Rye Brook, NY—July 12, 2019—CBLPath, Inc. (“CBLPath”) has been informed by Retrieval Masters Creditors Bureau d/b/a American Medical Collection Agency (“AMCA”) of a data security incident involving the AMCA payment website. AMCA is an independent collection agency that CBLPath and many other entities used for debt collection. The incident is limited to AMCA’s systems. The security of CBLPath’s systems was not affected by this incident.

According to AMCA, on March 21, 2019, AMCA became aware of facts indicating there had been a data security incident. After conducting an investigation, in May of 2019, AMCA notified CBLPath about the incident and informed CBLPath that an AMCA database containing information for some CBLPath patients had been affected. However, at the time of AMCA’s initial notification, AMCA did not provide CBLPath with enough information for CBLPath to identify potentially affected patients or confirm the nature of patient information potentially involved in the incident, and CBLPath’s investigation is on-going. Based on the information provided by AMCA, the following information belonging to CBLPath patients may have been affected by the incident: patient names, addresses, phone numbers, dates of birth, dates of service, balance information, credit card or banking information and treatment provider information. AMCA has advised CBLPath that its patients’ social security numbers were not involved in the incident.  CBLPath does not provide AMCA healthcare records such as laboratory results and clinical history. The impact of this incident is limited to patients whose accounts were referred for debt collection and who reside in the United States.

Individuals with questions about this incident or questions about precautionary steps they can take may call 833.297.6409 or visit https://ide.myidcare.com/CBLPath for additional information.

CBLPath takes the security of its patients’ information very seriously, including the security of data handled by vendors. The privacy and protection of patient information is a top priority. As a result of the investigation, CBLPath is no longer using AMCA for collection efforts.

CBLPath greatly appreciates the patience and loyalty of its patients as it works to respond to this incident.

While we are unaware of the misuse of any patient’s information, we are providing the following information to help those wanting to know more about steps they can take to protect themselves:

What steps can I take to protect my personal information?

• If you detect any suspicious activity on any of your accounts, you should promptly notify the financial institution or company with which the account is maintained. You should also promptly report any fraudulent activity or any suspected incidents of identity theft to proper law enforcement authorities.

• Obtain a copy of your credit report, free of charge, directly from each of the three nationwide credit reporting agencies.  To do so, free of charge once every 12 months, please visit www.annualcreditreport.com or call toll free at 877.322.8228. Contact information for the three nationwide credit reporting agencies is listed at the bottom of this page.

• Please notify your financial institution immediately of any unauthorized transactions made or new accounts opened in your name.

• You can take steps recommended by the Federal Trade Commission to protect yourself from identify theft. The FTC’s website offers helpful information at www.ftc.gov/idtheft.

• Additional information on what you can do to better protect yourself is included in your notification letter.

What should I do to protect myself from payment card/credit card fraud?

We suggest you review your debit and credit card statements carefully for any unusual activity.  If you see anything you do not understand or that looks suspicious, you should contact the issuer of the debit or credit card immediately.

How do I obtain a copy of my credit report?

You can obtain a copy of your credit report, free of charge, directly from each of the three nationwide credit reporting agencies. To order your credit report, free of charge once every 12 months, please visit www.annualcreditreport.com or call toll free at  877.322.8228. Contact information for the three nationwide credit reporting agencies is included in the e-mail and letter, and is also listed at the bottom of this page:

How do I put a fraud alert on my account?

You may consider placing a fraud alert on your credit report. This fraud alert statement informs creditors to possible fraudulent activity within your report and requests that your creditor contact you prior to establishing any accounts in your name. To place a fraud alert on your credit report, contact Equifax, Experian or TransUnion and follow the Fraud Victims instructions. To place a fraud alert on your credit accounts, contact your financial institution or credit provider. Contact information for the three nationwide credit reporting agencies is included in the letter and is also listed at the bottom of this page.

Contact information for the three nationwide credit reporting agencies is as follows:

AUSTIN, Texas, April 29, 2019 /PRNewswire/ -- Validation of ThyroSeq® Genomic Classifier performance in an expanded range of sample types has been presented at the 28th Annual Scientific and Clinical Congress of the American Association of Clinical Endocrinologists (AACE) in Los Angeles, California. ThyroSeq, commercially offered by CBLPath, a Sonic Healthcare Company, is a comprehensive molecular test for thyroid nodules and cancer that is typically performed using a dedicated sample collected during fine needle aspiration (FNA) procedure. This study demonstrates that ThyroSeq can be performed using routine cytology smears, while maintaining the robust diagnostic accuracy.

In this study, ThyroSeq performance was assessed in routinely prepared Diff-Quik® and Papanicolaou-stained cytology smears. Adequate DNA results for mutations and copy number alterations were obtained in 93% of nodules and RNA results for gene fusions and gene expression in 79% of nodules. In addition, ThyroSeq performance was evaluated in reference cytology slides included in a worldwide ring trial study on quantitative cytological molecular reference specimens. ThyroSeq demonstrated accurate detection of all mutations down to 3-5% of allele frequency. 

