Ch 25 Onocology Flashcards
Generally speaking, what alterations results in the formation of cancer?
Activation of tumour-promoting factors via oncogenes
or
Loss of innate tumour inhibitory effects via tumour suppressor genes (e.g. p53 “guardian of the genome”)
What are the phenotypic characterisitics of cancer cells?(6)
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion and metastasis
Limitless replicative potential > Both human and canine neoplastic tissues have been shown to exhibit high levels of telomerase activity
Sustained angiogenesis
Evasion of apoptosis > Lack of apoptosis is considered a hallmark of carcinogenesis and a key characteristic of cancer cells
tumor suppressor gene p53
Oncogenes can be activated by
chromosomal translocation
gene amplification
point mutations
viral insertions
Point mutations can be induced by ionizing radiation and chemical carcinogens or may involve mutations in proto-oncogenes such as K-ras, the epidermal growth factor receptor, and the c-kit growth factor receptor
cell division - what the main phases and checkpoints?
interphase
- starts with doubling of genetic material
- GI, G2, and S phases.
- GI and G2 serve as checkpoints that ensure normal DNA synthesis and cell division
- restriction point = critical checkpoint for continued progression of the cell cycle
- S phase = synthesis/doubling of new DNA
mitosis (M)
- division of the doubled genetic material into two daughter cells
- Regulation via proteins called cyclin-dependent kinases
Initiation, promotion, and progression of a cell toward a malignant phenotype
applied to genetic factors leading to cancer formation, as well as to chemical carcinogenesis.
Which forms of neoplasia have confirmed, true genetic heritability in animals?
Osteosarcoma of Scottish Deerhounds
Renal cystadenocarcinoma in GSD
Nodular dermatofibrosis in GSD
List some biologic carcinogens in animals
FeLV and lymphoproliferative diseases
Feline sarcoma virus and FSA (must also be infected with FeLV)
Papillomavirus in puppies. Papilloma can klead to formation of SCC in rare cases
Spircocerca lupi and viral oesophageal sarcomas in dogs
Transmissible venereal tumour by direct cellular transmission
List some physical carcinogens (5)
Asbestos and mesothelioma in humans
Injection-site sarcoma in cats
Post-trauma ocular sarcomas
Microchip-associated FSA
TPLO metallurgy and canine OSA
List the four possible mechanisms which can transform genes into oncogenes
Oncogenes are mutated versions of normal genes that drive the formation of cancer. The normal counterparts of these genes, called protooncogenes, become transformed by
- Retrovirus-mediated transduction
- Translocation mutation
- Amplification
- Proviral insertion
Translation of oncogenes leads to transcription of key proteins such as….
Growth factors
Growth factor receptors
Cytoplasmic kinases/Ras
Transcription factors
Antiapoptotic proteins
What are Ras oncogenes
Lead to production of membrane-associated proteins that have a key role in cell signalling leading to activation of various cell-proliferative pathways
What are the two forms of tumour suppressor genes
Gate keepers - Inhibit growth while promoting cell death (eg. p53)
Care takers - Ensure DNA repair while maintaining genomic stability
p53 is one of the most common mutations. It is crucial for normal cell cycle and serves as a checkpoint for entry into apoptosis
Three major routes of metastasis are
(1) hematogenous,
(2) lymphatic, and
(3) direct seeding.
In general, how do carcinomas, round cell tumoura and sarcomas metastasise?
Carcinomas and round cell tumours via lymphatics
Sarcomas via haematogenous routes
How do metastatic cells survive in their new environment?
Progressive hypoxia due to proliferation (need to be 100-200mcm from capillary bed for continued growth)
Hypoxia activates hypoxia-induced factor (HIF1alpha), an oxygen-dependant transcription factor
HIF-1a induced transcription of tumour-derived growth factos such as VEGF
Growth factors lead to endothelial recruitment and eventual organisation in capillaries
Tumor staging is a diagnostic process in which the extent of disease progression from the primary site is determined. The diagnostic tests indicated are dictated by tumor type, so staging is often performed after the tumor type has been determined.
What factors need to be considered when choosing a biopsy?
