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3D Bioprinted Model for the Study of Precancerous Breast Disease Aims to Reduce Unnecessary Treatment

Researchers at the University of Pittsburgh Cancer Institute (UPCI) and materials and biomedical engineers at Carnegie Mellon University (CMU) will address the overdiagnosis and overtreatment of a non-invasive precancerous breast tumor by creating the first-ever 3D bioprinted breast ductal structure to identify markers for low-risk premalignant disease.

The scientists were awarded nearly $800,000 in a two-year grant from the U.S. Congressionally Directed Medical Research Program of the Department of Defense.

Improvements in mammography screening have resulted in earlier detection of invasive breast cancer, and this is also associated with an increase in the detection of non-invasive breast cancer, such as ductal carcinoma in situ (DCIS) – the earliest form of breast cancer where the disease has not spread out of the milk duct.  Over 60,000 women are diagnosed with DCIS each year, and the majority of non-invasive lesions will not progress to invasive diseases if left untreated. However, the majority of these women undergo unnecessary surgeries, treatments and therapy.

“More research is required to identify the minority of DCIS lesions that will progress to invasive disease and thus require treatment,” explained Adrian Lee, PhD, professor of pharmacology and chemical biology at UPCI. “Our hope is that our research will reveal novel biomarkers that will be useful for predicting which DCIS are likely to progress. We can then offer personalized therapy to those who require intervention, while reducing the overtreatment of DCIS in those who don’t. This could have a major impact upon thousands of women each year.”

UPCI researchers will collaborate with materials and biomedical engineers at CMU and use 3D bioprinting to print a breast ductal system in the laboratory. They will then grow DCIS cells in the printed duct. By printing a replica of a mouse ductal system, experts will be able to create a unique model to study why some DCIS progress to invasion while others remain indolent. Genes involved in progression may serve as biomarkers indicating the need to treat DCIS.

“3D bioprinting is transforming how we can build tissues. By allowing us to use medical imaging data to accurately recreate complex biology, this has the potential to revolutionize bioengineering and tissue regeneration,” said Adam Feinberg, PhD, associate professor in CMU’s departments of Materials Science and Engineering and Biomedical Engineering. “Printing of cells and organs has been challenging because these are soft materials. Our novel technology solves this, and we are excited by the opportunity to collaborate with our colleagues at UPCI to advance our understanding of DCIS and invasion.”

The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program, under Award No. W81XWH-16-1-0017 & W81XWH-16-1-0018.

Easy Ways to Improve Patient Comfort During Skin Cancer Screenings

New research from the University of Pittsburgh School of Medicine suggests two simple ways dermatologists can make patients more comfortable during full-body skin cancer checks: respect patient preferences for the physician’s gender as well as whether, and how, they prefer to have their genitals examined. The findings are published online today in JAMA Dermatology.

“This study identifies barriers to getting skin checks. Giving patients choices that reduce embarrassment during an exam may make a person more likely to get regular skin checks, leading to higher rates of skin cancer detection,” said lead author Laura Ferris, MD, PhD, associate professor, Department of Dermatology, Pitt School of Medicine and member of the Melanoma Program, University of Pittsburgh Cancer Institute.

Estimates suggest that one in five people will develop skin cancer over the course of a lifetime. Rates of melanoma, which account for less than one percent of skin cancer cases but the vast majority of skin cancer deaths, have tripled over the last 40 years.

The best way to prevent skin cancer is to use adequate protective measures during sun exposure, perform regular self-examinations, and, for those patients at increased risk of developing skin cancer, obtain annual full-body screenings from a dermatologist, said Ferris.

The current study was born out of an observation from Ferris’ own dermatology practice: many women wanted female physicians and were uncomfortable having male students in the room during their exams. While a strong preference for a same gender physician has been documented among patients undergoing colonoscopies, there wasn’t much data available about dermatology, Ferris explained.

In the new study, the researchers at three institutions, including UPMC, administered an anonymous survey to 443 adults undergoing a full-body screening for skin cancer.

Overall, people generally preferred a physician who shared their gender. Breaking the data down by gender, one third of women and nearly one fifth of men expressed a gender preference. Among this group, nearly all (99 percent) of the women preferred a female physician, and almost two thirds of the men preferred a male physician.

The biggest predictor of preferring a female physician among women was being under age 30. Young women have one of the fastest growing rates of melanoma, so taking physician gender preference into account in this group may have an especially large impact, Ferris noted.

