ONCOLOGY - Neoplasia Diagnosis and Management Flashcards
What are the three presentations of neoplasia?
Superficial mass
Clinical signs
Paraneoplastic syndrome
What is paraneoplastic syndrome?
Paraneoplastic syndrome is the range of clinical signs that result from the secretion of substances by neoplastic cells. These substances can cause a range of clinical signs that can be unrelated to the actual tumour itself
What is the first step involved in neoplasia diagnosis based on mass identification?
Taking a thorough patient history
Which six questions should be asked when taking a thorough history?
Has there been any recent trauma or injury?
When was the mass first noticed?
What is the rate of growth of the mass?
Has the patient had any previous masses?
What is the age, sex and breed of the patient?
Is the mass hot or painful?
Why should you ask if the mass is hot or painful when taking a thorough history?
A hot or painful mass could indicate an infectious aetiology rather than neoplasia
Which two techniques can be used to investigate a mass for neoplasia?
Biopsy
Fine needle aspirate (FNA)
What information can be obtained from a biopsy?
Cell type present
How the tumour interacts with surrounding tissue
Allows for tumour grading
What is the main advantage of a biopsy?
A biopsy is diagnostic
What are the main disadvantages of a biopsy?
A biospy requires the animal to be sedated or under general anaesthetic which is both expensive and time-consuming
How much tissue should you take when carrying out a biospy?
When carrying out a biopsy, take as much tissue as you can within reason
What are the five biopsy techniques?
Incisional (wedge) biopsy
Excisional (whole mass) biopsy
Surface grab biopsy
Punch biopsy
Needle core biopsy
When is an incisional (wedge) biopsy most appropriate?
An incisional (wedge) biopsy is most appropriate when the mass is large or in a location that makes removal challenging
When is an excisional (whole mass) biopsy most appropriate?
An excisional (whole mass) biopsy is most appropriate when the mass is small and easily accessible
When is a surface grab biopsy most appropriate?
A surface grab biopsy is most appropriate for a mucosal tissue biopsy
When is a punch biopsy most appropriate?
A punch biopsy is most appropriate for a skin biopsy
What are the two types of needle used for a needle core biopsy?
Tru-cut needle
Jamshidi needle
When is a tru-cut needle most approproate for a needle core biopsy?
A tru-cut needle is used for a soft tissue biopsy
When is a Jamshidi needle most appropriate for a needle core biopsy?
A Jamshidi needle is used for a bone/bone marrow biopsy
Which biopsy technique would you use for this oral mass? Justify your answer.
Surface grab biopsy as this is the most appropriate technique for mucosal tissues
Which biopsy technique would you use for this skin mass? Justify your answer.
Punch biopsy or an incisional (wedge) biopsy as both of these techniques are appropriate for skin sampling, especially for large lesions such as this
Which biopsy technique would you use for these skin lesions? Justify your answer.
Excisional (whole mass) biopsy as there multiple small lesions and one of the whole lesions could be biopsied
How do you carry out a fine needle aspirate (FNA)?
Use a needle and syringe to aspirate the cells from the mass, expel and smear the aspirate onto a glass slide, stain the slide and examine under the microscope or send the sample to cytology
What information can be obtained from a fine needle aspirate (FNA)?
Cell type present
What are the main advantages of a fine needle aspirate (FNA)?
Fine needle aspirates (FNA) are quick, cheap and easy
What is the main disadvantage of a fine needle aspirate (FNA)?
A fine needle aspirate (FNA) is does not provide a definitive diagnosis as only the cells can be examined and thus you cannot examine how the tumour is interacting with the surrounding tissues
What is tumour grading?
Tumour grading is the assessment of the degree of malignancy of a tumour
Who carries out tumour grading?
Pathologists
Which seven factors are assessed by pathologists to determine the grade of a tumour?
Cellular differentiation
Cellular pleomorphism (variation)
Mitotic index/count
Invasiveness
Necrosis
Overall cellularity
Inflammation
Describe how pathologists carry out a mitotic index/count
Pathologists will count the number of mitotic cells over ten high power fields (hpf), which is equivalent to 2.37mm2 of tissue
What is the tumour grading scheme?
