprotein (P-gp). Oral paclitaxel could be more convenient, less resource intensive, and more tolerable than intravenous administration. Encequidar (HM30181A) is a novel, minimally absorbed gut-specific P-gp inhibitor. We tested whether administration of oral paclitaxel with encequidar (oPac+E) achieved comparable AUC to intravenous paclitaxel (IVP) 80 mg/m2 . METHODS: We conducted a multi-centre randomised crossover study with two treatment periods. Patients (pts) with advanced cancer received either oral paclitaxel 615 mg/m2 divided over 3 days and encequidar 15 mg orally 1 hour prior, followed by IVP 80 mg/m2 , or the reverse sequence. PK blood samples were taken up to Day 9 for oPac+E and Day 5 for IVP. RESULTS: Forty-two patients were enrolled; 35 completed both treatment periods. AUC0-∞ was 5033.5 ± 1401.1 ng.h/mL for oPac+E and 5595.9 ± 1264.1 ng.h/mL with IVP. The geometric mean ratio (GMR) for AUC was 89.50% (90% CI 83.89-95.50). Mean absolute bioavailability of oPac+E was 12% (CV% = 23%). PK parameters did not change meaningfully after 4 weeks administration of oPac+E in an extension study. G3 treatment-emergent adverse events occurred in seven (18%) pts with oPac+E and two (5%) with IVP. Seventy-five per cent of patients preferred oPac+E over IVP. CONCLUSIONS: GMR for AUC was within the predefined acceptable range of 80-125% for demonstrating equivalence. oPac+E is tolerable and there is no evidence of P-gp induction with repeat administration. With further study, oPac+E could be an alternative to IVP.

Developing clinical indicators for oncology: the inaugural cancer care indicator set for the Australian Council on Healthcare Standards.

INTRODUCTION: The Australian Council on Healthcare Standards (ACHS) sponsored an expert-led, consensus-driven, four-stage process, based on a modified Delphi methodology, to determine a set of clinical indicators as quality measures of cancer service provision in Australia. This was done in response to requests from institutional health care providers seeking accreditation, which were additional and complementary to the existing radiation oncology set. The steering group members comprised multidisciplinary key opinion leaders and a consumer representative. Five additional participants constituted the stakeholder group, who deliberated on the final indicator set. METHODS AND RECOMMENDATIONS: An initial meeting of the steering group scoped the high level nature of the desired set. In stage 2, 65 candidate indicators were identified by a literature review and a search of international metrics. These were ranked by survey, based on ease of data accessibility and collectability and clinical relevance. The top 27 candidates were debated by the stakeholder group and culled to a final set of 16 indicators. A user manual was created with indicators mapped to clinical codes. The indicator set was ratified by the Clinical Oncology Society of Australia and is now available for use by health care organisations participating in the ACHS Clinical Indicator Program. This inaugural cancer clinical indicator set covers high level assessment of various critical processes in cancer service provision in Australia. Regular reviews and updates will ensure usability. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This is the inaugural indicator set for cancer care for use across Australia and internationally under the ACHS Clinical Indicator Program. Multidisciplinary involvement through a modified Delphi process selected indicators representing both generic and specific aspects of care across the cancer journey pathway and will provide a functional tool to compare health care delivery across multiple settings. It is anticipated that this will drive continual improvement in cancer care provision.

AMTRA: a multicentered experience of a web-based monitoring and tailored toxicity management system for cancer patients.

