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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.
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Genomics , Neoplasms , Precision Medicine , Humans , Precision Medicine/methods , Neoplasms/genetics , Genomics/methods , Australia , Health Services Accessibility , Medical Oncology/methods , Genetic Testing/methodsABSTRACT
Background: This study explored vaccination hesitancy, diabetes-specific COVID-19 vaccination concerns, and whether they predicted vaccination uptake in people with diabetes. Methods: Quantitative, cross-sectional, and predictive approaches were used. An online survey was conducted with people with diabetes attending four Australian health services, using convenience sampling (n = 842). The survey data collected included clinico-demographic characteristics, COVID-19 vaccine hesitancy, and attitudes around COVID-19 vaccine confidence and complacency. Clinico-demographic characteristics that predicted vaccination status, vaccine hesitancy, and vaccine-related attitudes were identified using regression analyses. Results: Most participants received at least one COVID-19 vaccine dose. Younger age and type 1 diabetes were associated with lower vaccination status, and they were partially mediated through higher vaccine hesitancy. Younger age and English as a dominant language were associated with higher negative attitudes towards speed of vaccine development. Conclusions: Despite an overall high vaccination rate, general and diabetes-specific COVID-19 vaccine concerns are a barrier to uptake for some people with diabetes, particularly in those who are younger or have type 1 diabetes. A detailed understanding of concerns for particular subgroups can help tailor information to increase vaccine acceptance, particularly in the context of requiring booster doses.
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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.
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OBJECTIVES: We aimed to evaluate the activity of selinexor, an oral selective inhibitor of nuclear export, in patients with recurrent or metastatic salivary gland tumors (SGT). METHODS: GEMS-001 is an open-label Phase 2 study for patients with recurrent or metastatic SGT with two parts. In Part 1 of the protocol, patients had tumor samples profiled with targeted next generation sequencing as well as immunohistochemistry for androgen receptor, HER-2 and ALK. For Part 2, patients with no targeted therapies available were eligible to receive selinexor 60 mg given twice weekly every 28 days. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival (PFS) and prevalence of druggable alterations across SGT. RESULTS: One hundred patients were enrolled in GEMS-001 and underwent genomic and immunohistochemistry profiling. A total of 21 patients who lacked available matched therapies were treated with selinexor. SGT subtypes (WHO classification) included adenoid cystic carcinoma (n = 10), salivary duct carcinoma (n = 3), acinic cell carcinoma (n = 2), myoepithelial carcinoma (n = 2), carcinoma ex pleomorphic adenoma (n = 2) and other (n = 2). Of 18 evaluable patients, stable disease (SD) was observed in 17 patients (94%) (SD ≥6 months in 7 patients (39%)). However, no objective responses were observed. The median PFS was 4.9 months (95% confidence interval, 3.4-10). The most common treatment-related Grade 1-2 adverse events were nausea [17 patients (81%)], fatigue [16 patients (76%)], and dysgeusia [12 patients (57%)]. Most common treatment-related Grade 3-4 adverse events were hyponatremia [3 patients (14%)], neutrophil count decrease [3 patients (14%)] and cataracts [2 patients (10%)]. No treatment-related deaths were observed. CONCLUSIONS: Although tumor reduction was observed across participants, single agent selinexor anti-tumor activity was limited.
Subject(s)
Carcinoma, Acinar Cell , Salivary Gland Neoplasms , Humans , Salivary Gland Neoplasms/drug therapy , Salivary Gland Neoplasms/pathology , Hydrazines/adverse effects , Triazoles/adverse effectsABSTRACT
BACKGROUND: We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). METHODS: This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1-21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. RESULTS: In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses. CONCLUSIONS: Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. CLINICAL TRIAL REGISTR ATION: Clinicaltrials.gov (NCT03475251).