High grade tumour
Intermediate grade tumour
Low grade tumour
How should a high grade tumour be treated?
A high grade tumour should undergo aggressive treatment and chemotherapy
How should an intermediate grade tumour be treated?
An intermediate grade tumour should undergo local treatment with or without chemotherapy
How should a low grade tumour be treated?
Local surgery is usually sufficient for a low grade tumour
What is tumour staging?
Tumour staging is the assessment of the anatomical extent of a tumour in terms of the primary site and any metastases
Who carries out tumour staging?
Clinicians
What are the four purposes of tumour staging?
To help decide on the extent of treatment required
To help determine prognosis
Provides a precise record of tumour extent at that period of time
To monitor how the tumour changes with time
What is the TNM classification system used for tumour staging?
The TNM system is a system used to descibe the extent and spread of neoplasia throughout the body. T describes the size and extent of the primary tumour; N describes the extend of the spread of neoplasia to nearby lymph nodes; and M describes metastasis
What do you use to determine the size of the primary tumour for tumour staging?
Rulers
Calipers
How do you determine the invasiveness of the primary tumour for tumour staging?
Assess for local invasion using palpation and diagnostic imaging such as radiography, ultrasound, CT and MRI
How should you investigate for neoplasia in nearby lymph nodes for tumour staging?
Palpate lymph nodes
Diagnostic imaging
Fine needle aspirate (FNA)
Biopsy
What is the best diagnostic imaging technique to visualise lymph nodes?
CT
What are sentinel lymph nodes?
Sentinel lymph nodes is a term used to describe the first lymph nodes most likely to drain the primary tumour area and thus the lymph nodes most likely to become neoplastic
Which technique can be used to identify sentinel lymph nodes?
Sentinel mapping
What should be done if the senitel lymph nodes are neoplastic?
If the senitel lymph nodes are neoplastic, surgically remove the lymph node and carry out more aggresive treatment
How should you investigate for external metastasis for tumour staging?
Physical examination
How should you investigate for internal metastasis for tumour staging?
Diagnostic imaging such as endoscopy, radiography, ultrasound, CT and/or MRI
Which two techniques can be used to confirm metastasis?
Biopsy
Fine needle aspirate (FNA)
What can be done in a radiography to gain an optimal view of the lungs to investigate for metastasis?
Put the animal under general anaesthesia and carry out a manual breath hold
Which three views should be carried out when radiographing the lungs to investigate metastasis?
Left lateral
Right lateral
Dorso-ventral (DV)
When is euthanasia sometimes the only option for cancer treatment?
If the cancer is too advanced
If there is concurrent disease
Financial limitations
What should always be done before determining a course of cancer treatment?
Tumour grading
Tumour staging
What are the two main classifications of cancer treatment?
Local treatment
Systemic treatment
What are the two main methods of local cancer treatment?
Surgery
Radiotherapy
What are the two main methods of systemic cancer treatment?
Immunotherapy
Chemotherapy
Select combinations of systemic AND local treatment
What are the three treatment options most appropriate for a primary tumour (T)?
Surgical excision
Radiotherapy
Combined surgery and radiotherapy
What are the three treatment options most appropriate for sentinel lymph nodes?
Surgical excision
Radiotherapy
Chemotherapy if the neoplasia has high metastatic potential
What are the two treatment options most appropriate for metastases?
Chemotherapy
Immunotherapy
When performing oncological surgery for tumour excision, what are the three possible aims of the surgery?
Definitive/curative surgery
Cytoreductive surgery
Palliative surgery
What is cytoreductive surgery?
Cytoreductive surgery is excising as much as the tumour as possible to reduce the tumour in the body even if complete removal is not possible followed by other treatments such as radiotherapy or chemotherapy
What is palliative surgery?
Palliative surgery refers to surgery that aims to improve quality of life for patients with advanced or incurable cancer
What are the four methods of definitive/curative tumour excision?
Marginal excision/excisional biopsy
Local excision
Wide local excision
Radical local excision
When would a marginal excision/excisional biopsy be the most appropriate surgical technique for tumour excision?