BACKGROUND: Technology-based interventions are increasingly being introduced in routine clinical cancer care. There is a need for reliable systems to monitor treatment-related toxicity in a standardized manner. Such electronic tools bridge the gap in providing quality home-based monitoring. METHODS: From July 2017 to December 2017, we performed a multicentered, non-randomized prospective cohort analysis with patients who were receiving routine chemotherapy for various solid tumors, using a web-based patient-reported toxicity registration, management, and intervention system called AMTRA (ambulatory Monitoring of cancer Therapy using an interactive Application) linked to the homecare nursing organization Remedus®. Twelve common toxicities plus pain and two biometrics could be registered daily or more frequently as required. These were processed centrally to generate tailored advice for lesser symptoms or a phone call from a dedicated nurse in case of severe or prolonged toxicity. A compliance tool to monitor oral therapies was incorporated in the system. RESULTS: One hundred sixty-eight patients (92%) were enrolled, with 31,514 registrations analyzed. One hundred eight patients reported severe toxicity (> 1461 registrations), resulting in 102 clinical interventions ranging from self-management advice, supplemental consultations to hospitalizations. Compliance to oral chemotherapy was high using AMTRA with a median of 98.7% (95 confidence interval (CI) [93.5-100.0%]). Seventy-nine percent of patients stated that the availability of AMTRA self-reports was useful in communication with the care provider, while 75% felt more in control while managing their treatment. CONCLUSIONS: The application of an interactive PRO-system in routine symptom management of cancer patients allowed standardized documentation of toxicities and recorded a high compliance with oral treatment. It allows for rapid interaction for toxicities and cancer-related symptoms experienced at home.

Anti-cancer therapy made easier: a 25-year update.

In 1993, the Internal Medicine Journal published 'Chemotherapy made easier', outlining developments in supportive care of patients undergoing chemotherapy. This described the contemporary state of anti-emetics, colony stimulating factors, cardiac toxicity, neurotoxicity, development of drug analogues and venous access devices. Twenty-five years later, we update the measures that improve the tolerability of the plethora of new anti-cancer therapies, which have extended well beyond traditional chemotherapy agents to include immunotherapy and targeted therapies. Optimisation of supportive care is paramount to allow safe delivery with the least possible impact on quality of life of these new treatments, many of which have resulted dramatically improved outcomes across multiple cancer types. This state of the art update summarises advances in supportive care therapies relating to improving the patient experience during and after anti-cancer treatment, including new anti-emetics, hair preservation techniques, bone marrow support and improved venous access devices; the ongoing challenge of neurotoxicity; and the advent of multidisciplinary sub-specialised fields such as cardio-oncology and oncofertility. Supportive care medications for immuno-oncology therapies is a new section; these highly effective (although not universally so) agents were a mere illusion in 1993.

Medical Oncology Group of Australia position statement: COVID-19 vaccination in patients with solid tumours.

People with cancer are vulnerable to increased morbidity and mortality from the coronavirus disease 2019 (COVID-19). COVID-19 vaccination is key to protecting the population of people with cancer from adverse outcomes of SARS-CoV-2 infection. The Medical Oncology Group of Australia aimed to address the considerations around COVID-19 vaccination in people with cancer, in particular, safety and efficacy of vaccination. The assessment of patients with generalised allergic reaction to anti-cancer therapy containing vaccine components and practical implementation of vaccination of people on active anti-cancer therapy are also discussed.

The experiences, attitudes and understanding of research amongst medical students at an Australian medical school.

BACKGROUND: Research engagement plays an integral role in developing clinicians that practice effective, evidence-based medicine. Research participation by clinicians, however, is declining. Given the link between research during medical school and future research output, promotion of medical student research is one avenue by which this shortage can be addressed. Student research attitudes and participation in Australia are not well-documented in the literature. This study therefore aims to investigate research practices, motivators, and barriers amongst Australian medical students in order to determine whether there is a need for further integration of research within Australian medical school curriculums. METHODS: A cross-sectional study design was used to explore research experience and attitudes, as well as the enablers and barriers to research amongst students enrolled in all years of the five-year medical course at Monash University. A questionnaire was created by combining questions from several surveys on medical student research and comprised Likert scales, multiple choice options and free-text responses assessing research experience, attitudes, motivators, and barriers. RESULTS: Seven hundred and four respondents (69.4% female; survey response rate 36.7%) reported variable research experience and interest. Less than half of the cohort (n = 296; 44.9%) had contributed to a research project. Increasing employability for specialty training programs was the primary motivating factor (n = 345; 51.9%) for pursuing research, with only 20.5% (n = 136) citing an interest in academia as a motivator. Time constraints (n = 460; 65.3%) and uncertainty surrounding how to find research opportunities (n = 449; 63.8%) were the most common barriers to research. CONCLUSIONS: Medical students at Monash University are interested in but have limited experience with research. Students are, however, primarily motivated by the prospect of increasing employability for specialist training; medical schools should therefore focus on encouraging intrinsic motivation for pursuing research. Greater integration of research education and opportunities within medical school curricula may also be required to provide students with the skills necessary to both pursue research and practice evidence-based medicine.

Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial.

Importance: Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven. Objective: To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. Design, Setting, and Participants: A double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized. Interventions: Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. Main Outcomes and Measures: The co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). Results: Of 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group. Conclusions and Relevance: Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001403426.

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer.

BACKGROUND: The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. METHODS: Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). RESULTS: The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407). CONCLUSIONS: The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.

Medical Oncologists' Perspectives on How the Results of the IDEA Collaboration Impact the Adjuvant Treatment of Stage III Colon Cancer.

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy are noninferior to 6 months. Our study objectives were to characterize medical oncologists' perspectives toward the results of the IDEA collaboration and to evaluate how IDEA impacted prescribing patterns of adjuvant FOLFOX and CAPOX in colon cancer. MATERIALS AND METHODS: A list of questions developed by four medical oncologists regarding IDEA results were formulated and distributed online to gastrointestinal medical oncologists globally. Descriptive statistics and chi-square tests were used to summarize information. RESULTS: Of 174 responses, 145 were complete and analyzed. Responses were obtained globally from South America (53%); the U.S. and Canada (28%); Europe, Australia, and New Zealand (12%); and Asia (7%). Most clinicians (98%) were aware of the IDEA study. Prior to IDEA, clinicians preferred FOLFOX over CAPOX (81% vs. 19%). Subsequent to IDEA, 55% of clinicians preferred CAPOX over FOLFOX (odds ratio, 5.0; 95% confidence interval, 3.0-8.5; p < .01 compared with pre-IDEA). Two thirds (68%) of responders tailored duration of adjuvant therapy based on risk stratification. Most oncologists (76%) were more willing to discontinue oxaliplatin early if toxicities develop after the results of IDEA. Half of responders (50%) found that IDEA increased their confidence in decision making for adjuvant treatment; 36% were unchanged, and 15% indicated decreased confidence. Less than half (48%) were comfortable communicating the study results and the concept of a noninferiority trial with patients. CONCLUSION: IDEA appears to have shifted clinician preference from FOLFOX to CAPOX for adjuvant therapy, and most clinicians now use a risk-stratified approach in determining duration of adjuvant therapy. Patient education resources may facilitate better communication of IDEA results to patients. IMPLICATIONS FOR PRACTICE: This global survey illustrates that most gastrointestinal medical oncologists now use a risk-stratified approach for determining the duration of adjuvant chemotherapy for stage III colon cancer. Clinicians are five times more likely to choose CAPOX over FOLFOX after the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration results.

Towards new models of cancer care in Australia: lessons from Victoria's response to the COVID-19 pandemic.

In response to the COVID-19 pandemic, the Department of Health and Human Services Victoria (DHHS), the Monash Partners Comprehensive Cancer Consortium (MPCCC) and Victorian Comprehensive Cancer Centre (VCCC) pooled their combined infrastructure to establish the Victorian COVID-19 Cancer Network (VCCN) backed by a Taskforce of expert members. In a few short months, this state-wide clinical network implemented a number of new models of care including clinics to manage acutely presenting cancer patients away from emergency departments, chemotherapy in the home, telehealth models and addressing sustainability of clinical trials.

Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence.

We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York's and 17% of Sydney's population are immunosuppressed. The highest smallpox infection rates were in persons 0-19 years of age, but the highest death rates were in those >45 years of age. Because of the low level of residual vaccine immunity, immunosuppression was more influential than vaccination on death and infection rates in our model. Despite widespread smallpox vaccination until 1980 in New York, smallpox outbreak severity appeared worse in New York than in Sydney. Immunosuppression is highly prevalent and should be considered in future smallpox outbreak models because excluding this factor probably underestimates death and infection rates.

SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer.

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULTS: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSIONS: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.