Oncology Case Report Example
“Trey” a seven-year-old, castrated male, 53 kg, Alaskan Malamute, presented to the Animal Medical Center (AMC) for epistaxis, mainly from the left side. He also recently started snoring and was trying to rub or scratch at his face. A CBC, serum biochemistry panel, urinalysis, and a coagulation panel were obtained. A buccal mucosal bleeding time was also obtained and was normal. The owner took him home to be monitored and was instructed to come back, if the symptoms persisted, for a computed tomography (CT) scan and possible rhinoscopy. The differentials for the epistaxis were neoplasia, infection, foreign body, hypertension, coagulopathy, chronic inflammation, or hyper viscosity syndrome.(1) The blood tests showed a mildly increased ALT and BUN. The ALT was 112 IU/L (normal range 5-60 IU/L) and BUN was 31 mg/dl (7-27 mg/dl). Everything else was within normal limits. The owner then called back within two weeks to schedule a CT scan since the symptoms had persisted.
Imaging, such as a CT scan, is recommended to identify abnormalities in the nose and to find if there is anything to biopsy. A magnetic resonance imaging (MRI) could also be done and may be indicated if there is concern that there could be brain involvement. CT scan can be performed more quickly and it is easier to interpret lesions involving the bone using CT. With nasal tumors there is often bone destruction. With an MRI you can get images in multiple planes such as a sagittal, axial or dorsal views. Skull radiographs are another option; however they do not provide the same anatomic detail as CT or MRI. Skull radiographs are two-dimensional and do not always show if there is a mass in the nasal cavity. A systolic blood pressure was performed before anesthesia and was 120 mmHg. This was done to rule out hypertension as the cause for the epitaxis. Abdominal ultrasound and thoracic radiographs were done as well and no abnormalities were noted. The CT scan revealed a contrast enhancing soft tissue mass causing nasal turbinate lysis in the left nasal cavity. The mass displaced the nasal septum to the right. The lymph nodes in the neck were normal. During a CT scan contrast is given to help enhance the tumor. The contrast contains iodine that goes through permeable vessels. Tumors, as they grow, make their own vessels that are weak and very permeable which is why the contrast is picked up. Trey recovered without incident and was sent home the same day. The biopsy results revealed a moderate suppurative rhinitis. Based on the CT scan there was concern that the initial biopsy was not representative of the mass so a second procedure to obtain a sample was performed. Again, the procedure was uneventful and he was sent home. The biopsy results, this time, came back as intermediate-grade, malignant lymphoma. Since nasal lymphoma is a rare tumor in a dog the biopsy was reviewed to confirm the diagnosis.
Lymphoma is typically a systemic disease that can be found in the lymph nodes, bone marrow, liver, spleen and other organs. In dogs, prognosis depends on the stage of the lymphoma, the cell type (i.e. B cell or T cell) and how the cancer responds to chemotherapy. Surgery was not considered to be an option for Trey due to the location of the tumor. Surgery would have had a high risk for complications and is unlikely to get complete margins. Therefore, radiation therapy was recommended for local tumor control. Chemotherapy was also recommended since lymphoma has a high potential to spread in most cases in dogs. Since there are few cases reported of dogs with nasal lymphoma and their treatment, it was thought the best way to treat Trey was to treat him as if he were a cat. In cats, nasal lymphoma has been shown to be a local tumor in most cases, which is unlikely to metastasize. (2) It can usually be controlled with a combination of radiation therapy and chemotherapy. Survival times have been shown to be two or more years.(3,4) Cats are treated at the AMC with six radiation treatments of 5 Grey (Gy) each delivered once a week. They also receive chemotherapy at the same time.