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Colonic Neoplasms , Rectal Neoplasms , Humans , Pyridines , Phenylurea Compounds , Colonic Neoplasms/drug therapy , Rectal Neoplasms/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
PURPOSE: The Asia-Pacific (APAC) region is a major focus for multinational clinical trials, although its cultural, linguistic, economic, and regulatory diversity pose significant challenges for trial conduct, particularly for academic clinical trials. METHODS: We describe our experience running the investigator-initiated phase III randomized, fully accrued, Aspirin for Dukes C and high-risk Dukes B Colorectal cancer trial (ASCOLT, ClinicalTrials.gov identifier: NCT00565708, N = 1,587), studying the benefit of aspirin in resected high-risk colorectal cancer. ASCOLT opened in 2008 and is the first large academic adjuvant trial fully conducted in the APAC region. Centrally coordinated by the Trial Management Team at the National Cancer Centre Singapore, it has involved 74 sites across 12 APAC countries/regions, including five middle-income countries. RESULTS: Challenges encountered included regulatory complexity, communication and logistical barriers, limited funding and resources, disparate experience and infrastructure across sites, recruitment holds because of changes in local laws, patient attrition, and disruptions caused by the COVID-19 pandemic. Over 100 contracts and 49 ethics board reviews were required, contributing to a lengthy prestudy preparation time of 2 years and start-up times of approximately 6 months per site. Some of the mitigating actions included engaging local cooperative groups (eg, the Australasian Gastro-Intestinal Trials Group in Australia and New Zealand) and seven contract research organizations to manage sites, regular communication with the central team, transition to electronic data management, and a centralized drug-dispensing system. CONCLUSION: To ensure an efficient and patient-centered clinical trials environment in the APAC region and sustained growth, we suggest coordinated approaches to harmonize regulatory processes, APAC academic oncology trials consortia to streamline processes and provide governance, and ongoing commitment from governments, funding agents, and industry.
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COVID-19 , Colorectal Neoplasms , Humans , Pandemics , Asia/epidemiology , Colorectal Neoplasms/therapy , Aspirin/therapeutic useABSTRACT
BACKGROUND: Some patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) respond poorly to anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) treatments. Combination with other agents may improve the outcomes. This open-label, multicenter, phase 1b trial investigated the combination of sitravatinib, a spectrum-selective tyrosine kinase inhibitor, plus anti-PD-1 antibody tislelizumab. METHODS: Patients with locally advanced/metastatic NSCLC were enrolled (Cohorts A, B, F, H, and I; N=22-24 per cohort). Cohorts A and F included patients previously treated with systemic therapy, with anti-PD-(L)1-resistant/refractory non-squamous (cohort A) or squamous (cohort F) disease. Cohort B included patients previously treated with systemic therapy, with anti-PD-(L)1-naïve non-squamous disease. Cohorts H and I included patients without prior systemic therapy for metastatic disease, no prior anti-PD-(L)1/immunotherapy, with PD-L1-positive non-squamous (cohort H) or squamous (cohort I) histology. Patients received sitravatinib 120 mg orally one time per day plus tislelizumab 200 mg intravenously every 3 weeks, until study withdrawal, disease progression, unacceptable toxicity, or death. The primary endpoint was safety/tolerability among all treated patients (N=122). Secondary endpoints included investigator-assessed tumor responses and progression-free survival (PFS). RESULTS: Median follow-up was 10.9 months (range: 0.4-30.6). Treatment-related adverse events (TRAEs) occurred in 98.4% of the patients, with ≥Grade 3 TRAEs in 51.6%. TRAEs led to discontinuation of either drug in 23.0% of the patients. Overall response rate was 8.7% (n/N: 2/23; 95% CI: 1.1% to 28.0%), 18.2% (4/22; 95% CI: 5.2% to 40.3%), 23.8% (5/21; 95% CI: 8.2% to 47.2%), 57.1% (12/21; 95% CI: 34.0% to 78.2%), and 30.4% (7/23; 95% CI: 13.2% to 52.9%) in cohorts A, F, B, H, and I, respectively. Median duration of response was not reached in cohort A and ranged from 6.9 to 17.9 months across other cohorts. Disease control was achieved in 78.3-90.9% of the patients. Median PFS ranged from 4.2 (cohort A) to 11.1 months (cohort H). CONCLUSIONS: In patients with locally advanced/metastatic NSCLC, sitravatinib plus tislelizumab was tolerable for most patients, with no new safety signals and overall safety profiles consistent with known profiles of these agents. Objective responses were observed in all cohorts, including in patients naïve to systemic and anti-PD-(L)1 treatments, or with anti-PD-(L)1 resistant/refractory disease. Results support further investigation in selected NSCLC populations. TRIAL REGISTRATION NUMBER: NCT03666143.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Crocus , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , B7-H1 Antigen , Crocus/metabolism , Lung Neoplasms/drug therapyABSTRACT