Invasiveness of procedure
Potential for haemorrhage
Seeding of tumour cells
Will it change the treatment plan
incisional biopsy
perform if knowing the specific behavior of a tumor may affect sx treatment or when knowing the identity of the tumor would alter the treatment plan.
excisional biopsy
The main advantage > biopsy and gross tumor removal are performed in a single procedure. disadvantage> if the tumor is highly invasive
imaging
radiography
three-view (ventrodorsal, left lateral, and right lateral projections) thoracic radiographs to evaluate for pulmonary metastatic
Ultrasonography
evaluation of intra-abdominal neoplasia, particularly hepatic, adrenal, and urogenital tumors, and sublumbar node metastasis.
Guide needles and needle-core biopsy for tissue sampling
CT
evaluation of primary tumors of the axial skeleton, particularly skull, vertebral, and pelvic tumors, and for evaluation of primary and metastatic intrathoracic tumors
3D reconstructions can be manipulated at a computer workstation to help the surgeon
CT-guided biopsy
MRI
preferred for tumors of the central and peripheral nervous system and perhaps intra-abdominal organs.
determining the proximity of tumors to important neurovascular structures ((STIR) MRI)
How can nuclear scintigraphy be applied to dogs with OSA? What substance is used for this?
Technetium-99m hydromethylene diphosphate used for a whole body scan to detect aymphtomatic synchronous or asymptomatic lesions
In one study, 7.8% of 399 dogs with appendicular OSA were diagnosed with a second asymptomatic lesion. Not good candidates for amputation
List some uses of nuclear scintigraphy
Technetium-99m hydromethyl diphosphate for OSA to detect multiple lesions or to define margins for limb-sparing
Technetium-99m diethylenetriaminepentaacetic acid for GFR prior to nephrectomy
Technetium-99m for thyroid tumours to identify metastatic or ectopic disease
Indium-111 pentetreotide (somatostatin receptor scan) to identify primary and metastatic lesions in dogs with functional insulinomas
What is a PET-CT?
What are its limitations?
A radiopharmaceutical (F-fluorodeoxyglucose FDG) is used with is transported into and trapped inside tumour cells because it is not utlised in the glycolic pathway. Signal is higher in tumour cells as they have a higher uptake of glucose
Limitations
- Not all tumours will have increased uptake
- Non-specific (inflammation reacts similarly)
- Not readily available
What size metastatic lesions can be seen on thoracic radiographs and CT?
6mm on radiographs
1mm on CT
What are the major potential side effects of doxorubicine and cisplatin?
Doxorubicine can cause cardiotoxicity
Cisplatin can cause nephrotoxicity
What are the 4 categories of tumour excision?
surgical dose
Debulking
Marginal
Wide
Radical
Perioperative Management
Comorbid Conditions
Chemotherapy, radiation therapy, and/or surgery can be altered, incorporated, or eliminated on the basis of comorbid conditions
Pain and Analgesia
Tumor-associated pain
Wide and Radical Resections
provides the best chance for cure
considered curative-intent surgeries because the intention is to resect both macroscopic and microscopic disease, including biopsy tracts, and thus prevent local tumor recurrence and improve overall survival times
evidence suggests that tumor size also influences the extent of microscopic tumor extension, with larger tumors of the same histologic type having greater microscopic extension and hence requiring larger margins than smaller tumors. 28 Margins are three-dimensional; hence, lateral and deep margins must be considered when planning surgical resections of tumors
Deep margins are determined by natural tissue barriers because deep margins (1 to 3 cm) may not be possible
> muscle fascia
> cartilage
> bone
are resistant to neoplastic invasion and provide a good natural tissue barrier
Radical resection, which is defined as the removal of an entire tissue compartment
The deep margin is the most common site of failure.
What are the general rules for lateral margins of soft tissue sarcomas, MCT and carcinomas
Sarcomas and MCT - 2-3cm lateral margins
Carcinomas - 1cm usually sufficient
A study by Simpson et al revealed what regarding lateral margins for MCT excision?
All grade 1 MCT were completely excised with 1cm margins
Only 75% of grade 2 MCT were completely excised with 1cm margins, increasing to 100% with 2cm margins
2cm margins recommended for grade 1 and 2, not enough data to make recommendations for grade 3 so should aim for 3cm if possible
Marginal resection
is performed by dissecting just peripheral to the tumor pseudocapsule in the reactive zone
malignant neoplasms, this approach usually fails due to failure to remove microscopic satellite tumor cells
Planned marginal resection, when combined with postoperative radiation therapy
What are the 4 options when incomplete excision is achieved?
