Tina's Journey

Introduction

Feb 25, 2023

This submission is an attempt to follow the details of a case of a dog diagnosed with osteosteosarcomat may serve as a guide to those pet owners with affected dogs as to what to expect when the dog is given the standard of care treatment.

This past year two of my pet Greyhounds, Tina and Kinsey, were struck down by osteosarcoma. Both dogs received the standard of care for osteosarcoma i.e. chemotherapy, and in Tina's case, amputation of the affected leg. In addition, Tina was given experimental immunotherapy drugs.

Kinsey was deemed too old for amputation of the affected leg and was given only chemotherapy. She lasted only three months after diagnosis. Tina survived for a year.

Kinsey (left) and Tina (right)

This past year has been an agonizing experience for all three of us. Early in Tina's treatment, in a desperate search for newer cancer treatments, I found that an immunotherapy vaccine had been developed at Yale by

Prof. Mamula. It had shown promise in an earlier trial with canine osteosarcoma. But that trial was closed and the vaccine was unavailable.

But now, two years later, as of January 2023, a new trial has been approved and is open to all comers.

Funds have been made available to cover the cost of the production of the vaccine. Thus there will be no charge for the vaccine itself. Hopefully, this will result in more dogs being treated and thus more happy outcomes.

Tina’s Journey

Tina, a red female Greyhound, was born at a Texas Greyhound racing kennel on August 28, 2013. She was a bit small for racing so she was put up for adoption.

She came into my life on Christmas Eve of 2014. Like all Greyhounds she was an individual, very loving toward people, but also very bossy around her Greyhound friends; there was lots of growling and rough talk but never any biting. She usually slept in my bed and loved to be petted. Her way of thanking me for the attention was to try to wrap her front leg around the forearm that was doing the petting.

Medically things were uneventful until July 8 of 2021. Her veterinarian noted that her urine protein creatinine ratio was 4.0, a significant increase from her May 7 reading of 1.7. She was started on Enalapril to help control this problem.

I will describe in some detail Tina's medical history from the time the osteosarcoma was first suspected. This is a critical period if there is to be any hope of an extended remission, or of a cure. Tina's treatment after amputation follows the more or less standard of care and thus is presented in an outline form (Tina's

treatment from February 1 to August 14, 2022).

On July 15, 2021, I brought her back for examination of a slight limp, At that time the limp was barely noticeable and no significance was assigned.

Her limp became more apparent, and on August 26 radiographs revealed a mass-like structure on her left humerus. The examining veterinarian noted that the radiologists are "leaning toward her having a primary bone tumor". At the time I did not realize how understated this suspicion was.

It was recommended that she have the x-ray repeated and a needle aspirate taken in two or three weeks.

On September 9 the fine needle aspirate confirmed osteosarcoma. A consultation was scheduled for September 20 to asses her overall mobility, to check for metastasis, and to schedule her leg amputation. The possibility of trying one of the newer immunotherapies was investigated. I requested that we proceed with the core biopsy before amputation. Little did we know that future events would limit our treatment options.

Thus on October 8, she broke her left humerus while she was playing.

Amputation was scheduled for October 19, with plans to make an experimental vaccine from a sample of the tumor. The amputation surgery was moved forward to October 13.

Thus there was a 7-week period from the first suspicion of osteosarcoma on August 26 to surgery on October 13. This delay likely sealed Tina's fate. Her only chance of long-term remission, be it only a small chance, was immediate amputation of the affected limb.

The amputation surgery revealed a nearby lymph node contained suspicious cells.

Two days later, on October 15, she received her first Carboplatin treatment. That same day a biopsy confirmed osteosarcoma.

On November 3, Tina was treated for an infection at the amputation site. On November 5 she returned for further treatment of the infection and was hospitalized until November 12.

She received her second carboplatin treatment on November 12.

At that time she was checked for potential side effects from the carboplatin. She received her third and fourth carboplatin treatments on December 3 and December 22, 2021.

Tina's treatment from February 1 to August 14, 2022:

2/1

Chest x-ray shows no metastasis

The first dose of Torigen vaccine (made from her tumor sample) administered

2/8

Second dose Torigen vaccine

2/15

Third dose of Torigen vaccine

Clinical trial investigation. Checked for the availability of the Yale EGFR cancer vaccine.

4/19

Lung metastasis suspected.

Radiographs reveal a single nodule in the lung.