Excisional biopsy
Encapsulated benign tumours (i.e. Lipoma)
Why is a marginal excision/excisional biopsy not very reliable for definitive/curative treatment?
A marginal excision/excisional biopsy is not very reliable for definitive/curative treatment because this method involves removing only a small margin (1-2mm) of healthy tissue around the tumour which may not be sufficient to remove all of the cancer cells
What is the typical margin of healthy tissue removed during a local excision?
1cm
When would a local excision be the most appropriate surgical technique for tumour excision?
Benign, non-invasive tumours
What is the typical margin of healthy tissue removed during a wide local excision?
2 - 3cm and one fascial plane
When would a wide local excision be the most appropriate surgical technique for tumour excision?
Malignant tumours
What is the typical margin of healthy tissue removed during a radical local excision?
3 -5cm margins including all tissue i.e skin, connective tissue, vessels and nerves down to tumour free fascial planes
When would a radical local excision be the most appropriate surgical technique for tumour excision?
Large, infiltrative malignant tumours
Recurrent tumours
What are the three methods of wound reconstruction following tumour excision?
Primary closure
Reconstruction techniques i.e. skin grafts
Healing by second intention
What is primary closure?
Primary closure is the direct apposition of the wound edges through sututing to promote healing by first intention
When performing radiotherapy, what are the three possible aims of the treatment?
Definitive/curative radiotherapy
Semi-definitive radiotherapy
Palliative radiotherapy
What are the advantages of radiotherapy?
Radiotherapy avoids removing large volumes of tissue
Preserves function of surrounding tissues
What are the disadvantages of radiotherapy?
May not kill all cancerous cells
Can cause side effects
Can cause further tumours development or make benign tumours malignant
What machine is typically used for radiotherapy?
Linear accelerator
Describe briefly how a linear accelerator works
A linear accelertor converts electrical energy into a beam of X-rays or electrons. The beam is carefully shaped and directed to target the cencerous cells whist minimising damage to the healthy tissue
Which tissues are more likely to respond well to radiotherapy when it comes to treating tumours?
Tumours arising from radiosensitive tissues are more likely to respond better to radiotherapy
Give three examples of tumours that arise from radiosensitive tissues
Lymphoma
Carcinomas
Mast cell tumours
i.e. epithelial tumours
Give three examples of tumours that arise from radioresistant tissues and are thus challenging to treat with radiotherapy
Sarcomas
Osteosarcomas
Brain/spinal tumours
Despite being radioresistant, when would radiotherapy be appropriate for treating osteosarcomas?
Radiotherapy would be appropriate as palliative treatment for osteosarcomas when amputation isn’t feasible
When do acute side effects of radiotherapy usually arise?
The acute side effects of radiotherapy usually arise during or a few weeks after treatment
Give seven examples of the acute side affects of radiotherapy
Mucositis
Moist epidermal inflammation
Keratitis
Alopecia
Hyperpigmentation
Conjunctivitis
Uveitis
When do chronic side effects of radiotherapy usually arise?
The chronic side effects of radiotherapy usually arise a few months or years after treatment
Give five examples of the chronic side affects of radiotherapy
Necrosis
Fibrosis
Non-healing ulceration
Demyelination
Mutagenesis
What is fractionation?
Fractionation is altering the fraction size and frequency of radiation dose in order to reduce the risk of radiotherapy side effects
What is the main advantage of large radiation fractions delivered infrequently?
The animals don’t have to be under general anaesthetic as often which will be less expensive
What are the disadvantages of large radiation fractions delivered infrequently?
The total dose delivered to the patient will be lower
Leads to more chronic side effects
What are the advantages of very small fractions of radiation delivered very frequently?
The total dose delivered to the patient will be higher
The treatment is more likely to be curative
Avoids harmful chronic side effects
What are the disadvantages of very small fractions of radiation delivered very frequently?
Leads to more acute side effects
The animals will have to be under general anaesthetic more often which will be expensive
What is immunotherapy?
Immunotherapy is systemic treatment that modulates the host immune system to kill tumour cells
When is immunotherapy most effective?
