Treatment Pathways For Patients Research Articles

Rational design of an essential diagnostics network to support Universal Health Coverage: a modeling analysis

BackgroundDiagnostic investigations, including pathology and laboratory medicine (PALM) and radiology, have been largely absent from international strategies such as the Sustainable Development Goals. Further, there is little international guidance on which health system tiers different diagnostics should be placed, a critical step in developing a country-level diagnostics network. We describe a modeling strategy to produce tier-specific diagnostic recommendations based on disease burden, current treatment pathways, and existing infrastructure in a country.MethodsThe relational model assumes that diagnostics should be available at the lowest tier where patients might receive medical management. Using Ghana as an exemplar, the 20 diseases forecasted by 2030 and 2040 to cause the greatest burden in low- and middle-income countries were mapped to three generalized tiers in the Ghanaian health system (Primary, Secondary, and Tertiary care) for three levels of each disease (triage, uncomplicated, and complicated). The lowest tier at which a diagnostic could potentially be placed was restricted by existing infrastructure, though placement still required there be a medical justification for the diagnostic at that tier.ResultsThe model recommended 111 unique diagnostic investigations with 17 at Primary tier, an additional 45 at Secondary tier and a further 49 at Tertiary tier. Estimated capital costs were $8,330 at Primary tier and between $571,000 to $777,000 at Secondary tier. Twenty-eight different laboratory tests were recommended as send-outs from Primary to Secondary tier, and twelve as send-outs to Tertiary tier.ConclusionsThis model provides a transparent framework within which countries can customize diagnostic planning to local disease priorities, health system patient treatment pathways, and infrastructural limitations to best support Universal Health Coverage.

Assessing variability in breast cancer management across the world: results of a questionnaire survey amongst global international experts in breast cancer management.

Breast cancer is the most common cancer in women worldwide with an estimated 2.3 million breast cancer cases diagnosed annually. The outcome of breast cancer management varies widely across the globe which could be due to a multitude of factors. Hence, a blanket approach in standardisation of care across the world is neither practical nor feasible. To assess the extent and type of variability in breast cancer management across the globe and to do a gap analysis of patient care pathway. An online questionnaire survey and virtual consensus meeting was carried out amongst 31 experts from 25 countries in the field of breast cancer surgical management. The questionnaire was designed to understand the variability in diagnosis and treatment of breast cancer, and potential factors contributing to this heterogeneity. The questionnaire survey shows a wide variation in breast surgical training, diagnosis and treatment pathways for breast cancer patients. There are several factors such as socioeconomic status, patient culture and preferences, lack of national screening programmes and training, and paucity of resources, which are barriers to the consistent delivery of high-quality care in different parts of the world. On-line survey platforms distributed to global experts in breast cancer care can assess gaps in the diagnosis and treatment of breast cancer patients. This survey confirms the need for an in-depth gap analysis of patient care pathways and treatments to enable the development of personalised plans and policies to standardise high quality care.

Clinical Characteristics and Treatment Pathway of Patients Treated with Helicobacter pylori Infection-A Single Center Cohort Study Using Common Data Model

Background/Aims: Changing trends in the <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication protocol have not been investigated after the publication of the third-revised Korean guideline in 2013. We aimed to analyze the clinical characteristics of <i>H. pylori</i>-infected patients alongside their treatment protocols using a common data model (CDM).Materials and Methods: A 16-year electronic health record (of 1,689,604 patients from 2004 to 2019) was converted into a CDM in Kangdong Sacred Heart Hospital. We extracted records of patients who underwent the rapid urease test or serum anti-<i>H. pylori</i> IgG assay. The treatment protocols were visualized using a sunburst plot. We investigated the clinical characteristics and medication history of patients who underwent a urea breath test after clarithromycin-based eradication therapy.Results: Out of 29,458 patients tested for <i>H. pylori</i> infection, 7,647 received a treatment protocol. Among them, 72.5% received a 7~14 days protocol comprising a proton pump inhibitor (PPI), amoxicillin, and clarithromycin. The proportion of patients treated with the first-line protocol (PPI, bismuth, tetracycline, and metronidazole) slightly increased from 1.9% (before 2014) to 3.3% (after 2014) (P<0.001). The percentages of patients with of previous exposure to macrolides (14.7% vs. 5.5%, P<0.001) or amoxicillin (10.6% vs. 7.3%, P=0.006) were higher in patients with previous clarithromycin-based eradication failure.Conclusions: The <i>H. pylori</i> treatment protocol was not significantly modified despite the updates in the clinical guideline. There was only 1.4 percentage point increase in bismuth-based quadruple therapy as first-line eradication therapy even after the announcement of revised Korean guideline in 2013.