Background: People with chronic illnesses have increased morbidity and mortality associated with COVID-19 infection. The influence of a person's serious and/or comorbid chronic illness on COVID-19 vaccine uptake is not well understood. Aim: To undertake an in-depth exploration of factors influencing COVID-19 vaccine uptake among those with various serious and/or chronic diseases in the Australian context, using secondary data analysis of a survey study. Methods: Adults with cancer, diabetes and multiple sclerosis (MS) were recruited from 10 Australian health services to undertake a cross-sectional online survey (30 June to 5 October 2021) about COVID-19 vaccine uptake, vaccine hesitancy, confidence and complacency and disease-related decision-making impact. Free-text responses were invited regarding thoughts and feelings about the interaction between the participant's disease, COVID-19, and vaccination. Qualitative thematic analysis was undertaken using an iterative process and representative verbatim quotes were chosen to illustrate the themes. Results: Of 4683 survey responses (cancer 3560, diabetes 842, and MS 281), 1604 (34.3%) included free-text comments for qualitative analysis. Participants who provided these were significantly less likely to have received a COVID-19 vaccination than those who did not comment (72.4% and 86.2%, respectively). People with diabetes were significantly less likely to provide free-text comments than those with cancer or MS (29.0%, 35.1% and 39.9%, respectively). Four key themes were identified from qualitative analysis, which were similar across disease states: (1) having a chronic disease heightened perceived susceptibility to and perceived severity of COVID-19; (2) perceived impact of vaccination on chronic disease management and disease-related safety; (3) uncertain benefits of COVID-19 vaccine; and (4) overwhelming information overload disempowering patients. Conclusions: This qualitative analysis highlights an additional layer of complexity related to COVID-19 vaccination decision making in people with underlying health conditions. Appreciation of higher susceptibility to severe COVID-19 outcomes appears to be weighed against uncertain impacts of the vaccine on the progression and management of the comorbid disease. Interactions by clinicians addressing individual factors may alleviate concerns and maximise vaccine uptake in people with significant underlying health conditions.
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BACKGROUND: Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors. METHODS: Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted >28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed. RESULTS: No DLTs occurred in parts A (n=18) or B (n=85). Grade 3-5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35). CONCLUSIONS: Intravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy. TRIAL REGISTRATION NUMBER: NCT02043665.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Oncolytic Viruses , Male , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/adverse effectsABSTRACT
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.
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BACKGROUND: Vaccination is the cornerstone of the global public health response to the COVID-19 pandemic. Excess morbidity and mortality of COVID-19 infection is seen in people with cancer. COVID-19 vaccine hesitancy has been observed in this medically vulnerable population, although associated attitudes and beliefs remain poorly understood. METHODS: An online cross-sectional survey of people with solid organ cancers was conducted through nine health services across Australia. Demographics, cancer-related characteristics and vaccine uptake were collected. Perceptions and beliefs regarding COVID-19 vaccination were assessed using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-6. RESULTS: Between June and October 2021, 2691 people with solid organ cancers completed the survey. The median age was 62.5 years (SD = 11.8; range 19-95), 40.9% were male, 71.3% lived in metropolitan areas and 90.3% spoke English as their first language. The commonest cancer diagnoses were breast (36.6%), genitourinary (18.6%) and gastrointestinal (18.3%); 59.2% had localized disease and 56.0% were receiving anti-cancer therapy. Most participants (79.7%) had at least one COVID-19 vaccine dose. Vaccine uptake was higher in people who were older, male, metropolitan, spoke English as a first language and had a cancer diagnosis for more than six months. Vaccine hesitancy was higher in people who were younger, female, spoke English as a non-dominant language and lived in a regional location, and lower in people with genitourinary cancer. Vaccinated respondents were more concerned about being infected with COVID-19 and less concerned about vaccine safety and efficacy. CONCLUSIONS: People with cancer have concerns about acquiring COVID-19, which they balance against vaccine-related concerns about the potential impact on their disease progress and/or treatment. Detailed exploration of concerns in cancer patients provides valuable insights, both for discussions with individual patients and public health messaging for this vulnerable population.