"The results of this study show that ThyroSeq Genomic Classifier achieved high performance in adequately cellular routine cytology smears," said Yuri Nikiforov, MD, PhD, Vice Chair of the Department of Pathology and Director of Molecular and Genomic Pathology at University of Pittsburgh Medical Center, who presented the study at the annual meeting. "The expansion of acceptable sample types will enable more patients to benefit from ThyroSeq testing, save expenses associated with another office visit and repeated FNA biopsy, while offering the same high diagnostic accuracy to optimize patient management".

The ThyroSeq test can help avoid costly diagnostic thyroid surgeries by reliably distinguishing between benign and cancerous thyroid nodules. When a dedicated sample is not collected for molecular testing, cytology smears may be the only specimens available. Expansion of ThyroSeq testing to cytology smears means that patients with indeterminate cytology will not have to come back into a physician's office to have another sample taken, instead the available smears can be sent for testing. Previously validated and acceptable specimen types for ThyroSeq include fresh FNA samples collected into ThyroSeqPreserve solution, which remains the gold standard of specimen quality, cytology cell blocks, and FFPE tissue. 

These results were presented in the oral presentation "Performance of ThyroSeq v3 Genomic Classifier in Fixed Cytology Smears" on Saturday, April 27, 2019 at 10:30-10:45 am during the meeting.

About Sonic Healthcare USA

Sonic Healthcare USA is a subsidiary of Sonic Healthcare Limited, one of the world's largest medical diagnostic companies, providing laboratory services to medical practitioners, hospitals and community health services, with operations in eight countries, on three continents and providing care to over 100 million patients each year. Sonic Healthcare USA is a leading provider of state-of-the-art laboratory services throughout the USA with nine operating divisions and over eight thousand US based employees. Sonic Healthcare USA utilizes a federated business model that emphasizes medical leadership and community based testing services to provide outstanding quality and service to the doctors and patients that they serve. For more information, visit the Sonic Healthcare website at www.sonichealthcareusa.com.

About CBLPath, Inc.

CBLPath, a Sonic Healthcare Company, is a leading provider of sub-specialized anatomic pathology and molecular diagnostic laboratory services. In addition, CBLPath is a Center of Excellence in the interpretation of fine needle aspiration (FNA) of thyroid nodules having a staff of expert cytopathologists dedicated to the interpretation of over 40,000 thyroid FNAs annually. For more information, please visit www.cblpath.com.

About ThyroSeq 

ThyroSeq® Genomic Classifier is an innovative test for thyroid nodules and cancer that utilizes next-generation sequencing technology and a proprietary genomic classifier to analyze 5 classes of alterations in DNA and RNA collected from a thyroid nodule, with reported results empowering physicians to individualize patient management. With more than a 10-year history of continuous refinement, it incorporates all major scientific discoveries and technological advances to provide the most accurate diagnosis of benign or malignant disease in thyroid nodules.

MEDIA CONTACTS:

Sonic Healthcare USA
Dr. Jerry Hussong, MD, MBA
Chief Executive Officer
jhussong@sonichealthcareusa.com
512.531.2216

SOURCE Sonic Healthcare USA

Related Links

sunriselab.com

• by Kristen Monaco, Staff Writer, MedPage Today April 28, 2019 

• This article is a collaboration between MedPage Today® and:

LOS ANGELES -- The ThyroSeq v3 Genomic Classifier was able to effectively classify thyroid nodules with samples collected through fine needle aspiration (FNA), researchers reported here.

In an analysis of 33 cytology smears from 14 thyroid nodules collected through FNA samples that had indeterminate cytology, DNA analysis was obtained in 93% of samples, while RNA results were informative in 79% of cases for accurate detection of mutations, according to Lindsey Tolino, MBA, of the University of Pittsburgh Medical Center in Pennsylvania, and colleagues.

In smears that were comprised of at least 10% of mutated cells, the molecular test was able to accurately detect several different mutations, including BRAF, NRAS, KRAS, and PIK3CA. In smears that had at least 200-300 cells, the test was also able to accurately detect all of these genetic alterations in samples comprised of only 5% mutations. Finally, ThyroSeq was also able to detect the BRAF mutation at smears at only 1% of allele frequency, they reported at the American Association of Clinical Endocrinologists (AACE) annual meeting.

"We were pleasantly surprised that this high-complexity test ... can be reliably performed in most thyroid [FNA] smears and provide the same accuracy of detecting thyroid cancer markers in thyroid nodules with indeterminate cytology," co-author Yuri Nikiforov, MD, PhD, also of the Pittsburgh center, told MedPage Today.

The authors performed the ThyroSeq analysis on 33 routinely prepared slides, either air-dried prepared Romanowsky-type stained (Diff-Quik) or alcohol fixed Papanicolaou-stained slides. All slides were soaked in xylene for 1 to 3 days prior to isolation of DNA and RNA using a QIAcube extractor.

All analyzed slides had from 200-1,000 cells in each, while two smears that had <200 cells failed the RNA analysis. These slides were then compared to FNAs that were collected with ThyroSeqPreserve, a preservative solution.

