Global, regional, and national burden of ovarian cancer among young women during 1990-2019.

BACKGROUND: Ovarian cancer, the most devastating tumor in women globally, significantly impacts young women, compromising their daily lives and overall well-being. Ovarian cancer represents a significant public health concern due to its extensive physical and psychological consequences. MATERIAL AND METHODS: Data from the Global Burden of Disease were used to assess the global, regional, and national burden of ovarian cancer in young women aged 20-39 from 1990 to 2019. This analysis focused on trends measured by the estimated annual percentage change and explored the socioeconomic impacts via the socio-demographic index (SDI). RESULTS: During 1990-2019, the incidence and prevalence of ovarian cancer among young women increased globally, with annual rates of 0.74% and 0.89%, respectively. The mortality rate and disability-adjusted life years also rose annually by 0.20% and 0.23%, respectively. A significant burden shift was observed toward regions with lower SDI, with high fasting plasma glucose, BMI, and asbestos exposure identified as prominent risk factors, particularly in lower SDI regions. CONCLUSION: Our findings underscore ovarian cancer in young women as an escalating global health challenge, with the burden increasingly shifting toward lower socioeconomic areas. This underscores the necessity for targeted prevention and control strategies for ovarian cancer, focusing on reducing the identified risk factors and ensuring equitable health resource distribution.

Basement membrane-related lncRNA signature for the prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main type of primary liver cancer. This study aimed to develop a basement membrane (BM) related lncRNAs risk signature to evaluate the prognosis of HCC patients. We screened differentially expressed BM-related lncRNAs (DE-BMRlncRNAs) for risk evaluation, and identified six DE-BMRlncRNAs (AC072054.1, NUP50-DT, AC026412.3, AC109322.2, POLH-AS1 and LINC00595) for prognostic risk signature. HCC patients were divided to high or low risk according to median risk score. Our prognostic model predicted that patients with higher risk score had worse prognosis. We also created a nomogram to assist clinical decision-making according to risk score and clinicopathological features. Meanwhile, we confirmed the expression of six lncRNAs in HCC tissue and cells. POLH-AS1 knockdown inhibited the migration and invasion of HCC cells. In conclusion, we established a predictive model based on BMRlncRNAs to predict the prognosis of HCC. Our findings offer a rationale to further explore BM-related biomarkers for HCC.

Towards proactive palliative care in oncology: developing an explainable EHR-based machine learning model for mortality risk prediction.

BACKGROUND: Ex-ante identification of the last year in life facilitates a proactive palliative approach. Machine learning models trained on electronic health records (EHR) demonstrate promising performance in cancer prognostication. However, gaps in literature include incomplete reporting of model performance, inadequate alignment of model formulation with implementation use-case, and insufficient explainability hindering trust and adoption in clinical settings. Hence, we aim to develop an explainable machine learning EHR-based model that prompts palliative care processes by predicting for 365-day mortality risk among patients with advanced cancer within an outpatient setting. METHODS: Our cohort consisted of 5,926 adults diagnosed with Stage 3 or 4 solid organ cancer between July 1, 2017, and June 30, 2020 and receiving ambulatory cancer care within a tertiary center. The classification problem was modelled using Extreme Gradient Boosting (XGBoost) and aligned to our envisioned use-case: "Given a prediction point that corresponds to an outpatient cancer encounter, predict for mortality within 365-days from prediction point, using EHR data up to 365-days prior." The model was trained with 75% of the dataset (n = 39,416 outpatient encounters) and validated on a 25% hold-out dataset (n = 13,122 outpatient encounters). To explain model outputs, we used Shapley Additive Explanations (SHAP) values. Clinical characteristics, laboratory tests and treatment data were used to train the model. Performance was evaluated using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC), while model calibration was assessed using the Brier score. RESULTS: In total, 17,149 of the 52,538 prediction points (32.6%) had a mortality event within the 365-day prediction window. The model demonstrated an AUROC of 0.861 (95% CI 0.856-0.867) and AUPRC of 0.771. The Brier score was 0.147, indicating slight overestimations of mortality risk. Explanatory diagrams utilizing SHAP values allowed visualization of feature impacts on predictions at both the global and individual levels. CONCLUSION: Our machine learning model demonstrated good discrimination and precision-recall in predicting 365-day mortality risk among individuals with advanced cancer. It has the potential to provide personalized mortality predictions and facilitate earlier integration of palliative care.