- No treatment
- Staged resection of the scar
Staging resection therefore can be used to determine whether animals need to be subjected to additional expensive, time-consuming > xcision of the surgical wound with ≤10-mm margins - Wide scar revision
- Combination with radiation or chemo
78% of STS reported as incompletely excised do not have any evidence of residual tumour following further resection
Is LN size based on palpation a predictor of mets? Give an example from the literature
No
A study of 100 dogs with oral malignant melanoma, 40% of dogs with normal-sized LN had metastasis and 49% of dogs with enlarged LN did not have metastasis
sentinel lymph node
- based on the theory that the metastatic process occurs in an orderly progression within the lymphatic system, with tumor cells draining into a specific lymph node (i.e., the sentinel lymph node) in a regional lymphatic field before draining into other regional lymph nodes.
- The sentinel lymph node has an important role as a filter and barrier for disseminating tumor cells.
- distant metastasis should not be present if the sentinel lymph node does not have evidence of a tumor burden
List some methods of identifying the sentinel lymph node (4)
lymphoscintigraphy
peritumoral injection of blue dye,
intraoperative cytology/histopathology
Idocyanine green fluroscence
Lymph Node Dissection
advantage is that of cytoreduction
Halsteads
theory of “contiguous” development of metastases, surgeon would remove the primary tumor and the draining regional lymph node if it is known to contain tumor cells with the expectation it preventing spread to the next lymph node in the chain or systemically
Cady-Fisher view
cancer is a systemic disease, and that lymphadenectomy, does not affect survival.
cancer cells are assumed not to spread in an orderly manner, and regional lymph nodes are viewed ineffective barriers > biologic indicators of cancer spread that merely guide therapy and prognosis
What are some considerations regarding surgical technique for oncologic surgeries? (7)
Early haemostasis to prevent release of tumour emboli
Careful handling to prevent exfoliation
Structures adhered to the tumour should be resected en bloc if possible (57% rate of invasion in humans)
Not Multifilament > associated with an increased risk of recurrence
Ideally avoiding drains as can extend margins if resection if incomplete
Reconstructive surgery is ideally done as a second procedure once histology results have confirmed clean margins
Gloves and instruments changes prior to closure or between mass removals
What IHC markers are used for carcinomas and sarcomas?
increasingly malignant, cells become increasingly similar histologically
Cytokeratin (found in epithelial calls) stain for carcinomas
Vimentin (found in mesenchymal cells) stain for sarcomas (and melanoma)
immunohistochemistry can help determine the cell of origin
poorly differentiated tumors commonly lose expression of these markers
margins
surgical intent (i.e., whether the excision is to be curative-intent [radical, wide, and occasionally marginal] or palliative-intent [marginal and intralesional]).
local behavior of the tumor determine the dose of surgery required to achieve local control
surgical margin can be split into
- metric approach (distance from primary tumor in three dimensions)
- barrier approach (use of resistant anatomic boundaries; e.g., fascia, periosteum, air)
clean but close —in one study in soft tissue sarcoma, this was described as tumor cells found within 1 to 3 mm of the margin.
Descriptions such as “tumor is close to the margins” or “tumor cells do not appear to extend to the margins of the excision” > Whether or not this is classified as a clean margin depends on the tumor grade (low vs. high) and also on the surgeon’s interpretation
pathology samples is tissue shrinkage
oral surgery in healthy dogs
- mean shrinkage of tissue from initial resection to final microscopic assessment ranged from 30.7% to 47.3%
- reatest proportion of shrinkage occurred immediately upon resection, with further shrinkage noted once fixed in formalin.
- obtain 5 mm of pathologically clear margin, an in situ margin of resection of at least 8 to 10 mm needs to be taken
- normal dog skin, fixed in formalin and then processed, have been shown to decrease in length and width by as much as 32% and to increase in thickness by 75.8%
What to Do With Incomplete Margins
ability to predict behavior of tumor of one individual is less clear
i.e. phenomenon of local recurrence after wide tumor negative margins have been achieved or following wide resection of scars containing too few tumor cells to even be detected histologically.