There are many options for lymphoma in terms of chemotherapy protocols. Most protocols are a variant of a multi-agent CHOP protocol, which includes the following drugs, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone. The AMC uses the University of Madison Wisconsin protocol. This protocol is 25 weeks. It has had a remission rate of 90% in dogs and a mean survival time of a year.(2) The protocol consists of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisone. (5) With each chemotherapy drug there are potential side effects. The main side potential side effects are described with BAG, which stands for Bone Marrow, Alopecia and Gastrointestinal (GI). Bone marrow suppression, such as neutropenia and thrombocytopenia, is one of the main side effects to worry about. A decrease in WBC is expected but if the patient gets severely neutropenic than they usually need to be admitted for IV fluids and antibiotics. The other side effect that can limit the dose is GI toxicity. A patient may have mild to severe vomiting and diarrhea. Usually patients can be sent home with medications such as metaclopramide or metronidazole to help with these side effects. Hair loss is also a side effect especially in certain breeds, such as the Old English sheepdog. L-Asparaginase (Elspar) is a bacteria-derived enzyme that may cause anaphylactic shock and the patient needs to be monitored for a period of time after administration. Hypersensitivity reactions can include vomiting, diarrhea, edema, urticaria, pruritis, dyspnea, hypotension or collapse. With each dose the risk of having a reaction is thought to increase. Vincristine (Oncovin) is an antitubulin agent and it can cause severe perivascular tissue reaction with accidental extravasation. This would cause an acute burning sensation and tissue necrosis (slough) of the affected area. Cyclophosphamide (Cytoxan) is an alkylating agent that may cause bone marrow suppression. It may also cause sterile hemorrhagic cystitis in dogs, which is irritation of the bladder. Furosemide is often given with the drug to prevent the hemorrhagic cystitis. Furosemide is a diuretic and helps to eliminate the chemotherapy quicker from the bladder. Doxorubicin (Adriamycin) is an anthracycline drug that can cause myelosuppresion, GI upset, cardiac toxicity (in dogs), hypersensitivity during administration and is a potent vesicant. Some extravasations can cause such severe soft tissue necrosis that an amputation may be required. Prednisone is a hormone that may cause polyuria, polydipsia, polyphagia, hepatomegaly, hair loss, muscle wasting, panting and iatrogenic hypercortisolism. The drug also has the potential to cause GI ulcerations. (2)
The oncologist recommended doing a bone marrow aspirate and starting chemotherapy that day on Trey. Radiation would be started with the second chemotherapy treatment. The bone marrow aspirate was done to see if there were any cancer cells in the marrow. The results of a bone marrow aspirate do not typically change the treatment options for lymphoma, but in this case radiation may not have been recommended if there was lymphoma in the marrow. The bone marrow was done and Trey was induced with L-Asparginase. Trey was monitored after receiving this treatment to make sure he did not have any reactions. He was also started on prednisone. He was sent home and was scheduled to come back in one week for his first radiation treatment and his second dose of chemotherapy. His bone marrow results came back as normal cellularity and activity, with no evidence of neoplasia. Even with these results it was still difficult to give the owner a prognosis due to fact that this particular tumor is rare in dogs. The World Health Organization (WHO) staging system is used to stage canine lymphoma. Stage I indicates that the tumor is isolated to one lymph node or lymphoid tissue in a single organ. Stage II is involvement of many lymph nodes in a regional area. Stage III is generalized lymph node involvement. Stage IV is liver and/or spleen involvement. Stage V is spread to the blood and involvement of bone marrow and/or other organ systems. It can also be classified with substages a or b. Substage a is absence of systemic signs while b is presence of systemic signs.(2) With this information Trey would be classified as a Stage Ia. Trey returned one week later to start radiation and continue chemotherapy. Trey was treated with Cobalt 60 radiation. A CBC was taken to check his white blood cells to see if they were in the normal range. A CBC is needed before chemotherapy is given to check that an animal is not neutropenic or thrombocytopenic. Trey was induced for anesthesia using propofol (6 mg/kg) and diazepam (5 mg/kg). Atropine (0.02 mg/kg) was used as a premedication and he was maintained on Isoflurane. His anesthesia and recovery were uneventful. He was also given vincristine (0.7 mg/m2).
