VICC News & Publications Fri, 24 Oct 2014 22:24:32 +0000 en-US hourly 1 VICC Investigators Earn Breast Cancer Grants Thu, 23 Oct 2014 16:00:54 +0000 Three Vanderbilt-Ingram Cancer Center (VICC) investigators have been awarded breast cancer research grants from the Susan G. Komen organization. The grants, which total $830,000, are part of the non-profit organization’s commitment to young scientists, as well as established investigators who are searching for more effective breast cancer therapies.

Justin Balko, Pharm.D., Ph.D., research assistant professor of Medicine, will receive $450,000 to determine if MEK inhibitor drugs may be beneficial when used in combination with neoadjuvant chemotherapy or following surgery to improve rates of survival in patients with triple negative breast cancer (TNBC) – an aggressive form of breast cancer with a poor prognosis.

Kareem Mohni, Ph.D., research fellow in the Department of Biochemistry, has been awarded $180,000 to study the mechanisms that control DNA repair in breast cancer. Mohni will examine specific genetic interactions with the protein ATR to try to create novel cancer therapies, particularly for TNBC.

Jennifer Pietenpol, Ph.D., Benjamin F. Byrd Jr. Professor of Oncology and director of VICC, will receive $200,000 in continued Komen Scholar funding. The support will help Pietenpol build upon previous Komen-funded research which led to the discovery of six subtypes of TNBC, each with distinct biological properties. Pietenpol and her team are working to translate this discovery into the development of novel targeted therapies for TNBC.

“The financial support from the Susan G. Komen foundation has been crucial to many of our discoveries and we are grateful for their continued confidence in the importance of our scientific endeavors to improve therapies for breast cancer patients,” said Pietenpol.

Komen’s total research investment in Tennessee is $11.7 million since 1982. The research program is funded, in part, by contributions from local Komen Affiliates which annually contribute 25 percent of net funds raised in their local community to Komen’s research program.

Over the past 12 years, the Greater Nashville Affiliate has awarded more than $4 million to community programs serving local women and men.

“We’re very proud that the funds we’ve raised in Middle Tennessee are not only providing real-time help to our neighbors but coming back to our universities and hospitals for research that can save lives,” said Patty Harman, executive director of the Komen organization’s Greater Nashville chapter.

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Study Seeks to Improve Lymphedema Care Thu, 16 Oct 2014 21:00:50 +0000 A new Vanderbilt University School of Nursing (VUSN) study may lead to earlier detection and better outcomes for the 20-30 percent of breast cancer patients with lymphedema, the painful and stigmatizing arm swelling that often results from treatment.

The study is testing bioimpedance spectroscopy, a device where electrodes are placed on the patient’s arms so that the fluid buildup can be accurately measured. The randomized study is enrolling 1,100 research subjects over two years at five sites in the United States and Australia.

“Many in the health care community, and even breast cancer patients, don’t understand that this lifelong arm swelling is a possible result of breast cancer treatment, but others of us have been working on this issue for decades,” said principal investigator Sheila Ridner, Ph.D., MSN, R.N., Martha Rivers Ingram Professor of Nursing.

Typically, lymphedema measurements are done with a tape measure, much like a household tape measure. The condition is often managed using compression garments and exercise. This study will take a closer look to see if early detection with bioimpedance spectroscopy prevents progression to chronic lymphedema.

“The ultimate goal is to help those with lymphedema have better health outcomes and increased quality of life living with this condition,” Ridner said.

Ridner is also conducting research funded by the National Cancer Institute, the American Cancer Society and the National Center for Complementary and Alternative Medicine.
This study is funded by ImpediMed, based in Brisbane, Australia.

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Indiana Couple Supports Melanoma Research Thu, 16 Oct 2014 16:00:48 +0000 A Vanderbilt-Ingram Cancer Center (VICC) melanoma patient is using his passion for golf to support melanoma research efforts at VICC.

This summer, Gerald (Jerry) Schreiber, 78, with the help of his wife, Phyllis, organized and hosted the first annual Melanoma Research Golf Classic in Evansville, Indiana.