Characterization of Patients with Chronic Obstructive Pulmonary Disease Initiating Single-Inhaler Long-Acting Muscarinic Antagonist/Long-Acting β2-Agonist Dual Therapy in a Primary Care Setting in England.

PurposeTreatment pathways of patients with chronic obstructive pulmonary disease (COPD) receiving single-inhaler dual therapies remain unclear. We aimed to describe characteristics, prescribed treatments, healthcare resource use (HCRU) and costs of patients with COPD who initiated single-inhaler long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual therapy in primary care in England.Patients and MethodsRetrospective study using linked data from Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. Patients with COPD with ≥1 single-inhaler LAMA/LABA prescription between June 2015 and December 2018 (index) were included. Demographic and clinical characteristics, prescribed treatments, HCRU and costs were evaluated in the 12 months pre-index. Data are presented for patients not receiving concomitant inhaled corticosteroids at index (non-triple users).ResultsOf 10,991 patients initiating LAMA/LABA, 9888 were non-triple users, of whom 21.3% (n=2109) received aclidinium bromide/formoterol, 18.1% (n=1785) received indacaterol/glycopyrronium, 12.0% (n=1189) received tiotropium bromide/olodaterol and 48.6% (n=4805) received umeclidinium/vilanterol. Demographic and clinical characteristics were similar across indexed therapies. LAMA monotherapy was the most frequently prescribed respiratory therapy at 12 (18.4–25.8% of patients) and 3 months (23.9–33.7% of patients) pre-index across indexed therapies; 42.5–59.0% of patients were prescribed no respiratory therapy at these time points. COPD-related HCRU during the 12 months pre-index was similar across indexed therapies (general practitioner consultations: 62.0–68.6% patients; inpatient stays: 19.3–26.1% patients). Pre-index COPD-related costs were similar across indexed therapies, with inpatient stays representing the highest contribution. Mean total direct annual COPD-related costs ranged from £805–£1187.ConclusionCharacteristics of patients newly initiating single-inhaler LAMA/LABA dual therapy were highly consistent across indexed therapies. As half of non-triple users were not receiving respiratory therapy one year prior to LAMA/LABA initiation, there may be an opportunity for early optimization of treatment to relieve clinical burden versus current prescribing patterns in primary care in England.

Challenges in Diagnosis of Uretero-Arterial Fistulas after Complex Pelvic Oncological Procedures-Single Center Experience and Review of the Literature.

Introduction: Uretero–arterial fistula (UAF) represents a rare condition that manifests as massive or intermittent hematuria and requires collaboration between a urologist, vascular surgeon and interventional radiologist. In this article, we present our experience with UAF diagnosis, treatment pathways and the results of a nonsystematic review of the literature published in the last decade regarding modern diagnostic procedures. Material and method: We analyzed the clinical data of nine consecutive patients from our institution diagnosed with UAF in the interval of 2012–2022 who underwent open or endovascular surgical treatment. We reviewed patient characteristics, diagnoses and treatment pathways. The literature search resulted in 14 case series, published from 2012 to 2022, describing a total of 670 cases of UAF. Results: The mean age of patients in our cohort was 65.3 years (IQR: 51–79). UAFs were more common in women (77.7%). All patients presented a history of surgical intervention and ir-radiation for pelvic malignancy with permanent ureteric stenting. Overall, 88.8% of patients had urinary diversion, either via ileal conduit or cutaneous ureterostomy. The most common clinical manifestation of UAF was gross hematuria with or without clots accompanied by flank pain due to stent obstruction, while three patients presented with hypovolemic shock. Angiography represents the best option for diagnosis, followed by angioCT, with a sensitivity of 59.83% and 47.01%, respectively. There is no definitive imaging modality associated with high accuracy in detecting UAF and negative findings do not exclude the disease. In emergency cases with massive bleeding, surgical exploration remains the most appropriate management option for both diagnosis and treatment. Endovascular stent graft placement is preferred over open surgery in stable hemodynamic patients. Conclusions: Uretero–arterial fistulas represent a life-threatening complication and must be treated with great awareness. Angiography represents the best modality for diagnosis, followed by computed tomography. However, there is no definitive imaging modality and, in some cases, open approach remains the only option for diagnosis and treatment.