Comparing situational influences on differential healthcare utilization trajectories in patients on home palliative care: A qualitative study.

OBJECTIVES: Patients with terminal cancer receiving home palliative care present differential healthcare utilization trajectories before death. It remains unclear which situational elements influence these trajectories among disparate patient groups. The aim of this study was to compare situational influences on "persistently high" and "low stable" trajectories of healthcare utilization in patients who received palliative care support at home. METHODS: Bereaved family caregivers were recruited from our prior quantitative study investigating healthcare utilization trajectories in oncology patients on home-based palliative care. In-depth interviews were conducted with 30 family caregivers. Data were analyzed using thematic analysis. RESULTS: Analysis of data uncovered how the 2 utilization trajectories were influenced by the interplay of 1 or more of 4 situational elements. Perceived symptom control in patients, influenced by their determination to die at home, shapes the susceptibility to situational contingencies, resulting in differential utilization trajectories. Caregivers' mental readiness in dealing with unexpected circumstances has a significant impact on the overall manageability of care, ultimately affecting decisions related to healthcare utilization. The concordance between symptom needs and scope of homecare services in a given situation proves to be an important determinant. Lastly, perceived accessibility to informal support in times of need acts as a contextual reinforcement, either preventing or precipitating decisions regarding healthcare utilizations. SIGNIFICANCE OF RESULTS: Our findings hold important implications for the provision of homecare services, in particular, the need for comprehensive assessment of end-of-life wishes during homecare enrolment and strengthening psychological preparedness of caregivers. Expansion of home-based clinical interventions tailored to high utilizers, and funding for temporary in-home respite should be considered to optimally manage potentially preventable acute healthcare utilization.

Can an Integrated Palliative and Oncology Co-rounding Model Reduce Aggressive Care at the End of Life? Secondary Analysis of an Open-label Stepped-wedge Cluster-randomized Trial.

BACKGROUND: Clinical trial evidence on the effect of palliative care models in reducing aggressive end-of-life care is inconclusive. We previously reported on an integrated inpatient palliative care and medical oncology co-rounding model that significantly reduced hospital bed-days and postulate additional effect on reducing care aggressiveness. OBJECTIVES: To compare the effect of a co-rounding model vs usual care in reducing receipt of aggressive treatment at end-of-life. METHODS: Secondary analysis of an open-label stepped-wedge cluster-randomized trial comparing two integrated palliative care models within the inpatient oncology setting. The co-rounding model involved pooling specialist palliative care and oncology into one team with daily review of admission issues, while usual care constituted discretionary specialist palliative care referrals by the oncology team. We compared odds of receiving aggressive care at end-of-life: acute healthcare utilization in last 30 days of life, death in hospital, and cancer treatment in last 14 days of life between patients in two trial arms. RESULTS: 2145 patients were included in the analysis, and 1803 patients died by 4th April 2021. Median overall survival was 4.90 (4.07 - 5.72) months in co-rounding and 3.75 (3.22 - 4.21) months in usual care, with no difference in survival (P = .12). We found no significant differences between both models with respect to receipt of aggressive care at end-of-life. (Odds Ratio .67 - 1.27; all P > .05). CONCLUSION: The co-rounding model within an inpatient setting did not reduce aggressiveness of care at end-of-life. This could be due in part to the overall focus on resolving episodic admission issues.

Synovial Metastasis From Urothelial Carcinoma of the Renal Pelvis Causing Recurrent Hemarthrosis: A Rare Presentation.

Synovial metastases are rare for any malignancy. This case report discusses a case of synovial metastasis from urothelial carcinoma of the renal pelvis presenting with recurrent hemarthrosis. The diagnosis of malignant synovitis can be obtained by synovial fluid aspiration, which is a quick and minimally invasive method, especially when imaging is unyielding or unspecific. Unfortunately, the diagnosis is associated with a poor prognosis of about five months, and treatment is often palliative. While no clinical guidelines exist, a multimodal and multidisciplinary management approach can help address the physical and psychosocial losses suffered.