The golf scramble held July 28 at the Evansville Country Club attracted 72 players and raised $19,000 for VICC melanoma research spearheaded by Igor Puzanov, M.D., MSCI, associate professor of Medicine and director of Melanoma Clinical Research.

Gerald and Phyllis Schreiber with Igor Puzanov , M.D.

Igor Puzanov, M.D., talks with patient Gerald (Jerry) Schreiber and his wife, Phyllis, at the Vanderbilt-Ingram Cancer Center. The Schreibers recently organized a golf tournament in Indiana to benefit melanoma research.

Schreiber describes himself as a lifelong golfer who has won the Evansville city golf tournament nine times. But all of that sun exposure also had a downside.

In 2003, he noticed a spot on his eyelid and a biopsy revealed melanoma, the most deadly form of skin cancer. His physician referred him to M.D. Anderson Cancer Center in Texas, where he was successfully treated.

But when the melanoma recently returned, this time with tumors in his lungs and liver, he was referred to VICC and enrolled in a clinical trial of a new therapy for patients with advanced melanoma.

The experimental immunotherapy is an antibody that targets PD1 proteins on immune cells to allow the immune system to recognize and attack the cancer. The new drug, pembrolizumab, was recently approved by the U.S. Food and Drug Administration (FDA).

Since beginning the treatment, Schreiber’s tumors have been shrinking.

“They’ve reduced in size by 50 percent with this particular drug. It might be the reason I’m still here.”

The need for better therapies sparked the couple’s decision to raise funds for research.

“You’re always hearing about all of the other diseases except melanoma,” explained Phyllis.
And Jerry decided golf was the perfect vehicle for fundraising in southern Indiana because “…everybody knows me through golf.”

Puzanov said support like this is important for the research effort.

“We have a very successful melanoma research program here at Vanderbilt and we are working closely with pharmaceutical firms and other academic research centers to bring the most promising therapies to our patients,” Puzanov said.

“We are very appreciative of the efforts of all those who are helping us improve the lives of patients.”

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New Approach for Treating Retinoblastoma Thu, 09 Oct 2014 22:00:44 +0000 Jude Kee, mother Amy, and grandmother Ann Westerbeck

Amy Kee plays with her son, Jude, as his grandmother, Ann Westerbeck, looks on. Jude is undergoing a new therapy at Vanderbilt to treat his retinoblastoma.

Conventional therapy for patients diagnosed with retinoblastoma, the most common ocular cancer in children, includes systemic chemotherapy, external beam radiation and/or surgical removal of the eye.

Doctors at Vanderbilt University Medical Center are on track to radically change the way the disease is treated using an emerging therapeutic approach called intra-arterial chemotherapy, or IA chemo.

The procedure, performed on an outpatient basis, delivers chemotherapy directly to the tumor via the ophthalmic artery, using a catheter that is inserted into the groin and threaded to the eye under X-ray guidance.

In this way, IA chemo is able to limit the adverse effects typically associated with systemic chemotherapy.

“It is transformative,” said Anthony Daniels, M.D., assistant professor of Ophthalmology and Visual Sciences at the Vanderbilt Eye Institute. “We are able to tailor this treatment to each individual patient and each tumor. It is our expectation that this will become the primary modality of treatment of retinoblastoma at Vanderbilt.”

Eighteen-month-old Jude Kee, Vanderbilt’s first patient, is showing signs of improvement. After two treatments in both eyes, administered four weeks apart, the tumors are shrinking — indicators of the success of the novel therapy.

Initially concerned that Jude had lazy eye, his mother took him to the pediatrician who referred them to a specialist. She soon discovered that her son had bilateral retinoblastoma (tumors were present in both eyes).

Upon seeing Daniels, Jude’s parents were given the choice of following the traditional treatment route or becoming trailblazers for future pediatric patients at Vanderbilt.

Amy Kee was familiar with the newest therapeutic option via a family friend dealing with the same diagnosis. She was aware that Daniels had come to Vanderbilt to offer IA Chemo.

“We will come out on the other side of this just fine. He is able to go to school and be normal. We have not had any worries about his immune system being suppressed or any of the other issues typically associated with systemic chemo.“We feel very fortunate to have this treatment available at Vanderbilt,” Kee said. “It is phenomenal. Jude has not been limited whatsoever and that is a huge blessing.

