To be a great veterinarian is one thing, but the ability to maintain compassion and caring sets you apart from the rest.
Drs. Craig Clifford, Siobhan Haney, and Kate Vickery will be hosting a whole day track on various oncology topics at this year’s 2014 Atlantic Coast Veterinary Conference in Atlantic City, NJ. Please click on the links below for more details.
Stereotactic radiosurgery (SRS) is a treatment delivery technique that utilizes a single high dose of radiation to ablate a tumor, hence the term “surgery”, although this is a non-invasive treatment modality. The word stereotactic refers to a three-dimensional coordinate system that enables accurate correlation of a tumor visualized in the patient’s diagnostic images with the actual tumor position in the patient’s body. This technique is typically used for brain and spinal tumors; however, it may be used for other types of tumors as well. Stereotactic body radiation therapy (SBRT) refers to the same delivery method, but a given dose is delivered in multiple treatments over several days. Both of these treatment methods rely on accurate patient positioning, strict quality assurance, on-board imaging and highly conformal delivery methods, which result in a steep dose gradient between the edge of the tumor and surrounding normal tissue. This results in a high dose of radiation being received by the tumor and a relatively low dose being received by surrounding tissue. As such, there is an exceedingly low probability of normal tissue toxicity (manifesting as side effects). This is compared to conventional radiation therapy (RT) techniques and protocols, in which a total dose of radiation is delivered in multiple small daily fractions that may span a 4-6 week period. Using conventional methods, breaking up the total dose into many smaller doses is necessary because of the relatively large amount of normal tissue surrounding the tumor that needs to be included in a given field. With conventional techniques, there is a very high probability of acute radiation side effects in the normal tissue included in a given field. Acute radiation toxicity and associated side effects are self-limiting and will resolve in 1-3 weeks. Radiation therapy for veterinary patients requires anesthesia, as accuracy of dose delivery depends on patient immobilization. Conventional radiotherapy requires daily anesthesia over 4 weeks. Stereotactic radiotherapy treatments may only require 1-3 anesthetic episodes, which are typically performed in one week or less.
Stereotactic radiosurgery may be delivered using a conventional linear accelerator that is equipped with special cones and collimators that allow precise radiation delivery to a tumor. Rigid immobilization may or may not be required for a patient, depending on the type of linear accelerator being used. Planning software utilizes a pre-treatment CT or MRI scan which allows the radiation oncologist to sharply delineate the tumor and define sensitive surrounding tissues that will be avoided. Immediately prior to a treatment, a cone beam CT scan is typically performed, which allows visualization of the tumor and surrounding anatomy and ensures proper dose delivery. The success of radiosurgery depends on rigid quality assurance and delivery of radiation with sub millimeter accuracy.
Technological advancements have also allowed the development of a compact linear accelerator mounted on a robotic arm. Accuray in Sunnydale, CA manufactures the CyberKnife® system. This method of delivering radiation is accomplished by directing the source of radiation from up to 1200 different angles around a tumor. A robotic arm accomplishes rapid repositioning of the linear accelerator during a patient’s treatment. In addition, reimaging of the patient and robot corrections for tumor movement is done continuously throughout a treatment. The CyberKnife® system does not rely on rigid immobilization, but instead tracks tumor position via bony anatomy or by utilizing the placement of fiducial markers, which are tiny gold seeds that are implanted in or around a tumor. These fiducial markers are tracked by the use of orthogonal kilovoltage x-ray sources and floor panel detectors (see Figure 1). These allow tracking by the robot in real-time and can account for changes in patient position during a treatment. Advances in the CyberKnife® system have allowed tumors that are constantly moving, such as lung or liver tumors, to be treated with sub-millimeter accuracy, as the robotic arm moves the beam of radiation with the tumor as it changes position with the varying phases of respiration. As with the previous SRS/SRT delivery method, the CyberKnife® relies on computerized software planning, strict adherence to quality assurance and a team of radiation oncologists and medical physicists.