Typically, patients are asked to completely disrobe for a skin cancer screening. When asked about clothing preferences, nearly half of women and 40 percent of men preferred to leave their undergarments in place during the exam.

“What we learned is that a substantial number of people preferred to leave their undergarments on and have us work around them,” said Ferris.

Less than 1 percent of melanomas are found in the genital region, so with 31 percent of women and 13 percent of men preferring not to have their genitals examined at all, another important message from the study is that physicians need to balance the benefit of occasionally finding a genital melanoma with causing a lot of people discomfort or anxiety, she added.

The researchers are now focused on putting their findings into practice. “When we think about the relative risks and benefits of cancer screening, if we’re causing people discomfort, then we need to think of that as doing harm. Our study provides some easy ways to reduce that harm,” Ferris said. “In the age of personalized medicine, taking simple steps, such as offering a choice of physician gender and degree of disrobement during an examination, can allow us to personalize the skin cancer screening examination to minimize discomfort.”

Co-authors of the study include Neil Houston, BA, and Westley Mori, BA, both of Pitt School of Medicine; Aaron Secrest, MD, PhD, and Mark Eliason, MD, both of University of Utah; and Ryan Harris, MD, and Charles Phillips, MD, both of East Carolina University.

The study was funded by National Institutes of Health grants UL1-TR-000005 and P50CA121973.

Watercress Extract Detoxifies Carcinogens in Smokers, Clinical Trial Demonstrates

Watercress extract taken multiple times a day significantly inhibits the activation of a tobacco-derived carcinogen in cigarette smokers, researchers at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter, demonstrated in a phase II clinical trial presented today at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans.

The trial also showed that the extract detoxifies environmental carcinogens and toxicants found in cigarette smoke, and that the effect is stronger in people who lack certain genes involved in processing carcinogens. This trial was supported by a grant from the National Cancer Institute (NCI).

“Cigarette smokers are at far greater risk than the general public for developing lung cancer, and helping smokers quit should be our top cancer prevention priority in these people,” said Jian-Min Yuan, MD, PhD, associate director of the UPCI’s Division of Cancer Control and Population Science and an epidemiologist with Pitt’s Graduate School of Public Health. “But nicotine is very addictive, and quitting can take time and multiple relapses. Having a tolerable, nontoxic treatment, like watercress extract, that can protect smokers against cancer would be an incredibly valuable tool in our cancer-fighting arsenal.”

Dr. Yuan, who also is Pitt’s Arnold Palmer Endowed Chair in Cancer Prevention, and his colleagues enrolled 82 cigarette smokers in the randomized clinical trial. The participants either took 10 milligrams of watercress extract mixed in 1 milliliter of olive oil four times a day for a week or they took a placebo. Each group of participants then had a one week “wash-out” period where they didn’t take anything and then switched so that those getting the placebo now received the extract. They all continued their regular smoking habits throughout the trial.

In one week, the watercress extract reduced activation of the carcinogen known as nicotine-derived nitrosamine ketone in the smokers by an average of 7.7 percent. It increased detoxification of benzene by 24.6 percent and acrolein by 15.1 percent, but had no effect on crotonaldehyde. All the substances are found in cigarette smoke.

Participants who lacked two genes involved in a genetic pathway that helps the antioxidant glutathione remove carcinogens and toxicants from the body saw an even bigger benefit to taking the watercress extract, which increased their detoxification of benzene by 95.4 percent, acrolein by 32.7 percent and crotonaldehyde by 29.8 percent.

A phase III clinical trial in hundreds of people must be performed before the treatment could be recommended for smokers, and Dr. Yuan warned that while eating cruciferous vegetables, such as watercress and broccoli, is good for people, they are unlikely to have the same pronounced effect as the extract.

Additional researchers on this project are Irina Stepanov, PhD, Sharon E. Murphy, PhD, Steven G. Carmella, BA, Heather H. Nelson, PhD, Dorothy Hatsukami, PhD, and Stephen S. Hecht, PhD, all of the University of Minnesota.

This research was funded by NCI grant R01CA122244.

Four Young Researchers from the Same UPCI Lab Receive AACR Scholar-in-Training Awards

Four young investigators from the same laboratory at the University of Pittsburgh Cancer Institute, partner with UPMC CancerCenter,  have been recognized with American Association for Cancer Research (AACR) scholar-in-training awards for AACR’s annual meeting in New Orleans, April 16 to 20.