Anthony Daniels, M.D., and  Joshua Carlson, M.D.

Anthony Daniels, M.D., right, examines Jude Kee’s eyes while Joshua Carlson, M.D., watches the monitor.

“I have read about the effects of chemo. I have read the stories about children having their eye or eyes removed. I know that we are extremely fortunate to have Dr. Daniels right here offering IA.”

Vanderbilt, the only center offering IA chemo in the region, is one of just a few centers in the country offering the novel therapy.

Daniels, along with neurointerventionalist Michael Froehler, M.D., Ph.D., are able to offer the full spectrum of treatment for patients.

Patients are referred to Daniels, who makes the initial diagnosis and develops a treatment plan based on the classification of the tumor as well as the specific needs of the child.

While traditional chemotherapy (systemic delivery) has its uses in certain circumstances, the only patients who are not considered candidates for IA chemo are those whose tumors are so small that they can be treated with laser or cryotherapy alone, or if the tumor has destroyed the eye, requiring removal.

Daniels and his team work with pediatric oncologists at Monroe Carell Jr Children’s Hospital at Vanderbilt to ensure the patients are closely monitored post treatment.

On average, patients undergo at least three treatments to fully destroy the tumor.

“The other amazing thing about IA chemotherapy is that it has the ability to prevent new retinoblastoma tumors from forming elsewhere in the eye,” Daniels said. “Historically, we would kill the tumor, only to have new tumors pop up elsewhere in the eye. With IA chemotherapy the patient almost never gets another new tumor in the eye because any early cancer cells that are present are killed before they can grow.”

Performed in the angiography suite at Children’s Hospital, Froehler uses the same technique used to treat brain aneurysms.

He inserts a tiny catheter into the patient’s groin and threads it to the arterial branch leading to the tumor in the eye. He then injects the chemotherapy cocktail prescribed by Daniels.

The technique allows for a high concentration of chemotherapy to kill the tumor while limiting the toxic effects on the rest of the body.

“The endovascular approach allows the treatment to be specifically tailored to each unique tumor and eye within the same patient,” Froehler said. “Sometimes the arterial supply to one eye is different from the other, and frequently the tumor on one side is bigger or more severe than the other.

“By recognizing these differences, we can individualize the catheter placement and IA chemo regimen to optimize treatment effect.”

The Kees are hopeful that IA chemo will open a new door for children diagnosed with retinoblastoma.

“We have had huge success so far,” Kee said. “I am hopeful that we will not need to do any other kinds of treatments.

“I just keep going back to the fact that if I had not noticed that he had lazy eye, we may not have caught it in time. Not only would the possibility of removing his eye been much greater, but the cancer could have gone to his brain.

“This treatment has made a huge, huge difference. The entire center of one of his eyes has opened up and they think that he may be able to see a little bit out of that eye now,” Kee said.

Jude’s next examination and IA treatment are scheduled for Oct. 20 and 23.

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Aspirin’s Protective Effect in Cancer Explained Thu, 02 Oct 2014 16:00:48 +0000 For years, scientists have known that regular aspirin use may reduce the risk of cancer.

“Studies have shown that aspirin administration for five or more years reduces the incidence of all cancers by 38 percent,” said Pierre Massion, M.D., professor of Medicine and Cancer Biology and director of the Thoracic Program at Vanderbilt-Ingram Cancer Center.

Aspirin was thought to work by inhibiting the cyclooxygenase-1 (COX-1) molecular pathway in cells. COX-1 is an enzyme expressed in most tissues in the body.The benefit is seen even at the low doses of aspirin (typically 81 mg daily) recommended for patients for a variety of ailments or healthcare risks.

Pierre Massion, M.D.

Pierre Massion, M.D.

However, a new study led by John Oates, M.D., Thomas F. Frist Sr. Professor of Medicine, Olivier Boutaud, Ph.D., research associate professor of Pharmacology, and Massion found that low-dose aspirin appears to work by inhibiting both COX-1 and COX-2 pathways.

Massion presented the data at the 13th Annual AACR International Conference in Cancer Prevention Research, held Sept. 28 – Oct. 1 in New Orleans.

