Oncology Clinicians’ Challenges to Providing Palliative Cancer Care—A Theoretical Domains Framework, Pan-Cancer System Survey

Despite the known benefits, healthcare systems struggle to provide early, integrated palliative care (PC) for advanced cancer patients. Understanding the barriers to providing PC from the perspective of oncology clinicians is an important first step in improving care. A 33-item online survey was emailed to all oncology clinicians working with all cancer types in Alberta, Canada, from November 2017 to January 2018. Questions were informed by Michie’s Theoretical Domains Framework and Behaviour Change Wheel (BCW) and queried (a) PC provision in oncology clinics, (b) specialist PC consultation referrals, and (c) working with PC consultants and home care. Respondents (n = 263) were nurses (41%), physicians (25%), and allied healthcare professionals (18%). Barriers most frequently identified were “clinicians’ limited time/competing priorities” (64%), “patients’ negative perceptions of PC” (63%), and clinicians’ capability to manage patients’ social issues (63%). These factors mapped to all three BCW domains: motivation, opportunity, and capability. In contrast, the least frequently identified barriers were clinician motivation and perceived PC benefits. Oncology clinicians’ perceptions of barriers to early PC were comparable across tumour types and specialties but varied by professional role. The main challenges to early integrated PC include all three BCW domains. Notably, motivation is not a barrier for oncology clinicians; however, opportunity and capability barriers were identified. Multifaceted interventions using these findings have been developed, such as tip sheets to enhance capability, reframing PC with patients, and earlier specialist PC nursing access, to enhance clinicians’ use of and patients’ benefits from an early PC approach.

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Barriers to providing palliative care to patients with advanced cancer: A province-wide survey of oncology clinicians’ perceptions.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.34_suppl.88 ◽

2018 ◽

Vol 36 (34_suppl) ◽

pp. 88-88

Author(s):

Sharon Watanabe ◽

Sharlette Dunn ◽

Madalene Earp ◽

Lisa Shirt ◽

Patricia Biondo ◽

...

Keyword(s):

Palliative Care ◽

Health Professionals ◽

Theoretical Domains Framework ◽

Allied Health Professionals ◽

Behaviour Change Wheel ◽

Tumor Group ◽

Care Systems ◽

Negative Perceptions ◽

Multifaceted Interventions ◽

Competing Priorities

88 Background: Despite known benefits, cancer care systems struggle to provide early, integrated palliative care (PC). Previously, we identified barriers to providing early PC as perceived by gastrointestinal oncology clinicians in Alberta, Canada (top barrier: time/competing priorities). Here, we expand on the previous study to better understand barriers to early PC for clinicians working with all tumor groups across Alberta. Methods: A 33-item survey was emailed to oncology clinicians in Alberta between November 2017 - January 2018. Questions were informed by Michie’s Theoretical Domains Framework (TDF) and Behaviour Change Wheel (BCW) and queried (a) providing PC in oncology clinics, (b) referral to specialist PC consultation, and (c) working with PC consultants and homecare. Results: Respondents (n = 268) were nurses (42%), physicians (25%), and allied health professionals (20%). Barriers most frequently identified were "patients’ negative perceptions of PC” (68%), “my limited time/competing priorities” (66%), and "capability to manage patients’", social (65%) and spiritual (63%) concerns. These factors map to all three BCW domains: motivation, opportunity, and capability. In contrast, least frequently identified barriers were in clinician’s own motivation, e.g. perceived benefits of PC. There were few significant differences in response by tumor group or profession (χ2 test, responses coded: disagree [1-3], neutral [4], agree [5-7]). Most notably, tumor groups differed in their perception that “the criteria for PC services are too restrictive” (p = 0.003), while nurses and allied staff reported that patients’ negative perception of PC is a barrier more frequently than physicians (p = 0.003). Conclusions: Surveying across clinicians and tumor groups using Michie’s TDF/BCW revealed that the challenges to an early integrated PC approach include all three sources of behavior, though not equally for all clinicians. Determining this has allowed us to tailor multifaceted interventions, e.g. tip sheets to enhance capability, re-framing PC with patients, and earlier secondary PC nursing access, to enhance clinicians use and patients benefit from an early PC approach.

