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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as the preferred treatment in early-stage follicular lymphoma; however, despite strong supporting evidence, it has been replaced by alternative management strategies including observation without initial treatment and novel systemic therapies.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.

UPCI Researcher Named Outstanding Investigator by NCI, Awarded $6.3M for Studying How Food Can Lower Cancer Risks

 Thomas Kensler, Ph.D., professor of pharmacology and chemical biology and co-leader for the Cancer Epidemiology and Prevention Program at the University of Pittsburgh Cancer Institute (UPCI), was awarded a $6.3 million Outstanding Investigator Award from the National Cancer Institute (NCI). This new award acknowledges experienced researchers and provides them with long-term support for their exceptional work.
Dr. Kensler’s research focuses on chemoprevention, or how food can be used to lower the risk of developing cancer caused by unavoidable environmental toxins.
“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.”
The seven-year grant is one of just 60 awarded in its inaugural year.
Research has shown that controlling diet, increasing exercise and quitting smoking can decrease the risk of developing cancer; however, environmental toxins such as fossil fuel combustion products are more difficult to mitigate. Past studies by Dr. Kensler’s team in China, where environmental controls are less rigorous, have examined the bioactive molecules in broccoli and how they may help people there detoxify air pollutants.
“Pollution is a global problem and its effects are seen most often among the elderly, disabled, children and minorities. We need effective and affordable interventions, and using food-based strategies could be the ideal way to address this,” Dr. Kensler said.
He and his team will focus on a biological pathway known to play a role in detoxification, identify and validate biomarkers of its activity, and examine the molecular consequences of its chronic activation.
“It’s truly an honor for Dr. Kensler to be among the first to receive this prestigious award. He has pioneered our understanding of how chemically reactive constituents in foodstuffs can profoundly and positively impact tissue defense and repair mechanisms. We’re proud of the work he is doing to try and lessen the burden of cancer, not only in western Pennsylvania but around the globe,” said Bruce Freeman, Ph.D., UPMC-Irwin Fridovich Professor and Chair of Pharmacology and Chemical Biology.
Research reported in this publication was supported by the NCI under award number 1R35CA197222-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

UPCI Researcher Named Outstanding Investigator by NCI, Awarded $6.3M for Studying How Food Can Lower Cancer Risks

PITTSBURGH, Aug. 6, 2015 Thomas Kensler, Ph.D., professor of pharmacology and chemical biology and co-leader for the Cancer Epidemiology and Prevention Program at the University of Pittsburgh Cancer Institute (UPCI), was awarded a $6.3 million Outstanding Investigator Award from the National Cancer Institute (NCI). This new award acknowledges experienced researchers and provides them with long-term support for their exceptional work.

Dr. Kensler’s research focuses on chemoprevention, or how food can be used to lower the risk of developing cancer caused by unavoidable environmental toxins.

“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.”

The seven-year grant is one of just 60 awarded in its inaugural year.

Research has shown that controlling diet, increasing exercise and quitting smoking can decrease the risk of developing cancer; however, environmental toxins such as fossil fuel combustion products are more difficult to mitigate. Past studies by Dr. Kensler’s team in China, where environmental controls are less rigorous, have examined the bioactive molecules in broccoli and how they may help people there detoxify air pollutants.

“Pollution is a global problem and its effects are seen most often among the elderly, disabled, children and minorities. We need effective and affordable interventions, and using food-based strategies could be the ideal way to address this,” Dr. Kensler said.

He and his team will focus on a biological pathway known to play a role in detoxification, identify and validate biomarkers of its activity, and examine the molecular consequences of its chronic activation.

“It’s truly an honor for Dr. Kensler to be among the first to receive this prestigious award. He has pioneered our understanding of how chemically reactive constituents in foodstuffs can profoundly and positively impact tissue defense and repair mechanisms. We’re proud of the work he is doing to try and lessen the burden of cancer, not only in western Pennsylvania but around the globe,” said Bruce Freeman, Ph.D., UPMC-Irwin Fridovich Professor and Chair of Pharmacology and Chemical Biology.

Research reported in this publication was supported by the NCI under award number 1R35CA197222-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Cancer Researcher at Children’s Hospital of Pittsburgh of UPMC Receives Grant from St. Baldrick’s Foundation

PrintPITTSBURGH, Aug. 6, 2015 Edward V. Prochownik, M.D., Ph.D., director of oncology research at Children’s Hospital of Pittsburgh of UPMC, and the Paul C. Gaffney Professor of Pediatrics, has been awarded a research grant of $100,000 from the St. Baldrick’s Foundation, a volunteer-driven charity dedicated to raising money for childhood cancer research.