Longitudinal patterns and predictors of healthcare utilization among cancer patients on home-based palliative care in Singapore: a group-based multi-trajectory analysis.

BACKGROUND: Home-based palliative care (HPC) is considered to moderate the problem of rising healthcare utilization of cancer patients at end-of-life. Reports however suggest a proportion of HPC patients continue to experience high care intensity. Little is known about differential trajectories of healthcare utilization in patients on HPC. Thus, we aimed to uncover the heterogeneity of healthcare utilization trajectories in HPC patients and identify predictors of each utilization pattern. METHODS: This is a cohort study of adult cancer patients referred by Singapore Health Services to HCA Hospice Service who died between 1st January 2018 and 31st March 2020. We used patient-level data to capture predisposing, enabling, and need factors for healthcare utilization. Group-based multi-trajectory modelling was applied to identify trajectories for healthcare utilization based on the composite outcome of emergency department (ED) visits, hospitalization, and outpatient visits. RESULTS: A total of 1572 cancer patients received HPC (median age, 71 years; interquartile range, 62-80 years; 51.1% female). We found three distinct trajectory groups: group 1 (31.9% of cohort) with persistently low frequencies of healthcare utilization, group 2 (44.1%) with persistently high frequencies, and group 3 (24.0%) that begin with moderate frequencies, which dropped over the next 9 months before increasing in the last 3 months. Predisposing (age, advance care plan completion, and care preferences), enabling (no medical subsidy, primary decision maker), and need factors (cancer type, comorbidity burden and performance status) were significantly associated with group membership. High symptom needs increased ED visits and hospitalizations in all three groups (ED visits, group 1-3: incidence rate ratio [IRR] 1.74-6.85; hospitalizations, group 1-3: IRR 1.69-6.60). High home visit intensity reduced outpatient visits in all three groups (group 1-3 IRR 0.54-0.84), while it contributed to reduction of ED visits (IRR 0.40; 95% CI 0.25-0.62) and hospitalizations (IRR 0.37; 95% CI 0.24-0.58) in group 2. CONCLUSIONS: This study on HPC patients highlights three healthcare utilization trajectories with implications for targeted interventions. Future efforts could include improving advance care plan completion, supporting care preferences in the community, proactive interventions among symptomatic high-risk patients, and stratification of home visit intensity.

Impact of cancer diagnoses on the outcomes of patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The COVID-19 has caused significant mortality and morbidity across the globe. Patients with cancer are especially vulnerable given their immunocompromised state. We aimed to determine the proportion of COVID-19 patients with cancer, their severity and mortality outcomes through a systematic review and meta-analysis (MA). METHODS: Systematic review was performed through online databases, PubMed, Medline and Google Scholar, with keywords listed in the Methods section (1 November 2019-31 December 2020). Studies with clinical outcomes of at least 10 COVID-19 patients and at least one with a diagnosis of cancer were included. The studies for MA were assessed with PRISMA guidelines and appraised with Newcastle-Ottawa Scale. The data were pooled using a random-effects model using STATA software. The main outcomes were planned before data collection, including proportion of patients with cancer among COVID-19 populations, relative risk (RR) of severe outcomes and death of patients with cancer compared with general COVID-19 patients. RESULTS: We identified 57 case series (63 413 patients), with 230 patients with cancer with individual patient data (IPD). We found that the pooled proportion of cancer among COVID-19 patients was 0.04 (95% CI 0.03 to 0.05, I2=97.69%, p<0.001). The pooled RR of death was 1.44 (95% CI 1.19 to 1.76) between patients with cancer and the general population with COVID-19 infection. The pooled RR of severe outcome was 1.49 (95% CI 1.18 to 1.87) between cancer and general COVID-19 patients. The presence of lung cancer and stage IV cancer did not result in significantly increased RR of severe outcome. Among the available IPD, only age and gender were associated with severe outcomes. CONCLUSION: Patients with cancer were at a higher risk of severe and death outcomes from COVID-19 infection as compared with general COVID-19 populations. Limitations of this study include publication bias. A collaborative effort is required for a more complete database.

