Chapter 23 - Tumors of the Respiratory System Flashcards
In which spp is cancer of the nasal planum more common?
Most common type of nasal planum cancer overall?
Cats - common
Dogs - uncommon
SCC
Development of SCC of the nasal planum has been associated with what 2 factors?
UV light exposure and lack of protective pigment; mainly cats in the case of nasal planum SCC
Papillomavirus infection; more common in non-UV induced carcinomas
How are SCC categorized according to their degree of invasiveness?
In situ
Superficial (<2mm deep)
Infiltrative
Nasal planum SCC behavior?
Locally invasive
Rarely metastasizes to the LN in advanced dz and even more rare for it to spread to the lungs
What treatment modality is effective for nasal planum SCC in cats, but not in dogs?
RT
Tx of choice for cats and dogs with invasive nasal planum SCC?
Most common complication in cats?
MST?
Nasal planectomy
Stricture of nasal orifice
Cats MST >22 months; 80% dx free at 1-yr
Dogs MST 1.4- 4.2 yrs
What % of dogs with nasal SCC that undergo nasal planectomy with bilateral labial mucocutaneous rotational flap experience complications?
Most common complications (2)?
What % required revision surgery?
Pulmonary metastatic rate?
73% overall complication rate
50% dehiscence
20% narrowing of nasal orifice
35% revision surgery
18% pulmonary mets at ~1 yr post diagnosis
How common is develpoment of additional SCC lesions after local tx?
Common because of UV changes that cannot be reversed; 33% in one study
Prognosis for nasal planum SCC?
Good as long as local control is achieved
ORR, recurrence rate, and ST in cats with in situ nasal planum SCC in situ when treated with Strontium?
ORR 100%
RR 0%
ST > 3000d
ORR, PR, CR, recurrence rate, PFI, and OST in cats with superficial nasal planum SCC when treated with Strontium?
What % developed new lesions at a different location?
ORR 98% (CR 88%, PR 10%)
RR 20% at median time of 308d only in cats with T1+, but no in situ
ST > 3000d; better for those with a CR vs PR
New lesions 33%
ORR, CR, PR in cats with all degrees of invasive nasal planum SCC when treated with strontium?
ORR 100% (CR 87%, PR 13% )
RR 13% - only in the 2 cats that had a PR which also had T2 dz at 81 and 141d
RT and +/- IL chemotherapy can achieve local control in cats with nasal planum SCC in what %?
60%
ECT with bleomycin in cats with superficial SCC results in a complete response in what %? Duration of response?
82%
2m to >3yrs
Most common canine nasosinal tumors?
2/3 carcinomas (TCC 19%, SCC 12%)
1/3 sarcomas (FSA, chondrosarcoma, OSA, undifferentiated)
Overall metastatic rate of nasosinal tumors at the time of diagnosis and death? Which nasal tumor is most likely to spread?
10 to 25% at diagnosis
40-50% at death
LN most commonly
Carcinoma most commonly associated with mets vs sarcoma
What percentage of nasosinal carcinomas over-express COX-2 in dogs (range)?
70-95%
VEGF, EGFR, PDGFRa, and PDGFRB expression in nasal carcinomas in dogs?
Which one has been shown to be phosphorylated and potentially activated?
VEGFR 85-90% - mostly cytoplasmic-membranous
EGFR 50%
PDGFRa 70% - cytoplasmic
PDGFRb 40% - cytoplasmic
EGFR hyperphosphorylated in 63%
Most common clinical signs in dogs with nasosinal tumors?
Others?
What clinical signs could make you be more concerned about neoplasia vs non-neoplasia?
Unilateral epistaxis and/or mucopurulent discharge of 2 to 3 months duration
Other: facial deformity, sneezing, unwillingness to open mouth, dyspnea or stertorous breathing, exophthalmos, ocular discharge (due to mechanical obstruction of nasolacrimal duct)
Facial deformity, stridor -> cancer
Systemic clinical signs -> non-neoplastic (bleeding disorders, hypertension, tick-borne dz, bacterial infection)
What clinical sign in dogs with nasosinal dz is significantly noted to be more common with neoplasia, foreign bodies, and nasal mycosis?