Immunotherapy is most effective for treating patients with minimal (microscopic) tumour burden
What is the main technique used to modulate the innate immune system in immunotherapy?
Non-specific activation of biological response markers (BRMs)
Give an example of an immunotherapy treatment that uses non-specific activation of biological response markers (BRMs)
Muramyl tripeptide (MTP-PE)
How does Muramyl tripeptide (MTP-PE) enhance the innate immune response?
Muramyl dipeptide is a component of mycobacterial cells wall and is a potent activator of monocytes and macrophages. Muramyl tripeptide (MTP-PE) is a lipophillic analogue of muramyl dipeptide which when introduced into the body can stimulate and enhance the innate immune system, particularly monocytes and macrophages to enhance anti-tumour activity through cytokine release
What are the two main techniques used to modulate the adaptive immune system for immunotherapy?
Monoclonal antibodies
Tumour vaccination
How do monoclonal antibodies modulate the adaptive immune system for immunotherapy?
Monoclonal antibodies can specifically target and bind to certain molecules on cancerous cells and trigger immune responses to enhance the adaptive immune system
What are the three different types of tumour vaccination?
Whole tumour cell vaccinations
Viral vector vaccinations
Dendritic cell vaccinations
How do whole tumour cell vaccinations work?
Whole tumour cell vaccinations use whole irradiated tumour cells as a source of antigens which can trigger an immune response against the cancerous cells
How do viral vector vaccinations work?
Viral vector vaccinations use modified viruses to deliver tumour antigens into the body which can trigger an immune response against the cancerous cells
How do dendritic cell vaccinations work?
Dendritic cell vaccinations use dendritic cells that have been harvested from the patient and loaded with tumour antigens to introduce tumour antigens into the body which can trigger an immune response against the cancerous cells
What is chemotherapy?
Chemotherapy is a systemic treatment that uses cytotoxic drugs to kill tumour cells
What is conventional chemotherapy?
Conventional chemotherapy is the use of cytotoxic drugs which have a non-specific effect on all rapidly dividing cells in the body
What is the fraction kill hypothesis of chemotherapy?
The fraction kill hypothesis suggests that a given dose of cytoxic drugs in chemotherapy kills a fixed percentage of cancer cells
What is dose limiting toxicity (DLT)?
Dose limiting toxicity (DLT) refers to the dose of cytotoxic drugs in chemotherapy which cause severe toxicity or unacceptable side effects
What is maximum tolerated dose (MTD)?
Maximum tolerated dose (MTD) refers to the highest dose of cytotoxic drugs that can be administered in chemotherapy without causing severe toxicity or unacceptable side effects
Why are haematopoietic tumours so chemosensitive?
Haematopoietic tumours, which include cancers of the blood and bone marrow, are so chemosensitive due to the high rate of cell division of these tumour cells
Why are sarcomas and carcinomas so chemoresistant?
Sarcomas and carcinomas are chemoresistant due to their low rate of cell division and poor vascularisation which results in these tumours receiving lower concentrations of chemotherapy drugs
How should chemoresistant tumours be treated?
For chemoresistant tumours, cytoreductive surgery can be used to excise as much as the tumour as possible followed by chemotherapy to kill any residual primary tumour cells and to delay the growth of subclinical metastases
In which phase of the cell cycle are cells resistant to chemotherapy?
G0 phase of the cell cycle
Which chemotherapy drug classification specifically targets the M-phase of the cell cycle?
Vinca alkaloids
What is the mechanism of action of vinca alkaloids?
Vinca alkaloids inhibit the mitotic spindle which will prevent chromosomes from being pulled apart during metaphase, resulting in metaphase arrest and cell death
How are vinca alkaloids administered?
Vinca alkaloids are administered via an intravenous (I.V.) bolus
What are two of the specific side affects associated with vinca alkaloids
Neurotoxicity
Neuropathy
List two examples of vinca alkaloid drugs
Vincristine
Vinblastine
What is the trade name for vincristine?
Oncovin
In which chemotherapy protocol is vincristine commonly used?
Vincristine is commonly used in chemotherapy protocols for lymphoma
For which tumour is vincristine used as a single drug chemotherapy protocol?
