oncology 4 Flashcards
first line diagnostic for lymphoma? what info do we want from pathologist, at a basic level?
FNA
- neoplastic vs not neoplastic?
- malignant vs benign?
lymphoma diagnostic options
- cytology ± flow cytometry
- ± Histology ± Immunohistochemistry (IHC)
- ±Polymerase chain reaction (PCR) of antigen
receptor rearrangements of lymphocytes (PARR)
relevance of clonal proliferation to lymphoma diagnosis with PCR
Cancer (usually) arises from a single cell, one which has developed a growth advantage &
that has lost normal controls on proliferation
- can examine cells with PCR of antigen receptor rearrangements (PARR) of lympohocytes
- single or few bands indicate clonal expansion in malignancies
- multiple bands in normal tissue
how common in lymphoma in dogs? what breeds and age group especially?
- 7‐24% canine neoplasia
- 13-24/100,000
> boxers, basset, Rottweiler, Golden Retriever, Bernese mountain dog, cocker spaniel, st. bernard, Scottish, Airedale, bulldog - middle-aged to older
> 6-9 years
how common is lymphoma / lymphosarcoma in cats? what is the nature of 1/3 of the tumors? whats breeds and ages?
– highest incidence of LSA
- 1/3 of tumors are hematopoietic
- 200/100,000
> siamese
- bimodal age dist.
> 2 years (often FeLV +vs)
> 10-12 years
purpose and use of staging tumours
- Defines the extent of disease
- Aids in planning treatment
- Allows more accurate prognostication
- Assists in evaluation of therapy
- Allows communication between clinicians
- Nomenclature: ‘TNM’ System
staging for LSA - what do the stages mean?
I - single LN
II - regional LN
III - generalized LN
IV - liver +/- spleen
V - bone marrow
()
a - without systemic signs
b - with systemic signs
what does lymphoma staging require
- CBC
- biochem profile
> (paraneoplastic hypercalcemia) - Urinalysis
- FeLV / FIV status
- ± thoracic radiographs
- ± abdominal ultrasound
- ± bone marrow
- ± CSF tap
- ±CT/MRI/bonescan
anatomic types of lymphoma
- multicentric
- mediastinal
- alimentary (GI)
> solitary, multifocal, or diffuse - extranodal
> renal, cutaneous, neural, ocular, etc.
canine anatomic types of lymphoma by how common they are:
- multicentric: 80-85%
- alimentary (GI): ~7%
- skin: 6%
- mediastinal: ~3%
- extranodal: <3%
canine anatomic types of lymphoma by how common they are:
- multicentric: 20-30% (FeLV > 30-80% +ve)
- alimentary (GI): 30-70% (FeLV > 30% +ve)
- mediastinal: 10-20% (FeLV > 90% +ve)
- extranodal:
> nose: 5-10% (FeLV > -ve)
> renal: ~5% (FeLV > 25% +ve)
> CNS: 1-3% (FeLV > ??)
clinical signs of lymphoma vary with what?
form (location) of LSA
canine phenotypic types of lymphoma? which is most common? how do we diagnose?
- B cell: 75-80%
> CD79a - T cell
> CD3 - null (neither B nor T)
- determined by flow cytometry or IHC
in T cell lymphomas, expression of what is correlated with longer survival and PFI?
- MHC II expression
> MHC II negative has short survival
> CD4+/MHCII- = shortest survival and PFI
> CD4-, CD8-, MHCII- = next shortest survival
what histologic grade do most canine lymphomas have?
80% high grade (vs low or intermediate)
what histologic grade do feline lymphomas have?
- low : 8.6%
- intermediate: 35.1%
- high: 55.2%
canine lymphoma prognostic factors
- WHO clinical stage: V < I/II
- WHO clinical sibstage: b < a
- immunophenotype: T < B
- hypercalcemia: negative
- prolonged steroid pretreatment: negative
- anatomic form:
> leukemia, mediastinal, cutaneous, alimentary < multicentric
feline lymphoma prognostic factors
- complete remission (CR): positive
- feline leukemia status: negative
- WHO clinical stage: early
- WHO clinical substage: b < a
- anatomic form:
> mediastinal worse
> nasal best
indications for chemotherapy for lymphoma
- Systemic neoplasia
- metastatic neoplasia
- cytoreduction
- nonresectable neoplasia
contraindications for chemotherapy for lymphoma treatment
– severe multiple organ dysfunction
– substitute for surgery
purpose of combination chemotherapy
- protocols often consist of combinations of
drugs with different effects on tumour cells &
different toxicities on the host - manipulate growth kinetics of cells
- additive therapeutics with subadditive toxicities
- biologic synergistic effect
- delay of resistance
() - more effective than single agent
- action on more than one cell stage simultaneously (greater fractional cell kill)
problems with chemotherapy
– tumour resistance*
– toxicity
– lack of efficacy
- cost
chemotherapy classifications based on mode of action
- alkylating agents
- plant alkaloids
- antimetabolites
- antitumour antibiotics
- hormones
- miscellaneous agents
- enzymes
dosing of chemotherapy drugs is based on?
- most chemotherapeutic drugs are dosed based on body surface area (m^2)
> correlates with metabolic rate (better than body weight)
Cornerstone of medical oncology practice
MAXIMUM TOLERATED DOSE “MTD” CHEMOTHERAPY
MAXIMUM TOLERATED DOSE “MTD” CHEMOTHERAPY
> how important? does it work? issues? how does it work?
- Cornerstone of medical oncology practice
> highly effective for some tumors
> significant resistance in established metastasis - Target is the rapidly dividing cell
> log relationship between dose and cancer cell kill - Mandatory break period
common options for lymphoma chemotherapy protocols
- single agent
> prednisone
> doxorubicin
> lomustine - multidrug
> CHOP (L-CHOP)
> COP (COAP)
what is the COP chemotherapy protocol?
- Cyclophosphamide
- Oncovin (Vincristine)
- Prednisone
prognosis of canines receiving lymphoma chemotherapy? vs untreated?
- 70 - 90% complete remission
- 12 - 16 months median survival
- 20-30% survival at 2 years
() - untreated: 1-2 month median survival
prognosis of felines receiving lymphoma chemotherapy? vs untreated?
- 60% complete remission
- 6-7 month median survival
- 20% survival > 1 year
- small cell GI > 2 years
() - untreated: 1-2 month median survival
Tanovea in a drug for lymphoma treatment that work via what mechanism? contraindications?
‐converted intracellularly to its active metabolite PMEGpp, acts at the level of the cellular DNA polymerases
* contraindicated in dogs with pulmonary
fibrosis, chronic bronchitis & West Highland white terriers
– associated with life‐threatening or fatal pulmonary fibrosis
Vedinexor is a lymphoma medication that works via what mechanism?
- Oral medication given twice/ week
- prevents tumour suppressing proteins from leaving the nucleus of cells, resulting in disruption of cancer cell survival and eventual cancer cell death
is immunotherapy good for trewating lymphoma
- use in humans for non-hodgkinn’s, but not animals at this point