Emergency department evaluation, treatment, and functional outcomes among patients presenting with low back pain

ObjectivesLow back pain (LBP) leads to more than 4.3 million emergency department (ED) visits annually. Despite the number of ED visits for LBP, emergency medicine societies have not established clear guidelines for the evaluation and care of these patients. This study aims to describe patterns in the evaluation, treatment, and outcomes of patients presenting to an urban, academic ED for atraumatic LBP. MethodsWe prospectively identified a convenience sample of patients presenting with LBP to the University of Utah Hospital ED between January 2017 and June 2018. We collected baseline demographic information and calculated the Patient-Reported Outcomes Measurement Information System Physical Function Short Form 12a (PROMIS PFSF-12a) score to assess patient function and mobility (50 = average PROMIS PFSF-12a score, with higher scores indicating better function). We contacted patients 6 weeks after the ED visit to assess outpatient follow-up and functional outcomes. ResultsOver the 18-month study period, 103 patients presented with a chief complaint of LBP and agreed to participate in the study. Average age of the cohort was 48.5 years (SD = 18.3) and 55 (53.4%) were female. Notably, 61 patients (59.2%) had been seen previously in the ED for LBP and 32 (31.1%) had received an opioid for LBP in the preceding 3 months. In the ED, 35.9% of patient received an opioid while 18.5% had an opioid prescription at discharge. While in the ED, 37 (35.9%) had an x-ray and 47 (45.6%) underwent computed tomography or magnetic resonance imaging. At 6-week follow-up, 22 of 68 (32.4%) patients reported having missed work due to pain. PROMIS PFSF-12a score improved from 32.2 (“low” range) at time of ED visit to 42.0 (“low-average” range) at the 6-week follow up. Regarding outpatient follow-up after the ED visit, 22 patients (21.4%) saw a primary care provider, 12 patients (17.8%) saw orthopedics or neurosurgery, and 8 patients (11.8%) attended physical therapy. ConclusionsPatients receiving ED care for LBP had a significant improvement in PROMIS PFSF-12a scores 6 weeks after the ED but return to function continued to lag despite interventions. Imaging patterns, medication prescriptions, and outpatient follow-up varied widely, emphasizing the needs for clear guidelines and treatment pathways for ED patients with LBP.

PB2098: ‘REAL-WORLD’ TREATMENT PATTERNS AND PATHWAYS OF SECOND LINE DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS IN UK, CANADA, FRANCE, GERMANY, ITALY AND SPAIN USING A PROSPECTIVE SURVEY OF PHYSICIANS