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Characterization of the Survival Influential Genes in Carcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22094384 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4384

Author(s):

Divya Sahu ◽

Yu-Lin Chang ◽

Yin-Chen Lin ◽

Chen-Ching Lin

Keyword(s):

Cell Cycle ◽

Cox Regression ◽

Monte Carlo Algorithm ◽

Functional Modules ◽

Protective Genes ◽

Cancer Types ◽

Underlying Mechanisms ◽

Patient Prognosis ◽

Pan Cancer

The genes influencing cancer patient mortality have been studied by survival analysis for many years. However, most studies utilized them only to support their findings associated with patient prognosis: their roles in carcinogenesis have not yet been revealed. Herein, we applied an in silico approach, integrating the Cox regression model with effect size estimated by the Monte Carlo algorithm, to screen survival-influential genes in more than 6000 tumor samples across 16 cancer types. We observed that the survival-influential genes had cancer-dependent properties. Moreover, the functional modules formed by the harmful genes were consistently associated with cell cycle in 12 out of the 16 cancer types and pan-cancer, showing that dysregulation of the cell cycle could harm patient prognosis in cancer. The functional modules formed by the protective genes are more diverse in cancers; the most prevalent functions are relevant for immune response, implying that patients with different cancer types might develop different mechanisms against carcinogenesis. We also identified a harmful set of 10 genes, with potential as prognostic biomarkers in pan-cancer. Briefly, our results demonstrated that the survival-influential genes could reveal underlying mechanisms in carcinogenesis and might provide clues for developing therapeutic targets for cancers.

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Chromosomal copy number heterogeneity predicts survival rates across cancers

Nature Communications ◽

10.1038/s41467-021-23384-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Erik van Dijk ◽

Tom van den Bosch ◽

Kristiaan J. Lenos ◽

Khalid El Makrini ◽

Lisanne E. Nijman ◽

...

Keyword(s):

Copy Number ◽

Cancer Survival ◽

Survival Rates ◽

Cancer Prognosis ◽

Disease Outcomes ◽

Distinct Disease ◽

Cancer Types ◽

Chromosomal Copy Number ◽

Chromosomal Copy ◽

Pan Cancer

AbstractSurvival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.

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Pan-Cancer Transcriptional Models Predicting Chemosensitivity in Human Tumors

Cancer Informatics ◽

10.1177/11769351211002494 ◽

2021 ◽

Vol 20 ◽

pp. 117693512110024

Author(s):

Jason D Wells ◽

Jacqueline R Griffin ◽

Todd W Miller

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Human Tumors ◽

Molecular Characteristics ◽

Survival Times ◽

Chemotherapy Drugs ◽

Testing Dataset ◽

Cancer Models ◽

Cancer Types ◽

Pan Cancer

Motivation: Despite increasing understanding of the molecular characteristics of cancer, chemotherapy success rates remain low for many cancer types. Studies have attempted to identify patient and tumor characteristics that predict sensitivity or resistance to different types of conventional chemotherapies, yet a concise model that predicts chemosensitivity based on gene expression profiles across cancer types remains to be formulated. We attempted to generate pan-cancer models predictive of chemosensitivity and chemoresistance. Such models may increase the likelihood of identifying the type of chemotherapy most likely to be effective for a given patient based on the overall gene expression of their tumor. Results: Gene expression and drug sensitivity data from solid tumor cell lines were used to build predictive models for 11 individual chemotherapy drugs. Models were validated using datasets from solid tumors from patients. For all drug models, accuracy ranged from 0.81 to 0.93 when applied to all relevant cancer types in the testing dataset. When considering how well the models predicted chemosensitivity or chemoresistance within individual cancer types in the testing dataset, accuracy was as high as 0.98. Cell line–derived pan-cancer models were able to statistically significantly predict sensitivity in human tumors in some instances; for example, a pan-cancer model predicting sensitivity in patients with bladder cancer treated with cisplatin was able to significantly segregate sensitive and resistant patients based on recurrence-free survival times ( P = .048) and in patients with pancreatic cancer treated with gemcitabine ( P = .038). These models can predict chemosensitivity and chemoresistance across cancer types with clinically useful levels of accuracy.