Transmissible venereal tumour
In which chemotherapy protocol is vinblastine commonly used?
Vinblastine is commonly used in chemotherapy protocols for mast cell tumours
Which chemotherapy drug classification specifically targets the S-phase of the cell cycle?
Antimetabolites
What is the mechanism of action for antimetabolites?
Antimetabolites intefere with DNA and protein synthesis through mimicking essential molecules such as pyrines and pyramidines. The antimetabolites will be incorporated into the genetic material, disrupting DNA and protein synthesis, resulting in cell death
List five examples of antimetabolites
Cytosinearabinoside
Rabacfosadine
Hydroxyurea
5-fluorouracil
Methotrexate
Which four antimetabolite drugs can be involved in the chemotherapy protocol for lymphoma?
Cytosinearabinoside
Rabacfosadine
Hydroxyurea
Methotrexate
What is the specific side effect associated with rabacfosadine?
Pulmonary fibrosis
For which tumour is hydroxyurea used as a single drug chemotherapy protocol?
Hydroxyurea is used as a single drug chemotherpay protocol for chronic granulocytic leukaemia
In which chemotherapy protocol is 5-fluorouracil commonly used?
5-fluorouracil is commonly used in chemotherpay protocols for carcinomas
What is the specific mechanism of action for methotrexate?
Methotrexate competitively inhibits dihydrofolate reductase, preventing the conversion of folate into its active form which is required for thymidine synthesis, which is required for DNA replication
List three classifications of cell cycle phase non-specific chemotherapy drugs
Alkylating agents
Antitumour antibiotics
Miscellaneous chemotherapy drugs
What is the mechanism of action for alkylating agents?
Alkylating agents contain an alkyl group that can bind to DNA resulting in inter- and intrastrand cross-linking which will impair DNA replication resulting in cell death
What are the two mechanisms of administration for alkylating agents?
Oral
Intravenous (I.V.)
List four examples of alkylating agents
Cyclophosphamide
Melphanan
Chlorambucil
Lomustine
Why is it important to check a patient’s liver function before administering cyclophosphamide?
Cyclophosphamide is a prodrug and thus is inactive until metabolised by the liver, so healthy liver function is essential
What is the specific side affect associated with cyclophosphamide?
Haemorrhagic cystitis
How does cyclophosphamide cause haemorrhagic cystitis?
When cyclophosphamide is metabolised by the liver, one of the metabolites produced is acrolein. When acrolein comes into contact with the bladder wall, this can cause inflammation and haemorrhagic cystitis
What are the three clinical signs of haemorrhagic cystitis?
Haematuria
Straining to urinate
Frequent urination
What is the consequence of untreated haemorrhagic cystitis secondary to cyclophosphamide administration?
Chronic fibrosis of the bladder wall
Which two alkylating agents can be used to substitute cyclophosphamide?
Melphanan
Chlorambucil
Why is lomustine used in the chemotherapy protocol for brain tumours?
Lomustine can cross the blood brain barrier (BBB)
What are the three specific side effects associated with lomustine?
Myelosupression
Thrombocytopenia
Hepatotoxicity
What are the three mechanisms of action for antitumour antibiotics?
Directly inhibit DNA replication and protein synthesis
Inhibit topoisomerase enzyme
Produce free radicals
List two examples of antitumour antibiotics
Doxorubicin
Actinomycin D
In which chemotherapy protocols is doxorubicin commonly used?
Doxorubicin is commonly used in chemotherapy protocols for lymphoma, sarcomas and carcinomas
What are the two specific side affects associated with doxorubicin?
Cardiotoxicity
Nephrotoxicity
What are the acute effects of cardiotoxicity due to doxorubicin administration?
Arrhythmias
Variable ECG findings
What are the chronic, cumulative effects of cardiotoxicity due to doxorubicin administration?
Dilated cardiomyopathy
Congestive heart failure
Which drug with fewer cardiotoxic effects can be used as an alternative to doxorubicin?
Epirubicin
In which chemotherapy protocol is actinomycin D commonly used?