Compared with the turnaround time of about 5-7 days with ThyroSeqPreserve, fixed cytology smears assessed with the ThyroSeq had a turnaround time of around 8-9 days because of the additional steps during preparation.

"The availability of ThyroSeq testing in fixed cytology smears will increase patient access and save expanses associated with the second office visit and repeat FNA biopsy," Nikiforov noted. "Indeed, in those situations when a dedicated sample for molecular test was not collected during the initial biopsy procedure, and the nodule was found to have indeterminate cytology, currently, most patients have the repeat FNA biopsy performed in order to collect material for molecular testing."

"Based on the results of this study, the treating physician can instead request that the available cytology smears are sent to ThyroSeq testing and expect informative test results in 80%-90% of cases," he added. "At the end, more patients with thyroid nodules will avoid unneeded surgeries, which is the primary purpose of ThyroSeq testing."

AACE attendee David Lieb, MD, of Eastern Virginia Medical School in Norfolk, called the study "very exciting," and inquired about the age of the slides. Nikiforov replied that the oldest smear included in this study was 6 years old, and failed RNA analysis because of degraded nucleic acids. He noted that there's still a good chance to get results from slides that are several years old, but cautioned that smears are destroyed during the analysis, and recommended scanning and saving digital images of the smears in the laboratory.

"We are continuing this study in collaboration with physicians at the University of Pennsylvania to not only provide expanded analytical validation but also demonstrate clinical validity of ThyroSeq in routine thyroid cytology smears," Nikiforov said.

Nancy A. Melville

November 09, 2018

The multigene classifier test ThyroSeq Version 3 (University of Pittsburg/CBLPath) shows high accuracy in diagnosing indeterminate thyroid nodules, allowing for more than 60% of patients with such nodules to avoid diagnostic surgery, according to the final results of a multicenter, double-blinded study.

"Our study showed ThyroSeq can help avoid surgery in the vast majority of patients with benign nodules where the initial biopsy returns an ambiguous result," senior author Yuri Nikiforov, MD, PhD, professor of pathology and director, Division of Molecular and Genomic Pathology, University of Pittsburgh School of Medicine, Pennsylvania, said in a press statement from his institution.

"With such a high proportion of preventable surgeries, this test should practically resolve the decades-long struggle and inefficiency of medical care for patients with indeterminate cytology thyroid nodules," he added.

The research was previously described at the 2017 annual meeting of the American Thyroid Association. Final results were published online November 8 in JAMA Oncology. 

All False Negatives Were Low-Risk Cancers

Although fine-needle aspiration (FNA) biopsy is highly effective in classifying most nodules as being either benign or malignant, approximately 20% of nodules remain indeterminate and require surgery to confirm a diagnosis.

Molecular testing of the nodules with genetic classifiers has emerged in the past decade and has improved the diagnostic accuracy of FNA. However, such tests have relatively low specificity and positive predictive value (PPV), provide limited clinical validation, or are limited in their capacity to provide specific molecular information, the researchers explain.

In the prospective evaluation of the ThyroSeq V3 genetic classifier, which is designed to detect up to 112 genes, a total of 286 nodules from 256 patients were subjected to blinded molecular analysis at 10 medical centers.

Of 257 indeterminate nodules that could be analyzed by ThyroSeq as well as by diagnostic surgery, 154 were classified as Bethesda category III, 93 as Bethesda IV, and 10 as Bethesda V.

For the primary outcome of accuracy in diagnosing Bethesda III and IV nodules, the ThyroSeq test showed high sensitivity, with a PPV of 94%, as well as high specificity, with a negative predictive value (NPV) of 82%. For 61% nodules, test results were negative.

Of the 28% of nodules that were malignant (24%) or noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP; 4%), the ThyroSeq test had an NPV of 97% and a PPV of 66%.

The false negative rate was 3%, which is similar to that of FNA for benign nodules. All of the cancers that were incorrectly diagnosed as negative were low-risk tumors, the authors note.

"Although no test has perfect accuracy, it is reassuring that all false-negative cases in the study were low-stage and low-risk cancers by the American Thyroid Association criteria," the investigators write.

ThyroSeq Provides Detailed Genetic Profile of the Malignant Nodules

Of the nodules that did test positive, the genetic alterations were associated with probabilities of malignancies ranging from 59% to 100%.

The test's capability of diagnosing all types of thyroid cancer, particularly Hurthle cell nodules, for which existing molecular tests typically have low specificity, is highly important, said first author David Steward, MD, professor of otolaryngology at the University of Cincinnati College of Medicine and director of head and neck surgery at UC Health, in Ohio, in the press statement.

"Beyond simply differentiating benign and malignant nodules, the study shows that ThyroSeq also provides a detailed genetic profile of the positive nodules," he said. "Since thyroid cancer is known to progress differently based on the mutation involved, ThyroSeq potentially allows physicians to employ a precision medicine approach, modifying treatment for each patient based on the mutations present."

The test's benefit in reducing unnecessary surgeries could have far-reaching implications, the authors underscore.

