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BACKGROUND: There is a disparity in health outcomes between indigenous and nonindigenous Australians, with higher chronic disease burden and shorter life expectancy in this minority population. Although rates of breast cancer among indigenous women are lower than nonindigenous women, they face a higher breast cancer-associated mortality, which may not entirely be explained by socio-economic disadvantage. METHODS: This retrospective cohort study investigated previously described pathologic prognostic factors in indigenous Australians in the Northern Territory. RESULTS: Data analyzed confirmed that indigenous women were more likely to have poorer prognostic disease features, including ER/PR negative and human epidermal growth factor receptor 2 amplified tumors, larger tumors, and higher stage disease. CONCLUSION: These pathologic features portend to a poor prognosis, raising the possibility these factors contribute to the disparity in health outcomes between indigenous and nonindigenous women with breast cancer, in addition to known socio-economic factors.
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OBJECTIVES: To understand how and why Australian cancer physicians interact with the pharmaceutical industry. DESIGN: Qualitative study using semistructured interviews, performed by a medical oncologist. Thematic analysis using a combination of deductive and inductive codes. SETTING: Given the evidence on industry influences on clinical practice and the importance to the market of oncology drugs, we sought to better understand cancer physicians' experiences. Practising consultant medical oncologists and clinical haematologists from four Australian states were interviewed over Zoom. PARTICIPANTS: 16 cancer physicians were interviewed between November 2021 and March 2022, from 37 invited (response rate 43%). Most were medical oncologists (n=12 of 16, 75%) and male (n=9 of 16, 56%). OUTCOME MEASURES: The analysis of all interviews was based on grounded theory. Transcripts were coded and then codes formed into themes with supporting quotes. The themes were then placed into categories, used to describe the broad areas into which the themes could be grouped. RESULTS: Six themes were identified that fell within two broad categories: cancer physicians' views and experiences of interactions and management of these interactions. Views and experiences included: the transactional nature of relationships, risks of research dependence, ethical challenges and varied attitudes based on interaction type. Management themes included: lack of useful guidance and reduced interactions during the COVID-19 pandemic. These led to an overarching seventh theme, on the desire for a 'middle road'. Cancer physicians identified the transactional nature of industry relationships and felt uncomfortable with several types of interactions, including those with sales representatives. Most wanted less contact with industry, and the forced separation that occurred with the COVID-19 pandemic was generally welcome. CONCLUSIONS: Cancer physicians may have difficulty balancing the perceived need to interact with industry in modern cancer care while maintaining distance to minimise conflicts of interest. Further research is needed to assess management strategies in this area.
Subject(s)
Drug Industry , Medical Oncology , Physicians , Humans , Male , Attitude of Health Personnel , Australia , Conflict of Interest , COVID-19 , Neoplasms , Pandemics , Qualitative Research , FemaleABSTRACT
OBJECTIVE: To evaluate the frequency with which relevant and accurate information about the benefits and related uncertainties of anticancer drugs are communicated to patients and clinicians in regulated information sources in Europe. DESIGN: Document content analysis. SETTING: European Medicines Agency. PARTICIPANTS: Anticancer drugs granted a first marketing authorisation by the European Medicines Agency, 2017-19. MAIN OUTCOME MEASURES: Whether written information on a product addressed patients' commonly asked questions about: who and what the drug is used for; how the drug was studied; types of drug benefit expected; and the extent of weak, uncertain, or missing evidence for drug benefits. Information on drug benefits in written sources for clinicians (summaries of product characteristics), patients (patient information leaflets), and the public (public summaries) was compared with information reported in regulatory assessment documents (European public assessment reports). RESULTS: 29 anticancer drugs that received a first marketing authorisation for 32 separate cancer indications in 2017-19 were included. General information about the drug (including information on approved indications and how the drug works) was frequently reported across regulated information sources aimed at both clinicians and patients. Nearly all summaries of product characteristics communicated full information to clinicians about the number and design of the main studies, the control arm (if any), study sample size, and primary measures of drug benefit. None of the patient information leaflets communicated information to patients about how drugs were studied. 31 (97%) summaries of product characteristics and 25 (78%) public summaries contained information about drug benefits that was accurate and consistent with information in regulatory assessment documents. The presence or absence of evidence that a drug extended survival was reported in 23 (72%) summaries of product characteristics and four (13%) public summaries. None of the patient information leaflets communicated information about the drug benefits that patients might expect based on study findings. Scientific concerns about the reliability of evidence on drug benefits, which were raised by European regulatory assessors for almost all drugs in the study sample, were rarely communicated to clinicians, patients, or the public. CONCLUSIONS: The findings of this study highlight the need to improve the communication of the benefits and related uncertainties of anticancer drugs in regulated information sources in Europe to support evidence informed decision making by patients and their clinicians.
