ACHSHUND Update DA NESTLÉ PURINA PUBLICATION DEDICATED TO DACHSHUND ENTHUSIASTS VOLUME 17 | SPRING 2019

HEMANGIOSARCOMA RESEARCH Artificial Intelligence Aids Early Detection of Cancer SPRING 2019

DACHSHUNDS MAY BENEFIT FROM HEMANGIOSARCOMA RESEARCH ADVANCES Twelfth Night Dachshund breeder It happened three times, Anne Carson takes to heart the though Gibson always recov- importance of educating Dachs- ered overnight — until the last hund fanciers about hemangio- time. Carson, of Atlanta, took sarcoma. Her firsthand experiences Gibson to a veterinary neuro- losing dogs to the aggressive, surgeon, presuming her special silent cancer that snares its male would need back surgery. “Gibson,” pictured above at 11 months old, died of hemangiosarcoma at age 10. victims without a sign of illness The energetic, funny Gibson His breeder and owner, Anne Carson, are insightful and passionate. had won her over as a puppy said the Longhaired Dachshund was doing well after surgery and chemo- Sharing her stories at the annual becoming the keeper, though therapy, but sadly, the cancer had meeting of members of the Dachs- it was his brother she had metastasized throughout his body. hund Club of America (DCA) planned would stay. at the 2018 National Specialty, “The neurosurgeon confirmed Carson asked those attending to that Gibson had no neurological stand up if they had lost a dog issues, but blood tests led him to to hemangiosarcoma. Next, she conclude that Gibson’s anemia asked if anyone had lost a dog to without elevated BUN (blood urea a tumor with no clear diagnosis, nitrogen) could be the result of and last, if anyone had found a internal bleeding,” recalls Carson, dog dead after a day or two of a member of the DCA board of vague symptoms. More than half directors for 12 years. of the attendees were standing. “That fear was aŽrmed after All were listening closely. Gibson’s regular veterinarian Because of the high prevalence did an abdominal X-ray that of back problems in Dachshunds, showed a large tumor on the it can be a fine line determining spleen,” she says. “I took him to whether spinal pain or some- an oncologist who removed the thing else causes a dog to not spleen and the tumor the next want to get up. In 2018, when day. Meanwhile, the lab results “Gibson” (GCH Twelfth Night confirmed that the tumor was Braveheart L), a 10-year-old red hemangiosarcoma.” male Longhaired Dachshund, was Carson, who has bred Long- reluctant to stand and refused haired Dachshunds since 1982, to eat, Carson attributed the about one litter every two years, problem to back pain. made plans to begin chemo-

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therapy treatment as soon as Gibson healed from the surgery. “I had trouble keeping him calm and confined after the surgery,” she says. “He was in a room by himself but could see the other dogs and wanted to play.” Seventeen days after beginning chemotherapy, Gibson died. “The cancer had metastasized,” Carson says. “I was totally shocked by his death, because I thought he was doing so well.” Gibson was not her first Dachs- hund to die from hemangiosarcoma. Carson lost “Scarlett” (CH Twelfth Night’s Miss Scarlett L) in 2002 at 10 years of age and “Hope” (CH Twelfth Night Hope Diamond L) in 2008 at 12 ½ years of age. Both females were related to Gibson. Scarlett lived three days following surgery to remove her spleen, and Hope survived four months after surgery and 12 weeks of chemotherapy. “With hemangiosarcoma, how it often goes with heman- when a dog is sick, it’s often too giosarcoma, a cancer believed late,” Carson says. “They feel to be responsible for the deaths weak because the tumor bleeds, of tens of thousands of dogs in then when the bleeding stops, the U.S. each year. dogs feel fine again. The best Hemangiosarcoma is an unpre- advice I can give is to act fast if dictable cancer that develops you notice anything abnormal. painlessly. As with Gibson, Scarlett If a dog fails to eat or drink, has and Hope, it is often advanced by pale gums, unexplained vomit- the time it is discovered. Severe ing, or refuses to perform usual internal bleeding and sudden activities, then you should see death are not unusual with this your veterinarian. Even if the dog disease. A dog’s breed, age, seems perfectly normal the next gender, diet, and environment are day, as Gibson did.” not likely to impact the progression of the cancer, experts say. CLASSIFYING TUMORS “It is virtually impossible to The heart-crushing agony of pigeonhole this tumor into losing a beloved dog to cancer categories that work for other is bad enough. When the cancer cancers,” says Jaime F. Modiano, takes a dog without signs of ill- VMD, PhD, the Perlman Endowed ness, it can be traumatic. This is Chair in Animal Oncology at the