Actinomycin D is commonly used in chemotherapy protocols for lymphoma
List two of the miscellaneous chemotherapy drugs
Cisplatin
L-asparaginase
Why is cisplatin very rarely used in veterinary medicine?
Cisplatin causes severe nephrotoxicity and thus patients on cisplatin would require overnight hydration and diuresis
Which drug can be used as an alternative to cisplatin?
Carboplatin
For which tumour is carboplatin used as a single drug chemotherapy protocol in combination with radiotherapy/surgery?
Osteosarcoma
What is the mechanism of action for L-asparaginase?
L-asparaginase depletes the levels of the amino acid asparagine within the body. Cancer cells cannot produce their own asparagine and thus require endogenous asparagine for survival. Depleting asparagine leads to the death of cancer cells
Why are glucocorticoids often incorporated into chemotherapy protocols?
Glucocorticoids are used to reduce inflammation and promote appetite while a patient is on chemotherpay in order to improve quality of life
Give an example of a glucocorticoids often incorporated into chemotherpay protocols
Prednisolone
Why should you not administer glucocorticoids prior to diagnosis if lymphoma is suspected?
If lymphoma is suspected, it is not recommended to adminster glucocorticoids prior to diagnosis as glucocorticoids can actually kill lymphoma cells, potentially making it difficult to accurately diagnose the cancer
What are the three main combined chemotherpay protocols?
COP protocol
CHOP protocol
ALP protocol
(T/F) COP protocol is lower toxicity than CHOP protocol
TRUE.
Which drugs are included in the COP combined chemotherapy protocol?
Cyclophosphamide
Oncovin (Vincristine)
Prednisolone
Which drugs are included in the CHOP combined chemotherapy protocol?
Cyclophosphamide
Hydroxydaurubicin (Doxorubicin)
Oncovin (Vincristine)
Prednisolone
Which drugs are included in the ALP combined chemotherapy protocol?
L-asparaginase
Prednisolone
What are the three generalised side affects of chemotherapy?
Myelosuppression
Alopecia
Gastrointestinal disturbances
What are two of the generalised delayed side effects of chemotherapy?
Infertility
New tumour introduction
Why is it so important to administer intravenous (I.V.) chemotherapy correctly?
Incorrect administration of intravenous (I.V.) chemotherapy drugs can lead to a perivascular reaction causing erythema, moist desquamation and necrosis
How are chemotherapy drugs dosed for large and medium sized dogs?
Chemotherapy drugs are dosed based on body surface area
How are chemotherapy drugs dosed for small dogs and cats?
Chemotherapy drugs are dosed based on weight
What are the five mechanisms of chemotherapy drug resistance?
Decreased drug uptake into cancerous cells
Decreased drug activation within cancerous cells
Drug cleavage within cancerous cells
Alter drug target within the cancerous cells
Increased drug efflux
The expression of which p-glycoprotein allows for chemotherapy drug efflux from cancerous cells?
p-glycoprotein p,170
Why is the expression of p-glycoprotein p,170 of such concern in terms of chemotherapy drug resistance?
The expression of p,170 allows for the efflux of chemotherapy drugs from cancerous cells which can result in multi-drug resistance
Which two classifications of chemotherapy drugs are very prone to resistance?
Vinca alkaloids
Antitumour antibiotics
Which three classifications of chemotherapy drugs are NOT prone to resistance?
Alkylating agents
Carboplatin
L-asparaginase
Which two methods can be used to reduce the risk of chemotherapy drug resistance?
Use the maximum tolerated dose (MTD) to maximise the fractional kill of cancerous cells
Use chemotherapy drugs when the tumour burden is at a minimum
What is targeted chemotherapy?
Targeted chemotherapy is the use of drugs which specifically target critical molecular structures/signalling pathways associated with specific cancer cells
What are the three main mechanisms of targeted chemotherapy?
Growth factor receptor inhibitors
Tyrosine kinase inhibitors (TKI)
Angiogenesis inhibitors
List three examples of tyrosine kinase inhibitors (TKI)
Imatinib
Mastinib
Toceranib
What is metronomic chemotherapy (MC)?
Metronomic chemotherapy (MC) is the daily administration of low doses of cytotoxic drugs