What about with cancer specifically?
Pure or mixed hemorrhagic discharge
Stridor, facial deformity (can happen with fungal and angiomatous proliferation too)
What can be performed in cases of uncontrolled hemorrhage after nasal samples are obtained?
Ipsilateral carotid artery ligation
What staging system for dogs with nasosinal neoplasia have been associated with prognostic significance when RT is used?
Adams
Modified Adams
Describe the modified Adams staging system
Stage I - confined to one nasal passage, paranasal sinus, or frontal sinus, with NO bone involvement beyond turbinates
Stage II - ANY bone involvement beyond turbinates, BUT NO evidence of orbit/subcutaneous/submucosal mass
Stage III - involvement of orbit and/or nasopharyngeal, subcutaneous, or submucosal mass
Stage IV - cribriform plate lysis
How has the modified Adams’ staging system been associated with prognosis in dogs with nasosinal tumors that are treated with RT?
Dogs with stage IV dz based on CT images have shorter DFI and ST when treated with definitive RT
What is the MST and DFI of dogs with stage I vs stage 2 dz when treated with definitive RT?
Stage I - MST 2 yrs, DFS 6.5m
Stage IV - MST 7m, DFS 4m
Which staging system is the least clinically relevant in dogs or cats with nasosinal tumors?
WHO staging system
What paraneoplastic syndromes have been rarely associated with nasal tumors in dogs (2)?
Erythrocytosis
Hypercalcemia
What is the overall MST of dogs with untreated nasal carcinomas?
3m (95d)
What is the MST in dogs with untreated nasal carcinoma that have epistaxis vs in dogs w/o?
Epistaxis - 3m (88d)
Without - 7.5m (224d)
What is the MST in dogs with nasal tumors treated with surgery alone?
What is the problem with this tx modality?
MST 3 to 6 months
Does not significantly improve ST compared to no treatment and is associated with high morbidity
What is the MST of dogs with nasal tumors when tx with definitive RT alone?
1-yr and 2-yr survival rates?
What % of carcinomas experience tumor volume reduction compared to sarcomas?
7 to 20 months
1-yr survival rate 40-70%
2-yr survival rate 10-45%
Carcinomas - 70%
Sarcomas - 20%
What is the MST of dogs with nasal tumors tx with a combination of 1) surgery followed by RT and 2) RT followed by sx?
What is the problem with these combination?
7 to 13m - sx followed by RT; does not improve ST vs RT alone
47m - RT followed by sx; improved ST but increased incidence of late effects including rhinitis, fistula, osteomyelitis (high morbidity)
What RT boost technique were recently published in dogs with nasal tumors when treated with IMRT with the goal of administering a higher dose and decreasing side effects and what was the outcome?
Boost technique: GTV receives a higher dose while maintaining same CTV
Ocular changes were negligible
33% developed VRTOG grade 3 mucositis
Late AE not evaluated
Median PFI and ST not reached
What is the MST in dogs with nasal tumors when treated with palliative RT?
What % of dogs have improvement of clinical signs?
Median duration of response?
MST 5 to 10months
65-100% improvement of CS
Duration of response: 4 to 10m
What are some identified positive (2) and negative (5) prognostic factors in dogs with nasal tumors when tx with palliative RT?
Positive for complete resolution of CS:
- Adams stage I dz
- CS present for >90d
Negative PF:
- CS present for <90 days prior to dx associated with higher risk of relapse
- Adams stage IV dz - MST ~4.8m
- Age of <10yrs
- Non-dolichocephalic breeds
- Dyspnea
What are some acute SE from definitive RT and how long do they take to resolve?
Oral mucositis, KCS, blepharitis, rhinitis, skin desquamation
Within 2-8 weeks after tx
What are some late SE from definitive RT?