The authors wanted to determine whether low-dose aspirin worked by blocking platelet function by inhibiting the COX-1 pathway, and if it also reduced levels of prostaglandin E2 (PGE2), by inhibiting the COX-2 pathway.

The PGE2 molecule is linked to the spread of cancer, also known as metastasis.

“We found that potency of low-dose aspirin in inhibiting COX-2 in the tumor cells is as great or greater than its potency of COX-1 in the platelet,” said Oates. “This indicates that at a cellular level, aspirin is not selective for the platelet but could also block COX-2 in cancers.”

The finding that aspirin also is important as a COX-2 inhibitor is likely surprising to most investigators, according to Massion.

“Our findings may explain how even a very low dose of aspirin taken daily can produce such a substantial reduction in cancer deaths and metastasis,” said Massion.

The researchers used urine samples from 54 patients who took 81 mg aspirin tablets for two weeks and demonstrated that aspirin inhibited PGE2 production by 45 percent and prostacyclin by 37 percent, as measured by their urinary metabolites.

The investigators also found that in blocking COX-1, aspirin also interfered with the platelets’ ability to stick to cancer cells to prevent metastasis.

This suggests that the two mechanisms act together to reduce the risk of cancer death.

This study has not yet been published in a peer-reviewed journal.

The research was supported by an American Heart Association National Fellow to Faculty Award (13FTF17400011), the National Cancer Institute, which is a division of the National Institutes of Health (CA 090949, CA 102353), and the Department of Defense (#W81XWH-10-1-1007).

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Program Focuses on Heart Health in Cancer Thu, 02 Oct 2014 16:00:21 +0000 The Vanderbilt Cardio-Oncology program has fostered a special collaborative relationship combining the expertise of cardiologists and oncologists to understand the effects of cancer therapy on the heart. This type of collaboration is now helping to define the cardiovascular health of more than 14 million cancer survivors in the United States.

“A dramatic increase of effective new cancer treatments has given us an enlarging group of cancer survivors,” said Michael Neuss, M.D., chief medical officer of the Vanderbilt-Ingram Cancer Center. With nearly 3 million breast cancer survivors, and even more surviving prostate cancer in the United States, preventing or managing their heart disease has significant public health implications.

Cardio-Oncology Group

Members of the Vanderbilt Cardio-Oncology program include, from left, Daniel Lenihan, M.D., Deborah Friedman, M.D., Javid Moslehi, M.D., and David Slosky, M.D.

“Survivorship care is designed to address both the short- and long-term effects of these treatments. At Vanderbilt we are fortunate to have national leaders in this new area, including specific programs addressing the cardiac and neurologic consequences of cancer.”

The incidence of heart disease has increased in cancer survivors in part as a direct result of cancer therapy itself and can manifest in various forms. This is especially true for breast cancer.

“Heart failure can be caused by breast cancer therapy, especially anthracyclines or trastuzumab. We have also begun to appreciate radiation therapy for breast cancer as a significant risk factor for heart attacks in breast cancer survivors,” said Javid Moslehi, M.D., who recently joined Vanderbilt Heart and Vascular Institute (VHVI) as the director of Cardio-Oncology.

“Early and aggressive efforts to reduce cardiac risk factors through lifestyle modification or with medical therapy represent the most important intervention to prevent [cardiovascular disease in cancer survivors],” Moslehi recently wrote in an editorial for the New England Journal of Medicine.

Moslehi, who came to Vanderbilt from Harvard Medical School in Boston, is collaborating with oncologist Deborah Friedman, M.D., surgical urologist David Penson, M.D., interventional cardiologist David Slosky, M.D., and heart failure specialist Daniel Lenihan, M.D., to implement guidelines to prevent cardiovascular disease in cancer survivors.

At the heart of the guidelines is a simple concept that Moslehi refers to as ABCDE of cardiovascular disease prevention in cancer survivors: awareness, prophylactic aspirin; blood pressure control; cholesterol lowering, cigarette smoking cessation; diet, dose of chemotherapy, diabetes management; and exercise.

“These guidelines are going to be our platform for the Cardio-Oncology survivorship program here at Vanderbilt and is a simple way for cardiologists, oncologists and primary care physicians to address cardiovascular wellness in cancer survivors,” Moslehi said.