Exploration and Development of a Simpler Respiratory Distress Observation Scale (modRDOS-4) as a Dyspnea Screening Tool: A Prospective Bedside Study.

Introduction: End-of-life patients face difficulties in reporting respiratory distress. The Respiratory Distress Observation Scale (RDOS) is a well-known tool; however, field implementation has been challenging from ground feedback. We sought to develop a simpler scale. Setting: Patients referred for palliative consult in a tertiary hospital in Singapore were recruited. Methods: A priori, we identified 18 dyspnea physical signs and documented their presence through bedside observation. Dyspnea severity was self-reported. The cohort was randomly split into training and test sets. Partial least square regression with leave-one-out cross-validation was used to develop a four-point model from the training set. Using the test set, data fit was compared using Akaike and Bayesian Information Criterion. Discrimination was assessed using receiver operating characteristics. Results: Of 122 patients, mean age was 67.9 years (range 23-93, standard deviation 12.9), 71.3% had a primary cancer diagnosis, and 58.1% were chair/bedbound with a Palliative Performance Scale of ≤50. Median reported dyspnea scale was 5 (interquartile range 3-7). Our model (modRDOS-4) consisted of four predictors (grunting, respiratory rate, accessory muscle use, paradoxical breathing). A modRDOS-4 of ≥6 identified moderate-to-severe dyspnea with a sensitivity of 0.78 and specificity of 0.90. Using the test set, with the modRDOS-4, the Akaike Information Criterion (AIC) is 149.8, Bayesian Information Criteria (BIC) is 154.1, and the receiver operating characteristics (ROC) is 0.74. With the original RDOS, the AIC is 145.2, BIC is 149.5, and ROC is 0.76. Conclusion: For a quick assessment of dyspnea, we developed a four-item tool with a pilot web-based nomogram. External validation is needed.

Perceptions of healthcare professionals towards palliative care in internal medicine wards: a cross-sectional survey.

BACKGROUND: The extension of palliative care services to meet the needs of patients with chronic non-malignant life-limiting conditions faces misconceptions amongst healthcare professionals. A study of prevailing perceptions of healthcare professionals on this wider palliative care service was thus conducted to identify current obstacles, guide the education of local healthcare professionals and improve service accessibility. METHODS: A cross-sectional study was carried out at the Singapore General Hospital. An anonymised and close-ended online questionnaire was disseminated to 120 physicians and 500 nurses in the Department of Internal Medicine. The online survey tool focused on participant demographics; perceptions of palliative care and its perceived benefits; roles and indications; and attitudes and behaviours towards palliative care referrals. RESULTS: Forty four physicians and 156 nurses suggested that care of terminally ill patients with chronic non-malignant life-limiting conditions are compromised by concerns over the role of palliative care in non-cancer care and lapses in their prognostication and communication skills. Respondents also raised concerns about their ability to confront sociocultural issues and introduce palliative care services to patients and their families. CONCLUSIONS: Gaps in understanding and the ability of nurses and physicians to communicate end of life issues, introduce palliative care services to patients and their families and confront sociocultural issues suggest the need for a longitudinal training program. With similar concerns likely prevalent in other clinical settings within this island nation, a concerted national education program targeting obstacles surrounding effective palliative care should be considered.

Characteristics of unplanned hospitalisations among cancer patients in Singapore.

INTRODUCTION: Cancer is a pervasive global problem with significant healthcare utilisation and cost. Emergency departments (EDs) see large numbers of patients with oncologic emergencies and act as "gate-keepers" to subsequent hospital admissions. A proportion of such hospital admissions are rapidly discharged within 2 days and may be potentially avoidable. METHODS: Over a 6-month period, we conducted a retrospective audit of active cancer patients presenting to the ED with subsequent admission to the Department of Medical Oncology. Our aims were to identify independent factors associated with a length of stay ≤2 days; and characterise the clinical and resource needs of these short admissions. RESULTS: Among all medical oncology admissions, 24.4% were discharged within 2 days. Compared to longer stayers, patients with short admissions were significantly younger (P=0.010), had lower National Early Warning Scores (NEWS) (P=0.006), and had a lower proportion of gastrointestinal and hepatobiliary cancers (P=0.005). Among short admissions, common presenting medical problems were infections (n=144, 36.3%), pain (n=116, 29.2%), gastrointestinal complaints (n=85, 21.4%) and respiratory complaints (n=76, 19.1%). These admissions required investigations and treatments already available at the ED. CONCLUSION: Short admissions have low resource needs and may be managed in the ED. This may help save valuable inpatient bed-days and reduce overall healthcare costs.