When do they usually develop?
Cataracts, corneal keratitis, corneal atrophy, KCS, uveitis, retinal hemorrhage and degeneration, neuronal tissue SE (brain necrosis causing neuro changes or seizures, optic nerve degeneration), skin fibrosis.
Months to years after therapy; irreversible
What arethe most common and clinically relevant late effects in dogs with nasal tumors treated with RT?
Ocular changes - usually occur 6 to 9 months after RT
KCS, cataract formation, blindness
What radiation tx modality has resulted in bilateral ocular sparing in dogs tx for nasal tumors? Any change in ST?
IMRT; same ST but less SE
Is there a difference in survival time between dogs with carcinoma and nasal sarcomas when treated with RT?
Not really, usually the same and many papers don’t demonstrate a survival difference
What is the overall MST and PFS in dogs with nasal tumors when treated with SRT (3 papers)?
MST specifically for carcinoma, sarcoma, and OSA?
Overall MST 8.5- 19.5m
PFS 1yr
Carcinoma - 10.4m
Sarcoma - 10.7m
OSA - 3.1m
What is the overall response or clinical response rate in dogs with nasal tumors when treated with SRT?
95-100%
What % of dogs with nasal tumors treated with SRT develop acute and late side effects?
What % of dogs are euthanized due to late AE?
Acute 23-32%
Late 17-40%; highest with SRS single fraction
7% mortality rate
What is the 1 and 2 yr SR in dogs with nasal tumors treated with SRT?
1 yr - 70%
2 yr 40%
In dogs with nasal tumors treated with SRS, what has been associated with increased acute AE?
GTV > 50cm3
When gemcitabine is used as a radiosensitizer in dogs and cats with nasosinal carcinoma that are treated with RT, what % requires dose reductions?
Cats 50%
Dogs 80%
Neutropenia or local acute tissue damage
Advantage of IMRT for nasal tumors?
- Allows for an dose to tumor while sparing normal tissues
- Reduced RT morbidity
- Decreased dose delivered to eyes and late effects
- Highly conformal compared to others
- Could result in improved tumor control
What % of dogs with nasal tumors that are re-irradiated respond to therapy?
MST after 2nd RT course?
70-88%
MST 6m
Responde duration 80d
What is the ORR and MST in dogs with nasal tumors treated with cisplatin alone?
ORR 30% (1 CR)
MST 5 months
ORR, MST, and resolution of clinical signs in dogs with advanced nasal tumors when treated with doxorubicin, carboplatin, and piroxicam based on CT images?
75% ORR (4 CR, 2PR, 2 SD)
MST 7m
All experienced resolution of clinical signs
When all treatments fail to control epistaxis, unilateral or bilateral carotid artery ligation can result in palliation of CS for ___ months or longer without damage to the brain.
3 months
What prognostic factors have been identified in dogs with nasal tumors (6)?
Negative: >10yrs epistaxis duration of clinical signs (<90d) stage/stage IV dz metastasis histologic type (anaplastic CA, undifferentiated CA, SCC) failure to achieve resolution of CS
What is the overall MST in dogs with nasal sarcomas when treated with RT?
MST for OSA, CSA, FSA?
Does RT protocol impact survival?
Overall 15m (444d) OSA 21m (624d) CSA 15m (463d) FSA 13m (379d) Undifferentiated 11m (344d)
Curative intent RT > palliative (21m vs 10m)
Daily fractionation > M, W, F (21m vs 12m)
Nasosinal tumors in cats are malignant in ___% of cases.General behavior?
> 90%
Locally agressive and low metastatic rate
What are the 1st and 2nd most common nasal tumor in cats?
#1 lymphoma #2 carcinoma
When comparing histopathology and cytology samples from cats with nasosinal masses, what is the % of agreement between them?
Exception to this?
90% agreement
Lymphoma; can be hard to differentiate from lymphoid inflammation
What is the MST of cats with non-lymphomatous nasal tumors when treated with RT?
~12m