Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Patients enrolled in POG who initiated WGTA between July 2014 and December 2017

Matched controls who received usual care and were diagnosed with metastatic cancer prior to December 2017

POG-related WGTA generally involves collecting biopsy samples, applying whole-genome and transcriptome sequencing, and using bioinformatics analysis to interpret sequence data and inform clinical decision-making.

Initiation of POG-related WGTA

Usual care, not involving the initiation of POG-related WGTA

Usual care

This study aims to determine the clinical effectiveness of whole-genome and transcriptome analysis (WGTA) to guide advanced cancer care. The study setting is the British Columbia (BC) Personalized OncoGenomics (POG) program, a single group research study of WGTA guiding treatment planning for patients with advanced, incurable cancers (NCT02155621). To characterize clinical effectiveness, the survival impacts of POG's approach compared to usual care in matched controls will be estimated.

WGTA provides an opportunity to improve health outcomes for patients by tailoring treatments to each individual's genomic profile. The BC POG Program is a single arm research study integrating WGTA information into clinical decision-making for patients with advanced stage, incurable cancers.The clinical effectiveness of POG's approach is unknown. This retrospective quasi-experimental observational study will estimate the real-world effectiveness of WGTA for guiding advanced cancer care. To identify a counterfactual for POG's single-arm approach, matching methods combined with administrative healthcare data will be used. The survival impacts of POG's approach compared to usual care in matched controls will then be estimated.

Specific Aims and Hypotheses

This study aims to estimate the overall survival effects of POG's approach versus usual care for patients with advanced cancers.

Hypothesis (null): there is no difference in survival across POG and usual care patients

Hypothesis (alternative): POG patients who initiated WGTA live longer, on average, than usual care patients

Study Design

This study will apply a retrospective cohort design. Cohorts will include patients who consented to POG and underwent a biopsy for WGTA between July 2014 and December 2017 and matched usual care controls. POG patients who enrolled prior to July 2014 will be excluded from our study because during this feasibility period, referring clinicians employed a high level of case-by-case recruitment selection. Usual care patients will be matched to POG patients using supervised learning techniques. The study period will range from patient's time of metastatic cancer diagnosis to December 31 2018.

Data Sources

De-identified linked population-based administrative datasets will be obtained from BC Cancer for all adult patients (\>18 years) diagnosed with cancers in BC prior to December 2017. POG patients will be identified from the BC Cancer Outcomes and Surveillance Integration System (OaSIS) POG Module Database. Eligible control patients will be identified from the BC Cancer Registry, a population-based provincial cancer registry. These data will be linked with data from the BC Cancer Pharmacy Database, Radiotherapy Database, and Cancer Agency Information System (CAIS) using agency-specific identifiers.

Statistical Approach

The investigators will match POG patients and usual care patients based on their date of metastatic disease diagnosis. They will apply 1:1 genetic algorithm-based matching (1:2 in sensitivity analysis) and match patients on propensity scores and baseline covariates, including patient demographics, clinical characteristics, treatment histories, and healthcare utilization prior to metastatic disease diagnosis. When necessary, matching analyses will be stratified to account for variation across cancer types.

To estimate overall survival in POG patients and matched controls, non-parametric and parametric survival analyses will be used. These analyses will be adjusted for censoring. The investigators will explore heterogeneity in clinical effectiveness across cancer subtypes through subgroup analysis and use scenario analysis to determine the impact of future changes in the application of WGTA on clinical effectiveness.

Real-world Clinical Effectiveness of Whole Genome and Transcriptome Analysis to Guide Advanced Cancer Care

Retrospective Observational Study Determining the Clinical Effectiveness of Whole Genome and Transcriptome Analysis to Guide Advanced Cancer Care

The patient-level administrative data used in this retrospective study are confidential and will not be made available in a public repository, in accordance with institutional policies.