“I am delighted the efforts of my students have been so successful and look forward to the next steps they take in their promising research careers,” said lab leader Shivendra Singh, PhD, professor of pharmacology and chemical biology, and UPMC Chair in Cancer Prevention Research, Pitt School of Medicine. His lab focuses on examining enzymes that play a role in drug metabolism and cellular defenses against environmental toxins, as well as exploring the anti-carcinogenic effects of certain natural agents found in edible plants.

Three researchers received scholar-in training awards in memory of Dr. Lee W. Wattenberg, a pioneer in cancer prevention research, who served as AACR president in 1992. According to AACR, these awards are presented to young investigators presenting high-quality papers relating to cancer prevention research.

Those awardees are:

Su Hyeong Kim, PhD: “Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane” (Abstract 822).

In this project, Dr. Kim showed that sulforaphane, which naturally occurs in broccoli and other cruciferous vegetables, can inhibit prostate cancer in lab tests because it blocks the effects of c-Myc, a gene that regulates cancer growth. This investigation was supported by grant CA115498 of the National Cancer Institute (NCI), part of the National Institutes of Health.

Subrata K. Pore, PhD: “Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis” (Abstract 826).

Dr. Pore and colleagues built on previous work showing that benzyl isothiocyanate (BITC), found in edible cruciferous vegetables such as garden cress, inhibits breast cancer in a mouse model of the disease. In advanced breast cancer, bone loss can occur, which can be deadly with spreading disease. In this project, the team showed that BITC can limit bone breakdown by reducing the production of bone-resorbing cells called osteoclasts. This study was supported by NCI grant CA129347.

Krishna Beer Singh, PhD: “c-Myc is a novel target of prostate cancer cell growth inhibition by honokiol” (Abstract 831).

Dr. Singh led a project that showed honokiol, a naturally occurring agent derived from magnolia trees, suppressed activity of c-Myc and other genes that play key roles in prostate cancer growth. This study was supported by NCI grants CA101753 and CA115498.

In addition, a fourth researcher from the Singh Lab received a $1,500 AACR-Triple Negative Breast Cancer Foundation scholar-in-training award.

Ruchi Roy, PhD: “Benzyl isothiocyanate mediates glucose uptake through AKT activation in breast cancer cells” (Abstract 833).

Dr. Roy showed in animal models that BITC’s effects in suppressing Her-2-driven breast tumors could be enhanced with the addition of an agent that inhibits the protein AKT. This study was supported by NCI grant CA129347.

Pitt-led International Panel Reclassifies Thyroid Tumor to Curb Overdiagnosis of Cancer, Unneeded Treatment

Led by researchers at the University of Pittsburgh School of Medicine, an international panel of pathologists and clinicians has reclassified a type of thyroid cancer to reflect that it is noninvasive and has a low risk of recurrence. The name change, described today in JAMA Oncology, is expected to reduce the psychological and medical consequences of a cancer diagnosis, potentially affecting thousands of people worldwide.

The incidence of thyroid cancer has been rising partly due to early detection of tumors that are indolent or non-progressing, despite the presence of certain cellular abnormalities that are traditionally considered cancerous, explained senior investigator Yuri Nikiforov, MD, PhD, professor of pathology and director of Pitt’s Division of Molecular and Genomic Pathology.

“This phenomenon is known as overdiagnosis,” Dr. Nikiforov said. “To my knowledge, this is the first time in the modern era a type of cancer is being reclassified as a non-cancer. I hope that it will set an example for other expert groups to address nomenclature of various cancer types that have indolent behavior to prevent inappropriate and costly treatment.”

In particular, a tumor type known as encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has increased in incidence by an estimated two- to three-fold over the past 20 to 30 years and makes up 10 to 20 percent of all thyroid cancers  diagnosed in Europe and North America, the panel noted. Although studies have shown EFVPTC is not dangerous, it is typically treated as aggressively as other types of thyroid cancer. At the recommendation of the National Cancer Institute, the panel sought to revise the terminology and to see if the word “cancer” could be dropped from its name.

Two dozen experienced pathologists from seven countries and four continents independently reviewed 268 tumor samples diagnosed as EFVPTC from 13 institutions. The experts established diagnostic criteria, including cellular features, tumor invasion and other factors. In a group of more than 100 noninvasive EFVPTCs, there were no recurrences or other manifestations of the disease at a median follow-up of 13 years, the panel found.

These experts decided to rename EFVPTC as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” or NIFTP. The new name cites key features to guide pathologists in diagnosis, but omits the word “cancer,” indicating that it need not be treated with radioiodine or other aggressive approaches.