Background: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of Non-Hodgkin Lymphoma, representing 25% to 35% of cases annually1. Despite this, there is a lack of research into treatment patterns of real-world patients, especially in the 2nd line (2L) setting. Aims: To determine the ‘real-world’ treatment patterns and treatment pathway of DLBCL patients treated at the second line, with a focus on patients who are ‘fast progressors’ as defined below. Methods: In this study ‘real-world’ data were drawn from the Adelphi DLBCL Disease Specific Programme™ (DSP), a point-in-time survey of clinicians and their next 6 presenting patients with DLBCL. The survey was conducted in France, Germany, Italy, Spain, the United Kingdom (UK) and Canada between Jan-May 2021. Patients who were refractory/relapsed <12 months from 1st line (1L) therapy, eligible for a stem cell transplant (SCT) at initial relapse/refractory, had an ECOG performance score of 0-1 and had no history of hepatitis B or C or CNS events were studied. Results: 47 patients met the criteria. Mean age of the patients was 58.0 (SD: 11.7) years, 68% were male and 26% were retired. At 1L, 94% of patients received R-CHOP with a median of 171.2 days (IQR: 61.0-247.5) between the end of their 1L and the start of their 2L treatments. All patients received salvage chemotherapy (SC) in the form of R-ESHAP, R-DHAP or R-GDP in most cases (Figure 1). 49% of the patients had a complete response (CR) to SC, 21% had partial response (PR), 30% stable/no response. In total 26 (55%) patients received high-dose therapy-SCT (HDT-SCT). Figure 1 shows the response to 2L treatments across patients and indicates why some patients did not progress to SCT despite being previously eligible. Patients receiving SCT had a median time from 2nd line SCT to relapse/refractory of 189.0 (IQR: 94.0-333.0) days. 54% of patients received chimeric receptor antigen T-cell (CAR-T) therapies at 3L (Figure 1), with the majority having previously received SCT. CAR-T use was higher in UK (67%), Canada (63%) and Germany (60%) than in other regions. Image:Summary/Conclusion: Despite all patients with DLBCL observed being SCT eligible at their first relapse, only half of these patients went on to receive an SCT. Unacceptable response to SC, progressive disease and patient choice were common reasons for not going on to receive SCT. Despite seemingly favourable responses to SCT, these patients progressed quickly and were likely to receive a CAR-T treatment in 3L, indicating an unmet need and highlighting potentially high resource use and substantial impacts to quality of life.

Clinical Considerations for Use of SGLT2 Inhibitor Therapy in Patients with Heart Failure and Reduced Ejection Fraction: A Review.

Heart failure (HF) continues to increase in prevalence, representing a significant burden to healthcare systems in the USA. Despite several established HF therapies, particularly for HF with reduced ejection fraction (HFrEF), rates of HF hospitalizations and cardiovascular (CV) mortality remain very high. Type 2 diabetes (T2D) is an important risk factor for HF, with the two conditions often occurring concurrently. Several CV outcomes trials have shown that the sodium–glucose cotransporter 2 inhibitor (SGLT2i) class of antihyperglycemic drugs reduces the risk of HF-related outcomes in patients with T2D and either established CV disease or multiple CV risk factors. Subsequently, there have been large clinical studies that have investigated the effects of SGLT2is in patients with HFrEF, with or without T2D, which have shown that both dapagliflozin and empagliflozin have significant reductions in hospitalization for HF and CV mortality. These data led to US Food and Drug Administration approval of dapagliflozin and empagliflozin as a novel treatment pathway for patients with HFrEF; empagliflozin has subsequently been approved for the treatment of HF regardless of ejection fraction. A clinical practice algorithm can assist cardiologists in identifying patients who may be eligible for SGLT2i treatment as well as the appropriate timeframe for initiating therapy and the parameters for patient monitoring. Given the evidence that SGLT2is are beneficial in the management of HF, specifically HFrEF, irrespective of underlying T2D, evidence-based recommendations and greater clinician familiarity can facilitate the integration of SGLT2is into general HF therapeutic management.

Consensus on a standardised treatment pathway algorithm for lumbar spinal stenosis: an international Delphi study.