Approximately one week later Trey came in for his second radiation treatment, however he was depressed. After speaking to the owner, the clinician learned that Trey also had a decreased appetite and diarrhea. Upon examination he was also febrile at 103.2 degrees F. The rest of his physical exam was within normal limits. A CBC was performed and he was transferred to an intermediate care ward for observation and supportive care. His temperature increased to 105.4 degrees F. He was given a three-liter bolus of fluid and started on IV enrofloxacin (250 mg q 24hrs) and ampicillin (1100 mg q 8hrs) as well as IV fluids Plasmalyte with 5 mEq of potassium. His temperature was monitored every six hours. His radiation treatment was postponed. His CBC results were back and he was neutropenic. His total WBC count was 2.0 thous/ul and his neutrophil count was 0.240 thous/ul. Trey improved overnight. His fever resolved by the next morning. He had a good appetite overnight. A CBC was repeated the next day and his WBC count increased to 17.7 thous/ul and neutrophil count was 8.85 thous/ul. He was sent home later that day with oral enrofloxacin (272 mg q 24hrs) and amoxicillin/clavulanic acid (750 mg q 12 hrs), as well as metronidazole (750mg q 12 hrs). He returned one week later for his second radiation treatment and a CBC and cytoxan. He received both treatments without incident. The following week he only received his third radiation treatment but no chemotherapy because he was neutropenic again. The following week he received the fourth radiation treatment and vincristine. This time the vincristine dose was reduced by 20% because of his previous episode of neutropenia following vincristine. Dose reductions of chemotherapy agents have to be used carefully because they can decrease the drug efficacy. It is reported that even a 20% dose reduction can lead up to a 50% decrease in drug efficacy. (2) Again, he returned to get his fifth radiation treatment and received doxorubicin. Trey finished his six scheduled radiation treatments the following week and a nadir CBC was drawn. At that point he had mild oral mucositis and conjunctivitis in his right eye from the radiation, and was sent home with Nolvadent oral rinse. The owners were instructed to feed him only soft food.
Trey continued with his chemotherapy schedule. As well as the 20% dose reduction for vincristine, all his chemotherapy drug doses were calculated using his lean body weight. Trey tolerated his chemotherapy well after a dose reduction. He completed his chemotherapy protocol without incident. His side effects from the radiation resolved as well a few weeks after completing radiation. He returned in one month for a follow up visit. At that time, he was in clinical remission. The client was instructed to come back in six weeks for an abdominal ultrasound and three view thoracic radiographs.
Before Trey was scheduled to recheck he was brought to an emergency hospital for a gastric dilatation-volvulus (GDV). During the visit, the veterinarian had taken thoracic radiographs and was concerned that there was a nodule in Trey’s lungs. He had an abdominal exploratory to correct the GDV and a gastropexy. He recovered from his surgery. He then came to the AMC two weeks after his surgery for an ultrasound, blood work and thoracic radiographs. His CBC and chemistry panel were within normal limits. His ultrasound and radiographs showed no evidence of disease. Trey was having some diarrhea at the time, so metronidazole (500 mg PO q 12 hrs) was prescribed. The owner called a month later to report he was doing well but having nasal discharge when he sneezed. He was put on a course of amoxicillin/clavulanic acid (750 mg q 12 hrs) and his owner was told to continue to monitor him at home. Differentials for the nasal discharge are rhinitis caused by the radiation treatment, an infection or tumor regrowth. He is due to recheck with oncology in one month for imaging or sooner if his symptoms persist or worsen. He will continue to recheck every two months for the first year.