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Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature

Cells ◽

10.3390/cells10010045 ◽

2020 ◽

Vol 10 (1) ◽

pp. 45

Author(s):

Darío Rocha ◽

Iris A. García ◽

Aldana González Montoro ◽

Andrea Llera ◽

Laura Prato ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Uncertainty Assessment ◽

Cell Cycle Checkpoints ◽

Molecular Signature ◽

Cancer Subtypes ◽

United States Food ◽

Cancer Types ◽

Molecular Patterns ◽

Pan Cancer

Studying tissue-independent components of cancer and defining pan-cancer subtypes could be addressed using tissue-specific molecular signatures if classification errors are controlled. Since PAM50 is a well-known, United States Food and Drug Administration (FDA)-approved and commercially available breast cancer signature, we applied it with uncertainty assessment to classify tumor samples from over 33 cancer types, discarded unassigned samples, and studied the emerging tumor-agnostic molecular patterns. The percentage of unassigned samples ranged between 55.5% and 86.9% in non-breast tissues, and gene set analysis suggested that the remaining samples could be grouped into two classes (named C1 and C2) regardless of the tissue. The C2 class was more dedifferentiated, more proliferative, with higher centrosome amplification, and potentially more TP53 and RB1 mutations. We identified 28 gene sets and 95 genes mainly associated with cell-cycle progression, cell-cycle checkpoints, and DNA damage that were consistently exacerbated in the C2 class. In some cancer types, the C1/C2 classification was associated with survival and drug sensitivity, and modulated the prognostic meaning of the immune infiltrate. Our results suggest that PAM50 could be repurposed for a pan-cancer context when paired with uncertainty assessment, resulting in two classes with molecular, biological, and clinical implications.

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Exome-Wide Pan-Cancer Analysis of Germline Variants in 8,719 Individuals Finds Little Evidence of Rare Variant Associations

Human Heredity ◽

10.1159/000519355 ◽

2021 ◽

pp. 1-10

Author(s):

Zoe Guan ◽

Ronglai Shen ◽

Colin B. Begg

Keyword(s):

Rare Variant ◽

Rare Variants ◽

Association Studies ◽

The Cancer Genome Atlas ◽

Considerable Proportion ◽

Genome Wide Association Studies ◽

Sequencing Data ◽

Risk Variants ◽

Cancer Types ◽

Pan Cancer

Background: Many cancer types show considerable heritability, and extensive research has been done to identify germline susceptibility variants. Linkage studies have discovered many rare high-risk variants, and genome-wide association studies (GWAS) have discovered many common low-risk variants. However, it is believed that a considerable proportion of the heritability of cancer remains unexplained by known susceptibility variants. The “rare variant hypothesis” proposes that much of the missing heritability lies in rare variants that cannot reliably be detected by linkage analysis or GWAS. Until recently, high sequencing costs have precluded extensive surveys of rare variants, but technological advances have now made it possible to analyze rare variants on a much greater scale. Objectives: In this study, we investigated associations between rare variants and 14 cancer types. Methods: We ran association tests using whole-exome sequencing data from The Cancer Genome Atlas (TCGA) and validated the findings using data from the Pan-Cancer Analysis of Whole Genomes Consortium (PCAWG). Results: We identified four significant associations in TCGA, only one of which was replicated in PCAWG (BRCA1 and ovarian cancer). Conclusions: Our results provide little evidence in favor of the rare variant hypothesis. Much larger sample sizes may be needed to detect undiscovered rare cancer variants.

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Exploration of the MSI landscape in Chinese pan-cancer patient by Next-Generation Sequencing.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e14576 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e14576-e14576

Author(s):

Xinlu Liu ◽

Jiasheng Xu ◽

Jian Sun ◽

Deng Wei ◽

Xinsheng Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Correlation Analysis ◽