There are two CyberKnife® facilities on the east coast that are dedicated to veterinary use. One is at the VCA Animal Specialty Center in Yonkers, NY and the second is the privately owned Veterinary CyberKnife Cancer Center in Malvern, PA. CyberKnife® radiosurgery has allowed treatment of tumors that were rarely treated with radiation therapy in veterinary medicine, such as lung and liver tumors. This advancement has also allowed successful treatment of tumors such as bone bladder/ urethral tumors and prostate tumors (see Figure 2), as the concern for normal tissue toxicity has previously kept us from attempting radiotherapy using conventional methods.
These novel therapies are on par with many human facilities and offer our patients options never before thought possible in veterinary medicine. These options will enable treatment for cancers never thought possible with previous therapy units. Although the term stereotactic radiotherapy has become more commonplace in veterinary oncology, many facilities use the term loosely but are not truly “sterotactic”. For the primary care clinician, it is important to recognize the difference and to also ensure that a radiation oncologist is “on site” to evaluate the patient and play an active role in the therapy protocol. A search for radiation oncologist can be found via http://www.acvr.org/public/search
Submittted by Dr. Siobhan Haney; Radiation Oncologist Hope Veterinary Specialists
Figure 1. The CyberKnife® Radiosurgery system
Figure 2. This is an axis CT image at the level of the pelvis. The orange circle at the center of the image is the urethra, which is effaced with transitional cell carcinoma. The colored lines around this area represent the different isodose lines, or the amount of radiation that is being received by the surrounding tissue. The colon is directly above the urethra and is receiving a very small portion of the dose of radiation. This decreased the chance of normal tissue side toxicity to an almost negligible level.
Ollie, a 7 year male neutered Golden retriever presented for a consultation regarding options of a abdominal mass. He had recent history of worsening orthopedic issues and would not rise one week ago. A workup by the primary care veterinarian revealed unremarkable bloodwork and chest radiographs. An abdominal ultrasound revealed two splenic nodules and a mass associated with the cecum. He was started on NSAID and his orthopedic issues resolved. He presented to the oncology and surgery service to discuss treatment options for the cecal tumor. Although his recent clinical signs were unrelated to the cecal tumor, it was recommended to pursue surgery to remove the tumor.
The patient was placed in dorsal recumbency and the ventral abdomen was clipped and prepped aseptically. A standard ventral midline abdominal incision was made. There was a 4 cm cecal mass, multiple 2-3 cm splenic masses, and 1 cm masses throughout the liver parenchyma. A typhlectomy was performed using a GIA 50 stapler and the staple line was oversewn with 4-0 PDS in a simple continuous pattern. A splenectomy was performed using a vessel sealing device. A liver biopsy was obtained from the left lateral liver lobe using a 6 mm punch biopsy and the Gelfoam was used to control hemostasis. The abdomen was flushed using sterile saline. The site of splenic removal and liver biopsy were reevaluated for bleeding and none was noted. The abdomen was closed routinely. The linea alba was closed using 0 PDS in a simple continuous pattern. The subcutaneous tissue was closed using 2-0 PDS in a simple continuous pattern. The intradermal tissue was closed using a subcuticular pattern using 3-0 Monocryl and the skin was closed using staples. The skin mass over the right elbow was removed with electrosurgery and two staples placed in the skin. The spleen/mass, cecal mass, skin tag mass, and liver biopsy were submitted for histopathology.
Histopathology was consistent with a low grade sarcoma of cecum, presumptive gastrointestinal stromal tumor (GIST) with a complete resection. Splenic nodular hyperplasia, with extramedullary hematopoiesis was documented in the spleen and hepatic glycogen accumulation in the hepatic sample evaluated.
Immunohistochemical (IHC) stains were performed and positive for CD-117 confirming the diagnosis of a gastrointestinal stromal tumor (GIST).
Image 1: Positive C-kit expression differentiates a gastrointestinal stromal tumor (GIST) from a leiomyosarcoma. Image courtesy of Matti Kiupel.
Outcome: Based upon the diagnosis of a low grade gastrointestinal stromal tumor (GIST) with a complete excision and clean staging, no adjuvant therapy was recommend. Ollie is to return q 4-6 months for restaging for the next 2 years.