"This indicates that ThyroSeq V3...can prevent diagnostic surgeries for up to 61% of all of indeterminate Bethesda III to IV cytology nodules and as many as 82% of all benign nodules that yielded indeterminate cytology diagnosis," they point out.

"This should maximize the effect of molecular testing on the avoidance of surgery, reduction of health care costs, and improvement of patient quality of life.

"This is particularly important during what is widely considered as the era of thyroid cancer overdiagnosis and overtreatment," they write.

The study received funding from a Head and Neck Cancer SPORE grant to University of Pittsburgh and a Thyroid Cancer SPORE grant to the Ohio State University. The authors' relevant financial relationships are listed in the original article.

JAMA Oncol. Published November 8, 2018. Abstract

Medscape Medical News © 2018

Cite this article: ThyroSeq Test Helps Avoid Unnecessary Thyroid Surgeries - Medscape - Nov 09, 2018.

Printable Version 

11/8/2018

PITTSBURGH – A genetic test developed by researchers at UPMC and the University of Pittsburgh School of Medicine can help avoid costly diagnostic surgery that involves removing one or both lobes of the thyroid gland, by reliably distinguishing between benign and cancerous thyroid nodules using a very small sample of cells, according to the results of an international clinical trial published today in the journal JAMA Oncology. 

The performance of the test, called the ThyroSeq® Genomic Classifier, was assessed in a prospective double-blinded study conducted across 10 medical centers. The study involved 257 thyroid nodules with an ambiguous biopsy result evaluated by ThyroSeq and diagnostic surgery. The results showed that the test was highly sensitive, correctly identifying cancerous nodules as positive 94 percent of the time. The test also demonstrated a high specificity, correctly identifying benign nodules as negative 82 percent of the time. The researchers compared the performance of ThyroSeq with other molecular tests and showed that it can prevent the highest number of unnecessary diagnostic surgeries. 

"Our study showed ThyroSeq can help avoid surgery in the vast majority of patients with benign nodules where the initial biopsy returns an ambiguous result," said Yuri Nikiforov, M.D., Ph.D., professor of pathology at Pitt’s School of Medicine and director of the UPMC Molecular & Genomic Pathology Division, and the senior study author. "With such a high proportion of preventable surgeries, this test should practically resolve the decades-long struggle and inefficiency of medical care for patients with indeterminate cytology thyroid nodules. In an era of overdiagnosis and overtreatment, ThyroSeq can improve quality of life for patients by sparing them a lifetime of synthetic thyroid medications and specialist visits, while significantly reducing health care costs.”

ThyroSeq was recently approved for Medicare coverage, making it accessible to more than 50 million Medicare patients nationwide.

The thyroid is a butterfly-shaped gland in the neck that is important to hormone regulation and development. Thyroid nodules are common, and approximately 600,000 patients with nodules undergo a fine needle aspiration (FNA) biopsy every year, where cells are extracted from the nodule and examined to determine whether it is benign or cancerous. While the biopsy test is mostly accurate, it returns an indeterminate finding in approximately one-in-four to -five cases, which forces patients to undergo either a repeat FNA, or diagnostic surgery where at least half of the patients’ thyroid is removed for further assessment. 

ThyroSeq is a next-generation sequencing-based test that uniquely evaluates cells collected by FNA from a thyroid nodule for alterations in 112 genes linked to thyroid cancer. It is designed to diagnose all types of thyroid cancer, including Hurthle cell cancer, as well as medullary carcinoma and parathyroid lesions.

“Beyond simply differentiating benign and malignant nodules, the study shows that ThyroSeq also provides a detailed genetic profile of the positive nodules,” said David Steward, M.D., a professor of otolaryngology at the University of Cincinnati (UC) College of Medicine and director of head and neck surgery at UC Health, and the first author of the study. “Since thyroid cancer is known to progress differently based on the mutation involved, ThyroSeq potentially allows physicians to employ a precision medicine approach, modifying treatment for each patient based on the mutations present.” 

The impact on health care costs of adopting ThyroSeq could be significant, noted Nikiforov, pointing to an independent analysis by Mayo Clinic researchers recently published in the journal Endocrine Practice that found ThyroSeq testing saved thousands of dollars compared to when patients underwent diagnostic thyroid surgery.

A full list of study authors and their affiliations, along with relevant conflict-of-interest disclosures, is available with the online version of the study. 

This study was supported in part by the National Institutes of Health grants P50CA097190 to the University of Pittsburgh and P50CA168505 to The Ohio State University.

For Journalists

Arvind Suresh

Manager

412-647-9966

suresha2@upmc.edu

Allison Hydzik

Manager

412-647-9975

hydzikam@upmc.edu 

Want to Make an Appointment or Need Patient Information?

Contact UPMC at

1-800-533-UPMC (8762).

Go to Find a Doctor to search for a UPMC doctor.

Printable Version

Thyroid cancer is a common endocrine malignancy with a continuously growing incidence over the last several decades in the United States. However, most of thyroid cancers are indolent and rarely result in patient death. As a result, recent patient management guidelines advocate a more limited surgery (removal of only one thyroid lobe) and overall less aggressive treatment of patients with thyroid cancer that has low to intermediate risk for disease progression.