Positive microscopic margins following soft tissue sarcoma > 10x increased risk of local recurrence
wait and see > A low recurrence rate of mast cell tumors has been described after incomplete excision of grade 2 mast cell tumors, and the recurrence rate following intentional marginal excision of low-grade sarcomas on the extremities was only 11% in one study
MCT recurrence rate
- recurrence rate following complete surgical excision of grade 2 mast cell tumors is 11%
- only 18% to 35% of incompletely excised grade 2 mast cell tumors recur.
What proliferation markers can be used to help predict recurrence of incompletely excised grade 2 MCT?
Ki67 (low vs high have signifcantly prognosis)
Proliferating cell nuclear antigen (PCNA) combined with Ki67 is prognostic for recurrence
What are the advantages of neoadjuvant radiation therapy vs adjuvant radiation therapy
Neoadjuvant
- (prior to surgery) is theoretically more effective due to unimpaired vascular supply (better oxygenated, less hypoxic and therefore more radiosensitive)
- Irradiated skin is more likely to develop incisional complications
Adjuvant radiation
- can also increase incisional complications, especially if started before 7 days post-op
- Radiation is much more effective against microscopic disease and there is no delay in surgery with adjuvant radiation
For dogs with soft tissue sarcoma, adjuvant (postoperative) radiation therapy is much more effective against microscopic disease, with 1-year disease-free control rates >95% for residual microscopic disease and only 50% for dogs with macroscopic tumor burden
Cell Kill
VAT, PAD, BIT
chemotherapeutics kill rapidly dividing cells in a nonselective manner.
Rapidly dividing cells include neoplastic cells + epithelium of the gastrointestinal tract and bone marrow, hair
Cell cycle–specific drugs refer to those that are in the synthesis (S) or M phase of the cell cycle
Non–cell cycle–specific drugs are capable of cytotoxicity in any phase of the cell cycle
timing of chemo
chemotherapy is administered in the adjunctive setting, usually starting at 10 to 14 days postoperatively to allow for adequate healing and recovery.
risk of wound complications is low because this allows wound fibroplasia and neovascularization to begin while still maintaining a favorable environment for the antineoplastic effects of the chemotherapy agents, such as low tumor burden and few drug-resistant cells.
Define “maximally tolerated dose” chemotherapy
Chemotherapy where toxicity, dosage and interval of treatment are base on phase I clinical trials . This data is not often available for vet patients and is extrapolated from human date. Drug doses delivered in vet med are typically half that in humans
Define metronomic chemotherapy
Frequent, even daily, administration of chemotherapeutics at doses significantly below maximally tolerated dose, with no prolonged drug-free breaks
Aims to control or minimise angiogenesis and invasion rather than cytotoxicity
Alkylating agents
- Non cell cycle specific
- inserting bulky alkyl groups onto DNA/RNA strands, leading to interference in DNA replication and RNA translation.
- Loumustine (Histiocytic sarcoma, MCT). Severe hepatotoxicity 6%
- Cyclophosphamide (lymphoma). Furosemide can reduce occurence of sterile haemorrhagic cystitis
Doxorubicin
- non cell cycle specific
- multiple mechanisms of action: topoisomerase inhibition, DNA intercalation, and formation of iron-mediated free radicals that lead to DNA damage.
- Lymphoma, HSA, high grade STS, high grade carcinoma, OSA
- Can cause DCM like damage in dogs, renal insufficiency in cats
- Significant myelosuppression and GI toxicity
Platinum agents
- Non cell cycle specific
- caused covalent binding of DNA, restricting replication and protein systhesis
- Carboplatin and cisplatin - OSA, rescue for other sarcoma and carcinomas
- Cisplatin fatal to cats! Fatal pulmonary oedema
Nephrotoxicity
Microtubule inhibitors (Vinca Alkaloids and Taxanes)
- Cell cycle specific
- affect spindle apparatus during mitosis
- Vincristine (lymphoma)
- Vinblastine (MCT)
Minimally myelosuppresive and well tolerative. Can cause paralytic ileus and extravasation phlebitis
Bisphosphonates
Inhibits osteoclast activity - palliative Tx for osteolytic disease from OSA, multiple myeloma and metastatic bone disease
IV is preferred (low oral bioavailability, cause reflux)
Pamidronate most common - approx 30% successful palliation
Zoledronate - shorter infusion time, improved inhibition or resorption (100x potency), potential for less frequent treatment
tyrosine kinase inhibitor
- inhibits tyrosine kinases.