“We determined that if NIFTP is carefully diagnosed, the tumor’s recurrence rate is extremely low, likely less than 1 percent within the first 15 years,” Dr. Nikiforov said. “The cost of treating thyroid cancer in 2013 was estimated to exceed $1.6 billion in the U.S. Not only does the reclassification eliminate the psychological impact of the diagnosis of ‘cancer,’ it reduces the likelihood of complications of total thyroid removal, and the overall cost of health care.”

The team included researchers from the University of Bologna, Italy; University of Pennsylvania; University of Pisa, Italy; Harvard Medical School; and others.

The project was funded in part by University of Pittsburgh Cancer Institute, UPMC and an education grant from CBLPath, Inc.

Researcher Named UPCI’s 2nd NCI Outstanding Investigator, Awarded $6.4M for Discovering Cancer Viruses

Patrick Moore, MD, MPH, has received the National Cancer Institute (NCI) Outstanding Investigator Award, a top honor given to accomplished cancer researchers, and was awarded $6.4 million to further his work into the link between viruses and cancer. This NCI grant recognizes exceptional past achievements to provide seven years of secured support, giving the investigator freedom from the pressure of ongoing grant competitions.

Dr. Moore’s award makes him the second researcher at the University of Pittsburgh Cancer Institute (UPCI) to receive this highly coveted recognition, given to just 60 people in the country since the grant program was created in 2014. UPCI’s Thomas Kensler, PhD, who studies chemoprevention, or how food can be used to lower the risk of developing cancer caused by unavoidable environmental toxins, was awarded the honor last year.

Dr. Moore is a distinguished professor and leader of the UPCI Cancer Virology Program, holding The Pittsburgh Foundation Chair in Innovative Cancer Research at Pitt. Together with his research partner and wife, Yuan Chang, MD, Dr. Moore identified two different viruses that cause Kaposi sarcoma and Merkel cell carcinoma.

“To have the NCI recognize not just one but two of our faculty really reflects the strength of our research here at UPCI,” said Nancy E. Davidson, MD, director of UPCI, partner with UPMC CancerCenter. “We have a strong bench of talent here, and the work Dr. Moore is doing is making a real difference in our quest to end cancer.”
The award will fund Dr. Moore’s research in three key areas:

1. Understanding the mechanism by which the virus that causes Merkel cell carcinoma turns normal cells into cancer.
2. Investigating unusual ways that the virus causing Kaposi sarcoma makes oncoproteins.
3. Identifying new ways to find viruses that cause cancer in humans.
Recently, the Moore-Chang lab found a new mechanism that cancer viruses use to regulate how cells translate RNA into proteins and developed an assay to discover a class of viruses called polyomaviruses.

“I am hopeful this research will help provide new insights into methods to reliably determine the role of viruses in human cancers and to uncover new common cancer pathways that are at work in both infectious and noninfectious tumors,” Dr. Moore said. “This is an exciting time in cancer research based on past discoveries, and I’m honored that the NCI has chosen to recognize my work with this award.”

The NCI Outstanding Investigator Award provides funding to investigators with outstanding records of productivity in cancer research to continue or embark upon new projects of unusual potential in cancer research over an extended period of seven years. The award was developed to provide investigators with substantial time to break new ground or extend previous discoveries to advance biomedical, behavioral or clinical cancer research.

“The NCI Outstanding Investigator Award addresses a problem that many cancer researchers experience: finding a balance between focusing on their science while ensuring that they will have funds to continue their research in the future,” said Dinah Singer, Ph.D., director of NCI’s Division of Cancer Biology. “With seven years of uninterrupted funding, NCI is providing investigators the opportunity to fully develop exceptional and ambitious cancer research programs.”

UPMC CancerCenter Re-Accredited By American College of Radiation Oncology

UPMC CancerCenter has received re-accreditation by the American College of Radiation Oncology (ACRO), maintaining its position as the largest comprehensive cancer network in the country to be accredited in radiation oncology. Two of UPMC CancerCenter’s newer network sites, UPMC Altoona and Butler Radiation Oncology centers, each received accreditation for the first time.

“This three-year accreditation recognizes the high-quality radiation oncology care that our facilities provide to the patients in our communities each day,” said Dwight E. Heron, MD, director of radiation oncology services at UPMC CancerCenter, partner with the University of Pittsburgh Cancer Institute. “This accreditation exemplifies our ongoing commitment and the focused effort of our staff to exceed national quality standards set forth by our professional peers. I am extremely proud of our outcomes.”