Importantly, most recent molecular tools can help establish the probability of cancer in thyroid nodules with high accuracy, as well as predict how aggressive the cancer is likely to be. However, the latter requires the analysis of cells collected from thyroid nodules using ne needle aspiration (FNA) for a large group and various classes of genetic mutations that occur in thyroid cancer. This could not be achieved until recently as the genetic tools needed to simultaneously interrogate a large number of genes for multiple alterations types were missing.
The situation changed with the introduction of next generation sequencing. The availability of this technology, paired with increasing experience in detecting various genetic alteration types by early adopters of this technology, makes the prediction of thyroid cancer aggressiveness possible. In Cancer, my colleagues and I reported the results of a study validating the accuracy of an assay called ThyroSeq v3 Genomic Classier to detect five different classes of molecular alterations: single nucleotide point mutations, insertions/deletion (also called indels), gene fusions, copy number alterations, and abnormal gene expression. Using a large series of thyroid samples representing all major types of thyroid cancer, the authors showed that all types of alterations could be detected preoperatively when the sample collected from a given thyroid nodule contained at least 12% of the tumor’s cells.
Our results suggest that clinicians can accurately predict the probability of thyroid cancer in thyroid nodules, particularly those with indeterminate FNA cytology, as well as identify which cancers have the highest potential to harm the patient. This information, available preoperatively, should help offer a more individualized approach to the surgical and post-surgical treatment of patients with thyroid cancer.

Printable Version

NEWS PROVIDED BY

ThyroSeq

Jan 10, 2018, 13:00 ET

NEW YORK, Jan. 10, 2018 /PRNewswire/ -- ThyroSeq®, a joint partnership between UPMC and Sonic Healthcare USA, announced that Aetna has issued a positive coverage decision for ThyroSeq Thyroid Genomic Classier. Aetna and its more than 19 million members will now have access to ThyroSeq's highly accurate test which will result in better treatment options for patients with thyroid nodules and decrease a signicant number of avoidable diagnostic thyroid surgeries.

"We are excited about the positive coverage decision and that Aetna's members will now be able to benet from access to the ThyroSeq test," said Yuri Nikiforov, M.D., Ph.D., Professor of Pathology at University of Pittsburgh Medical Center, and principle of ThyroSeq. "The use of this test will prevent the largest number of avoidable thyroid surgeries and help to apply more individualized management to patients with thyroid nodules and cancer based on the cuttingedge genomic science."

"This positive coverage decision for ThyroSeq Genomic Classier by Aetna puts hand in hand with Sonic Healthcare's commitment to high quality patient care," says Jerry Hussong M.D., Chief Medical Ofcer of Sonic Healthcare USA

ThyroSeq's V3® is an effective tool for a denitive diagnosis in thyroid nodules that have indeterminate ne-needle aspiration cytology, enabling the most cost-effective patient care. ThyroSeq V3 has both very high sensitivity and high specicity and therefore can be used as a "rule-out" and "rule-in" test for cancer in thyroid nodules. ThyroSeq V3 provides additional valuable prognostic information, informing the most optimal, personalized surgery for cancerous nodules.

About ThyroSeq®

ThyroSeq is a joint partnership between UPMC and Sonic Healthcare. ThyroSeq is an innovative test for thyroid nodules and cancer. With a 10-year history of continuous renement, it incorporates all major scientic discoveries and utilizes advanced technology to provide the most accurate diagnosis of benign or malignant disease in thyroid nodules. For more information, visit ThyroSeq.com

About Sonic Healthcare

Sonic Healthcare is one of the world's largest medical diagnostics companies. It provides comprehensive laboratory medicine/pathology services to healthcare professionals within private and public medical communities and to commercial enterprises. Headquartered in Sydney, Australia, Sonic has grown to become one of the world's leading healthcare providers with operations in USA, Australia, Germany, Switzerland, United Kingdom, Belgium, Ireland and New Zealand. Sonic's unwavering commitment is driven by the leadership team, dedicated to its patients' health and physician clients' success. For more information, please visit SonicHealthcare.com. 

MEDIA CONTACT

Jeanine Wilson

(845) 548-1211

thyroseq@wmediagroup.com

Printable Version

AT ATA 2017

VICTORIA, B.C. – Several new and improved molecular classifiers show good performance for preoperatively assessing the nature of thyroid nodules, including histologic subsets that continue to pose diagnostic challenges, according to a trio of studies reported at the annual meeting of the American Thyroid Association.

ThyroSeq v3 classier

In a prospective, blinded, multi-institutional study, investigators validated the ThyroSeq v3 genomic classifier, which uses nextgeneration sequencing to test for mutations, fusions, gene expression alterations, and copy number variations in 112 genes.

The validation cohort consisted of 234 patients from 10 centers who had thyroid nodules with Bethesda III to V cytology and known surgical outcome, with central pathology review, and successful molecular testing. In total, they had 257 fine needle aspiration samples.