The award to Dr. Prochownik is one of 70 grants totaling more than $21.1 million nationally and internationally awarded by St. Baldrick’s in support of pediatric oncology research. These grants provide resources to institutions to conduct more research and enroll more children in ongoing clinical trials. Dr. Prochownik and his team will explore the implications of new observations of cancer cell growth.

“Cancer cells must alter their metabolism to provide the necessary energy and metabolic building blocks needed to support their rapid division,” said Dr. Prochownik, who also is professor of molecular genetics and biochemistry, University of Pittsburgh School of Medicine. “We have identified some of the key means by which the cell can control these changes. Confirming and extending these findings as we propose to do could provide novel and specific ways to interfere with this process and thus inhibit tumor growth while minimizing long-term side effects.”

Over the past year, Dr. Prochownik and his research team have developed a model of hepatoblastoma, the most common childhood liver cancer, which in advanced states is difficult to treat and requires use of drugs that can cause long-term toxicities.

“We have discovered that the mitochondria of these hepatoblastoma cells appear to be reprogrammed so as to allow them to function at maximal capacity and thus provide large amounts of energy and metabolic building blocks needed by the rapidly growing and dividing cancer cells,” explained Dr. Prochownik. “We hope that our observations at this level can be translated into new and specific ways of treating this cancer while at the same time reducing toxicity.”

This past year, three St. Baldrick’s head-shaving events were hosted in Pittsburgh, where more than 140 people “braved the shave” and raised nearly $86,000.

For more information about Dr. Prochownik, please visit www.chp.edu.

Ancient Proteins Involved in DNA Repair Could Shed Light on Tumor Development, Says Pitt Study

PITTSBURGH, July 28, 2015 – By studying the yeast used in beer- and bread-making, researchers at the University of Pittsburgh School of Medicine have uncovered the mechanism by which ancient proteins repair DNA damage and how their dysfunction could lead to the development of tumors. The findings, published online today in Nature Communications, could lead to new ways to tailor cancer therapies.

In humans, protein mutations called RAD51 paralogues have been associated with breast and ovarian tumors, said senior investigator Kara Bernstein, Ph.D., assistant professor of microbiology and molecular genetics at Pitt School of Medicine and the University of Pittsburgh Cancer Institute, partner with UPMC CancerCenter.

“These are proteins that have been present throughout evolution in many species, but very little has been known about what they do,” she said. “Our study shows for the first time the mechanism of how they are involved in the repair of damaged DNA.”

Because RAD51 paralogues are too difficult to work with in animal cells, the research team instead explored their function in yeast. They found the proteins interact with other proteins called the Shu complex to repair breaks in DNA strands, which can be caused by environmental toxins, radiation and other naturally occurring exposures.

Shu complex works synergistically with additional RAD51 paralogues to search for homologous, or complementary, DNA regions with double-strand breaks, in which both poles of the twisting DNA ladder have been broken, the researchers found. Pieces of the genetic code can be lost in such areas; the paralogues and complex repair the damage by filling in the missing pieces in a process called homologous recombination.

“Now that we understand what the proteins do, we can perhaps tailor therapies for patients who have cancer and mutations in these repair genes,” Dr. Bernstein said.

The team included Stephen K. Godin, Faiz F. Kabbinavar, and Andrew P. Van Demark, Ph.D., of Pitt; and William A. Gaines, Ph.D., Timsi Rao, Ph.D., and Patrick Sung, Ph.D., of Yale University. The project was funded by National Institutes of Health grants ES015252, ES007061, CA168635, GM088413 and GM101808.

UPCI Called ‘Outstanding’ as Comprehensive Cancer Center Grant Renewed by National Cancer Institute for $25.6M

PITTSBURGH, July 27, 2015 – The University of Pittsburgh Cancer Institute (UPCI) has been rated “outstanding” and renewed as a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, an award that recognizes the world-class research that sets the center among an elite group nationwide. The five-year grant is for $25.6 million and comes as UPCI celebrates its 30th year as a leader in working to reduce the burden of cancer.

UPCI is one of just 44 NCI-designated Comprehensive Cancer Centers in the U.S.

“The NCI renewal is an incredible accomplishment that comes after an extensive application and review process. The award recognizes our strength in basic, clinical and population research, education and community outreach and reflects the dedication of everyone here who is working toward a future without cancer,” said Nancy E. Davidson, M.D., director of UPCI and UPMC CancerCenter, Hillman Professor of Oncology and Distinguished  Professor of Medicine at Pitt, and president-elect of the American Association of Cancer Research.