Cancer Patients ◽

Cancer Type ◽

Multiple Tumor ◽

Treatment Plans ◽

Cancer Types ◽

Chinese Cancer Patients ◽

Colorectal Cancer Patients ◽

Pan Cancer

e14576 Background: Clinically, MSI had been used as an important molecular marker for the prognosis of colorectal cancer and other solid tumors and the formulation of adjuvant treatment plans, and it had been used to assist in the screening of Lynch syndrome. However, there were currently few reports on the incidence of MSI-H in Chinese pan-cancer patients. This study described the occurrence of MSI in a large multi-center pan-cancer cohort in China, and explored the correlation between MSI and patients' TMB, age, PD-L1 expression and other indicators. Methods: The study included 8361 patients with 8 cancer types from multiple tumor centers. Use immunohistochemistry to detect the expression of MMR protein (MLH1, MSH2, MSH6 and PMS2) in patients with various cancer types to determine the MSI status and detect the expression of PD-L1 in patients. Through NGS technology, 831 genes of 8361 Chinese cancer patients were sequenced and the tumor mutation load of the patients was calculated. The MSI mutations of patients in 8 cancer types were analyzed and the correlation between MSI mutations of patients and the patient's age, TMB and PD-L1 expression was analyzed. Results: The test results showed that MSI patients accounted for 1.66% of pan-cancers. Among them, MSI-H patients accounted for the highest proportion in intestinal cancer, reaching 7.2%. The correlation analysis between MSI and TMB was performed on patients of various cancer types. The results showed that: in each cancer type, MSI-H patients had TMB greater than 10, and 26.83% of MSI-H patients had TMB greater than 100 in colorectal cancer patients. The result of correlation analysis showed that there was no significant correlation between the patient's age and the risk of MSI mutation ( P> 0.05). In addition to PAAD and LUAD, the expression of PD-L1 in MSI-H patients was higher than that in MSS patients in other cancer types( P< 0.05). The correlation analysis between PD-L1 expression and TMB in patients found that in colorectal cancer, the higher the expression of PD-L1, the higher the patient's TMB ( P< 0.05). Conclusions: In this study, we explored the incidence of MSI-H in pan-cancer patients in China and found that the TMB was greater than 10 in patients with MSI-H. Compared with MSS patients, MSI-H patients have higher PD-L1 expression, and the higher the PD-L1 expression in colorectal cancer, the higher the TMB value of patients.

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An ultrasensitive method for noninvasive pan-cancer early detection based on targeted methylation sequencing of cell-free DNA.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10544 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10544-10544

Author(s):

Tiancheng Han ◽

Yuanyuan Hong ◽

Pei Zhihua ◽

Song Xiaofeng ◽

Jianing Yu ◽

...

Keyword(s):

Cancer Patients ◽

Cancer Detection ◽

Real World ◽

Early Stage ◽

Validation Dataset ◽

Cpg Sites ◽

Free Dna ◽

Cancer Types ◽

Discovery Dataset ◽

Pan Cancer

10544 Background: Screening the biomarkers from the cell-free DNA (cfDNA) of peripheral blood is a non-invasive and promising method for cancer diagnosis. Among diverse types of biomarkers, epigenetic biomarkers have been reported to be one of the most promising ones. Epigenetic modifications are widespread on the human genome and generally have strong signals due to the similar methylation patterns shared by adjacent CpG sites. Although some epigenetic diagnostic methods have been developed based on cfDNAs, few of them could be applied to pan-cancer and their sensitivities are barely satisfactory for early cancer detection. Methods: Targeted methylation sequencing was performed using our in-house-designed panel targeting regions with abundant cancer-specific methylation CpGs. The cfDNA samples from 80 healthy individuals and 549 cancer patients of 14 cancer types were separately sequenced. The dataset was randomly split into one discovery dataset and one validation dataset. Moreover, cfDNA samples from four cancer patients were diluted with the healthy cfDNAs to generate 12 in vitro simulated samples with low circulating tumor DNA (ctDNA) fraction. Additionally, DNAs extracted from 130 unmatched tumor formalin fixation and paraffin embedding (FFPE) samples of 10 cancer types were sequenced to screen the diagnostic biomarkers. Adjacent CpG sites were first merged into methylation-correlated blocks (MCB) according to their correlations of methylation levels in tumor DNAs. The MCBs with higher methylation levels in tumor DNAs than that of healthy cfDNAs (from the discovery dataset) were defined as our hypermethylation biomarkers. For each cfDNA sample, a hypermethylation score (HM-score) was computed to measure the overall methylation level difference of selected biomarkers. The performance of our method was evaluated with the real-world dataset, while the limit of detection was estimated using the simulated low-ctDNA samples. Results: Our model based on 37 hypermethylation MCB biomarkers achieved an area under the curve (AUC) of 0.89 and 0.86 in the real-world pan-cancer discovery and validation cfDNA datasets, respectively. Furthermore, the overall specificity and sensitivity are 100% and 76.19% in the discovery dataset, and 96.67% and 72.86% in the validation dataset. In the validation dataset, 28/40 (70%) of early-stage colorectal cancer patients and 10/20 (50%) of non-small-cell lung cancer patients were successfully diagnosed. Additionally, all the simulated samples with theoretical ctDNA factions over 0.5% were predicted as diseased, demonstrating the ability of our method to detect tumor signals at early stages. Conclusions: Our cfDNA-based epigenetic method outperforms currently available methods in various cancer types, and is promising to be applied to early-stage cancer detection and samples with low ctDNA fractions.