Of the 247 samples from nodules having Bethesda III or IV cytology – those of greatest interest – 28% were cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), reported senior author Yuri Nikiforov, MD, PhD, professor of pathology and director of the division of molecular & genomic pathology at the University of Pittsburgh Medical Center. “Both cancer and NIFTP are surgical diseases, so we felt they belong in one group,” he noted.

Among the Bethesda III or IV samples, ThyroSeq v3 had a sensitivity of 94%, a specificity of 82%, a positive predictive value of 66%, and a negative predictive value of 97%. Additional analyses showed that the test would still have a negative predictive value of 95% or better up to a cancer/NIFTP prevalence of 44%. 

All five false-negative cases in the entire study cohort were intrathyroidal nodules of low stage and without aggressive histology.

Of the 33 false-positive cases, 68% were diagnosed on pathology as Hurthle cell or follicular adenomas, 10% were initially diagnosed by local pathologists as cancer or NIFTP, and 94% harbored clonal oncogenic molecular alterations.

“So, these are not actually hyperplasia; these are true tumors. Probably at least some of them would have the potential to progress,” said Dr. Nikiforov. “I believe that this so-called false-positive rate may not be really false positive. This is a rate of detection of precancerous tumors, not hyperplasia, that still may require surgical excision.”

In this study, “we found very high sensitivity and negative predictive value of ThyroSeq v3, with robust negative predictive value in populations with different disease prevalence,” he concluded. “Robust performance was achieved in many thyroid cancer types, including Hurthle cell cancer.”

“Those patients very likely can be observed – not necessarily dismissed from medical surveillance, but observed – and could probably avoid surgery,” he said. “If patients have a positive test, it will depend on the type of mutation, because some of them confer a high risk and others confer low risk. So, there may be a spectrum of management based on combination of clinical parameters and molecular testing. But those are more likely to be surgical candidates.”

“This is a study that is desperately needed in this field,” session attendee Bryan McIver, MD, PhD, an endocrinologist and deputy physician-in-chief at the Moffitt Cancer Center in Tampa, said in an interview. “These are very challenging studies to do, because the marketing of these molecular tests has run ahead of a lot of the clinical studies.

“It’s very hard in the United States, at least, to find patients who are truly naive to molecular testing whom you can take to the operating room,” he explained. “And if you can’t take patients with a negative molecular test to the operating room, then you can’t actually calculate the true sensitivity and specificity of the test, and the whole evaluation of the test starts to become skewed.”

According to Dr. McIver, this study is noteworthy in that it largely fulfills four key criteria: There were no post hoc sample exclusions after unblinding of data, both pathology evaluation and decision to operate were blinded to classifier results, and patients were generally unselected, with little to no prior molecular testing.

“So, we actually have a proper high-quality validation study now available for this new test, the ThyroSeq v3,” he noted. “That sets the bar where it needed to be set a long time ago, and I can’t begin to tell you how excited I am to finally have a test that passed that bar. The fact that it shows a negative predictive value of 97% in this clinical study and a positive predictive value in the mid-60% range means that there is a potential for a clinical utility there that is backed by solid science. In this field, that’s almost unique.” 

Arma GSC with Hurthle classiers In a second study, investigators led by Quan-Yang Duh, MD, professor of surgery, division of general surgery, and chief, section of endocrine surgery, University of California, San Francisco, developed and validated a pair of classifiers to enhance performance of the Afirma platform among Hurthle cell specimens.

“The Hurthle cell lesions tend to give us trouble,” Dr. Duh said. On molecular analysis, those that are malignant seldom harbor mutations that would aid diagnosis, whereas those that are benign are usually classified as suspicious by the original Afirma Gene Expression Classifier (GEC).

“The specific group that is causing trouble are those that are Hurthle cell but not neoplasm, because they are the ones that give you the false positives,” Dr. Duh said. Therefore, it makes sense to stratify lesions on both of these factors, and then subject that specific subset to a more stringent threshold. 

The investigators developed two classifiers that work with the Afirma core Genomic Sequencing Classifier (GSC), which uses RNA sequencing and machine learning algorithms.

The first classifier uses differential expression of 1,408 genes to determine whether a sample contains Hurthle cells. The second classifier, applied only to lesions containing Hurthle cells, uses differential expression of 2,041 genes and assesses loss of heterozygosity – which is prevalent in Hurthle cell neoplasms – to determine whether a Hurthle cell lesion is a neoplasm.

The ensemble model then makes a final classification, using a higher threshold for suspicious lesions determined to be Hurthle cell but not neoplasm, and a normal threshold for all the rest.

The investigators validated the Afirma GSC with the two classifiers in blinded fashion using 186 thyroid lesion samples having Bethesda III or IV cytology that had been part of the overall multicenter validation of the original Afirma GEC (N Engl J Med. 2012 Aug 23;367[8]:705-15).

Among the 26 Hurthle cell lesions, specificity for identifying benign lesions improved from 11.8% with the original Afirma GEC to 58.8% with the Afirma GSC and new classifiers. That was an absolute gain of 47% (P = .012), Dr. Duh reported. Sensitivity for identifying cancer was 88.9%.

There were also smaller absolute gains in specificity of 18% among all lesions in the cohort (P = .0028) and 14% among non-Hurthle called benign in the Hurthle cell group who would not need an operation.”