Submitted by Rosemary Calderon, LVT
References:
(1) Tilley LP, Smith Jr. FWK; The 5-minute Veterinary Consult Canine and Feline, ed. 3, Baltimore, MD, 2004, p420-421
(2) Withrow SJ, Vail DM; Small Animal Clinical Oncology, ed. 4, Saunders, St. Louis, MO, 2007
(3) Sfiligoi G, Theon AP, Kent MS; Response of nineteen cats with nasal lymphoma to radiation therapy and chemotherapy, Radiology & Ultrasound, Vol. 48, No. 4, 2007, pp 388-393
(4) Arteaga T DVM, Farrelly J DVM, ACVIM (Oncology), ACVR (Radiation Oncology); personal communication, unpublished data
(5) Garret LD, Thamm DH, et al.; Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma, J Vet Intern Med, 2002, 16: 704-709
Imaging, such as a CT scan, is recommended to identify abnormalities in the nose and to find if there is anything to biopsy. A magnetic resonance imaging (MRI) could also be done and may be indicated if there is concern that there could be brain involvement. CT scan can be performed more quickly and it is easier to interpret lesions involving the bone using CT. With nasal tumors there is often bone destruction. With an MRI you can get images in multiple planes such as a sagittal, axial or dorsal views. Skull radiographs are another option; however they do not provide the same anatomic detail as CT or MRI. Skull radiographs are two-dimensional and do not always show if there is a mass in the nasal cavity. A systolic blood pressure was performed before anesthesia and was 120 mmHg. This was done to rule out hypertension as the cause for the epitaxis. Abdominal ultrasound and thoracic radiographs were done as well and no abnormalities were noted. The CT scan revealed a contrast enhancing soft tissue mass causing nasal turbinate lysis in the left nasal cavity. The mass displaced the nasal septum to the right. The lymph nodes in the neck were normal. During a CT scan contrast is given to help enhance the tumor. The contrast contains iodine that goes through permeable vessels. Tumors, as they grow, make their own vessels that are weak and very permeable which is why the contrast is picked up. Trey recovered without incident and was sent home the same day. The biopsy results revealed a moderate suppurative rhinitis. Based on the CT scan there was concern that the initial biopsy was not representative of the mass so a second procedure to obtain a sample was performed. Again, the procedure was uneventful and he was sent home. The biopsy results, this time, came back as intermediate-grade, malignant lymphoma. Since nasal lymphoma is a rare tumor in a dog the biopsy was reviewed to confirm the diagnosis.
Lymphoma is typically a systemic disease that can be found in the lymph nodes, bone marrow, liver, spleen and other organs. In dogs, prognosis depends on the stage of the lymphoma, the cell type (i.e. B cell or T cell) and how the cancer responds to chemotherapy. Surgery was not considered to be an option for Trey due to the location of the tumor. Surgery would have had a high risk for complications and is unlikely to get complete margins. Therefore, radiation therapy was recommended for local tumor control. Chemotherapy was also recommended since lymphoma has a high potential to spread in most cases in dogs. Since there are few cases reported of dogs with nasal lymphoma and their treatment, it was thought the best way to treat Trey was to treat him as if he were a cat. In cats, nasal lymphoma has been shown to be a local tumor in most cases, which is unlikely to metastasize. (2) It can usually be controlled with a combination of radiation therapy and chemotherapy. Survival times have been shown to be two or more years.(3,4) Cats are treated at the AMC with six radiation treatments of 5 Grey (Gy) each delivered once a week. They also receive chemotherapy at the same time.