BC Cancer Foundation

Genome British Columbia

British Columbia Cancer Agency

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Multiple Pulmonary Nodules

Solitary Pulmonary Nodule

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

In the usual care arm, clinicians will evaluate individuals with indeterminate pulmonary nodules as part of routine clinical care. No specific guidance regarding pulmonary nodule risk stratification will provided to evaluating clinicians.

In the experimental arm, evaluating clinicians will receive a Lung Cancer Prediction report from an artificial intelligence radiomics-based computer-aided diagnosis tool for risk stratification of pulmonary nodules.

The Optellum Virtual Nodule Clinic is an FDA-approved (Class II) device for risk stratification of pulmonary nodules. It uses a convolutional neural network to evaluate CT imaging data to provide an estimate of malignancy risk for indeterminate pulmonary nodules.

Optellum Virtual Nodule Clinic

Roger Y. Kim, MD, MSCE

Anil Vachani, MD, MSCE

Roger Kim, MD, MSCE

This is a pragmatic clinical trial that will study the effect of a radiomics-based computer-aided diagnosis (CAD) tool on clinicians' management of pulmonary nodules (PNs) compared to usual care. Adults aged 35-89 years with 8-30mm PNs evaluated at Penn Medicine PN clinics will undergo 1:1 randomization to one of two groups, defined by the PN malignancy risk stratification strategy used by evaluating clinicians: 1) usual care or 2) usual care + use of a radiomics-based CAD tool.

Accurate malignancy risk stratification of pulmonary nodules (PNs) is critical to ensuring that cancer is diagnosed in a timely manner and patients do not undergo unnecessary diagnostic procedures. Preliminary data suggests that a radiomics-based lung cancer prediction (LCP) computer-aided diagnosis (CAD) tool is effective in risk stratifying PNs and may improve clinicians' PN management decisions. This is a pragmatic clinical trial evaluating the effect of this CAD tool on clinicians' management of PNs compared to usual care. Individuals eligible for this study will include adults aged 35-89 years who are scheduled to be evaluated at a Penn Medicine PN clinic for a newly discovered PN 8-30mm in maximal diameter on CT imaging. Exclusion criteria include lack of CT imaging data at the time of index clinic visit, thoracic lymphadenopathy by CT size criteria, presence of pulmonary masses (\>3cm in maximal diameter), PNs with popcorn calcification (consistent with benign etiology), pure ground-glass subsolid PNs, a history of lung cancer, and history of any active cancer within 5 years. Enrolled participants will undergo 1:1 stratified randomization to one of two groups, defined by the PN malignancy risk stratification strategy used by evaluating clinicians: 1) usual care (clinician assessment) or 2) clinician assessment + CAD-based risk stratification using the LCP-CAD tool. The control arm will be usual care, defined as routine clinician assessment of PN malignancy risk. In the experimental arm, clinicians will be provided a report with the CAD tool estimate of malignancy risk for the PN being evaluated.

Assessment of a Radiomics-based Computer-Aided Diagnosis Tool for Pulmonary nodulES

Assessment of a Radiomics-based Computer-Aided Diagnosis Tool for Cancer Risk Stratification of Pulmonary Nodules

The composite proportion of benign pulmonary nodules managed with imaging surveillance and malignant pulmonary nodules managed with biopsy or empiric treatment. Final pulmonary nodule diagnosis will be categorized as malignant or benign based on pathologic evaluation. If pathology is unavailable or inconclusive (i.e., the biopsy was non-diagnostic), pulmonary nodule resolution, shrinkage, or diameter stability at 12 months will be defined as a benign diagnosis.

For patients with malignant pulmonary nodules, defined as the number of days between the index clinic visit and diagnosis of malignancy and receipt of treatment for malignancy (i.e., surgical resection, radiation therapy).

For patients undergoing biopsy, defined as procedural complications related to pulmonary nodule biopsy.

Using information found in pathology reports, defined as the proportion of biopsies with a definitive histopathologic diagnosis, for each type of diagnostic biopsy procedure.

The costs of all imaging studies and diagnostic testing associated with the pulmonary nodule diagnostic process, based on Medicare allowed amounts (amount paid by Medicare and the amount paid by the beneficiary and/or third parties).