The cardiovascular health of cancer survivors will be a new focus of the National Comprehensive Cancer Network (NCCN), an alliance of 25 cancer centers in the United States whose goal is to advance the quality, effectiveness and efficiency of oncology care so that cancer patients can live better lives.

Moslehi and Friedman represent Vanderbilt in the NCCN clinical practice guidelines in oncology survivorship.

The cardiovascular wellness guidelines in cancer survivors, which Moslehi is chairing, will be released later this year and will help define specifics of cardiovascular care for cancer survivors.

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Report Calls for Added Cancer Research Support Thu, 25 Sep 2014 17:00:50 +0000 There are now approximately 14.5 million cancer survivors in the United States, thanks in large part to advances in cancer research and the development of new anti-cancer therapies.

In the last year, the U.S. Food and Drug Administration (FDA) has approved six new anticancer therapeutics, two new imaging agents, a new screening test and new uses for five previously approved drugs.

These details were revealed in the American Association for Cancer Research (AACR) Cancer Progress Report 2014, released Sept. 16. This is the fourth annual edition of the report.

According to the AACR, the fast pace of these FDA approvals is a direct result of accelerating scientific discoveries, especially new revelations about the molecular underpinnings of many types of cancer and the creation of molecular therapies to target those genetic alterations.

Carlos L. Arteaga, M.D.

Carlos L. Arteaga, M.D.

Additional therapies designed to stimulate the body’s own immune system are also yielding durable patient responses in several types of cancer.

However, Carlos L. Arteaga, M.D., professor of Medicine and Cancer Biology at Vanderbilt University, said the pace of cancer research progress is being slowed by years of declining budgets at the National Institutes of Health (NIH) and the National Cancer Institute (NCI). Arteaga is the current president of AACR.

“If we are to fully realize the promise of science to transform cancer care, it will require leadership in Congress and within the administration to ensure that biomedical research in cancer becomes a major priority for our nation,” said Arteaga, director of the Center for Cancer Targeted Therapies and the Breast Cancer Program at the Vanderbilt-Ingram Cancer Center.

The recent approval of new therapies has been spurred by investments in the NIH and NCI which help fund much of the basic science and translational cancer research in the U.S.

The AACR Cancer Progress Report noted that budgets for the NIH and the NCI have failed to keep pace with inflation for the past decade, and direct federal cuts, including the sequester, slashed those budgets in 2011 and 2013.

Arteaga said many young cancer investigators are leaving or not joining the field because of these budgetary trends, and the nation is at risk of losing a generation of scientists.

Meanwhile, demographic trends in the U.S. will lead to a surge in cancer cases since advanced age is one of the primary risks for the development of cancer.

Even with new cancer therapies, an estimated 585,000 U.S. residents are predicted to die from the disease in 2014 and the annual economic burden is already $216 billion in direct and indirect costs.

These personal and budgetary realities have spurred what Arteaga and the AACR labeled “a call to action” for federal leaders to prioritize a predictable and robust rate of budgetary support that will at least keep pace with the rate of inflation.

The AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer.

AACR membership includes more than 35,000 laboratory, translational, and clinical researchers, population scientists, other health care professional and cancer advocates in 97 countries.

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Bradfords’ Support Boosts Melanoma Research Thu, 25 Sep 2014 17:00:39 +0000 When something attacks you, you want to attack it back.

That’s how Lillian “Tooty” Bradford views her late husband James “Jimmy” Bradford Jr.’s decision to make an initial gift to fund melanoma research at Vanderbilt-Ingram Cancer Center (VICC). The goal: to attack cancerous melanoma with the help of some of the greatest minds and researchers at Vanderbilt’s academic medical center, using the right confluence of technological advances in the field.

Lillian "Tooty" Bradford

Lillian “Tooty” Bradford and her late husband, James “Jimmy” Bradford Jr., funded gifts to support melanoma research at Vanderbilt-Ingram Cancer Center. (photo by Joe Howell)

Jimmy, a Nashville banking magnate, was diagnosed with advanced-stage melanoma at the end of summer 2008. In determining the best course of treatment, his care team — oncologist Jeffrey Sosman, M.D., surgeon James Netterville, M.D., and then Vanderbilt oncologist William Pao, M.D., Ph.D., — tested his cancer tissue for the most common melanoma-associated mutations in genes called BRAF and KIT, which respond well to targeted therapies. His tumor was negative for these mutations. Instead, he had a different mutation, later identified as BRAF L597, which left only standard chemotherapy for treatment.