There are many options for lymphoma in terms of chemotherapy protocols. Most protocols are a variant of a multi-agent CHOP protocol, which includes the following drugs, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone. The AMC uses the University of Madison Wisconsin protocol. This protocol is 25 weeks. It has had a remission rate of 90% in dogs and a mean survival time of a year.(2) The protocol consists of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisone. (5) With each chemotherapy drug there are potential side effects. The main side potential side effects are described with BAG, which stands for Bone Marrow, Alopecia and Gastrointestinal (GI). Bone marrow suppression, such as neutropenia and thrombocytopenia, is one of the main side effects to worry about. A decrease in WBC is expected but if the patient gets severely neutropenic than they usually need to be admitted for IV fluids and antibiotics. The other side effect that can limit the dose is GI toxicity. A patient may have mild to severe vomiting and diarrhea. Usually patients can be sent home with medications such as metaclopramide or metronidazole to help with these side effects. Hair loss is also a side effect especially in certain breeds, such as the Old English sheepdog. L-Asparaginase (Elspar) is a bacteria-derived enzyme that may cause anaphylactic shock and the patient needs to be monitored for a period of time after administration. Hypersensitivity reactions can include vomiting, diarrhea, edema, urticaria, pruritis, dyspnea, hypotension or collapse. With each dose the risk of having a reaction is thought to increase. Vincristine (Oncovin) is an antitubulin agent and it can cause severe perivascular tissue reaction with accidental extravasation. This would cause an acute burning sensation and tissue necrosis (slough) of the affected area. Cyclophosphamide (Cytoxan) is an alkylating agent that may cause bone marrow suppression. It may also cause sterile hemorrhagic cystitis in dogs, which is irritation of the bladder. Furosemide is often given with the drug to prevent the hemorrhagic cystitis. Furosemide is a diuretic and helps to eliminate the chemotherapy quicker from the bladder. Doxorubicin (Adriamycin) is an anthracycline drug that can cause myelosuppresion, GI upset, cardiac toxicity (in dogs), hypersensitivity during administration and is a potent vesicant. Some extravasations can cause such severe soft tissue necrosis that an amputation may be required. Prednisone is a hormone that may cause polyuria, polydipsia, polyphagia, hepatomegaly, hair loss, muscle wasting, panting and iatrogenic hypercortisolism. The drug also has the potential to cause GI ulcerations. (2)
The oncologist recommended doing a bone marrow aspirate and starting chemotherapy that day on Trey. Radiation would be started with the second chemotherapy treatment. The bone marrow aspirate was done to see if there were any cancer cells in the marrow. The results of a bone marrow aspirate do not typically change the treatment options for lymphoma, but in this case radiation may not have been recommended if there was lymphoma in the marrow. The bone marrow was done and Trey was induced with L-Asparginase. Trey was monitored after receiving this treatment to make sure he did not have any reactions. He was also started on prednisone. He was sent home and was scheduled to come back in one week for his first radiation treatment and his second dose of chemotherapy. His bone marrow results came back as normal cellularity and activity, with no evidence of neoplasia. Even with these results it was still difficult to give the owner a prognosis due to fact that this particular tumor is rare in dogs. The World Health Organization (WHO) staging system is used to stage canine lymphoma. Stage I indicates that the tumor is isolated to one lymph node or lymphoid tissue in a single organ. Stage II is involvement of many lymph nodes in a regional area. Stage III is generalized lymph node involvement. Stage IV is liver and/or spleen involvement. Stage V is spread to the blood and involvement of bone marrow and/or other organ systems. It can also be classified with substages a or b. Substage a is absence of systemic signs while b is presence of systemic signs.(2) With this information Trey would be classified as a Stage Ia. Trey returned one week later to start radiation and continue chemotherapy. Trey was treated with Cobalt 60 radiation. A CBC was taken to check his white blood cells to see if they were in the normal range. A CBC is needed before chemotherapy is given to check that an animal is not neutropenic or thrombocytopenic. Trey was induced for anesthesia using propofol (6 mg/kg) and diazepam (5 mg/kg). Atropine (0.02 mg/kg) was used as a premedication and he was maintained on Isoflurane. His anesthesia and recovery were uneventful. He was also given vincristine (0.7 mg/m2).
