Gland and Hormone Related Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Thyroid Diseases

Thyroid Nodule

Neoplastic Cells, Circulating

Endocrine System Diseases

Neoplasm Metastasis

Neoplastic Processes

Thyroid Neoplasms

Endocrine Gland Neoplasms

Head and Neck Neoplasms

circulating tumor cells test and FNAB will be performed at the same time

10 ml Peripheral blood are drawn from patients enrolled before surgery/FNAB and centrifuged to collect the peripheral blood mononuclear cells. Then, negative and positive immunomagnetic selections are used to exclude white blood cells and enrich tumor cells. After isolating mRNA, RT-PCR array is used to measure expression of target genes.

circulating tumor cells test

patients with potential malignant thyroid nodules are performed fine needle aspiration biopsy with the aid of ultrasound. The result of FNAB were classified by Bethesda rating system.

Fine needle aspiration biopsy

jie liu, MD

Thyroid nodule patients with suggestion of fine needle aspiration biopsy (FNAB) offered by ultrasound are enrolled in the study. CTCs tested by Optimizing method and FNAB will be performed simultaneously. This is a double blind trial which pathologists and inspectors of CTCs don't know the result of each other. Surgical pathology and diagnostic results of FNAB is the primary endpoint and comparison will be made to see if CTCs combined with ultrasound can get similar diagnostic performance as FNAB. The diagnostic results of FNAB included Bethesda class II and more than V which are defined as benign and malignant, respectively.

Some retrospective analysises showed CTCs is considered to be valuable for diagnosis, staging, prognosis and follow-up in several types of cancers and some mRNA markers are helpful in differentiating patients with benign versus malignant thyroid disease. However, the lack of sensitivity and specificity of mRNA measurements restricted their clinical application. The aim of this study is to see if optimizing test method combined with ultrasound can get similar diagnostic performance. 200 patients with thyroid nodules (≤2cm) which need to undergo FNAB will be enrolled in four centers of northern China. Patients will simultaneously undergo CTCs tests and FNAB. And following treatments will be performed according to the previous standard. Allowed by the patients, the investigators will obtain 10ml peripheral blood samples from the participants to make a CTCs test before any FNAB. The primary end point is the pathologically confirmed benign versus malignant thyroid disease, which including surgical pathology and diagnostic results of FNAB.

Diagnostic Significance of CTCs in Patients With Thyroid Nodules (Circulating Tumor Cells)

A Multicenter, Double-blind, Prospective Cohort Study of Diagnostic Significance of Circulating Tumor Cells in Patients With Thyroid Nodules

Patients with malignant results of FNAB (Bethesda V and VI)non-diagnostic results of FNAB (Bethesda class I , III, IV)will be suggested to undergo surgery. Those patients who underwent surgery are enrolled in our study and are performed a post-operative pathology, which have a higher evidence rank than FNAB. According to post-operative pathology, any type of thyroid carcinoma is defined as malignant, and patients who have not been strong enough to be diagnosed with carcinoma is defined as benign disease.

The result of FNAB are classified by Bethesda rating system. Bethesda class I is considered the sample is not qualified, Bethesda class II is defined as benign, Bethesda class III and IV are defined as non-diagnostic result, which need further verified by surgery.Bethesda class V and VI are defined as malignant.

China-Japan Friendship Hospital

Chinese PLA General Hospital

Beijing Chao Yang Hospital

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Clinical Professor

Skin and Connective Tissue Diseases

Eye Diseases

Rare Diseases

Melanoma

Uveal Neoplasms

Iris Neoplasms

Choroid Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Choroid Diseases

Iris Diseases

Ocular Melanoma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

J. William Harbour, MD

Up to half of patients with ocular melanoma (also called iris, choroidal or uveal melanoma) develop metastasis. We have found that certain molecular features of the eye tumor can be detected by gene expression profiling and accurately predict which patients will develop metastasis. This molecular test could eventually allow high risk patients to receive preventative therapy to delay or prevent the development of metastasis. The goal of this study is to prospectively validate the predictive accuracy of the gene expression-based molecular test and compare it to monosomy 3, the most common but potentially less accurate molecular marker for metastasis in ocular melanoma.