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Pan-Cancer Analysis of PIMREG as a Biomarker for the Prognostic and Immunological Role

Frontiers in Genetics ◽

10.3389/fgene.2021.687778 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hua Zhu ◽

Xinyao Hu ◽

Yingze Ye ◽

Zhihong Jian ◽

Yi Zhong ◽

...

Keyword(s):

Signaling Pathway ◽

Chemokine Receptors ◽

Antigen Processing ◽

Immune Cell ◽

Nk Cell ◽

Cell Lineage ◽

Cell Receptor ◽

The Cancer Genome Atlas ◽

Cancer Types ◽

Pan Cancer

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) localizes to the nucleus and can significantly elevate the nuclear localization of clathrin assembly lymphomedullary leukocythemia gene. Although there is some evidence to support an important action for PIMREG in the occurrence and development of certain cancers, currently no pan-cancer analysis of PIMREG is available. Therefore, we intended to estimate the prognostic predictive value of PIMREG and to explore its potential immune function in 33 cancer types. By using a series of bioinformatics approaches, we extracted and analyzed datasets from Oncomine, The Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia (CCLE) and the Human Protein Atlas (HPA), to explore the underlying carcinogenesis of PIMREG, including relevance of PIMREG to prognosis, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME) and infiltration of immune cells in various types of cancer. Our findings indicate that PIMREG is highly expressed in at least 24 types of cancer, and is negatively correlated with prognosis in major cancer types. In addition, PIMREG expression was correlated with TMB in 24 cancers and with MSI in 10 cancers. We revealed that PIMREG is co-expressed with genes encoding major histocompatibility complex, immune activation, immune suppression, chemokine and chemokine receptors. We also found that the different roles of PIMREG in the infiltration of different immune cell types in different tumors. PIMREG can potentially influence the etiology or pathogenesis of cancer by acting on immune-related pathways, chemokine signaling pathway, regulation of autophagy, RIG-I like receptor signaling pathway, antigen processing and presentation, FC epsilon RI pathway, complement and coagulation cascades, T cell receptor pathway, NK cell mediated cytotoxicity and other immune-related pathways. Our study suggests that PIMREG can be applied as a prognostic marker in a variety of malignancies because of its role in tumorigenesis and immune infiltration.

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Latent Profile Analysis of Perceptions and Attitudes Towards COVID-19 in a Sample of Chinese People

Frontiers in Public Health ◽

10.3389/fpubh.2021.727242 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhimin Niu ◽

Li Li ◽

Hongying Li ◽

Songli Mei ◽

Hui Jiang ◽

...

Keyword(s):

Health Education ◽

Predictive Factors ◽

Online Survey ◽

Latent Profile Analysis ◽

Profile Analysis ◽

Chinese People ◽

Place Of Residence ◽

Perceptions And Attitudes ◽

Negative Perceptions ◽

Novel Coronavirus

Background: The novel coronavirus-2019 (COVID-19) disease has spread quickly throughout China and around the world, endangering human health and life. Individuals' perceptions and attitudes as well as related health education measures may affect disease progression and prognosis during the COVID-19 outbreak. To promote and implement health education, research must focus on the perceptions and attitudes towards COVID-19 among Chinese people. The present study aimed to examine the profiles and predictive factors of the perceptions and attitudes towards COVID-19 in a sample of Chinese people.Methods: A sample of 2,663 Chinese people comprising medical staff and members of the general public completed an online survey on Wenjuanxing. The survey measured demographic variables (e.g., gender, age, education level, and place of residence) and perceptions and attitudes towards COVID-19.Results: Two profiles of perceptions and attitudes towards COVID-19 (positive and negative perceptions and attitudes) were identified in the sample. Place of residence during the COVID-19 pandemic and first response to COVID-19 were found to be independent predictive factors for COVID-19 related perceptions and attitudes.Conclusion: In addition to drug therapy and mental health services, the perceptions and attitudes of Chinese people towards COVID-19 should be considered when promoting health education during the COVID-19 pandemic.

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