Further validation is needed, he acknowledged. “For a while, I wouldn’t send my Hurthle cell aspirate patients for Afirma, because I knew it was going to come back suspicious. I think I will start to do it now, but we need to see what the answers look like” with additional validation.

Afirma GSC with medullary thyroid cancer classier

In a third study, investigators developed and validated a classifier for medullary thyroid cancer to be used with the Afirma GSC. They were led by Gregory Randolph, MD, professor of otolaryngology and the Claire and John Bertucci Endowed Chair in Thyroid Surgical Oncology at Harvard Medical School, and division chief of the general and thyroid/parathyroid endocrine surgical divisions at the Massachusetts Eye and Ear Infirmary, Boston.

Better preoperative identification of this cancer is key for several reasons, he maintained.

“We need to know for the timing of surgery, and for the extent of both thyroidal and nodal components of surgery,” Dr. Randolph noted. “We need to know because of the aggressive nature of these lesions and the potential to be prepared for finding invasion at surgery; for the potential of bilaterality if inherited disease is present; for the potential for parathyroid disease, if familial; and finally, for the potential for intraoperative death with unrecognized pheochromocytoma and an unprepared surgeon.”

Establishing the diagnosis from needle biopsy is challenging, because some features overlap with those of other thyroid lesions, according to Dr. Randolph. In about a third of patients with medullary thyroid cancer brought to the operating room, the diagnosis is unknown at the time, and that often results in inadequate initial surgery.

The investigators developed a medullary thyroid cancer classifier cassette that assesses differential expression of 108 genes. They then performed blinded, independent validation in a cohort of 211 fine-needle aspiration samples from thyroid nodules: 21 medullary thyroid cancers and 190 other benign and malignant neoplasms.

Results showed that the Afirma GSC with the medullary thyroid cancer classifier had sensitivity of 100% and specificity of 100%, reported Dr. Randolph.

“The Afirma GSC medullary thyroid cancer testing cassette, within the larger GSC system, uses RNA sequencing and advanced machine learning to improve the diagnostic detection of medullary thyroid cancer, which currently misses approximately a third of medullary thyroid cancer patients,” he said.

Session attendees wondered which patients are appropriate candidates and how much the test will cost.

“We have to have a discussion about that, because the missed medullaries are, frankly, widely distributed – they can be in any of the Bethesda categories, basically,” Dr. Randolph said. “So, there are cytopathologic mistakes made uniformly, including in the suspicious and frankly malignant Bethesda categories. In terms of cost, this is embedded in the GSC classifier; so, if you order that test, you will obtain this medullary cassette.”

Actual sensitivity of the classifier may ultimately be less than 100% with use in larger samples, he acknowledged. “I think a greater number of validation tests is absolutely in order. I imagine this classifier may not be perfect, but it is way better than the third we miss with just cytopathology.”

Dr. Nikiforov disclosed that he is owner of an IP for ThyroSeq, and that his laboratory has a contract to offer the test commercially. Dr. Duh disclosed that he had no relevant conflicts of interest. Dr. Randolph disclosed that he had no relevant conflicts of interest.

Printable Version

Routinely in the American workforce, employees visit their physicians with symptoms including anxiety, depression, fatigue, insomnia and weight gain only to walk out of the office with a prescription for an antidepressant. Weeks later, the patient may feel a bit better, but often times still reports being haunted by an underlying cause that’s still not being addressed. 

illnesses, especially in the workplace. In the early stages, thyroid problem symptoms are subtle and can include fatigue, weight gain, dry skin, muscle aches, and impaired memory, all symptoms that point to problems like fibromyalgia, menopause, post-partum depression, PSTD and even bipolar disorder.

Is it possible your illness has been caused by a thyroid malady?

Why Thyroid Dysfunction May Be Overlooked

Many of the same symptoms of mental health dysfunctions are also indicative of thyroid disorders, up to and including nodules which may be benign or malignant. Unfortunately, due to the similarity in symptoms associated with thyroid disorders and depression, thyroid disorders are often overlooked. They are written off to common mental health illnesses. In fact, some of the symptoms are so similar that doctors questioned whether or not there could be a link between a malfunctioning thyroid and forms of depression.

Studies were inconclusive, but there didn’t seem to be a direct link and so many doctors now dismiss the possibility that a thyroid disorder may be the underlying cause of ongoing depression. Many begin prescribing drugs ranging from tranquilizers to antipsychotic medications while others referred their patients to mental health professionals. What if the problem had nothing to do with depression whatsoever? What if it was a problem with that tiny butterfly-shaped gland in the neck known as the thyroid?

Why Hyperthyroidism mimics symptoms of Mental Health Illnesses?

In simple terms, the thyroid is responsible for producing two hormones which are released into the bloodstream. These are labeled T3 and T4. If you have too much of these substances being released it is called hyperthyroidism which can result in:

• Mood Swings
• Missed periods or light periods
• Excessive Sweating
• Irritability 
• Nervousness
• Difficulty sleeping
• Anxiety

 These very same symptoms are often associated with a host of depressions and when those symptoms continue for extended periods, of course a doctor is going to see them as abnormal. Instead of running a series of thyroid diagnostics, many doctors simply write it off to mental illness of some sort.