Abramson Cancer Center at Penn Medicine

Assistant Professor of Medicine

Behaviors and Mental Disorders

Quality of Life

One or more of the following:

* prioritisation of resources and everyday activities
* adaptation of activities
* adaptation of posture and seating positioning
* provision of assistive devices
* modification of the physical home environment And usual care from hospital and municipality

Usual care from hospital and municipality

Adaptive interventions aiming at compensating for functional limitations.

The Cancer Home Life Intervention

Karen la Cour, PhD

Åse Brandt, PhD

The purpose of this study is to examine the effectiveness and cost-effectiveness of the Cancer Home Life Intervention compared to usual care on performance of and participation in everyday activities and quality of life in people with advanced cancer living at home.

The sample size is based on the primary outcome measure: the mean Activty of Daily Living (ADL) motor ability 1.04 logits (SD 0.727) as measured by the Assessment of Motor and Process Skills (AMPS). A significance level of 0.05 would provide 80% power to detect a between-group difference of 0.3 logits requiring a sample size of N=184. An expected drop-out rate of 32% at 3 months follow-up means that 272 patients with advanced cancer must be included in the study from three hospitals.

Multiple imputation will be used to estimate a plausible value for missing data of participants that are lost to follow-up due to other reasons than death. This does not, however, apply to the primary outcome data where no estimations will be computed.

For normally distributed ratio data the intervention group will be compared with the control group using multiple linear regression analysis of mean changes from baseline. Logistic regression analysis will be used for ordinal data. Adjustments for hospital and for baseline values will be made. A modified intention-to-treat analysis will be applied. Subgroup analyses to identifiy groups that especially benefit from the intervetnion will be performed.

The cost-effectiveness analysis wil be performed with ADL motor ability as the clinical parameter, and the cost-utility analysis will be based on the calculation of Quality Adjusted Life Years (QALY). The Incremental Cost-effectiveness Ratio (ICER) will be calculated and the results summarised in a cost-effectiveness acceptability curve (CEAC).

The Cancer Home Life Intervention Study. A Randomised, Controlled Multicentre Trial and a Health Economic Evaluation

The Cancer Home Life Intervention Study Protocol: Effectiveness on Everyday Activities and Quality of Life in People With Advanced Cancer Living at Home. A Randomised, Controlled Multicentre Trial and a Health Economic Evaluation

Observed quality of Activity of Daily Living (ADL) motor ability

Everyday activities that the participant has problems with and prioritise to have solved

The participant records every ½ hour what he/she does, where, is together with, how he/she feels mentally and physically

Autonomy and participation is assessed regarding autonomy indoors, family roles, and social life and relationships

Cancer specific health-related quality of life

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Real-world Clinical Effectiveness of Whole Genome and Transcriptome Analysis to Guide Advanced Cancer Care	NCT04141397	Metastatic Canc... Advanced Cancer Cancers That Ca...	Initiation of P... Usual care	19 Years - 85 Years	British Columbia Cancer Agency
Real-world Clinical Effectiveness of Whole Genome and Transcriptome Analysis to Guide Advanced Cancer Care	NCT04141397	Metastatic Canc... Advanced Cancer Cancers That Ca...	Initiation of P... Usual care	19 Years - 85 Years	British Columbia Cancer Agency
Assessment of a Radiomics-based Computer-Aided Diagnosis Tool for Pulmonary nodulES	NCT05968898	Lung Cancer Pulmonary Nodul...	Optellum Virtua...	35 Years - 89 Years	Abramson Cancer Center at Penn Medicine
The Cancer Home Life Intervention Study. A Randomised, Controlled Multicentre Trial and a Health Economic Evaluation	NCT02356627	Activities of D... Everyday Activi... Palliative Care Cancer Quality of Life	The Cancer Home...	18 Years -	University of Southern Denmark

Spots Global Cancer Trial Database for clinical effectiveness