As was characteristic of Jimmy, he was thinking of others while battling his own cancer. He wanted doctors to use his tumor to find out how they could help future melanoma patients with a similar mutation. The Bradfords even made two gifts for a discovery grant to make the research possible. He died a little more than a year after his diagnosis.

The seeds he planted have grown and flourished into discoveries and a promising new therapy for other melanoma patients, beyond what was imagined at the time.

“When (Jimmy’s medical team) sat down, we thought, ‘what can we do with this money that will be meaningful both to him and to cancer treatment,’ said Sosman, professor of Medicine in Hematology/Oncology and director of the Melanoma and Tumor Immunotherapy Program. “I don’t think we imagined it would lead ultimately to a clinical trial and impact a whole set of other patients, but we knew we would learn something important,” he said.

Lillian “Tooty” Bradford and James “Jimmy” Bradford Jr.

Lillian “Tooty” Bradford and her late husband, James “Jimmy” Bradford Jr., on a ski trip in 2010.

The Bradfords’ gift would be used to examine the DNA of his tumor and look for mutations using whole genome sequencing, a time-intensive and costly process. Once they had the analysis, which took six months, and knew his tumor’s mutations, they could see if any emerging or existing therapies already in the pipeline could be an effective treatment. It just so happened that there was.

“When we looked, it seemed to be sensitive to a class of drugs — called MEK inhibitors — which were being investigated in a clinical trial,” said Sosman, Ingram Professor of Cancer Research.

“At the same time, we had a patient with a similar mutation who was being treated in a trial with an experimental MEK inhibitor and he had a positive response.”

“If Mr. Bradford came to us today, we would know this information and we would probably put him on one of these drugs. This has been a major sea change in the way we approach melanoma. We have real drugs that do work. At the time for him (just six years ago), chemotherapy was the only option,” Sosman continued.

Kimberly Brown Dahlman, Ph.D.

Kimberly Brown Dahlman, Ph.D.

Because of what researchers learned from Bradford’s tumor, made possible by his gift, doctors at Vanderbilt modified the mutation testing panel, so future patients with L597 could be identified. They are also conducting clinical trials.

“They sort of hit a home run,” Tooty Bradford said.

The Vanderbilt researchers published their findings on Jimmy’s mutation and the identification of a promising new therapy in the September 2012 issue of the journal Cancer Discovery. The article was featured on the front cover with an artistic representation of the genetic sequence of Jimmy’s tumor.

Vanderbilt co-authors, in addition to Sosman, Pao and Netterville, included: Kimberly Brown Dahlman, Ph.D., Zhongming Zhao, Ph.D., Cindy Vnencak-Jones, Ph.D., Donald Hucks, M.S., Donna Hicks, B.S., Pamela Lyle, M.D., Zengliu Su, M.D., Ph.D., Peilin Jia, Ph.D., Katherine Hutchinson, B.S., and Junfeng Xia, Ph.D.

James Netterville, M.D.

James Netterville, M.D.

Tooty said she and her family wanted to keep the hope for other patients going after Jimmy died in March 2010, and Vanderbilt’s unique position as a medical and academic powerhouse would make that possible.

Vanderbilt is one of only a few academic medical centers in the United States located on the same campus with leading scientists who are finding new treatments to be brought to the patient’s bedside. An investment in medical research at Vanderbilt is an investment in the future of medicine by providing support for the individuals who devote their lives to innovating by improving the quality and accessibility of therapies.

Tooty, a Vanderbilt alumna, made another gift in December 2010 in honor of the care Jimmy and her family received at VICC. With the help of Tooty, family, friends and the community, the James C. Bradford Jr. Endowed Fund in Melanoma Research was established in 2011 to serve as a continuous and permanent source of support for Vanderbilt researchers studying this type of cancer. To date, nearly $1 million has been pledged for the fund. The goal is to secure $2 million.