Subject(s)
Antineoplastic Agents , Prescription Drugs , Humans , Reproducibility of Results , Document Analysis , Antineoplastic Agents/therapeutic use , Europe , Communication , Drug ApprovalABSTRACT
PURPOSE: Interactions between cancer physicians and the pharmaceutical industry may create conflicts of interest that can adversely affect patient care. We aimed to survey cancer physicians regarding their attitudes toward and interactions with industry. METHODS: We surveyed Australian cancer physicians between December 2020 and February 2021, questioning how often they interacted with industry and their attitudes toward this. We also assessed factors associated with accepting payments from industry and the amount received, and opinions on policies and industry influence. We used logistic and linear regression to examine links between attitudes and behaviors. RESULTS: There were 116 responses (94 complete). Almost half (n = 53 of 115, 46.1%) felt that there was a positive relationship between cancer physicians and industry. Most (n = 79 of 104, 76.0%) interacted with industry at least once a month, and 67.7% (n = 63 of 93) had received nonresearch payments from industry previously, with a median value of 2,000 Australian dollars over 1 year. Most respondents believed that interactions could influence prescribing while simultaneously denying influence on their own prescribing (n = 66 of 94, 70.2%). Those who judged general sales representative interactions (odds ratio [OR] 9.37 [95% CI, 1.05 to 83.41], P = .045) or clinician sponsorship (OR 3.22 [95% CI, 1.01 to 10.30], P = .049) to be more acceptable also met with sales representatives more frequently. Physicians were more likely to accept industry payments when they deemed sponsorship of clinicians for conferences (OR 10.55 [95% CI, 2.33 to 47.89], P = .002) or honoraria for advisory board membership more acceptable (OR 3.91 [95% CI, 1.04 to 14.74], P = .04) or when they had higher belief in industry influence over own prescribing (OR 25.51 [95% CI, 2.70 to 241.45], P = .005). CONCLUSION: Australian cancer physicians interact with industry frequently, and those who feel positive about these interactions are likely to do so more often. More research is needed to understand the motivations behind these interactions.
Subject(s)
Neoplasms , Physicians , Attitude of Health Personnel , Australia , Drug Industry , Humans , Surveys and QuestionnairesABSTRACT
BACKGROUND: No previous review has assessed the extent and effect of industry interactions on medical oncologists and haematologists specifically. METHODS: A systematic review investigated interactions with the pharmaceutical industry and how these might affect the clinical practice, knowledge and beliefs of cancer physicians. MEDLINE, Embase, PsycINFO and Web of Science Core Collection databases were searched from inception to February 2021. RESULTS: Twenty-nine cross-sectional and two cohort studies met the inclusion criteria. These were classified into three categories of investigation: (1) extent of exposure to industry for cancer physicians as whole (n = 11); (2) financial ties among influential cancer physicians specifically (n = 11) and (3) associations between industry exposure and prescribing (n = 9). Cancer physicians frequently receive payments from or maintain financial ties with industry, at a prevalence of up to 63% in the United States (US) and 70.6% in Japan. Among influential clinicians, 86% of US and 78% of Japanese oncology guidelines authors receive payments. Payments were associated with either a neutral or negative influence on the quality of prescribing practice. Limited evidence suggests oncologists believe education by industry could lead to unconscious bias. CONCLUSIONS: There is substantial evidence of frequent relationships between cancer physicians and the pharmaceutical industry in a range of high-income countries. More research is needed on clinical implications for patients and better management of these relationships. REGISTRATION: PROSPERO identification number CRD42020143353.