BackgroundLumbar spinal stenosis (LSS) is a common degenerative spinal condition in older adults associated with disability, diminished quality of life, and substantial healthcare costs. Individual symptoms and needs vary. With sparse and sometimes inconsistent evidence to guide clinical decision-making, variable clinical care may lead to unsatisfactory patient outcomes and inefficient use of healthcare resources.MethodsA three-phase modified Delphi study comprising four consensus rounds was conducted on behalf of the International Taskforce for the Diagnosis and Management of LSS to develop a treatment algorithm based on multi-professional international expert consensus. Participants with expertise in the assessment and management of people with LSS were invited using an international distribution process used for two previous Delphi studies led by the Taskforce. Separate treatment pathways for patients with different symptom types and severity were developed and incorporated into a proposed treatment algorithm through consensus rounds 1 to 3. Agreement with the proposed algorithm was evaluated in the final consensus round.ResultsThe final algorithm combines stratified and stepped approaches. When indicated, immediate investigation and surgery is advocated. Otherwise, a stepped approach is suggested when self-directed care is unsatisfactory. This starts with tailored rehabilitation, then more complex multidisciplinary care, investigations and surgery options if needed. Treatment options in each step depend on clinical phenotype and symptom severity. Treatment response guides pathway entrance and exit points. Of 397 study participants, 86% rated their agreement ≥ 4 for the proposed algorithm on a 0–6 scale, of which 22% completely agreed. Only 7% disagreed. Over 70% of participants felt that the algorithm would be useful for clinicians in public healthcare (both primary care and specialist settings) and in private healthcare settings, and that a simplified version would help patients in shared decision-making.ConclusionsInternational and multi-professional agreement was achieved for a proposed LSS treatment algorithm developed through expert consensus. The algorithm advocates different pathway options depending on clinical indications. It is not intended as a treatment protocol and will require evaluation against current care for clinical and cost-effectiveness. It may, however, serve as a clinical guide until evidence is sufficient to inform a fully stratified care model.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12891-022-05485-5.

Routine treatment pathways of patients with major depression and active suicidal ideation with intent in Italy: interim results from the ARIANNA observational study

IntroductionMajor depressive disorder (MDD), especially in case of suicidal risk, is a psychiatric emergency, associated with high patient burden and healthcare resource utilization. Although active and urgent treatment is crucial, little is known on comprehensive care management of this condition in Italy.ObjectivesHere we report the ARIANNA study [NCT04463108] interim results to primarily describe the treatment utilization pathways of patients with MDD and active suicidal ideation with intent in the current clinical practice in Italy.MethodsThis observational prospective cohort study included adult patients with a moderate-to-severe major depressive episode (MDE) and active suicidality from 24 Italian sites. Real-world data on patient characteristics, treatments, clinical outcomes, and healthcare utilization were collected during a 90-day follow-up. Data collection is still ongoing.ResultsSixty-four evaluable patients were considered for this interim analysis: 41 (64.1%) females, mean [SD] age 46.0 [15.4] years, a concomitant psychiatric diagnosis in 7 (10.9%), and other comorbidities in 26 (40.6%). The baseline mean [SD] MADRS total score was 37.5 [7.2], with severe MDE and prior suicidal behavior in 30 (46.9%) and 21 (32.8%) patients, respectively. Median [25th;75th percentiles] duration of current MDE was 1.1 [0.3;2.1] months. Acute inpatient hospitalization was provided for 43 (67.2%) patients. Antidepressant augmentation with mood stabilizers and/or antipsychotic drugs and optimization were the most frequent early standard-of-care treatment regimens in 32 (53.3%) and 24 (40.0%) patients with available data (N=60), respectively.ConclusionsOur preliminary results suggest that initial treatment approaches in this critical population are mostly polypharmacological and delivered as inpatient care, with consequent intensive resource utilization.DisclosureThe ARIANNA study was sponsored by Janssen-Cilag SpA, Italy. DD and MA are employees of Janssen-Cilag SpA. DA and BR are employees of MediNeos S.U.R.L., a company subject to the direction and coordination of IQVIA Solutions HQ Ltd.

Can Beta-D-Glucan testing as part of the diagnostic pathway for invasive fungal infection reduce anti-fungal treatment costs?

Invasive fungal infection increases the risk of death in very sick people. So, treatment is started before test results are known. Beta-D-Glucan (BDG) test is faster than standard blood culture tests. We estimate that using BDG tests in how patients are diagnosed could save about £1643 per patient.

Assessment of Crystals in the Synovial Fluid of Psoriatic Arthritis Patients in Relation to Disease Activity.