Minimizing transmission of COVID-19 while delivering optimal cancer care in a National Cancer Centre.

The COVID-19 pandemic has disrupted current models of healthcare and adaptations will likely continue. With the gradual easing of lockdown measures worldwide, cancer centres must be prepared to implement novel means to prevent repeated waves of infection. There are two limitations unique to oncology - a higher susceptibility of patients to COVID-19 and the multidisciplinary approach required of cancer management. We describe the measures implemented in the largest cancer centre in Singapore to continue optimal cancer care in spite of the ongoing pandemic, with no nosocomial infections reported in our centre to date. We adopted a multipronged approach, with an overall committee supervising the entire COVID-19 management effort. A screening clinic was setup to triage patients prior to entry to the centre. Each Oncology Division within the cancer centre designed solutions tailored to the specific needs of their discipline. We explore in detail the screening criteria and workflow of the screening clinic, as well as modifications by individual divisions to reduce infection risk to patients and healthcare professionals. This approach can be modelled by other cancer centres during this prolonged COVID-19 pandemic.

The impact of COVID-19 on and recommendations for breast cancer care: the Singapore experience.

The ensuing COVID-19 pandemic poses unprecedented and daunting challenges to the routine delivery of oncological and supportive care to patients with breast cancer. Considerations include the infective risk of patients who are inherently immunosuppressed from their malignancy and therapies, long-term oncological outcomes from the treatment decisions undertaken during this extraordinary period, and diverted healthcare resources to support a coordinated whole-of-society outbreak response. In this review, we chronicle the repercussions of the COVID-19 outbreak on breast cancer management in Singapore and describe our approach to triaging and prioritising care of breast tumours. We further propose adaptations to established clinical processes and practices across the different specialties involved in breast oncology, with references to the relevant evidence base or expert consensus guidelines. These recommendations have been developed within the unique context of Singapore's public healthcare sector. They can serve as a resource to guide breast cancer management for future contingencies in this city-state, while certain elements therein may be extrapolatable to other medical systems during this global public health emergency.

Sociodemographic and clinical factors for non-hospital deaths among cancer patients: A nationwide population-based cohort study.

BACKGROUND: Factors associated with place of death inform policies with respect to allocating end-of-life care resources and tailoring supportive measures. OBJECTIVE: To determine factors associated with non-hospital deaths among cancer patients. DESIGN: Retrospective cohort study of cancer decedents, examining factors associated with non-hospital deaths using multinomial logistic regression with hospital deaths as the reference category. SETTING/SUBJECTS: Cancer patients (n = 15254) in Singapore who died during the study period from January 1, 2012 till December 31, 2105 at home, acute hospital, long-term care (LTC) or hospice were included. RESULTS: Increasing age (categories ≥65 years: RRR 1.25-2.61), female (RRR 1.40; 95% CI 1.28-1.52), Malays (RRR 1.67; 95% CI 1.47-1.89), Brain malignancy (RRR 1.92; 95% CI 1.15-3.23), metastatic disease (RRR 1.33-2.01) and home palliative care (RRR 2.11; 95% CI 1.95-2.29) were associated with higher risk of home deaths. Patients with low socioeconomic status were more likely to have hospice or LTC deaths: those living in smaller housing types had higher risk of dying in hospice (1-4 rooms apartment: RRR 1.13-3.17) or LTC (1-5 rooms apartment: RRR 1.36-4.11); and those with Medifund usage had higher risk of dying in LTC (RRR 1.74; 95% CI 1.36-2.21). Patients with haematological malignancies had increased risk of dying in hospital (categories of haematological subtypes: RRR 0.06-0.87). CONCLUSIONS: We found key sociodemographic and clinical factors associated with non-hospital deaths in cancer patients. More can be done to enable patients to die in the community and with dignity rather than in a hospital.