Jeffrey Sosman, M.D.

Jeffrey Sosman, M.D.

“Jimmy would be so touched by the people who have responded,” Tooty said. “He was such a sweet man. He had a smile for everybody. He was a good, kind person. He made us, as a family, think about going further (to support this research).”

Science has come a long way in the past few years since Jimmy’s tumor was first sequenced. Whole genome sequencing can now be compressed into a few weeks. Discovery grants and endowments like the Bradfords’ can be used to push the envelope even further and to capitalize on the potential for other novel therapies.

“When people give a Discovery Grant, it can be used to decipher a fundamental cellular mechanism that plays a role in the formation of cancer and/or treatment of the disease,” said Jennifer Pietenpol, Ph.D., director of VICC, the B.F. Byrd Jr. Professor of Molecular Oncology and professor of Biochemistry, Cancer Biology and Otolaryngology.

Zhongming Zhao, Ph.D.

Zhongming Zhao, Ph.D.

“This knowledge is critical for the future design of approaches to prevent and treat cancers. Alternatively, a Discovery Grant can be used to comprehensively sequence tumors from patients that either don’t respond to therapy or have an exceptional response. Knowledge of the mutations in a patient’s tumor that has either response is extremely valuable and critical for the design of new therapies and clinical trials. Further, in some cases the information can be translated to the clinical very quickly as an “actionable” mutation to which therapy can be aligned.”

The Bradford Discovery Grant is a prime example of the possibilities.

“Mr. Bradford’s vision to help others was realized in the Discovery Grant and was made possible, in part, due to the level of funding and also the timing of the grant relative to where we were with the molecular genetics and the technology of whole genome sequencing,” Pietenpol said.

“One would argue it was a most impactful gift from the standpoint of a discovery having immediate translation to patients. It did exactly what Jimmy wanted,” Pietenpol added.

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Accuracy of Lung Imaging Varies by Region Wed, 24 Sep 2014 17:00:18 +0000 A new analysis of published studies found that FDG-PET technology is less accurate in diagnosing lung cancer versus benign disease in regions where infections like histoplasmosis or tuberculosis are common.

The study by investigators at Vanderbilt University and the Tennessee Valley Healthcare System-Veterans Affairs was led by Vanderbilt first author Stephen Deppen, Ph.D., and principal investigator Eric Grogan, M.D., MPH, and appeared in the Sept. 24 issue of the Journal of the American Medical Association (JAMA). Misdiagnosis of lung lesions suspicious for cancer could lead to unnecessary tests and surgeries for patients, with additional potential complications and mortality. Histoplasmosis and other fungal diseases are linked to fungi that are often concentrated in bird droppings and are found in soils.

Positron emission tomography (PET) combined with fludeoxyglucose F18 (FDG) is currently recommended for the noninvasive diagnosis of lung nodules suspicious for lung cancer.

To estimate FDG-PET diagnostic accuracy, the authors reviewed lung cancer abstracts published in a 14-year period and included 70 studies in the meta-analysis. The studies included 8,511 nodules, 60 percent of which were malignant.

Stephen Deppen, Ph.D.

Stephen Deppen, Ph.D.

“The accuracy of FDG-PET for diagnosing lung nodules varied widely from study to study,” said Deppen, assistant professor of Thoracic Surgery. “FDG-PET scans had more false positive results and therefore were less specific in diagnosing lung cancer in regions of the world where infectious lung disease is common in the general population.”

These infections can cause inflamed nodules in the lungs (granulomas) that can be mistaken for cancerous lesions by radiographic imaging.The most prevalent fungal lung diseases in the United States are histoplasmosis, coccidioidomycosis and blastomycosis. All three fungi reside in soils. Histoplasmosis and blastomycosis are common across much of the Mississippi, Ohio and Missouri river valleys and through southern Ontario, Canada, and coccidioidomycosis is prevalent in the southwestern United States.

In previous meta-analyses, FDG-PET was reported to be 90 to 94 percent accurate in the characterization of malignant or benign lung nodules. However, the current analysis found that FDG-PET was less reliable in regions where fungal lung disease is endemic.