The incidence of intestinal tumors in dogs is low in comparison to people. Dogs can develop small intestinal tumors and large intestinal tumors and they tend to occur in older dogs (>6 years) Generally, clinical signs include anorexia, vomiting, weight loss, lethargy, diarrhea, and melena. Males and females tend to develop intestinal tumors at equal rates. The most common gastrointestinal tumors in dogs are lymphosarcoma, adenocarcinoma, leiomyosarcoma and gastrointestinal stromal tumor with adenocarcinoma being the most common primary intestinal tumor. Leiomyosarcomas are reported to be the most common sarcoma of the canine intestinal tract and comprise approximately 10% to 30% of all intestinal tumors in dogs. The advent of advanced immunohistochemistry (IHC) staining techniques has led to reclassification of gastrointestinal leiomyosarcomas (GILMSs). It has been recognized that tumors previously categorized as GILMSs are not composed entirely of smooth muscle but are principally derived from the interstitial cells of Cajal. These act as the pacemaker cells of the gastrointestinal tract and regulate intestinal motility and peristalsis. The ICC-derived tumors have been renamed GISTs. Gastrointestinal stromal tumors are IHC distinguishable from GILMSs or true smooth muscle tumors on the basis of expression of c-kit (CD- 117). Leiomyosarcomas do not express the c-kit protein. The c-kit protein is a transmembrane receptor with a tyrosine kinase component. GISTs often have activating c-kit mutations may be the driving force in gastrointestinal stromal tumor oncogenesis (similar to a proportion of mast cell tumors). The location of the mutation in GIST is similar in both humans and dogs.
Clinical signs in dogs are often nonspecific including anorexia, weight loss, and lethargy. Melena, hematemesis, and hematochezia are also commonly associated with GISTs. Some patients may present more emergent secondary to perforation of the gastrointestinal wall subsequent to tumor invasion (common when present in the cecum).
Staging includes routine bloodwork (CBC, serum chemistry, urinalysis), chest radiographs, and an abdominal ultrasound to ensure the disease is localized. A recent study noted ultrasonographic features including large tumor size, irregular margin and heterogeneous internal echogenicity with large hypoechoic areas, related closely with the presence of metastasis.
In regards to treatment, surgery is the mainstay of therapy and surgery alone is often associated with longterm survival. In one study a median survival time was 37.4 months for dogs with GISTs, vs. 7.8 months for dogs with GILMSs, and 2.9 months for dogs with undifferentiated sarcomas. The metastatic rate is generally considered low (most tumors are low grade). In humans, standard chemotherapy is associated with a low response rates and considered largely unsuccessful in the control of GISTs. The use of oral tyrosine kinase inhibitors are generally considered a standard of care in human in oncology and has resulted in prolonged survival times, compared with survival times associated with other treatments. In veterinary oncology anecdotal responses have been noted. Currently, only one product, toceranib phosphate (Palladia; Zoetis) is fully licensed by the FDA for use in dogs with MCT.
Russell KN, Mehler SJ, Skorupski KA, et al. Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003) J Am Vet Med Assoc. 2007;230:1329-33.
Gregory-Bryson E, Bartlett E, Kiupel M, et al. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11. BMC Cancer. 2010;10:559.
Kobayashi M, Kuroki S; Ito K, et al. Imatinib-associated tumour response in a dog with a non-resectable gastrointestinal stromal tumour harbouring a c-kit exon 11 deletion mutation. Vet J. 2013;198:271-4.
Congratulations to our Director of Nursing, Brandy Terry for her recent achievement award! Brandy received this year’s Pennsylvania Veterinary Medical Association award as Veterinary Technician of the Year for 2014!
She also received a volunteer shout out for being an active member of the PVMA and serving on their Scientific Program Committee. She was a founding member and former president of the Pennsylvania Veterinary Technicians Association and was integrally involved with the decision to merge with PVMA for the betterment of certified veterinary technicians, veterinary assistants and both organizations.
Way to go Brandy, we are so proud of you!
If you wish to make donations in honor of Hope to help provide for his care, please visit http://www.ccspca.org/donate/in-honor-of-donations/. Keep in mind that Hope will be transferred to the care of Chester County SPCA until the court hearing against James Myers is finalized. He is considered evidence and is not able to be adopted at this time. There are SO many cats and kittens that can be adopted at your local shelter in honor of Hope.
Thousands of people wish to be a hero to this one little kitten when there are thousands of cats that need just one hero to adopt them from their local shelter. They will be just as grateful and love you just as much!!