4/27

Lab testing. No finding of concern.

OncoK9 test finds no cancer signal.

Urine P/C 2.3

5/4

X-ray shows lung metastasis increased from 2.2cm to 3.2cm.

Second 2cm metastasis discovered.

Losartan and Palladia continued.

CBC and chemistry testing were repeated.

5/11

X-ray reveals a mild progression of lung metastasis.

Urine protein/creatinine increased to 4.3. CBC repeated.

Losartan and Palladia continued.

5/30

Tina is checked for high respiration rate, high blood pressure, not eating, and hind leg weakness.

Thigh muscles are painful and swollen.

X-rays show a slight increase in the size of lung metastasis to 4.1cm and 2.8cm.

Liver irregularities are evident. UPC 3.7, ALT 1306, ALP 130.

Fenbendazole is prescribed for hookworm.

Losartan & Palladia discontinued.

Enalapril resumed (to help with blood pressure)

Carprofen started (for relief of pain and inflammation).

6/8.

Hind leg muscle symmetry improves.

Diphenhydramine (Benadryl) and Doxorubicin started.

Wt. 28.7kg

6/15

Fine needle aspirates of rear leg biceps raise the concern of osteosarcoma.

7/22

Increased respiration rate and effort.

1.2 L of pleura effusion drained.

7/24

0.59L of pleural effusion drained.

Breathing much improved.

Wt 26 kg.

Continues Gabapentin.

Fentanyl patch started.

Started Lapatinib & Satraplatin.

7/25

Evaluated for breathing difficulty.

Ultrasound scan showed some pleural fluid and fluid around the heart.

7/28

Evaluated for breathing difficulty.

0.95L pleural fluid removed.

Elevated temperature.

No bacteria in pleural fluid.

White blood cell count normal.

Blood pressure normal.

Fever likely due to paraneoplastic reaction (immune system reaction) to osteosarcoma.

Resumed Lapatinib and Satraplatin.

7/29

Evaluated for vomiting episode.

Ultrasound scan revealed pleural fluid.

T = 102.3.

No pleural fluid drained.

8/1

Breathing difficulties

T = 103.5 on admission, decreased to 101.5.

W = 23.8Kg. Poor appetite.

BUN high 33mg/dL creatinine 2.6mg/dL

Started Entice (for appetite).

Discontinue Lapatinib.

Continue Satraplatin and Gabapentin.

8/6.

Presented for breathing difficulties and vomiting.

Fluid in chest.

Anemic with PCV = 29%. Pleural fluid PCV = 14%, total protein 2.8mg/dL.

Consistent blood loss into pleural space.

May require blood transfusion.

Tranexamic acid started (to prevent bleeding)

8/9

Progressive inappetence and increased respiratory rate and effort.

T = 102, Wt = 23.3Kg.

Removed 1.7L hemorrhagic fluid from right side of chest, fluid PCV = 31% with total protein of 6.9g/dL

8/11

Increase in respiratory rate and effort.

T = 103, W = 22.2Kg. 59mL fluid removed from right side,

PCV = 8% (Decrease). Peripheral PCV = 29% (2% decrease).

BUN = 71, creatinine= 3.4, phosphorus increasing,

Increase in white cells, possible infection.

Continue with Lapatinib, Gabapentin, tranexamic acid.

8/14

Tina was euthanized at recommended by the veterinarian on her case.

8/15

Necropsy report I requested confirms metastatic osteosarcoma in the following areas:

• Heart, large portions

• Lungs and kidneys

• Adrenal glands

• Skeletal muscle

• Right caudal lung lobe has rotated 360 degrees

Severely congested, airway filled with edema, contributing to respiratory difficulty.

Anemia caused by peripheral blood loss, hemorrhage,

Also noted were changes to the liver and spleen.

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During this very long year, Tina kept her spirits up. She quickly learned to get along on three legs.

Up to the end, she was asking to go for walks except on the last day when she tried with all her remaining strength not to go into the veterinarian’s office. Somehow she knew.

During the course of Tina’s treatment, I experienced some extreme emotional reactions.

One such reaction occurred on August 6 during our trip to see the veterinarian.

At that time the only metastasis that I could see, those on her back legs, were definitely decreasing in size and firmness. I imagined that the chemotherapy was finally beginning to take effect. We were winning.

During our trip I experienced a feeling of euphoria like I had never experienced; everything I looked at had a beautiful glow to it.