We have discovered a gene expression profile derived from primary uveal melanomas that accurately predicts which patients will develop metastasis. Tumors with a class 1 gene expression signature have a very low risk, and those with a class 2 signature have a high risk of metastasis. The molecular test was initially performed on tissue obtained from enucleated eyes using commercial microarray platforms. We are now able to perform the molecular test on fine needle biopsy specimens, and we have developed a customized test that has greater dynamic range and sensitivity than commercial microarray platforms. The goal of this study is to validate the prognostic accuracy of the customized platform by performing the molecular test on primary uveal melanomas obtained from enucleation, local tumor resection or fine needle biopsy. Each sample will be diagnosed as either class 1, class 2 or indeterminate. Outcomes will be collected and the ability of the molecular diagnosis to predict metastasis will be evaluated at regular intervals.

Validation of a Molecular Prognostic Test for Eye Melanoma

Validation of a Molecular Test for Predicting Metastasis in Patients With Uveal Melanoma

Washington University School of Medicine

Breast Neoplasms

Breast Diseases

Tumor RNA Disruption Assay™ (RDA) to generate RDA score from fine needle aspiration biopsy samples of breast cancer obtained 7-14 days after the first, second and third cycles of neoadjuvant chemotherapy; and, if there is a change of chemotherapy regimen, after the first cycle of the new chemotherapy.

Tumor RNA Disruption Assay™ (RDA)

Murray Krahn, MD,MSc,FRCPC

The purpose of this study is to find out if the pathological complete response (pCR) to chemotherapy given before surgery (neoadjuvant chemotherapy) could be predicted by the evaluation of the RNA (ribonucleic acids) disruption pattern (RNA Disruption Assay or RDA score) obtained from a biopsy of the tumor 7 - 14 days after the first, second and third cycles of chemotherapy treatment. If we can determine the optimal time during neoadjuvant chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast cancer management.

When administering neoadjuvant chemotherapy, the current practice of monitoring response to treatment is by measuring the size of the breast tumor after each cycle of chemotherapy. The drawback to this method is, it will take several weeks before we can actually measure a significant change in size; and the initial response to chemotherapy is often evident as a softening of the tumor without an apparent decrease of the tumor size. Finding a reliable way to identify early response to chemotherapy would be helpful to enable matching of chemotherapy to an individual's need.

In a previous trial of breast cancer treated with neoadjuvant chemotherapy, researchers have identified that the pCR to a full treatment of chemotherapy could be predicted by the change in RNA pattern obtained from a biopsy of the tumor half way through the chemotherapy course. \[Parissenti et al. 2010\] The purpose of this study is to determine if we can predict the pCR to neoadjuvant chemotherapy by examining the pattern of RNA disruption (RNA Disruption Assay or RDA score) from breast biopsy tissue obtained 7 to 14 days after the first, second and third cycle of chemotherapy. If we can determine the optimal time during neoadjuvant chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast cancer management. For example, if RDA score can identify non-responders earlier, we can switch to other chemotherapy agents and reduce the exposure to the unnecessary side-effects of ineffective treatment.

Study of Tumor RNA Disruption Assay™ (RDA)

Study of Tumor RNA Disruption Assay™ (RDA) and Its Association With a Response to Neoadjuvant Chemotherapy in Breast Cancer - A Prospective Mixed-Methods Study

The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and the pCR to neoadjuvant chemotherapy will be evaluated. pCR is defined as no evidence of invasive carcinoma in the breast and lymph nodes (ypT0/Tis ypN0/N0itc) on histology at the time of surgery (lumpectomy or mastectomy).

The capacity of RDA score to predict pCR to neoadjuvant chemotherapy will be assessed by exploring for a cut point on the RDA score to differentiate subjects with a high likelihood of achieving pCR versus those who are less likely to achieve pCR.

The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and clinical response to neoadjuvant chemotherapy treatment will be evaluated.

We shall seek to understand the experiences of patients with the FNAB procedure and with the cancer care they received while participating in the study by conducting qualitative interviews of study subjects.

The cost-effectiveness of using RDA score to guide neoadjuvant chemotherapy will be evaluated by measuring the cost-effectiveness of monitoring pCR to neoadjuvant chemotherapy through the RDA score and in modifying the neoadjuvant chemotherapy regimen for non-pCR patients accordingly.