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BACKGROUND: Insomnia and fatigue symptoms are common in breast cancer. Active cancer treatment, such as chemotherapy, appears to be particularly disruptive to sleep. Yet, sleep complaints often go unrecognised and under treated within routine cancer care. The abbreviated delivery of cognitive behavioral therapy for Insomnia (CBTI) and bright light therapy (BLT) may offer accessible and cost-effective sleep treatments in women receiving chemotherapy for breast cancer. METHODS: The Sleep, Cancer and Rest (SleepCaRe) Trial is a 6-month multicentre, randomized, controlled, 2 × 2 factorial, superiority, parallel group trial. Women receiving cytotoxic chemotherapy for breast cancer at tertiary Australian hospitals will be randomly assigned 1:1:1:1 to one of four, non-pharmacological sleep interventions: (a) Sleep Hygiene and Education (SHE); (b) CBTI; (c) BLT; (d) CBT-I + BLT combined and simultaneously delivered. Each sleep intervention is delivered over 6 weeks, and will comprise an introductory session, a mid-point phone call, and regular emails. The primary (insomnia, fatigue) and secondary (health-related quality of life, rest activity rhythms, sleep-related impairment) outcomes will be assessed via online questionnaires at five time-points: baseline (t0, prior to intervention), mid-point intervention (t2, Week 4), post-intervention (t3, Week 7), 3-months (t4, Week 18), and 6-months follow-up (t5, Week 30). CONCLUSIONS: This study will report novel data concerning the comparative and combined efficacy of CBT-I and BLT during chemotherapy. Findings will contribute to the development of evidence-based early sleep and fatigue intervention during chemotherapy for breast cancer. Clinical trial information Registered with the Australian New Zealand Clinical Trials Registry (http://anzctr.org.au/), Registration Number: ACTRN12620001133921.
Subject(s)
Breast Neoplasms , Sleep Initiation and Maintenance Disorders , Australia/epidemiology , Breast Neoplasms/complications , Breast Neoplasms/therapy , Cognition , Fatigue/etiology , Fatigue/therapy , Female , Humans , Phototherapy , Quality of Life , Sleep , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/therapy , Treatment OutcomeABSTRACT
As COVID-19 vaccinations became available and were proven effective in preventing serious infection, uptake amongst individuals varied, including in medically vulnerable populations. This cross-sectional multi-site study examined vaccine uptake, hesitancy, and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination. A 42-item survey was distributed to people with cancer, diabetes, or multiple sclerosis across ten Australian health services from 30 June to 5 October 2021. The survey evaluated sociodemographic and disease-related characteristics and incorporated three validated scales measuring vaccine hesitancy and vaccine-related beliefs generally and specific to their disease: the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-Six. Among 4683 participants (2548 [54.4%] female, 2108 [45.0%] male, 27 [0.6%] other; mean [SD] age, 60.6 [13.3] years; 3560 [76.0%] cancer, 842 [18.0%] diabetes, and 281 [6.0%] multiple sclerosis), 3813 (81.5%) self-reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas. Unvaccinated participants were more likely to report greater vaccine hesitancy and more negative perceptions toward vaccines. Disease-related vaccine concerns were associated with unvaccinated status and hesitancy, including greater complacency about COVID-19 infection, and concerns relating to vaccine efficacy and impact on their disease and/or treatment. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.
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INTRODUCTION: People with cancer are at higher risk of serious illness and death from COVID-19 infection. We investigated COVID-19 vaccine uptake among patients with solid organ and blood cancers and explored factors related to hesitancy. METHODS: Cross-sectional online survey of adults with a history of cancer at three health services across metropolitan and regional Victoria. Vaccine hesitancy was measured by the validated Oxford COVID-19 vaccine hesitancy scale. RESULTS: There were 1073 respondents: 56% female; median age 62 years (range 23 - 91). Commonest tumor types included breast 29%, gastrointestinal 19%, hematological 15%, genitourinary 15%, and lung 8%. Thirty-six percent had metastatic disease, and 54% were receiving active anticancer treatment. Eighty-four percent of respondents indicated positive intent toward COVID-19 vaccination, 10% were undecided, and 6% indicated negative attitudes. At least one vaccine dose had been received by 65% of respondents, leaving 35% unvaccinated. Fifty-eight percent of unvaccinated patients answered that they would "definitely" or "probably" take a vaccine. Higher vaccine uptake was significantly associated with older age, male gender, English as first language, longer time since cancer diagnosis, and not being on current anticancer treatment. Concerns regarding vaccine side effects, particularly thrombosis, and the desire for clear medical advice were prominent among unvaccinated respondents. CONCLUSION: Despite being eligible for COVID-19 vaccination since March 2021, a substantial minority of patients with cancer remained unvaccinated as of August 2021. Targeted communication and educational resources addressing vaccine safety in the context of cancer are key to promoting vaccine uptake in this vulnerable population.