With 320 faculty members from 42 Pitt departments, UPCI received $68 million in annual funding from NCI in 2015 to support cancer research activities.  Since the last renewal award, UPCI program members have published nearly 5,000 articles in peer-reviewed journals and received prestigious awards, including renewal of Specialized Programs of Research Excellence (SPOREs) grants in lung cancer, head and neck cancer, and melanoma and skin cancer and a new SPORE with another center in ovarian cancer.

Among other notable accomplishments, UPCI was also selected by the NCI as a National Clinical Trials Network Lead Academic Participating Site and as an Experimental Therapeutics-Clinical Trials Network Lead Academic Organization, both of which aim to streamline research trials.  In addition, UPCI is playing a key role in an international study examining how environmental and lifestyle exposures and genetics have affected the incidence, mortality and age-related outcomes of cancer in more than 81,000 Chinese men and women, an effort funded by the NCI.

“Our faculty members are among the most sought- after cancer experts in the country, and we’re proud of the work that sets UPCI apart from other cancer research centers,” said Arthur S. Levine, M.D., Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine.

Known colloquially as the “core grant,” NCI’s Cancer Center Support Grant is awarded every five years. Established in 1985, UPCI first received its status as an NCI-designated Comprehensive Cancer Center in 1990 and has retained this distinction since then.

Pitt Scientists Lead Consensus Guidelines for Thyroid Cancer Molecular Tests

PITTSBURGH, July 6, 2015 University of Pittsburgh Cancer Institute (UPCI) scientists recently led a panel of experts in revising national guidelines for thyroid cancer testing to reflect newly available tests that better incorporate personalized medicine into diagnosing the condition.

Their clinical explanation for when to use and how to interpret thyroid cancer tests is published in the July issue of the scientific journal Thyroid. The American Thyroid Association is revising its 2015 Guidelines for Thyroid Nodule and Thyroid Cancer Management to direct doctors to the scientific publication.

“Minimally invasive molecular testing for thyroid cancer has improved by leaps and bounds in the last several years,” said co-author Robert L. Ferris, M.D., Ph.D., professor and chief of the Division of Head and Neck Surgery in Pitt’s School of Medicine. “But different tests perform differently and, therefore, need to be interpreted carefully to make the best decisions regarding extent of surgery for patients with thyroid nodules. Our goal with this analysis is to give clinicians a clear understanding of what each type of test can tell them and when to use them to determine the best course of treatment.”

Cancer in the thyroid, which is located just below the “Adam’s apple” area of the neck, is the fifth most common cancer diagnosed in women. Thyroid cancer is one of the few cancers that continues to increase in incidence, although the five-year survival rate is 97 percent.

UPCI, partner with UPMC CancerCenter, has been a national leader in developing personalized genetic tests for thyroid cancer that have spared patients repeat or unnecessary surgeries. A low-cost test called ThyroSeq, developed by a team led by Yuri Nikiforov, M.D., Ph.D., director of Pitt’s Division of Molecular and Genomic Pathology, allows pathologists to simultaneously test for multiple genetic markers of thyroid cancer using just a few cells collected from the nodule.

This allows doctors to “rule-in” a specific cancer diagnosis with a high degree of certainty, without a biopsy to remove a large portion of the thyroid, which would then have to be followed with a second surgery if cancer is detected to remove the entire gland. As Dr. Nikiforov’s group added more genetic sequences to the ThyroSeq test to create a larger and more sensitive version of the test, it is now also performing as a “rule-out” test that can tell doctors with a high degree of certainty that a patient does not have cancer.

Other available tests use different technology to serve as accurate “rule-out” tools, but do not have the high sensitivity needed to also reliably “rule-in” cancer. And, in some cases, the accuracy of the “rule out” tests depends on the prevalence of cancer in the patients seen by each individual cancer institute. This is critical because clinicians must know this rate at their institution to correctly calculate the accuracy of “rule-out” test results for each patient.

In addition to Dr. Ferris and co-author Sally E. Carty, M.D., who is professor and chief of the Division of Endocrine Surgery in Pitt’s School of Medicine and co-director of the UPMC/UPCI Multidisciplinary Thyroid Center, the panel reviewing the tests was a multidisciplinary group from a dozen institutions in the U.S. and Canada.

“This was a very innovative and collegial initiative,” said Dr. Carty.  “Through an objective review of the existing tests and the scientific literature characterizing their performance, we are seeking to help clinicians make the best decisions for their patients.”