Background: This study examines the relationship between the presence of crystals in the synovial fluid of patients with psoriatic arthritis (PsA) and disease activity. Methods: The synovial fluid of 156 PsA patients was analyzed and compared to 50 patients with gonarthrosis (GoA). The Leica DM4500P polarization microscope was used for crystal detection. Results: The presence of crystals was observed in 23.71% of PsA patients and none of the GoA patients, p < 0.001. Monosodium urate crystals (67.58%) and calcium pyrophosphate crystals (21.62%) were prevalent. The presence of crystals in the synovial fluid of PsA patients was associated with high disease activity according to the Composite Psoriatic Disease Activity Index (OR = 18.75, 95%; CI: 7.13 to 49.25) and the Disease Activity for Psoriatic Arthritis (OR = 15.96, 95%; CI: 5.76 to 44.23), with severe disability according to the Health Assessment Questionnaire Disability Index (OR = 13.60, 95%; CI: 5.09 to 36.31), and with severe pain on the Visual Analog Scale (OR = 157.25, 95%; CI: 39.50 to 625.94). Conclusion: Our results suggest that synovial fluid examination should be included in the treatment pathway for PsA patients with active disease, to aid in determining whether urate-lowering therapy is required.

The use of preoperative NPI in predicting the need for oncotype test, a potential way to improve patient treatment pathways

The use of preoperative NPI in predicting the need for oncotype test, a potential way to improve patient treatment pathways

Parenchyma-sparing strategy and oncological prognosis in patients with colorectal cancer liver metastases

BackgroundPreliminary study results demonstrated parenchyma-sparing surgery (PSS) as an effective approach which allowed to remove colorectal cancer (CRC) metastatic lesions within the central liver cites and increased the probability of the liver re-resections.MethodsThe prospective analysis re-evaluation of the 185 CRC patients surgical treatment has been performed.ResultsAn overall 5-year survival (OS) of the 185 enrolled patients was 43 ± 7%, and the mean and median value for OS was 48.7 ± 1.9% and 55.2 ± 5 (95% CI: 44.4–66.1) months. The 5-year OS for CRC patients whose metastatic lesions were predominantly located within peripheral and central liver segments was 56 ± 8% and 27 ± 9%, respectively (p = 0.08). A 5-year disease-free survival (DFS) rates of patients with peripheral and central liver cites metastatic lesions were 31 ± 7 % and 15 ± 7%, p = 0,12. And the DFS median was 34.2 and 46.5 months for R1v and R0 cohorts, respectively, p = 0.62.ConclusionsParenchyma-sparing surgery should be a priority pathway for complex treatment of patients with deeply located lesions of the right liver lobe.Trial registrationThe study is registered in https://www.researchregistry.com/browse-the-registry#home/registrationdetails/5ed9f60863e9bf0016624456/, no. 5679.

A Real-World Data Study on the Healthcare Resource Use for Uncontrolled Moderate-to-Severe Atopic Dermatitis in Secondary Care in the United Kingdom Prior to the Introduction of Biologic Treatment.

BackgroundWhilst there is international evidence around the high healthcare resource utilization (HRU) associated with atopic dermatitis (AD), there is a lack of published data from the United Kingdom (UK).MethodsA retrospective, descriptive, observational study was conducted to evaluate the burden of moderate-to-severe AD on the National Health Service (NHS) in an adult UK population treated with traditional standard of care prior to the introduction of biologics. Patients (n=59) were recruited from 6 UK NHS Hospital Trusts and observed over three years.Results707 dermatology clinic visits were recorded over the observation period, amounting to 6.6 visits per patient-year, most commonly for routine check-ups most of which involved dermatology consultants (n=469, 66%). Physicians were the most consulted healthcare professional (n=652, 92%); emollients were the most common treatment (n=80 courses). 174 flares requiring additional medical advice were recorded in total (1.6 per patient-year).Discussion/ConclusionsComplex treatment pathways for adult patients in the UK with moderate-to-severe AD incur considerable HRU, particularly for those patients non-responsive to systemic therapies with broad immunosuppressant action. Recent advances in biologics-based AD management could possibly have a significant positive impact on HRU through significant reduction in the number of NHS touch points identified in this study.

Breast Density and Estradiol Are Major Determinants for Soluble TNF-TNF-R Proteins in vivo in Human Breast Tissue.