Subject(s)
COVID-19 Vaccines , COVID-19 , Hematologic Neoplasms , Neoplasms , Vaccines , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Parents , VaccinationABSTRACT
Immune checkpoint inhibitors (ICIs) are a major class of immuno-oncology therapeutics that have significantly improved the prognosis of various cancers, both in (neo)adjuvant and metastatic settings. Unlike other conventional therapies, ICIs elicit antitumor effects by enhancing host immune systems to eliminate cancer cells. There are 3 approved ICI classes by the U.S. Food and Drug Administration: inhibitors targeting cytotoxic T lymphocyte associated antigen 4, programmed death 1/programmed death-ligand 1, and lymphocyte-activation gene 3, with many more in development. ICIs are commonly associated with distinct toxicities, known as immune-related adverse events, which can arise during treatment or less frequently be of late onset, usually relating to excessive activation of the immune system. Acute cardiovascular immune-related adverse events such as myocarditis are rare; however, data suggesting chronic cardiovascular sequelae are emerging. This review presents the current landscape of ICIs in oncology, with a focus on important aspects relevant to cardiology.
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BACKGROUND: With the rapid influx of novel anti-cancer agents, phase I clinical trials in oncology are evolving. Historically, response rates on early phase trials have been modest with the clinical benefit and ethics of enrolment debated. However, there is a paucity of real-world data in this setting. AIM: To better understand the changing landscape of phase I oncology trials, we performed a retrospective review at our institution to examine patient and trial characteristics, screening outcomes, and treatment outcomes. METHODS AND RESULTS: We analyzed all consecutive adult patients with advanced solid organ malignancies who were screened across phase I trials from January 2013 to December 2018 at a single institution. During this period, 242 patients were assessed for 28 different trials. Median age was 64 years (range 30-89) with an equal sex distribution. Among 257 screening visits, the overall screen failure rate was 18%, resulting in 212 patients being enrolled onto a study. Twenty-six trials (93%) involved immunotherapeutic agents or molecular targeted agents either alone or in combination, with only two trials of cytotoxic agents (7%). Twenty-two (13.4%) of the 209 treated patients experienced a total of 33 grade 3 or higher treatment-related adverse events. There was one treatment-related death (0.5%). Of 190 response-evaluable patients, 7 (4%) had a complete response, 34 (18%) a partial response, and 59 (31%) experienced stable disease for a disease control rate of 53%. The median overall survival for our cohort was 8.0 (95% CI: 6.8-9.2) months. CONCLUSION: The profile of phase I trials at our institution are consistent with the changing early drug development landscape. Response rates and overall survival in our cohort are superior to historically reported rates and comparable to contemporaneous studies. Severe treatment-related toxicity was relatively uncommon, and treatment-related mortality was rare.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Trials, Phase I as Topic , Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Outcome and Process Assessment, Health Care , Retrospective Studies , Survival AnalysisABSTRACT
We report a case of synchronous p16+ SCC involving both the nasopharynx and base of tongue treated with definitive chemo-radiotherapy with concurrent high dose cisplatin. The nasopharyngeal lesion was detected incidentally on PET/CT imaging. Head and neck clinicians treating p16+ SCC should consider the possibility of synchronous lesions, including lesions which may be located in the lymphoid tissue of the nasopharynx.
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Current first-line systemic treatment in most patients with metastatic hormone receptor-positive, HER-2 negative breast cancer is an aromatase inhibitor in combination with a cyclin dependant kinase (CDK) 4/6 inhibitor. Frequently, these patients require palliative radiotherapy (RT) for symptomatic disease management. There is a paucity of data on the safety of combining a CDK 4/6 inhibitor with palliative RT, with conflicting case reports in the literature. We report on 5 cases at our institution where enhanced radiotherapy toxicity was observed when palliative doses of RT was delivered during or prior to treatment with a CDK 4/6 inhibitor. After review of pre-clinical and mechanistic data, we hypothesise that the effects of CDK4/6 inhibition on normal tissue and the tumour microenvironment may impede tissue recovery and exacerbate acute radiation and radiation recall toxicities. Further studies are required to clarify the potential toxicities of this combination. Clinicians should consider the potential risks when combining CDK 4/6 inhibitors with palliative RT and individualise patient management accordingly.