ACRO is the premier national organization dedicated to radiation oncology, and its validation confirms that UPMC CancerCenter delivers the highest-quality care to its patients. The lengthy and in-depth accreditation process included a thorough review of patient charts, technology, staff certifications and documentation of processes for each radiation oncology site, among other factors, followed by ACRO’s visits to each site to survey day-to-day operations.

At its treatment locations in western Pennsylvania, UPMC CancerCenter uses a variety of cutting-edge techniques to provide care for the approximately 7,000 cancer patients undergoing radiation at UPMC every year. These include external beam radiotherapy, such as intensity-modulated radiation therapy (IMRT) and 3-D conformal radiation therapy; stereotactic radiosurgery using the GammaKnife, CyberKnife and TrueBeam technologies, among others; and brachytherapy.

ACRO developed its voluntary accreditation program to help promote the highest standards for radiation oncology.

Chief of Hematology/Oncology at Children’s Hospital of Pittsburgh of UPMC Selected for Pediatric Cancer MoonShot Consortium

PrintLinda McAllister-Lucas, M.D., Ph.D., chief of the Division of Pediatric Hematology/Oncology at Children’s Hospital of Pittsburgh of UPMC, has been selected as a member of the prestigious Pediatric Cancer MoonShot Consortium.

The announcement was made at the Cancer MoonShot 2020 press conference held this week in Phoenix.

Dr. McAllister-Lucas is an internationally recognized expert in lymphoma whose research has provided new insights into the molecular basis of these types of cancers.

The Cancer MoonShot 2020 Program is a cancer collaborative initiative seeking to accelerate the potential of combination immunotherapy as the next-generation standard of care for cancer patients. This group aims to explore a new paradigm in cancer care by initiating randomized Phase II trials involving 20,000 patients with 20 tumor types within the next 36 months. These findings will inform Phase III trials and the aspirational “moonshot” to develop effective, vaccine-based immunotherapies to combat cancer by 2020.

The newly formed consortium will focus on bringing the promise of immunotherapy to children diagnosed with the disease. The group will seek to apply the most comprehensive diagnostic testing available—whole genomic and proteomic analysis—and leverage proven and promising combination immunotherapies and clinical trials under the QUantitative, Integrative Lifelong Trial (QUILT) Program within the Cancer MoonShot 2020 mission.

“Less than 1 percent of cancers in the United States occur in pediatric patients. And yet, the loss of years and quality of life to pediatric cancer is huge,” said Dr. McAllister-Lucas, also an associate professor of pediatrics at the University of Pittsburgh School of Medicine. “The Cancer MoonShot 2020 will pour resources into research investigating the cause, the diagnosis and the treatment of pediatric cancers. This MoonShot will start a new era of hope for our patients and their families, and will lead the way toward more effective, less toxic treatments, and higher quality, longer lives for children with cancer.”

Dr. McAllister-Lucas is one of 10 members from various academic centers across the United States to be included in the consortium. Other centers include: Ann & Robert H. Lurie Children’s Hospital of Chicago; Children’s Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center; Children’s Hospital of Orange County; Children’s Hospital of Philadelphia; Duke Department of Pediatrics – Duke University School of Medicine; Floating Hospital for Children at Tufts Medical Center; Huntsman Cancer Institute at the University of Utah and Intermountain Primary Children’s Hospital; Phoenix Children’s Hospital; and Sanford Health.

The Division of Pediatric Hematology/Oncology at Children’s provides diagnosis, treatment and follow-up for children, adolescents and young adults with cancer and blood disorders. The division is the largest, most comprehensive pediatric cancer and blood disease center in western Pennsylvania, eastern Ohio and northern West Virginia and has been a member of the Children’s Oncology Group, a multi-institutional pediatric cancer research organization sponsored by the National Cancer Institute, since 1961.

For more information on Dr. McAllister-Lucas, visit www.chp.edu.

Study: Radiation Therapy Often Underused for Common Type of Non-Hodgkin Lymphoma Despite Recommendations

Patients with an early-stage, indolent form of lymphoma are increasingly being given no treatment, chemotherapy or targeted drug therapies despite strong clinical evidence that shows radiation therapy can have better outcomes, according to a study by University of Pittsburgh School of Medicine researchers that is being presented at the 57th Annual Meeting of the American Society for Radiation Oncology(ASTRO). 

Guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology both list radiation therapy as the preferred treatment for low-grade follicular lymphoma, which is a common type of non-Hodgkin lymphoma that grows slowly. It is most likely to occur in people age 60 and older.  