Approximately one week later Trey came in for his second radiation treatment, however he was depressed. After speaking to the owner, the clinician learned that Trey also had a decreased appetite and diarrhea. Upon examination he was also febrile at 103.2 degrees F. The rest of his physical exam was within normal limits. A CBC was performed and he was transferred to an intermediate care ward for observation and supportive care. His temperature increased to 105.4 degrees F. He was given a three-liter bolus of fluid and started on IV enrofloxacin (250 mg q 24hrs) and ampicillin (1100 mg q 8hrs) as well as IV fluids Plasmalyte with 5 mEq of potassium. His temperature was monitored every six hours. His radiation treatment was postponed. His CBC results were back and he was neutropenic. His total WBC count was 2.0 thous/ul and his neutrophil count was 0.240 thous/ul. Trey improved overnight. His fever resolved by the next morning. He had a good appetite overnight. A CBC was repeated the next day and his WBC count increased to 17.7 thous/ul and neutrophil count was 8.85 thous/ul. He was sent home later that day with oral enrofloxacin (272 mg q 24hrs) and amoxicillin/clavulanic acid (750 mg q 12 hrs), as well as metronidazole (750mg q 12 hrs). He returned one week later for his second radiation treatment and a CBC and cytoxan. He received both treatments without incident. The following week he only received his third radiation treatment but no chemotherapy because he was neutropenic again. The following week he received the fourth radiation treatment and vincristine. This time the vincristine dose was reduced by 20% because of his previous episode of neutropenia following vincristine. Dose reductions of chemotherapy agents have to be used carefully because they can decrease the drug efficacy. It is reported that even a 20% dose reduction can lead up to a 50% decrease in drug efficacy. (2) Again, he returned to get his fifth radiation treatment and received doxorubicin. Trey finished his six scheduled radiation treatments the following week and a nadir CBC was drawn. At that point he had mild oral mucositis and conjunctivitis in his right eye from the radiation, and was sent home with Nolvadent oral rinse. The owners were instructed to feed him only soft food.
Trey continued with his chemotherapy schedule. As well as the 20% dose reduction for vincristine, all his chemotherapy drug doses were calculated using his lean body weight. Trey tolerated his chemotherapy well after a dose reduction. He completed his chemotherapy protocol without incident. His side effects from the radiation resolved as well a few weeks after completing radiation. He returned in one month for a follow up visit. At that time, he was in clinical remission. The client was instructed to come back in six weeks for an abdominal ultrasound and three view thoracic radiographs.
Before Trey was scheduled to recheck he was brought to an emergency hospital for a gastric dilatation-volvulus (GDV). During the visit, the veterinarian had taken thoracic radiographs and was concerned that there was a nodule in Trey’s lungs. He had an abdominal exploratory to correct the GDV and a gastropexy. He recovered from his surgery. He then came to the AMC two weeks after his surgery for an ultrasound, blood work and thoracic radiographs. His CBC and chemistry panel were within normal limits. His ultrasound and radiographs showed no evidence of disease. Trey was having some diarrhea at the time, so metronidazole (500 mg PO q 12 hrs) was prescribed. The owner called a month later to report he was doing well but having nasal discharge when he sneezed. He was put on a course of amoxicillin/clavulanic acid (750 mg q 12 hrs) and his owner was told to continue to monitor him at home. Differentials for the nasal discharge are rhinitis caused by the radiation treatment, an infection or tumor regrowth. He is due to recheck with oncology in one month for imaging or sooner if his symptoms persist or worsen. He will continue to recheck every two months for the first year.
Submitted by Rosemary Calderon, LVT
References:
(1) Tilley LP, Smith Jr. FWK; The 5-minute Veterinary Consult Canine and Feline, ed. 3, Baltimore, MD, 2004, p420-421
(2) Withrow SJ, Vail DM; Small Animal Clinical Oncology, ed. 4, Saunders, St. Louis, MO, 2007
(3) Sfiligoi G, Theon AP, Kent MS; Response of nineteen cats with nasal lymphoma to radiation therapy and chemotherapy, Radiology & Ultrasound, Vol. 48, No. 4, 2007, pp 388-393
(4) Arteaga T DVM, Farrelly J DVM, ACVIM (Oncology), ACVR (Radiation Oncology); personal communication, unpublished data
(5) Garret LD, Thamm DH, et al.; Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma, J Vet Intern Med, 2002, 16: 704-709