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University of Minnesota. “The more accuracy in classifying most challenging aspect of hemangiosarcoma tumors studying this disease has been based on their patterns, explains accepting that many, and per- Dr. Modiano. haps most, of our preconceived At the 2018 Connective Tissue notions about what we thought Oncology Society meeting in we knew about the disease Rome, Dr. Modiano’s research were incorrect. In order to make group introduced artificial in- progress, we needed to start telligence as a way to interpret with a blank slate.” the results of a test designed to Filling that blank slate even- detect cells associated with the tually led to employing artificial presence of hemangiosarcoma intelligence to analyze large and in the circulation of dogs. It is complex data sets that look for yet to be determined wheth- defined algorithms and statis- er these cells in the blood are tics to identify the cancer. This precursors to the tumor, actual type of analysis could lead to circulating tumor cells, or cells

WHEN A DOG HAS HEMANGIOSARCOMA A silent disease, hemangiosarcoma develops few hours or possibly within one to two weeks. painlessly. The only hints that a dog may have With treatment, the expected survival is four the cancer are recurring lethargy and pale mucous to six months, though this is dependent on the membranes due to anemia. Most dogs have an tumor’s location. Tumors that occur in or under advanced form of the cancer when it is discovered, the skin typically are less aggressive, and dogs which explains why severe internal bleeding and whose visible tumors are accessible tend to do sudden death occur frequently and unexpectedly. better with the standard of care. Although this cancer can a¡ect any dog of The standard of care is surgical removal of any age and gender, it is most common in older accessible tumors, depending on the location, dogs; more than half of the dogs that develop followed by chemotherapy. Treatment is meant hemangiosarcoma are over 10 years old. It usually to prevent fatal blood loss and to extend life, originates from a cell in the bone marrow that but is seldom curative. Chemotherapy delays settles in the thin layer of cells that line the interior the recurrence of metastasis, which occurs in of blood vessels. Although the most common sites virtually every dog diagnosed with the cancer. for tumor formation are the spleen, skin, heart, About 5 to 15 percent of dogs with heman- and liver, the tumor cells have access to the giosarcoma will survive a year or longer, even blood supply, allowing them to potentially seed with conservative treatment. Because there and grow in virtually any organ in the body. currently are no reliable tools to determine The disorganized growth of tumor cells in the which dogs are likely to be long-term survivors, walls lining the blood vessels disrupts normal anecdotal evidence of long-term survival with blood flow, leading to blood clots and hemor- alternative therapies is an unreliable indicator rhage. Mini-hemorrhages can heal quickly with of eŽcacy and could create false hopes and dogs showing only mild signs, but severe hem- unrealistic expectations for owners and veter- orrhage from within a tumor can be fatal. inarians. Thus, it is recommended that treat- Sadly, most dogs die before treatment can ment should be based on objective data. begin. Without treatment, dogs may die in a

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that are a component of the niche that allows the tumors to grow and eventually metastasize. “The goal is to deploy a blood test that can detect hemangio- sarcoma in its earliest stages before tumors actually form and to pair that detection with rational, targeted drugs that can prevent or significantly de- lay tumor formation and tumor progression,” Dr. Modiano says. The researchers at the University of Minnesota have been studying hemangiosarcoma for many years. In 2019, they will complete a three-year study, the Shine On Project, which was supported with $432,000 contributed by the Golden Retriever Founda- tion, the American Boxer Club Charitable Foundation and the Portuguese Water Dog Foun- dation, breeds that show a high prevalence of this cancer. dogs diagnosed with hemangio- “The unprecedented collabo- sarcoma. They also independently LOOKING TO REPRINT? ration among these three breed developed a promising chemo- club foundations and their ded- preventive drug called eBAT, Dachshund Update articles may ication to canine health have which is a targeted bacterial toxin be reprinted provided the article driven this project forward, that is exceptionally safe and has is used in its entirety and in a helping to make a significant demonstrated eŽcacy in the positive manner. To request di¡erence for all dogs,” says treatment of hemangiosarcoma. permission to reprint this article, Dr. Diane Brown, CEO of the With Shine On, their focus turned please contact the editor at: AKC (American Kennel Club) to refining the test to identify dogs [email protected]. Canine Health Foundation, at risk for developing heman- com. Reprints should include which administers and manages giosarcoma and those that have the following attribution: the grant. “This approach to a the suspect cells present in their Used with permission from particularly aggressive form of blood but have no evidence of a the Dachshund Update, Nestlé cancer in dogs has the potential tumor, and then using eBAT to Purina PetCare. to eventually change the land- attack the hemangiosarcoma stem scape and improve outcomes cells and kill them before they for all dogs diagnosed with this have a chance to form a tumor. horrible disease.” The three phases of the Shine Prior to the start of the Shine On Project are ongoing. They are: On Project, Dr. Modiano and his • Phase 1: Defining the param- team developed a blood test eters for using the blood test to detect the “suspect cells” in to confirm the presence of