Validation of Modified Breast Graded Prognostic Assessment for breast cancer patients with brain metastases: extra-cranial disease progression is an independent risk factor.

BACKGROUND: Breast cancer (BC) patients with brain metastases (BM) are heterogeneous with markedly variable survival. The Breast Graded Prognostic Assessment (B-GPA) and Modified B-GPA (mB-GPA) have been proposed as useful tools for stratifying survival in this population. However, extra-cranial disease progression, a clinically important variable, is not incorporated into the final model. We undertook the validation of B-GPA and mB-GPA in an Asian cohort and further explore extra-cranial disease progression as a prognostic factor. METHODS: Data of BC patients with newly diagnosed BM between 2006 and 2017 was extracted retrospectively from a prospectively maintained institutional database. Patients were classified based on their B-GPA and mB-GPA scores. Univariate (UVA) and multivariate analysis (MVA) using the Cox proportional hazard model were performed to investigate the factors prognostic of overall survival (OS). The Kaplan-Meier method was used to estimate OS and log-rank test to compare survival between scores. The performances of B-GPA and mB-GPA were compared using Harrell's concordance index (C-index) and Akaike information criterion (AIC). RESULTS: In our cohort of 282 patients, the B-GPA and mB-GPA were validated as prognostic tools for OS, demonstrating excellent separation between survival curves (P <0.001). In MVA, we found all components of mB-GPA (age, performance status, number of BM, tumour subtype) to be independent predictors of survival. C-index was 0.64 and AIC was 2,483.39 for B-GPA. mB-GPA demonstrated marginally better discrimination with a C-index of 0.65 and AIC of 2,445.78. Extra-cranial progression was an independent predictor for survival in our population (P <0.001). CONCLUSIONS: The mB-GPA incorporates four simple clinical variables each of independent prognostic significance. Both B-GPA and mB-GPA demonstrate moderate discriminative capabilities for OS with mB-GPA performing marginally better. Inclusion of extra-cranial disease progression as a factor in future model development may further improve its prognostic value.

Validity, Reliability, and Diagnostic Accuracy of the Respiratory Distress Observation Scale for Assessment of Dyspnea in Adult Palliative Care Patients.

BACKGROUND: The prevalence and severity of dyspnea increase at the end of life. Many of these patients have difficulty in reporting their symptoms. Accurate surrogate measures are needed for appropriate assessment and treatment. The Respiratory Distress Observation Scale (RDOS) is proposed as a possible scale although more external validation is needed. We set out to validate the RDOS in the context of palliative care patients near the end of life. MEASURES: We prospectively studied 122 palliative care patients in a tertiary hospital in Singapore. Prior RDOS training was done using a standardized instructional video. Dyspnea was assessed by RDOS, Dyspnea Numerical Rating Scale, and Dyspnea Categorical Scale. Pain was assessed by Pain Numerical Rating Scale. We measured RDOS inter-rater reliability, convergent validity, and divergent validity. We used area under receiver operating characteristics curve (AUC) analysis to examine the discriminant properties of RDOS using dyspnea self-report as benchmark. RESULTS: RDOS had good inter-rater reliability with an intraclass correlation of 0.947 (95% CI 0.919-0.976). It showed moderate-to-strong correlation with Dyspnea Numerical Rating Scale (r = 0.702) and Dyspnea Categorical Scale (r = 0.677) and negligible correlation to Pain Numerical Rating Scale (r = 0.080). It showed good discriminant properties of identifying patients with moderate and severe dyspnea with an AUC of 0.874 (95% CI 0.812-0.936). RDOS ≥ 4 predicted patients with moderate and severe dyspnea with a sensitivity of 76.6%, specificity of 86.2%, positive predictive value of 86.0%, and negative predictive value of 76.9%. CONCLUSIONS: The RDOS shows promise and clinical utility as an observational dyspnea assessment tool. Further studies in uncommunicative patients are needed to determine clinical usefulness and generalizability of results.