Approach to the Oncology Patient: Grading, Staging & Treatment Planning
ACVIM 2008
Laurel Williams, DVM, DACVIM (Oncology)
Raleigh, NC, USA

Introduction

Evaluation and treatment of dogs and cats with cancer is increasingly common due to our expanding knowledge of tumor biology and treatment modalities and clients' willingness to pursue more advanced care for their pets.

Tumor Types

Tumors can be grouped into three broad categories: round cell tumors, epithelial/glandular tumors, and mesenchymal tumors. There are five types of round cell tumors, including lymphoma, mast cell tumor, plasmacytoma, histiocytoma, and transmissible venereal tumor. The epithelial/glandular tumors are called carcinomas. Examples include hepatocellular carcinoma, bronchogenic carcinoma, and transitional cell carcinoma. Mesenchymal tumors originate from connective tissues and are called sarcomas. Osteosarcoma and hemangiosarcoma are two very common sarcomas. Other sarcomas originating in soft tissues of the skin and SQ can be grouped together under the umbrella category referred to as soft tissue sarcomas, a group of histologically distinct but behaviorally similar tumors which includes fibrosarcoma, liposarcoma, hemangiopericytoma, and others.

Grading and Staging

One of the more difficult jobs facing the veterinary practitioner is answering clients' questions about prognosis after their pet has been diagnosed with a malignant tumor. This requires that the veterinarian have a basic understanding of different tumor types in order to determine where additional diagnostic procedures and further treatment may be warranted. We know that histologic tumor type is predictive of clinical behavior, but we should also be aware of the usefulness of the histologic tumor grade. Reports of studies on dogs with many different tumor types demonstrate that there are specific histologic features that are highly predictive of clinical behavior and/or response to therapy. The list of tumor types where histopathology has been shown to be of prognostic value includes: cutaneous hemangiosarcoma, cutaneous melanoma, digital melanoma, lingual squamous cell carcinoma, lung tumors, mammary tumors, mast cell tumors, multilobular osteochondrosarcoma, oral melanoma, soft tissue sarcomas, splenic hemangiosarcoma, synovial cell sarcoma, thymoma, thyroid tumors, and uterine adenocarcinoma.1-8 For many of these tumors, pathology reports are incomplete if this important grading information is lacking.

Other important information that should always be part of any complete histopathology report includes a comment on the invasiveness of the tumor and the completeness of excision.9-10 For tumors that appear completely excised, the pathologist should comment on the extent of excision (i.e., narrow vs. wide), preferably using objective measurements in millimeters or centimeters. If the margins are free of tumor cells ("clean margins"), the excision may be presumed to be complete; however, it is always possible that tumor cells were present at the margin(s) not examined histologically. To ensure the most accurate information is provided by the pathologist, the veterinarian should always submit the entire excised specimen with clearly labeled margins and the submission request should contain a brief description of the way the sample was collected.

In addition to determining histologic tumor type and grade, staging is indicated to identify possible sites of cancer spread (metastasis) prior to initiating treatment. Staging tests may include aspiration cytology of draining lymph nodes, 3-view thoracic radiographs, abdominal sonography, and bone marrow aspiration, depending on tumor type and location. In general, lymph node aspiration cytology and thoracic radiographs are indicated for staging of any carcinoma or sarcoma.

Treatment

Cancer treatment may be thought of in terms of local and systemic therapy. Local therapy, including surgery and radiation therapy, is used to address the primary tumor. Systemic therapy, or chemotherapy, is used to treat systemic cancers, such as lymphoma and leukemia, or in conjunction with local therapy to delay or prevent metastasis. The goal of any cancer treatment is to maintain the patient's quality of life at the highest possible level for as long as possible. When considering chemotherapy, this requires a balance between the efficacy of a given drug and its potential toxicity.

Surgery

Surgical biopsy or removal of a tumor may be categorized as the following: incisional biopsy, which involves removal of a small portion of the tumor for histologic diagnosis; excisional biopsy, which involves removing only the grossly visible tumor for histologic diagnosis with no attempt at achieving wide surgical margins; wide excision, which involves removing all gross and microscopic tumor with an adequately wide margin of adjacent normal tissue; and radical excision, which involves removing the entire tissue compartment that contains the tumor (e.g., amputation, radical mastectomy, mandibulectomy).