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DACHSHUND CLUB OF AMERICA FUNDS TWO HEMANGIOSARCOMA STUDIES

The Dachshund Club of enable the cancer to grow and spread. Interest- America provided funding ingly, similar PI3K mutations are found in the of $20,000 in 2018 to support companion human cancer, called angiosarcoma. two canine hemangiosar- We are working with colleagues on the human coma studies. side studying this cancer to find new, more A donation of $15,000 helps e¡ective combination therapies to more e¡ec- support an AKC (American tively treat this cancer in both dogs and people.” Kennel Club) Canine Health A $5,000 donation to the Morris Animal Foun- Foundation-funded three-year, $168,857 study at dation is supporting a study at the University of Tufts University. Lead investigator Cheryl London, Minnesota led by Erin B. Dickerson, PhD, associate DVM, PhD, DACVIM (Oncology), research pro- professor of veterinary clinical sciences. The club fessor at the Cummings School of Veterinary also gave $5,000 to this study in 2017. Medicine of Tufts University and Tufts School of The $172,431 study, which began in 2016, is inves- Medicine, is studying how the PI3K/AKT/mTOR tigating the abnormal activation of signals that pathway contributes to hemangiosarcoma cell trigger or facilitate the development of cancer. growth, eventual spread and drug resistance. The “Signaling pathways are coordinated chemical goal of this research is to identify combinations activities in a cell that collectively control one or of drugs that can e¡ectively target this pathway more cell functions, and specific pathways are and more e¡ectively extend survival times. critical for tumor growth,” Dr. Dickerson explains. “Inhibitors of the PI3K pathway have shown “We are studying how these identified pathways promise in blocking the growth of hemangio- contribute to hemangiosarcoma growth and sarcoma cells in the laboratory,” Dr. London whether drugs can interrupt the process to says. “Exactly how this happens is not entirely reduce tumor growth and chemotherapy resis- known, but sometimes these tumors carry muta- tance. Our goal is to find a new approach to tions that activate the PI3K pathway and thus treat this aggressive cancer in dogs.”

hemangiosarcoma cells to to treatment and thus when help distinguish between a dog in remission might dogs that have the cancer relapse. More than 20 dogs from those that do not. About have been studied, indicating 80 dogs have been studied, that the number of suspect and the preliminary analy- cells in blood is relatively sis suggests that a family of stable until animals are treated. algorithms separates the four This number decreases with categories of samples being treatment, and so it is expect- collected: 1) no evidence of ed to help track the duration disease, 2) benign splenic ab- of remission. In future research, normalities, 3) hemangiosar- the team hopes to gain insights coma, and 4) cancers other into how therapy management than hemangiosarcoma. might extend remission times • Phase 2: Determining whether and prevent unexpected life- blood testing for hemangio- threatening bleeding episodes. sarcoma cells will help predict • Phase 3: Establishing how well when tumors become resistant the blood test works for early

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DOUBLE YOUR DONATION VIA THE CANINE CANCER RESEARCH INITIATIVE

Recognizing the challenges and slow progression in the development of new approaches for diagnosing and treating canine cancer, such as hemangiosacoma, the AKC (American Kennel Club) Canine Health Foundation (CHF) has launched the Canine Cancer Research Initiative. This fund- detection and how well eBAT humans who develop the rare raiser for cancer research is works to eliminate hemangio- cancer angiosarcoma, which is supported by the American sarcoma cells before tumors similar to hemangiosarcoma. A Kennel Club, which will match have a chance to form. About method to detect hemanigosar- donations and CHF Donor 140 dogs are enrolled in this coma in its earliest stages and Advised Fund transfers to part of the study. Although the an e¡ective mechanism for pre- the Canine Cancer Research analysis is in its early stages, venting it would be a giant leap Initiative up to $250,000 in Dr. Modiano says that patterns forward in the management of 2019. The match is provided to found in the blood suggest that this disease.” support research of canine- the test may be helpful in Carson welcomes the possibility specific cancers. Currently, the identifying risk for pathological of recognizing the cancer sooner. AKC Canine Health Foundation conditions, including splenic “If we could one day understand is supporting four hemangio- abnormalities and cancers. how to diagnose the cancer in the sarcoma studies totaling over “We are using artificial intel- early stages, it would be wonder- $906,089. ligence to analyze data from ful,” she says. “We need to support Phase 3,” says Dr. Modiano. “As research of this cancer and get we hone on the patterns, the involved in helping others to accuracy of how we classify understand hemangiosarcoma.” n samples will improve based on those patterns. Ultimately, we will assign classifications by predict- Purina appreciates the sup- ing, or inferring, the probability port of the Dachshund Club that unknown samples belong of America and particularly Charlotte Borghardt, chair of to particular groups that were the DCA Health Committee, defined in the training phase. in helping to identify topics “Our goal is to reduce the health for the Dachshund Update. burden of this cancer in dogs and 7 IF SOMEONE TOLD YOU THAT

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