“The frequency of benign lesions in these geographic regions could lead to unnecessary biopsies or lung surgeries in patients,” said Grogan, staff surgeon at Veterans Hospital, assistant professor of Surgery in the Department of Thoracic Surgery and assistant professor of Medicine in the Institute for Medicine and Public Health at Vanderbilt.

Eric Grogan, M.D., MPH

Eric Grogan, M.D., MPH

“However, some medical practices achieved greater test accuracy through robust reading methods, even in these regions.”

The authors suggest that the use of FDG-PET to diagnose lung cancer be limited to non-endemic regions unless an institution has substantial and proven expertise in FDG-PET interpretation.

Other Vanderbilt and VA investigators include Jeffrey Blume, Ph.D., Clark Kensinger, M.D., Ashley Morgan, B.E., Melinda Aldrich, Ph.D., MPH, Pierre Massion, M.D., Ronald Walker, M.D., Melissa McPheeters, Ph.D., MPH, and Joe (Bill) Putnam Jr., M.D.

Primary support for the study was from the Agency for Healthcare Research and Quality (R03H021554), and also included funding from the National Institutes of Health (KO7CA172294, UL1TR000011, CA90949, U01CA152662), the and the Department of Veterans Affairs (Grogan CDA 10-024).

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Grant Spurs Lung Cancer Surgery Research Thu, 18 Sep 2014 19:00:16 +0000 Joe B. (Bill) Putnam Jr., M.D., Ingram Professor of Cancer Research and chair of the Department of Thoracic Surgery, and colleague Felix Fernandez, M.D., assistant professor of Surgery, Emory University School of Medicine, Atlanta, have received a grant to investigate the most effective forms of surgery to treat lung cancer patients.

The award from the Agency for Healthcare Research and Quality (AHRQ), a division of the U.S. Department of Health and Human Services, will provide $954,000 in funding over four years.

Lung cancer is the leading cause of cancer death among men and women in the United States, with an estimated 224,210 new cases and 159,260 deaths expected in 2014. In addition to the human toll from the disease, there is an economic burden of an estimated $12 billion in direct costs annually.

Joe B. (Bill) Putnam Jr., M.D.

Joe B. (Bill) Putnam Jr., M.D.

While most patients are diagnosed when their disease is at an advanced stage, surgery provides cure rates between 77 and 92 percent when the disease is found early.

However, there is a lack of information about what type of surgery is most effective, with the lowest complication rates, and the financial costs associated with different types of surgery.

The standard surgical approach to treating lung cancer involves a thoracotomy, a major invasive procedure that involves dividing chest wall muscles and spreading the ribs to remove portions of the diseased lung. However, surgeons are increasingly using the less invasive video assisted thoracic surgery (VATS), during which they make three or four small incisions and use a video camera to help find and remove the cancerous tissue.

VATS does not require rib spreading and is associated with fewer complications, less pain and shorter recovery periods.

“While we know that VATS has many post-surgical advantages in terms of pain and recovery time, it is not clear if this minimally invasive approach provides the same level of accuracy when it comes to identifying lymph nodes that may harbor cancerous cells,” said Putnam. “It is crucial that we identify metastatic lymph nodes to ensure that a patient has the best chance of surviving their cancer.”

There is also a gap in knowledge about the effectiveness of removing an entire lung lobe, versus partial lobe removal.

To help determine the effectiveness of different surgical approaches, the AHRQ research led by Putnam and Fernandez will study information from the Society of Thoracic Surgeons General Thoracic Surgery Database (GTSD) which includes patient-level clinical details not found in any other database.

That data will be linked with disease and mortality outcomes information from the Centers for Medicare and Medicaid Services (CMS).

This research is innovative because linkage of the STS-GTSD information with the largest national administrative database of the Centers for Medicaid Services will create a longitudinal data source that is well suited for comparative effectiveness studies in lung cancer surgery.

Putnam said it is crucial to determine the most effective treatment methods based on individual patient characteristics because high-risk patients with a lengthy smoking history are now being encouraged to undergo lung cancer screening.

“As a result of these new screening guidelines, we expect to see far more patients who may be surgical candidates and we need accurate information to guide us in developing treatment guidelines that produce superior cancer outcomes, as well as prudent use of health care resources,” said Putnam.

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