Neoplasms

Symptoms and General Pathology

All Conditions

Gland and Hormone Related Diseases

Diseases and Abnormalities at or Before Birth

Musculoskeletal Diseases

Blood and Lymph Conditions

Neoplasm Metastasis

Thyroid Diseases

Congenital Abnormalities

Thyroid Neoplasms

Bone Neoplasms

Bone Marrow Diseases

Neoplastic Processes

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Bone Diseases

Hematologic Diseases

All Drugs and Chemicals

Antibodies

Immunoglobulins

Evaluation of month and year of birth, sex, referent doctor and surgeon

Administrative data

Evaluation of diagnostic circumstances, vital status at last follow up

Clinical data

Evaluation of Pathology report of thyroid surgery

Histological data

Imaging data

Evaluation of thyroglobulin, antithyroglobulin antibodies

Biological data

Evaluation of surgery, radiotherapy, targeted therapy

Further treatment

Claire BOURNAUD, MD

Claire MARX

Bone radioiodine (RAI) uptake without structural abnormality in thyroid cancer (TC) patients may be related to false positive or to microscopic foci of metastatic tissue. In such cases, outcome is reported to be excellent.

Indeed, Robenshtok et al. reported a serie of patients with RAI-avid bone metastases of TC without structural abnormality on imaging studies who have more favorable long-term prognosis than those harbouring structurally visible bone metastases and do not undergo skeletal-related complications.

The investigators report the case of Mrs D., who had been operated for a pathologic tumor stage 3: pT3(m) poorly differentiated TC at the age of 43. The first post-therapeutic whole body scan revealed 3 foci of bone uptake (right clavicle, L2, L3). The elevated level of thyroglobulin (157ng/mL) favoured the hypothesis of bone metastases despite the absence of any structural lesion on CT and MRI. She received 7 courses of radioiodine therapy. The right clavicle RAI uptake persisted, and subsequent CT disclosed an osteolytic lesion which was treated by radiofrequency and external beam radiation. Twenty-five years after the diagnosis, she has a persistent morphological disease with a 30x8mm progressive lesion on the right clavicle, for which surgery is planned.

The aim of the present study is to describe the natural history and evolution of radioiodine avid bone metastases from thyroid cancer without structural abnormalities and to identify prognosis factors.

Radioiodine-avid Bone Metastases From Thyroid Cancer Without Structural Abnormality

Radioiodine-avid Bone Metastases From Differentiated Thyroid Cancer Without Structural Abnormality, a Singular Entity With Heterogeneous Outcomes.

* Disappearance of pathologic radio iodine uptake, including bone uptake, on post-therapy scintigraphy
* No structural evidence of disease on high-resolution imaging
* Suppressed serum Tg \< 0.6 ng/mL, no detectable TgAb (thyroglobulin antibody)

Hospices Civils de Lyon

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radioiodine-avid Bone Metastases From Thyroid Cancer Without Structural Abnormality	NCT04141306	Bone Metastases Thyroid Cancer	Administrative ... Clinical data Histological da... Imaging data Biological data Further treatme...	18 Years - 80 Years	Hospices Civils de Lyon
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
Radioiodine-avid Bone Metastases From Thyroid Cancer Without Structural Abnormality	NCT04141306	Bone Metastases Thyroid Cancer	Administrative ... Clinical data Histological da... Imaging data Biological data Further treatme...	18 Years - 80 Years	Hospices Civils de Lyon

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