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Drug Industry/economics , Health Knowledge, Attitudes, Practice , Interprofessional Relations/ethics , Oncologists/economics , Physicians/economics , Practice Patterns, Physicians'/statistics & numerical data , Cross-Sectional Studies , Drug Industry/ethics , Humans , Oncologists/ethicsABSTRACT
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.
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Neoplasms , Radiation Oncology , Asia/epidemiology , Australia/epidemiology , Humans , Neoplasms/epidemiology , Neoplasms/therapy , New Zealand/epidemiologyABSTRACT
BACKGROUND: Payments to medical oncologists and clinical haematologists can negatively affect prescribing practice, but the extent of payments to these specialists is unknown in Australia. AIMS: To analyse the extent of payments from the pharmaceutical industry to Australian cancer physicians as reported during the first collated period of the Disclosure Australia website. METHODS: We performed a retrospective, cross-sectional analysis of payments made from November 2018 to April 2019, using a file downloaded from the Disclosure Australia website. We checked the names of listed medical practitioners against Medical Board of Australia records to assign specialties. The number of medical oncologists, clinical haematologists, other specialist physicians and non-specialist physician medical practitioners was calculated, along with the payments to each of these groups. RESULTS: A total of A$7 332 407 was paid to 2775 medical practitioners. Of these, 236 were medical oncologists, 189 were haematologists and 1145 were other specialist physicians. This represents 31.7% of Australian medical oncologists and 30.9% of Australian haematologists, compared with 11.7% of all other specialist physicians and 1.1% of all other non-specialist physician medical practitioners. Medical oncologists received significantly higher payments (median A$2131.26) than other specialist physicians (median A$1376.00, 2-tailed P = 0.004) and other medical practitioners (median A$709.00, 2-tailed P < 0.001), while haematologists received significantly higher payments (median A$1519.95) than other medical practitioners (2-tailed P < 0.001), but similar payments to other specialist physicians (2-tailed P = 0.08). CONCLUSIONS: Australian cancer physicians receive payments at a higher proportional frequency and in greater dollar amounts than other specialist physicians and other medical practitioners in general.
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Oncologists , Physicians , Australia/epidemiology , Conflict of Interest , Cross-Sectional Studies , Disclosure , Drug Industry , Humans , Retrospective Studies , United StatesABSTRACT
Hyperplasia of the thymus is commonly seen in myasthenia gravis and other autoimmune disorders. Thymic size also varies with age, corticosteroid use, infections, and inflammatory disease. Although thymic hyperplasia has been described following chemotherapy, there is no known association of true thymic hyperplasia with immune checkpoint inhibitor therapy. We present two cases of suspected true thymic hyperplasia in patients with stage IV melanoma who were treated with the combination of nivolumab and ipilimumab, which was complicated by immune-related toxicity requiring corticosteroid therapy, and then subsequently also by secondary hypoadrenalism requiring replacement hydrocortisone. In one patient, histological and flurocytometric analyses of an incisional biopsy of the thymus revealed findings consistent with true thymic hyperplasia. In the other case, the stable fluorodeoxyglucose positron emission tomography/Computed tomography (FDG-PET/CT) findings were consistent also with true thymic hyperplasia. These are the first described cases of true thymic hyperplasia following combination immune checkpoint inhibitor therapy for metastatic melanoma. We hypothesize that the true thymic hyperplasia in these cases results from initial lymphocyte depletion caused by intense corticosteroid therapy followed by rebound thymic hyperplasia during the period of relative hypocortisolism, which may have been aggravated by the onset of secondary hypoadrenalism.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Immunosuppressive Agents/adverse effects , Ipilimumab/adverse effects , Melanoma/drug therapy , Nivolumab/adverse effects , Skin Neoplasms/drug therapy , Thymus Hyperplasia/chemically induced , Adult , Female , Humans , Male , Melanoma/pathology , Middle Aged , Skin Neoplasms/pathology , Melanoma, Cutaneous MalignantABSTRACT
Diffuse pulmonary metastasis secondary to primary peritoneal malignant mesothelioma is rarely reported in the literature. In this report we describe a 59-year-old Caucasian women with no known previous asbestos exposure presenting with bilateral diffuse pulmonary opacities in association with primary malignant peritoneal mesothelioma. The diagnosis was confirmed by ultrasound guided abdominal and bronchoscopy, trans-bronchial lung biopsy. The biopsy demonstrated positive staining with AE1/3, CK7, CK5/6, WT1, calretinin and D2 40. The cells were negative for BerEP4, PAX8, CA125, ER, CD34, ERG, P63, P40, Melan A, Gata3 and mammaglobin. The morphology and immunohistochemical profile supported a diagnosis of epithelioid malignant mesothelioma.