- important mediators of gene transcription and are key to cell proliferation, as well as tumor growth and survival
- targeting the ATP binding sites of membrane and cytoplasmic tyrosine kinases that are crucial for phosphorylation
toceranib
- targets the tyrosine kinase, c-kit, which is often mutated in dogs with high-grade mast cell tumor
- Indicated for high grade or metastatic disease and work best on microscopic disease
What are the reported morbidity and mortality rates of chemotherapy patients as a whole?
15% require nonhospitalised medical attention
5% hospitalised
1% mortality rate
What is the most available form of immunotherapy?
Melanoma vaccine
DNA vaccine utilising human tyrosinase DNA which shows an unregulation of antibodies in dogs against human tyrosinase. Clinical studies show mixed efficacy…
When is the bone marrow nadir with chemotherapeutics?
At what level is chemo delayed?
Typically approx 7 days with the exception of carboplatin which is approx 10-14 days
Chemo is delayed by 5-7 days if neutrophils are less than 1500-2000/mcL and platelets less than 50,000/mcL
If neuts under 1000, prophylactic ABx initiated and future doses reduced by 20%
What is the most common mechanism of acquired chemotherapeutic resistance?
Mutation in the canine MDR-1 gene (Collies, Shelties, Australian Cattle Dogs may already have this mutation)
Neoadjuvant chemotherapy and radiation therapy in veterinary cancer treatment: a review
B. Wustefeld-Janssens 2021
Neoadjuvant chemotherapy and radiation therapy review
the results of neoadjuvant therapy equivocal
Used to improve the probability of a negative resection or reduce morbidity of
surgery in borderline resectable disease
MCT > prednisone neoadjuvant shown to be beneficial.
NRT extremity sarcoma > surgical site complication rate was doubled
complications 19x higher in dogs that had a flap as part of a salvage procedure for previously irradiated tumour
The studies concerning evaluation of COX-2 expression in animals revealed its overexpression in various types of canine and feline tumours found in the skin, mammary gland, urinary bladder, intestines, and bones
Sentinel lymph node detection differs when comparing
lymphoscintigraphy to lymphography using water soluble
iodinated contrast medium and digital radiography in dogs
Hlusko 2020
prospective, method comparison study was to compare
an SLN mapping protocol of lymphoscintigraphy to lymphography
An SLN
was identified in all dogs with lymphoscintigraphy and seven of eight dogs with lymphography.
Agreement between results of the lymphoscintigraphy and lymphography
studies was a completematch in three dogs, a partial match in four dogs, and nomatch
in one dog. The SLN detected differed based on the imaging modality used.
Diffusion weighted magnetic resonance imaging is a feasible
method for characterizing regional lymph nodes in canine
patients with head and neck disease
Stahle 2019
The objective of this prospective,
exploratory study was to evaluate diffusion-weighted MRI and ADC as potential methods for
detecting metastatic lymph nodes, eight client-owned canine
hypothesis that mean ADC values would
differ between benign and metastatic lymph nodes was not supported.
Lymph node size alone is suggested to be
insufficient for accurate clinical staging of diseases such as canine
oral melanoma, because normal sized lymph nodes may contain
microscopic metastatic disease and lymph node enlargement can
occur in absence of metastasis. Cytologic or histologic examination of
the regional lymph nodes is therefore recommended
Williams Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987– 2001). J AmVet Med Assoc. 2003;222:1234–1236.
Lymphadenectomy improves outcome in dogs with resected Kiupel high-grade cutaneous mast cell tumours and overtly metastatic regional lymph nodes
C. Chalfon 2022
no sentinal ln mapping??
retrospec, Forty-nine dogs were included, 18 not vs 31 lymphadenectomy
Dogs with a cytological diagnosis of regional lymph node metastasis that did not undergo lymphadenectomy were compared
Median time to progression was significantly shorter, MST lymphadenectomy 371 days vs 250 not
adjuvant medical treatment protocols were not standardised
Lymphadenectomy improves outcome in dogs with resected Kiupel high-grade cutaneous mast cell tumours and overtly metastatic regional lymph nodes
(supports Halstead theory of cancer mets)
Near-infrared fluorescent image-guided
lymph node dissection compared with
locoregional lymphadenectomies in
dogs with mast cell tumours
beer 2022
retrospectively, 35 near-infrared fluorescent image-guided lymph node dissection for MCT
identified at least one metastatic node in 68% of dogs (24 of 35) compared with 33% (14 of 43) when lymph node dissection was used without imaging
fluorescent nodes not corresponding to locoregional nodes in 15 of 35 dogs (40%)
deep nodes will be missed, though likely low percentage (medial iliac 1.7%) > ideally perform lymphoscintigraphy or CT lymphanigraphy.
