Page 526 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

504 PART IV Specific Malignancies in the Small Animal Patient

small. 182,196 In one study, 16 cats with nonlymphoproliferative cavity are less common. Sinonasal cancers are more frequent in
neoplasms were treated using a definitive course of radiation to men than in women. Some data indicate that various industrial
and environmental exposures may be related to sinonasal cancer,
a total dose of 48 Gy. The therapy was well tolerated, and MST
VetBooks.ir was 12 months with 44% and 16% of cats alive at 1 and 2 years, including exposure to wood, textile, and leather dusts, as well as
formaldehyde. Air pollution and tobacco smoke are also related.
In another report of RT for nonlymphoprolifera-
respectively.
182
tive tumors, this time treated using a coarse fractionation regime, Other factors associated with increased risk for all head and neck
results showed that the protocol was well tolerated, with a MST cancers include smoking and alcohol use, which may have an
of almost 13 months and a 63% 1-year survival rate reported. 196 additive effect. Importantly, human papillomavirus (HPV), a sex-
A report of 65 cats receiving palliative hypofractionated RT also ually transmitted infection, may be involved in the pathogenesis
determined acute and late side effects in addition to outcome. 197 of sinonasal cancer. HPV has been identified in 25% to 49% of
There were 29 high-grade lymphoma cases with the rest (n = 36) oropharyngeal head and neck cancers and is associated with a sig-
being a variety of carcinomas. Patients received RT weekly (6–8 nificant survival difference compared with HPV-negative oropha-
Gy) for a median total dose of 32 Gy. Many patients also received ryngeal cancers. There is striking evidence of improved outcomes
chemotherapy. Acute complications occurred in 58% of the cases in patients with HPV-positive oropharyngeal tumors. HPV status
but were considered acceptable. Late effects, typically ocular, is the strongest independent determinant of local and regional
occurred in 20% of the cases. The MST in all 65 cats was 432 control, disease specific survival, and overall survival in this group
days. There was no significant difference in MST between cats of head and neck cancers. Despite the dramatic influence of HPV
with lymphoma versus those with other tumor types. in oropharyngeal cancer, its role in the etiology and prognosis of
Recent reports of feline nasal and nasal pharyngeal lymphoma sinonasal head and neck tumors is less well defined.
treated with RT and/or chemotherapy indicate the potential for Sinonasal head and neck tumors are locally invasive and cure
long-term survival. 183–186,198 Although treatment protocols vary rates are generally poor. They are typically advanced at the time
between reports, in general, overall response rate for feline nasal of diagnosis because lesions in this area can go undetected for
lymphoma is high, between 70% and 90%. The inclusion of RT extended periods of time and clinical signs can mimic those of
appears to enhance overall survival, with MSTs for combination infectious or inflammatory disease. Nodal involvement and dis-
therapy ranging from 174 to 955 days. 184,185 Interestingly, sys- tant metastasis are infrequent at the time of diagnosis—reportedly
temic failure of disease at nonnasal sites is also reported in 13% between 10% and 15%. Locoregional recurrence accounts from
to 16% of cases, indicating that a combination of RT and chemo- the majority of cancer deaths.
therapy may be warranted in some patients. However, the tim- Surgery and RT are the mainstay of treatment when considered
ing of such treatment remains to be determined (concurrent vs. possible, based on stage and location of disease. Chemotherapy
sequential), as does which patients are at highest risk for local fail- can be useful in an adjuvant setting, but it is not curative when
ure. In an attempt to predict which feline nasal lymphoma cases used alone. Both RT and surgery have advantages and disadvan-
would respond better to RT, a study was done evaluating pretreat- tages as primary therapies. The OST at 5 years is approximately
ment biopsies in 30 cats looking at apoptotic index and Ki-67 60% and 30% for nasal cavity and parasinal tumors, respectively.
scores. 199 Cases with high proliferative scores were significantly More favorable prognoses are associated with smaller lesions in
more likely to have a response to RT and have prolonged survival which complete surgical resection is achievable. When adequate
compared with those with low scores. Furthermore, improved RT margins cannot be obtained, surgery and RT are often combined.
planning along with optimized RT schedules and doses may ulti- Incomplete local control of advanced tumors leads to local tumor
mately improve local control rates and reduce the risk of systemic recurrence in many cases.
failure without the addition of chemotherapy. Published reports The role of chemotherapy in sinonasal head and neck cancer is
of treatment of feline nasal tumors with SRT or more targeted not clear because these cases are usually reported in conjunction
treatment plans are lacking. with other head and neck tumors. Active chemotherapy agents
include the taxanes, 5-fluorouracil (5-FU), methotrexate, and
Comparative Aspects 200–205 the platinum drugs. Several studies have reported improved local
control and, in some cases, improved OSTs in treatment proto-
In humans, cancer of the nasal cavity and paranasal sinuses is clas- cols that combine traditional fractionated RT and chemotherapy;
sified with other cancers of the upper aerodigestive tract under however, the toxicity may also be increased. The optimal case
the all-encompassing title of tumors of the head and neck. Head selection, chemotherapy agents, and radiation schedule has yet to
and neck cancers arise from a variety of sites within the head and be defined.
neck region, which is divided into five basic areas: (1) oral cavity, Multiple targeted and immunotherapies for head and neck can-
(2) pharynx (oropharynx and nasopharynx), (3) larynx, (4) nasal cer have been investigated in clinical trials, most involving EGFR
cavity and paranasal sinuses, and (5) salivary glands. The major- and PD-1 antagonists. Other targeted therapies with potential
ity of tumors affecting these sites are SCC (head and neck SCC benefits include VEGF or VEGFR inhibitors and PI3K/AKT/
[HNSCC]); however, a range of other malignancies can develop mTOR pathway inhibitors. The U.S. Food and Drug Administra-
in the nasal cavity and paranasal sinuses, including adenocarci- tion has granted approval to three monoclonal antibodies for use
noma, neuroblastoma, lymphoma, melanoma, angiosarcoma, and in certain patients with HNSCC. These include EGFR inhibi-
tumors of connective tissues. Benign but potentially invasive pap- tor cetuximab (Erbitux), and anti-PD-1 antagonists pembroli-
illomas are also reported. zumab (Keytruda) and nivolumab (Opdivo). Because of the rarity
Tumors specifically of the nasal cavity and paranasal sinuses of sinonasal head and neck cancers, few molecular studies have
are rare in humans and represent less than 1% of all malignant been done to evaluate novel therapeutic strategies specifically for
tumors and only about 3% of head and neck cancers. The maxil- tumors in this location. In a study evaluating molecular mark-
lary sinus is most commonly affected. Tumors of the ethmoid, ers in sinonasal SCC (SNSCC), including EGFR, HER2, p53,
sphenoid and frontal sinuses, the nasal vestibule and the nasal KIT, Bax, MMP-2, MMP-9 and VEGFR, only EGFR expression