The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and DFS will be evaluated. DFS will be measured as the time from patient's enrollment to the event of cancer metastasis or recurrence, or death, whatever comes first.

University Health Network, Toronto

University of Toronto

MD, MSc, FRCPC

Digestive System Diseases

Pancreatic Neoplasms

Cysts

Pancreatic Cyst

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Pancreatic Cancer

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

One extra biopsy will be taken from the pancreas only in patients who are already undergoing biopsy of a mass or cyst.

fine needle aspiration biopsy

Sarah Rodriguez, MD

Pancreas cancer and precancerous cysts can be difficult to diagnose. Sometimes biopsies do not show cancer when cancer is actually present. We hypothesize that genetic differences exist in tissue that is malignant compared to nonmalignant. When patients present with a pancreas mass or cyst, we biopsy it by fine-needle aspiration during upper endoscopy with ultrasound guidance. We would like to use tissue obtained via endoscopic ultrasound guided fine needle aspiration to perform DNA microarray analysis, and compare the differences in gene expression level in the benign tissue compared to cancerous tissue in order to improve our diagnostic capabilities. DNA microarray measures gene expression level rather than germline mutations. The true diagnosis will be based on cytology, surgical pathology, or clinical followup. The performance of the microarray test as a diagnostic test will be compared to the performance of cytology.

DNA Microarray Study of Pancreas Cancer

DNA Microarray Analysis of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsies to Discriminate Benign From Malignant Pancreatic Lesions

Oregon Health and Science University

Physician

Patients with thyroid nodules with an indication for FNA biopsy to detect thyroid cancer. These patients will undergo FNA at the time of first visit and also when considered necessary by the clinician during the course of the study.

The study is intended for patients for whom a FNA biopsy of thyroid nodule/nodules is medically indicated for the detection of thyroid cancer. FNA biopsy should preferably be carried out under ultrasound guidance. The FNA samples will be collected either from the remaining material of FNA or there will be dedicated FNA sample in order to ensure an adequate quantity of material for molecular analysis. The patients will also be invited to take part in the mutation study in a separate consent form.

The samples of enrolled patients will be sent to the Diaxonhit Genomics Laboratory and analysed using Diaxonhit technology after checking the quantity and quality of the samples. Enrolled patients whose samples are inadequate in terms of quantity or quality for the various molecular tests will not be considered for the study. If necessary, mutation analyses can be carried out anonymously by an independent French laboratory and under the supervision of Diaxonhit.

FNA biopsy for thyroid nodule(s)

Olivier SOL, MD

1. Principal objective:

   The primary objective of this study is to validate the diagnostic performance of a Dx15 molecular test based on molecular transcriptomic signatures previously identified in distincts cohorts of samples to determine the malignant or benign profile of a thyroid nodule with indeterminate cytological analysis. The target population includes categories III \[Follicular lesion of undetermined significance or Atypia of undetermined significance (FLUS/AUS)\] and IV \[Follicular neoplasm / Suspicious for follicular neoplasm (FN/SFN)\] of the Bethesda classification.

   The expected target performance of the Dx15 molecular test in this target population is 95% for specificity with a lower limit of the 95% confidence interval of 87%, and 75% for sensitivity.
2. Secondary objectives:

   * To assess the performance of the Dx15 test in samples collected during the study by fine-needle aspiration (FNA) in each and in all of the indeterminate Bethesda classification categories (categories III, IV and V: suspected malignancy)
   * To assess the performance of the TI-RADS ultrasonography score for diagnosing thyroid cancer in patients presenting with a thyroid nodule and having available cytological analysis results.
   * To check the potential of performance of the molecular signature as well as of its combination with other tests by applying it in a blind manner to samples collected from patients presenting with thyroid nodules and whose aspiration biopsy result is benign (Bethesda category II), malignant (Bethesda category VI) or non-diagnostic (Bethesda category I)
   * To assess the performance of mutation tests (isolated mutations, chromosomal rearrangements) for diagnosing thyroid cancer in patients presenting with a thyroid nodule and with available cytological results.
   * To estimate the performance of the combination of the Dx15 test result and other diagnostic tools such as mutation tests and/or the TI-RADS score to diagnose thyroid cancer in patients presenting with a thyroid nodule and having an indeterminate cytology result (especially AUS/FLUS and FN/SFN). The combination of Dx15 diagnostic test results with other study parameters will also be considered in order to establish the option of an algorithmic approach for the diagnosis of thyroid cancer.
   * To compare the results of cytological and histological analyses obtained in the centres and by centralised reading and assessment of the impact of its results on the other study analyses and parameters.
   * Additional analyses deemed relevant on the basis of various parameters and data collected during the study.
3. Objective of exploratory research:

   * The use of all or part of the FNA samples for the purpose of research as part of thyroid cancers, especially with the objective of optimising or identifying additional molecular signatures.

The study is intended for patients for whom a fine-needle aspiration biopsy of thyroid nodule/nodules is medically indicated for the detection of thyroid cancer. Fine-needle aspiration biopsy should preferably be carried out under ultrasound guidance as part of the patient's standard management plan. In order to limit screening bias, the investigators should, wherever possible, ask all patients seen consecutively to participate in the study.

Eligible, screened patients will have been informed and will have signed a consent form prior to study-related activities which include notably the use and storage of some cells collected by fine-needle aspiration biopsy which have not been used for diagnostic purposes. The fine-needle aspiration biopsy samples will be collected either from the remaining material of FNA or there will be dedicated FNA sample in order to ensure an adequate quantity of material for molecular analysis, if necessary. The patients will also be invited to take part in the mutation study in a separate consent form.

The samples of enrolled patients will be sent to the Diaxonhit Genomics Laboratory and analysed using Diaxonhit technology after checking the quantity and quality of the samples. Enrolled patients whose samples are inadequate in terms of quantity or quality for the various molecular tests will not be considered for the study. If necessary, mutation analyses can be carried out anonymously by an independent French laboratory and under the supervision of Diaxonhit.

For each patient, the results of cytological and histological analyses or the monitoring program carried out by the centre will be recorded on electronic case report forms (e-CRF) generating an anonymous data base hosted by Clinfile - a data management company.

All of the patients will be followed up until the malignant or benign status of their nodule(s) is known following fine needle aspiration biopsy, histological analysis of the surgical specimen or, failing that, clinical monitoring.

Patients who have undergone surgery will be followed up until the histological results are obtained.

In the case of patients who have not undergone surgery, follow-up will be carried out over a minimal period of 1 year (12 months), as from the patient's enrolment. Patients who have not undergone surgery will be clinically followed up for a maximum of 12 months after enrolment of the last study patient in order to benefit from the extended follow-up of patients who enter the study at an early stage.

The results of the cytological and histological analyses will be confirmed by the centralised re-reading of the slides for statistical analysis, under blind status.

In conjunction with validating the identified signature and in an attempt to improve diagnostic testing for thyroid cancers, the Diaxonhit company reserves the right to carry out additional exploratory analyses of all or part of the samples collected in order to identify new molecular signatures. These potentially new signatures will be validated in other protocols.

The primary endpoint criterion will be the proportion of correct classifications for defining the malignant or benign nature of a fine-needle aspiration biopsy carried out in patients presenting with thyroid nodules and an indeterminate cytology for Bethesda categories III and IV. The results obtained with the signature will be compared to the histology results of the surgical specimen or, failing that, to the results of the monitoring program implemented by the clinician.

Evaluation of the performance of previously identified transcriptome signatures will also be carried out on every other category, which may or may not be indeterminate according to the Bethesda classification. This information will be considered as the secondary endpoint criterion. Other secondary endpoint criteria will include the proportion of correct classifications obtained when the signature is linked to other predictive tests such as mutation tests or the TIRADS score in order to define the malignant or benign nature of a fine-needle aspiration biopsy carried out in patients presenting with thyroid nodules and having an indeterminate cytology. The results obtained with the combination of tests will be compared to the histological analysis of the surgical samples or otherwise to the results of the monitoring program implemented by the clinician. The results of other study parameters, essentially clinical, laboratory or demographic, will also be combined in an attempt to define a potential algorithmic approach for diagnosing thyroid cancer.