High mammographic density and exposure to sex steroids are independent risk factors for breast cancer by yet unknown mechanisms. Inflammation is one hallmark of cancer and the tumor necrosis factor family of proteins (TNFSFs) and receptors (TNFRSFs) are key determinants of tissue inflammation. The relationship between TNFSFs/TNFRSFs and breast tissue density or local breast estradiol levels is unknown. We investigated whether TNFSFs and soluble TNFRSFs (sTNFRSFs) are dysregulated in vivo in human breast cancer and dense breast tissue of postmenopausal women. We explored TNFSF/TNFRSF correlations with breast density and estradiol, both locally in the breast and in abdominal subcutaneous (s.c.) fat as a measure of systemic effects. Microdialysis was used for local sampling of in vivo proteins and estradiol in a total of 73 women; 12 with breast cancer, 42 healthy postmenopausal women with different breast densities, and 19 healthy premenopausal women. Breast density was determined as lean tissue fraction (LTF) using magnetic resonance imaging. Microdialysis was also performed in estrogen receptor (ER) positive breast cancer in mice treated with the pure anti-estrogen fulvestrant and tumor tissue was subjected to immunohistochemistry. 23 members of the TNFSF/sTNFRSF families were quantified using proximity extension assay.Our data revealed upregulation of TNFSF10, 13 and 13B, TNFRSF6, 6B, 9, 11A, 11B, 13B, 14, and 19, and TNFR-1 and -2 in ER+ breast cancer in women. In dense breast tissue TNFSF10, 13, and 14, TNFRSF3, 6, 9, 10B, 13B, 14, 19, and TNFR-1 and -2 were upregulated. Certain TNFSFs/TNFRSFs were increased in premenopausal breasts relative to postmenopausal breasts. Furthermore, estradiol correlated with most of the TNFSF/sTNFRSF members, though LTF only correlated with some of the proteins. Several of these associations were breast tissue-specific, as very few correlated with estradiol in abdominal s.c. fat. Estrogen dependent regulations of TNFSF2 (TNF-α) and TNF-R2 were corroborated in ER+ breast cancer in mice. Taken together, our data indicate TNFSFs/sTNFRSFs may represent potential targetable pathways for treatment of breast cancer patients and in prevention of breast cancer development in women with dense breasts.

Novel Ex Vivo Models of Epithelial Ovarian Cancer: The Future of Biomarker and Therapeutic Research.

Epithelial ovarian cancer (EOC) is a heterogenous disease associated with variations in presentation, pathology and prognosis. Advanced EOC is typified by frequent relapse and a historical 5-year survival of less than 30% despite improvements in surgical and systemic treatment. The advent of next generation sequencing has led to notable advances in the field of personalised medicine for many cancer types. Success in achieving cure in advanced EOC has however been limited, although significant prolongation of survival has been demonstrated. Development of novel research platforms is therefore necessary to address the rapidly advancing field of early diagnostics and therapeutics, whilst also acknowledging the significant tumour heterogeneity associated with EOC. Within available tumour models, patient-derived organoids (PDO) and explant tumour slices have demonstrated particular promise as novel ex vivo systems to model different cancer types including ovarian cancer. PDOs are organ specific 3D tumour cultures that can accurately represent the histology and genomics of their native tumour, as well as offer the possibility as models for pharmaceutical drug testing platforms, offering timing advantages and potential use as prospective personalised models to guide clinical decision-making. Such applications could maximise the benefit of drug treatments to patients on an individual level whilst minimising use of less effective, yet toxic, therapies. PDOs are likely to play a greater role in both academic research and drug development in the future and have the potential to revolutionise future patient treatment and clinical trial pathways. Similarly, ex vivo tumour slices or explants have also shown recent renewed promise in their ability to provide a fast, specific, platform for drug testing that accurately represents in vivo tumour response. Tumour explants retain tissue architecture, and thus incorporate the majority of tumour microenvironment making them an attractive method to re-capitulate in vivo conditions, again with significant timing and personalisation of treatment advantages for patients. This review will discuss the current treatment landscape and research models for EOC, their development and new advances towards the discovery of novel biomarkers or combinational therapeutic strategies to increase treatment options for women with ovarian cancer.