Radiation Therapy

Radiation therapy may be used in conjunction with surgery to decrease the risk of local tumor recurrence. Radiation therapy has the main advantages of being non-invasive and able to reach tissues not amenable to surgical resection. Potential side effects of radiation include an early, reversible reaction to rapidly dividing tissues (mucosa, skin, hair) that develops midway through treatment, varies in severity, and lasts 2-4 weeks before healing. There is also the potential, though unlikely, for late irreversible side effects to slowly dividing tissues (bone, muscle, nerve).

Chemotherapy

Systemic chemotherapy targets rapidly dividing cells. Due to their rapid and often abnormal division and defective repair mechanisms, tumor cells can be destroyed by chemotherapy. Some normal tissues also have a high rate of cell turnover (mucosa, bone marrow, hair) and may also be sensitive to chemotherapy, though unlike cancer cells, these normal tissues are able to repair chemotherapy-induced damage. Potential side effects of chemotherapy include gastrointestinal upset 2-4 days following treatment, myelosuppression 7-10 days following treatment, and hair loss in breeds with continuously growing coats.11

In general, chemotherapy drugs target rapidly dividing cells. Cancer cells divide faster, abnormally, and with defective repair mechanisms when compared to normal tissues. Damage is therefore primarily directed at cancer cells. However, certain normal tissues (gastrointestinal mucosa, bone marrow, hair) also divide rapidly and may be more sensitive to chemotherapy. In addition to these general toxicoses, individual drugs may have unique or cumulative toxicities. Treatment must therefore be designed with a basic knowledge of both the general as well as the unique toxicity spectra for the different agents.

Gastrointestinal toxicity may result from direct stimulation of the chemoreceptor trigger zone or from damage to the gastrointestinal mucosa. In the former situation, nausea and vomiting are most notable on the day of drug administration. Drugs most commonly associated with this type of centrally mediated vomiting are streptozotocin and cisplatin. When gastrointestinal upset results from the latter situation, it is generally 2-4 days following treatment as a result of the 2-4 day turnover time of the gastrointestinal mucosa. Drugs most commonly associated with this type of peripherally mediated gastrointestinal upset include doxorubicin, mitoxantrone, actinomycin D, procarbazine, dacarbazine, methotrexate, 5-fluorouracil, cytarabine, and carboplatin.

Myelosuppression results from damage to the rapidly dividing bone marrow cells. The survival in circulation of red blood cells, platelets, and white blood cells (neutrophils) are approximately four months, four days, and four hours, respectively. Cells with the shortest survival in circulation and therefore the highest rate of turnover are most susceptible. Accordingly, myelosuppression is most commonly seen as a decrease in neutrophil, and less commonly, platelet counts. When neutropenia develops, it is generally 7-10 days following treatment as a result of the 7-10 days required for a neutrophil to mature. Though the severity of neutropenia varies among the different agents, the drugs most commonly associated with neutropenia and/or thrombocytopenia include vincristine, vinblastine, doxorubicin, mitoxantrone, actinomycin D, cyclophosphamide, ifosfamide, melphalan, CCNU, procarbazine, dacarbazine, 5-fluorouracil, cytarabine, gemcitabine, and carboplatin.

Dogs with continuously growing (anagen-phase) hair coats such as Afghan hounds, Old English sheepdogs, poodles, and many terrier breeds, may experience hair loss during chemotherapy.

References

1.  Patnaik AK, et al. Vet Pathol 1984;21:469.

2.  Simoes JPC, et al. Vet Pathol 1994;31:637.

3.  Bostock DE, et al. Vet Pathol 1980;17:581.

4.  Kuntz CA, et al. J Am Vet Med Assoc 1997;211:1147.

5.  Kurzman ID, et al. Semin Vet Med Surg (Small Anim) 1986;1:25.

6.  Castagnaro M, et al. J Comp Path 1998;119:263.

7.  McNiel EA, et al. J Am Vet Med Assoc 1997;211:1422.

8.  Vail DM, et al. J Am Vet Med Assoc 1994;205:1300.

9.  Simpson AM, et al. J Am Vet Med Assoc 2004;224:236.

10. Fulcher RP, et al. J Am Vet Med Assoc 2006;228:210.

11. Williams LE, et al. Vet Forum 1998;15:44.

Speaker Information
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Laurel Williams, DVM, DACVIM (Oncology)
North Carolina State University
Raleigh, NC


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