Radiation therapy is the use of high-energy x-rays to treat cancer, and was the first curative therapy for lymphoma. Radiation therapy has a long history as the preferred treatment in early-stage follicular lymphoma; however, despite strong supporting evidence, it has been replaced by alternative management strategies including observation without initial treatment and novel systemic therapies.

“Our study highlights the increasing omission of radiation therapy in non-Hodgkin’s lymphoma and its associated negative effect on overall survival at a national level. This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques which decrease risk of side effects,” said Austin Vargo, M.D., a radiation oncologist at UPMC CancerCenter, partner with the University of Pittsburgh Cancer Institute, and lead author of the study.  “More patients should be offered this effective yet underused treatment.”

Researchers analyzed patterns of care and survival outcomes for 35,961 patients diagnosed with early-stage follicular lymphoma as listed in the National Cancer Data Base. The study found that the use of radiation therapy in these patients decreased from 37 percent in 1999 to 24 percent in 2012 while there were increases in the use of single-agent chemotherapy and observation without any initial treatment. Patients who received radiation therapy had five-year and 10-year survival rates of 86 percent and 68 percent, respectively; those who did not have radiation therapy had rates of 74 percent and 54 percent.

“Survival with radiation therapy in these cases are higher and we think that an evidence-based approach should be used by more oncologists when discussing treatments for their patients,” said Dwight E. Heron, M.D., FACRO, FACR, director of radiation services, UPMC CancerCenter, and professor of Pitt’s Department of Radiation Oncology, Otolaryngology and Head & Neck Surgery.

Collaborators on the study were Beant S. Gill, M.D., of the University of Pittsburgh Cancer Institute; Goundappa K. Balasubramani, Ph.D., of the University of Pittsburgh Graduate School of Public Health; and Sushil Beriwal, M.D., Department of Radiation Oncology,Magee-Womens Hospital of UPMC.

Pitt/UPCI Next-Gen Sequencing Test Identifies Cancerous Thyroid Nodules with High Degree of Accuracy

A next-generation sequencing test is successfully predicting which thyroid nodules are cancerous and require surgical removal, reducing the need for multiple invasive diagnostic procedures, according to researchers at the University of Pittsburgh Cancer Institute (UPCI) and Pitt School of Medicine. Their findings were recently published online in the journal Thyroid.
In up to 80 percent of cases, examination of cells collected with a fine needle from a suspicious lump in the thyroid, a gland in the front of the neck, typically can tell a pathologist whether it is benign or malignant, said lead investigator Yuri Nikiforov, M.D., Ph.D., professor of pathology and director of Pitt’s Division of Molecular and Genomic Pathology.
“However, in 20 percent of cases, the result is indeterminate, meaning we can’t say for certain whether the nodule is cancerous,” he said. “That means the patient might have a repeat needle biopsy, or will go to the operating room to have the affected thyroid lobe removed for further assessment. If it turns out to be cancer, the patient has to have yet another surgery to have the rest of the thyroid taken out.”
Three-quarters of such diagnostic surgeries are performed on what turn out to be benign nodules. Such patients could have avoided surgery if physicians were confident without surgical excision that the nodules are very likely to be harmless.
In the new study, the researchers used the latest version of the test they developed, called ThyroSeq v2.1, to look for more than 300 cancer-associated mutations in 56 genes using cells obtained from fine-needle aspiration biopsies in more than 440 patients. Of that group, 96 patients had established diagnoses through surgery, allowing the team to assess ThyroSeq’s predictive power. The team found the test was able to correctly classify 20 out of 22 cancers with high precision and accuracy. Most importantly, when the test was negative, the residual risk of cancer in those nodules was so low that surgical excision was not needed.
“We finally have a test that offers high accuracy in predicting whether a nodule is cancerous or if it is benign,” Dr. Nikiforov said.
“This molecular testing panel holds great promise for streamlining and eliminating unnecessary surgery, not just here, but nationwide,” said co-author Sally E. Carty, M.D., professor and chief of endocrine surgery, Pitt School of Medicine, and co-director of the UPMC/UPCI Multidisciplinary Thyroid Center, which has been offering the test since 2014. It also is available to and used by thyroid clinics around the country.
“Thyroid cancer now is the fifth most common cancer diagnosed in women, and it is one of the few cancers that continues to increase in incidence,” she noted. “It’s important to get to the diagnosis quickly and correctly.”
The team included other researchers from Pitt and UPCI. The project was supported by UPCI, UPMC and the Richard A. & Leslie A. Snow Fund for Thyroid Cancer Research.
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