The performance of the Dx15 molecular test will be determined in the target population using Bethesda category III and IV samples.

The enrolment of 1000 patients is scheduled in order to achieve the necessary recruitment levels for categories III and IV.

For the purposes of the study, the Dx15 test may also be applied to a sample of cohorts in other Bethesda categories (I: non-diagnostic, II: benign, V: SMC, and VI: malignant) in order to identify test performance in these other categories.

Whenever possible, for the fine-needle aspiration samples tested with Dx15 and used to determine performance, the presence of a related histopathological result of the surgical specimen will be given priority.

A sample eligible for assessment is one that meets the Diaxonhit quality and quantity criteria in order to enable the scheduled molecular analyses.

Recruitment will be performed in centers specialized in the diagnosis and follow-up of thyroid cancer.

Clinical Validation of a Molecular Signature to Detect Cancer in Thyroid Nodules With Indeterminate Cytology

Clinical Validation of the Diagnostic Performance of a Molecular Signature to Determine the Malignant or Benign Profile of a Thyroid Nodule With Indeterminate Cytological Analysis

The primary endpoint criterion will be the proportion of correct classifications for defining the malignant or benign nature of a fine-needle aspiration biopsy carried out in patients presenting with thyroid nodules and an indeterminate cytology for Bethesda categories III and IV. The results obtained with the signature will be compared to the histology results of the surgical specimen or, failing that, to the results of the monitoring program implemented by the clinician.

Comparison of the results of mutation tests conducted under blind conditions and the histological results after re-reading or in patients involved in the monitoring programme (eg, the correlation of the presence of mutations with the presence of thyroid cancer diagnosed by histological analysis)

Predictive performances of the TI-RADS score by comparing the scores obtained with the histological results after reading or in patients involved in the monitoring programme (eg, verify if higher scores are correlated with an increased prevalence of cancer)

Diagnostic performances of the combination of the signature with other study tests and by comparing the scores from the combination of tests (ie, algorithm approach) with the histological results or the clinical follow-up outcome.

Any other relevant statistical analysis based on data collected during the study can be carried out and will be listed in the statistical analysis plan of the study.

* descriptive performance (sensitivity, specificity) of the Dx15 signature in any study subpopulation defined by data collected during the study (eg, male vs female; vs age range, vs different types of histology, vs existing thyroid familial history, vs specified type of thyroid mutations, vs volume of the thyroid nodule)
* descriptive data regarding time from FNA analysis to surgery with regards to the Bethesda cytology score
* descriptive data regarding prevalence of cancer vs thyroid nodule volume, TIRADS score and Bethesda results
* comparison of cytology inter-reader performance (center vs central reading) globally and for each Bethesda score

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Diagnostic Significance of CTCs in Patients With Thyroid Nodules (Circulating Tumor Cells)	NCT03772496	Thyroid Nodule Diagnoses Disea...	circulating tum... Fine needle asp...	18 Years - 70 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Diagnostic Significance of CTCs in Patients With Thyroid Nodules (Circulating Tumor Cells)	NCT03772496	Thyroid Nodule Diagnoses Disea...	circulating tum... Fine needle asp...	18 Years - 70 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Validation of a Molecular Prognostic Test for Eye Melanoma	NCT00406120	Uveal Neoplasms Choroid Neoplas... Iris Neoplasms	Fine needle asp...	-	Washington University School of Medicine
Study of Tumor RNA Disruption Assay™ (RDA)	NCT02239315	Breast Neoplasm...	Tumor RNA Disru...	18 Years -	University of Toronto
DNA Microarray Study of Pancreas Cancer	NCT00680420	Pancreas Cancer	fine needle asp...	18 Years -	Oregon Health and Science University
Clinical Validation of a Molecular Signature to Detect Cancer in Thyroid Nodules With Indeterminate Cytology	NCT02225509	Thyroid Nodule Thyroid Cancer	FNA biopsy for ...	18 Years -	Diaxonhit
Validation of a Molecular Prognostic Test for Eye Melanoma	NCT00406120	Uveal Neoplasms Choroid Neoplas... Iris Neoplasms	Fine needle asp...	-	Washington University School of Medicine

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