According to Bryan McIver, MD, Ph.D., Moffitt Cancer Center, “There are several endocrine-related illnesses that sometimes get misdiagnosed as a mental disorder because the symptoms a patient may exhibit include mood swings, anxiety and depression. Endocrine problems are notoriously difficult to diagnose accurately. Often the symptoms they cause affect multiple body systems and cause symptoms that don’t always seem to belong together. Amongst the most common of these are Thyroid disorders, which can affect the function of literally any organ in the body and cause symptoms that range from mood changes, changes in metabolism, changes in heart, lungs and intestines, and changes in the skin and hair.” 

Hypothyroidism May Also Be a Cause for Concern

Having too little of T3 or T4 is labeled hypothyroidism and that is just as serious as having too much of these hormones. Again, hypothyroidism can often be misdiagnosed as mental illness because the symptoms include:

• Difficulty with sleep patterns
• Fatigue
• Difficulty in focus or with concentration
• Depression
• Heavy periods which are frequent or prolonged

 Again, you can easily see why these symptoms may be written off to illnesses like postpartum depression or postnatal complications. However, from time to time you may find a doctor who recognizes the similarities and then will run a series of tests to determine thyroid function.

Even here, however, the results are often misdiagnosed. Dr. McIver goes on to say, “Thyroid illnesses are often misdiagnosed and some patients have even had their thyroid removed unnecessarily. But thanks to advances in technology, like the newly introduced ThyroSeq V3 diagnostic test, we are able to be more precise and really get down to the underlying medical condition a patient may have. I advise all patients to. 

The best advice for those patients who are experiencing prolonged issues as listed above, but don’t think you are simply suffering from mental illness, is to look into state-of-the-art sequencing tests like ThyroSeq V3 - which can determine if there really is an underlying problem with your thyroid and then an endocrinologist can act to prescribe the appropriate treatment.

Without an accurate diagnosis, treatments of any kind are ultimately doomed to fail.

Printable Version

Been Diagnosed with a Thyroid Issue – Questions You Need to Ask Your Doctor

Posted on November 15, 2017 by admin

Have you recently been diagnosed with a thyroid issue or are you currently waiting on results from thyroid testing? Learning you have a thyroid ailment can obviously be alarming and cause for concern especially if you’re not familiar with the different types of things that can go wrong with your thyroid. Knowing what to ask your doctor is imperative so you can feel better about your diagnosis, and make sure you take the correct steps forward for your health.

According to the American Thyroid Association, more than 20 million Americans have a thyroid condition. It is also believed that about 13 million have issues but are undiagnosed. What this means is that you aren’t alone, and there is plenty of information for you to learn. Here’s a look at the questions you’ll want to ask your doctor.

The Top Questions

Because it can be hard to think rationally in the moment, especially after receiving a thyroid diagnosis, it’s a good idea to prepare in advance. Write down a list of the top questions you should be asking and then either make notes during your appointment, or record your doctor’s responses with an audio recorder (you can even use an app on your smartphone). Here are the questions you’ll want to ask.

What are the indicators?

Your doctor will most likely name a number of indicators as thyroid conditions can cause all kinds of different symptoms depending on the conditions you have. These can include such things as a racing heartbeat, poor concentration, a tremor or nervous feeling, aches and pains, feeling bloated on a regular basis, feeling cold, always feeling hot, high levels of cholesterol, or weight gain.

If you haven’t been feeling yourself, many of the symptoms you are feeling could be due to a thyroid condition. It’s important to discuss your speci×c conditions with your doctor.

Is there some sort of blood test/level I can take?

There isn’t just one single test for thyroid disease, instead there are usually a few tests involved. These can include imaging tests, blood tests, a clinical evaluation by your doctor, and possibly a biopsy if you have a growth.

How can I search for a lump on my own?

Sometimes you may have a growth or lump on your thyroid which can be felt in a physical exam. More often than not though, these lumps will need to be detected by radiology.

What type of thyroid conditions are there?

The most common conditions are hyperthyroidism, hypothyroidism, or thyroid cancer. Thankfully all conditions are very treatable.

If it turns out that I have thyroid cancer what is the path forward?

ThyroSeq V3 is a brand new and extremely innovative procedure that is able to test for thyroid nodules and cancer. It’s able to provide personalized information and rule-in or rule-out cancer without having to remove the growth. This procedure can be well worth looking into. Of the patients who use this test, 60% of them are able to avoid surgery all together. Also, as with any illness, get a second or third opinion until you feel comfortable with the course of treatment recommended.

The good news is that most thyroid cancers are curable.

Early detection is key. Treatment will most definitely include having your thyroid gland surgically removed. Radioactive Iodine can also be given to help treat the cancer, but this isn’t needed in the majority of cases.

While it’s certainly scary to get any kind of diagnosis that states you have a problem with your thyroid, asking these questions can help to make you feel much better.

Printable Version