Treatment Patterns and Health Resource Utilization in Patients With Hepatocellular Carcinoma After Failure of Sorafenib in Real-World Setting in Taiwan

ObjectivesThis study aimed to characterize current treatment patterns and healthcare resource utilization (HRU) observed among patients with hepatocellular carcinoma (HCC) after the failure of sorafenib in real-world setting in Taiwan. MethodsA chart review was conducted in 130 patients; the inclusion criteria were patients with HCC who were aged 20 years or older and had received systemic therapy or best supportive care after failure of first-line systemic treatment with sorafenib between 2016 and 2018. Anonymized data on patient characteristics, treatment pathways, and survival were abstracted. ResultsThe mean age of patients was 61.7 years (range 27-84); of these 130 patients, 103 (79%) were male, 81 (62%) had high alpha-fetoprotein (AFP) levels (≥400 ng/mL), and 96 (78.0%) were deceased at the time of data abstraction. After sorafenib therapy, 60 patients (46%) received systemic therapy, including nivolumab monotherapy (42%) and chemotherapy (25%). Oncologist visits at a semiannual per-patient rate of 3.7 (95% confidence interval [CI] 3.4-4.0) and hospitalizations at rate of 1.1 (95% CI 1.0-1.3) were the key contributors to HRU. Semiannual per-patient hospitalization rate was 1.3 (95% CI 1.1-1.5) in the high-AFP group. Median survival from discontinuation of sorafenib was 6.9 months (95% CI 5.9-9.0). ConclusionsThis real-world evidence research on treatment patterns reflected substantial HRU consistent with the severity of HCC, particularly in the high-AFP group. Findings highlighted continuing high mortality in HCC, underlying a need for new treatments that can lengthen survival. Results can inform future evaluations of new HCC treatments that estimate the health economic impact of their adoption in Taiwan.

Evaluating potential delays and outcomes of patients undergoing surgical resection for locally advanced and recurrent colorectal cancer during a pandemic.

The COVID-19 pandemic resulted in a significant disruption of colorectal cancer (CRC) care pathways. This study evaluates the management and outcomes of patients with primary locally advanced or recurrent CRC during the pandemic in a single tertiary referral centre. Patients undergoing elective surgery for advanced or recurrent CRC with curative intent between March 2020 and March 2021 were identified. Following first multidisciplinary team discussion patients were broadly classified into two groups: straight to surgery (n=22, 45%) or neoadjuvant therapy followed by surgery (n=27, 55%). Primary outcome was COVID-19-related complication rate. Forty-nine patients with a median age of 66 years (interquartile range: 54-73) were included. No patients developed a COVID-19 infection or related complication during hospital admission. Significant delays were identified in the treatment pathway of patients in the straight to surgery group, mostly due to delays in referral from external centres. Nine of 22 patients in the straight to surgery group had evidence of tumour progression compared with 3 of 27 in the neoadjuvant group (p=0.015839). Seven of 27 patients in the neoadjuvant group showed evidence of tumour regression. During the study, surgical waiting times were reduced, and more operations were performed during the second wave of COVID-19. This study suggests that it is possible to mitigate the risks of COVID-19-related complications in patients undergoing complex surgery for locally advanced and recurrent CRC. Delay in surgical intervention is associated with tumour progression, particularly in patients who may not have neoadjuvant therapy. Efforts should be made to prioritise resources for patients requiring time-sensitive surgery for advanced and recurrent CRC.

Teletrials, the new norm? Expert recommendations for teletrials into the future: Findings from the Clinical Oncology Society of Australia Clinical Trial Research Professionals Group Workshop.

The Australasian Teletrial Model was piloted in co-funded sites across Australia. The purpose was to extend the reach of clinical trials using telemedicine to improve equity and access to this treatment pathway for oncology patients. Experts across Australia gathered to share the learnings of implementation so that future directions can be effective and sustainable. The 1-day workshop was attended in person and virtually. Attendees were invited to analyze and disseminate the results. Recordings from the presentations were coded independently by three researchers and synthesized. The results were sent to the authorship team for further review to build consensus on the findings in three drafts. Four key themes were identified: "Being on the Same Page," "Building Foundations," "Key Roles in Teletrials," and "Incentives." Although there were many successes that were accelerated by the COVID-19 pandemic, there is work still to be done. The Australasian Teletrial Model has been identified as acceptable and feasible. Future directions need to continue to work on streamlining regulatory processes, implementation and monitoring, and build knowledge to further build networks across Australia.