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Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a lethal disease with a poor 5-year survival. Systemic treatments can be used to control symptoms and prolong life. Cytotoxic chemotherapies are commonly administered, with combination treatments, such as fluorouracil, folinic acid, irinotecan and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine showing the largest clinical benefits. Newer genomic classifications of PDAC may provide a rationale for targeted therapies or immunotherapies, although at present these remain largely experimental. This review discusses the evidence behind the currently used regimens, while introducing the potential future of pancreatic cancer care.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/secondary , Carcinoma, Pancreatic Ductal/secondary , Drug Combinations , Fluorouracil/therapeutic use , Humans , Immunotherapy/trends , Irinotecan , Leucovorin/therapeutic use , Organometallic Compounds/therapeutic use , Oxaliplatin , Pancreatic Neoplasms/pathology , Practice Guidelines as Topic , Randomized Controlled Trials as TopicABSTRACT
Vast amounts of clinically relevant text-based variables lie undiscovered and unexploited in electronic medical records (EMR). To exploit this untapped resource, and thus facilitate the discovery of informative covariates from unstructured clinical narratives, we have built a novel computational pipeline termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator discovery (TEPAPA). This pipeline combines semantic-free natural language processing (NLP), regular expression induction, and statistical association testing to identify conserved text patterns associated with outcome variables of clinical interest. When we applied TEPAPA to a cohort of head and neck squamous cell carcinoma patients, plausible concepts known to be correlated with human papilloma virus (HPV) status were identified from the EMR text, including site of primary disease, tumour stage, pathologic characteristics, and treatment modalities. Similarly, correlates of other variables (including gender, nodal status, recurrent disease, smoking and alcohol status) were also reliably recovered. Using highly-associated patterns as covariates, a patient's HPV status was classifiable using a bootstrap analysis with a mean area under the ROC curve of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping tasks. These data support using this integrative approach to efficiently identify disease-associated factors from unstructured EMR narratives, and thus to efficiently generate testable hypotheses.
Subject(s)
Head and Neck Neoplasms/virology , Natural Language Processing , Papillomavirus Infections/pathology , Squamous Cell Carcinoma of Head and Neck/virology , Aged , Data Mining , Electronic Health Records , Female , Humans , Male , Middle Aged , Prognosis , Supervised Machine LearningABSTRACT
BACKGROUND: Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. METHODS: We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. RESULTS: Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p < 0.01, representing 43% and 53% variations from ESMO/NCCN guidelines, respectively). Using ten-fold cross-validation, the best classifiers achieved areas under the receiver operating characteristic curve (AUC) of 0.940 for chemotherapy (95% C.I., 0.922-0.958), 0.899 for the endocrine therapy (95% C.I., 0.880-0.918), and 0.977 for trastuzumab therapy (95% C.I., 0.955-0.999) respectively. Overall, bootstrap aggregated classifiers performed better among all evaluated machine learning models. CONCLUSIONS: A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.