More than two-thirds (69%) of patients treated by NIR-LND
had one or more metastatic lymph nodes. This rate of affected
patients was slightly higher than reported in other studies that
performed SLN mapping using lymphoscintigraphy and methylene
blue dye (12 of 19, 63%; Worley 2014) contrast-enhanced
ultrasound (21 of 35, 60%; Fournier et al. 2021) or indirect
CT lymphangiography (9 of 16, 56%; Lapsley et al. 2021).
Influence of locoregional lymph node aspiration cytology vs
sentinel lymph node mapping and biopsy on disease stage
assignment in dogs with integumentary mast cell tumors
lapsley 2021
lymph node aspiration cytology vs SLN mapping and biopsy (MCT) 17 dogs
Sentinel lymph node differed anatomically from LRLN in 25%. Metastases: histology 45% SLN vs 5% FNA of LRLN
Sentinel lymph nodes differed from LRLN in 25% tumors. Histopathological examination of SLN altered recommendations in 50% of dogs
Should have excised both the LRLN and the sentinel LN rather than comparing cytology to histology
SLN excision confer a survival advantage over LRLN excision or cytology uknown.
Previous studies in which scintigraphy was employed to identify the SLN have provided evidence that the SLN may differ from the LRLN in 40% of tumors.
The combination of low sampling success together with a previously reported 75% sensitivity of FNA cytology for identifying positive nodes in MCT disease brings in to question the advisability of using this technique in guiding treatment decisions
Biopsy of sentinel lymph nodes after injection of methylene
blue and lymphoscintigraphic guidance in 30 dogs with
mast cell tumors
Roberta Ferrari 2020
Clinical prospective cohort study
Sentinel lymph node mapping was applied to 34 MCT in 30 dogs without any complication. Sentinel lymph nodes were not identified in three of 34 tumors, all with previous scar tissue. Sentinel lymph nodes did not correspond
to expected RLN in 19 of 30 (63%) tumors. Histological examination confirmed an early or overt metastasis in 32 of 57 (56%) SLN extirpated.
Reductions in margin length after excision of grade II mast cell
tumors and grade I and II soft tissue sarcomas in dogs
Milan Milovancev 2018
resected canine mast cell tumors (MCT) and soft tissue sarcomas (STS) between the
time of collection and histopathology.
Study design: Prospective, hypothesis-driven, clinical study.
Sample population: Two hundred and thirty-seven margins from 69 excised tumors
(50 MCT and 19 STS) in 51 client-owned dogs.
was reduced by a median of 3.0,
5.0, 6.0, and 8.8 mm for MCT; 2.5, 2.0, 5.0, and 5.0 mm for STS. All processing steps
resulted in significant reductions
Surgical margin length reductions occur due to a combination of physical
factors (eg, tissue elasticity, myofibril contraction, and histologic processing) and
biological factors (eg, microscopic tumor infiltration into the grossly normal surgical
margin)
Seguin 2024 – review, general updates in surgical oncology
3D-printed endoprosthesis and cutting guides for limb-sparing surgery
- MCT: proportional margins excision (Pratschke 2013, Chu 2020, Saunders 2020, Itoh 2021)
high-grade MCT more likely → local recurrence ie. important px factor
- grade shifting = local recurrence of a different (usually higher) grade tumour vs resected
- Griffin 2023 - 1/5 MCT – low to high-grade at recurrence
7/15 STS – 4 higher, 3 lower at recurrence
Cunningham 2020 – extenion of subcutaneous wound bed after closure of tumour excision model
vet surg
marking of lateral excision margins recommended (clips, liquid fiducial markets)
The lateral extent of the subcutaneous wound bed extended past previously recommended revision margins of 2 to 3 cm in some defects measuring greater than 4 cm in diameter.
Clinical significance: Surgeons and radiation oncologists should consider the potential extent of the subcutaneous defect when planning revision therapy, especially after large resections.