Dr. Ferris agrees, noting that “this is an exciting time in personalized medicine, and these tests give us the ability to not only better diagnose and treat thyroid cancer, but also significantly reduce surgeries for people who don’t have cancer.”

Additional authors on this publication are Zubair Baloch, M.D., Ph.D., University of Pennsylvania Medical Center; Victor Bernet, M.D., Mayo Clinic; Amy Chen, M.D., Emory University; Thomas J. Fahey III, M.D., New York Presbyterian Hospital; Ian Ganly, M.D., Ph.D., and Ashok Shaha, M.D., both of Memorial Sloan-Kettering Cancer Center; Steven P. Hodak, M.D., and Kepal N. Patel, M.D., both of New York University Medical Center; Electron Kebebew, M.D., National Cancer Institute; David L. Steward, M.D., University of Cincinnati Medical Center; Ralph P. Tufano, M.D., Johns Hopkins University; and Sam M. Wiseman, M.D., St. Paul’s Hospital & University of British Columbia.

Pitt’s Dr. Yuan Chang Appointed to National Cancer Advisory Board

PITTSBURGH, June 23, 2015 – President Barack Obama recently appointed a pathologist in the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter, to a national board charged with identifying the most promising cancer research projects nationwide.

Yuan Chang, M.D., Distinguished Professor of Pathology in Pitt’s School of Medicine, has been Dr. Yuan Changappointed with four other scientists to serve as members of the National Cancer Advisory Board.

“I am honored that these talented individuals have decided to serve our country. They bring their years of experience and expertise to this administration, and I look forward to working with them,” President Obama said in announcing the appointments.

The National Cancer Advisory Board consists of 12 members appointed by the president to advise the National Institutes of Health’s (NIH) National Cancer Institute. The members review applications for grants and cooperative agreements for cancer research and training, and recommend approval of the projects that show the most promise of making valuable contributions to human knowledge.

“This is a great opportunity for me to professionally contribute to the directive of the National Institutes of Health,” said Dr. Chang, also UPMC Professor of Cancer Virology Research. “My goal is to bring my basic research expertise on infectious diseases and cancer to inform the administrative goals of the NIH.”

Dr. Chang joined the Pitt School of Medicine in 2002, after she and Patrick S. Moore, M.D., M.P.H., discovered Kaposi’s sarcoma-associated herpesvirus, which causes Kaposi’s sarcoma, the most common malignancy occurring in AIDS patients. The team then went on to discover Merkel cell polyomavirus, which causes a rare but deadly skin cancer.

Dr. Chang earned her Bachelor of Science degree from Stanford University and a medical doctorate from the University of Utah College of Medicine.

Prior to coming to Pitt, Dr. Chang served in several clinical and academic positions from 1993 to 2002 at the Columbia University College of Physicians and Surgery and Columbia Presbyterian Hospital. Before that she was a clinical instructor at Stanford University Medical Center.

Image credit: Joshua Franzos

Pitt Researchers Find Genetic Testing in Thyroid Cancer May Aid in Surgical Decision Making

PITTSBURGH, June 10, 2015 – A team of researchers led by Linwah Yip, MD, associate professor in the Department of Surgery, recently found that routine genetic testing to detect mutations implicated in thyroid carcinogenesis can help guide perioperative decision making.  Their research recently was presented by Dr. Yip at the annual meeting of the American Surgical Association in San Diego.

Dr. Yip and her colleagues at the University of Pittsburgh conducted a retrospective review of a consecutive series of 1,510 patients from the electronic medical record of a single institution. The patients had initial surgery for histologically confirmed thyroid cancer. All cancers in the study were tested for mutations in seven genes associated with thyroid carcinogenesis. Although risks associated with mutations are not always clear-cut, the researchers found that distant metastases were more common in thyroid cancer patients who were positive for the RET/PTC mutation, while thyroid cancer expressing BRAF V600E or RET/PTC was associated with higher-grade cancer on presentation and early recurrence.

Additional researchers on the study were Marina N. Nikiforova, MD, Jenny Yoo, MD, Kelly L. McCoy, MD, Michael T. Stang, MD, Kristina J. Nicholson, MD, Michaele J. Armstrong, PhD, Steven P. Hodak, MD, Robert L. Ferris, MD, PhD, Yuri E. Nikiforov, MD, PhD, Sally E. Carty, MD, all currently or formerly of the University of Pittsburgh.

For more information, please visit the American College of Surgeons webpage.

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