Veterinary Surgical Oncology. Группа авторов

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et al. 2015), with clinical staging being important regardless of histologic grade (Stefanello et al. 2015). Dogs with stage 2 (loco‐regional lymph node metastasis) grade II MCT, the use of prednisone, vinblastine, and lomustine after adequate local‐regional therapy can provide a median survival in excess of 40 months (Lejeune et al. 2015). In another paper, for dogs with grade 2, stage II MCTs, there was no significant difference in survival times between dogs with and without LN metastasis; however, removal of the metastatic LN may prolong survival (Baginski et al. 2014). Vinblastine‐prednisolone chemotherapy is given as adjuvant to surgery for high‐risk MCT (mucous membrane origin, node‐positive, high‐grade) (Thamm et al. 2006). Vinblastine‐prednisolone chemotherapy increased survival significantly compared to the tyrosine kinase inhibitor masitinib as adjuvant to high‐risk MCTs in another study (Miller et al. 2014). Another approach is marginal surgery with adjuvant chemotherapy (vinblastine and prednisolone) (Davies et al. 2004). In a study of dogs with a median number of 4 MCTs at presentation, 90% of dogs were treated with surgery, and 40% of dogs were treated with only surgery as the sole form of treatment, and 60% of dogs received chemotherapy. There was no significant difference in progression‐free survival or MST in those dogs that received chemotherapy compared to those dogs that did not. Incomplete surgical margins were not associated with decreased survival times (O'Connell and Thomson 2013). Chemotherapy may also be used for dogs with multiple cutaneous mast cell tumors or unresectable/metastatic disease. Multiple cutaneous MCTs may represent multiple de novo events rather than metastatic disease, with a disease‐free survival time of >5 years in 54 dogs reported (Mullins et al. 2006), and no difference in outcome compared to stage 1 dogs in another study (Murphy et al. 2006). However in another study, if any one of multiple cutaneous MCTs was identified as high grade, then there was a worse prognosis (O'Connell and Thomson 2013), and Kiupel et al.(2005) found that dogs presenting with multiple synchronous MCTs had a significant decrease in survival time (Kiupel et al. 2005). In another paper, 23 dogs with MCTs treated with incomplete resection and adjuvant prednisolone and vinblastine chemotherapy, there was a 57% 1‐ and 2‐year disease‐free rate, and some of these dogs had multiple MCTs (Thamm et al. 1999). Other chemotherapy agents include lomustine, vincristine, prednisolone/cyclophosphamide/vinblastine, cyclophosphamide/vincristine/prednisolone/hydroxyurea, lomustine/vinblastine, chlorambucil/prednisolone (McCaw et al. 1997; Elmslie 1997; Gerritsen et al. 1998; Rassnick et al. 1999; Thamm et al. 1999; Davies et al. 2004; Taylor et al. 2009; Cooper et al. 2009), vinorelbine (Grant et al. 2008; Wouda et al. 2015), and inhibitors of tyrosine kinase toceranib phosphate which possess both direct anti‐tumor and anti‐angiogenic activity (Liao et al. 2002; London et al. 2003). Dogs with grade II or III MCTs treated with the tyrosine kinase inhibitor masitinib had a longer time to disease progression (178 days) vs dogs receiving placebo (75 days), although MST was only improved in dogs with KIT mutations (417 days vs 182 days with placebo) (Hahn et al. 2008). In a subsequent study, the MSTs of dogs treated with masitinib or placebo were not significantly different (Hahn et al. 2010). The tyrosine kinase inhibitor Toceranib phosphate (Palladia®) was used to treat bulky (non‐resectable) grade II or III MCTs with an overall 43% partial or complete response rate, and 12% stable disease, with 82% of dogs with KIT mutations responding compared to 54% for those without (London et al. 2009). Vinblastine – toceranib phosphate combination showed a 71% objective response rate in one study (Robat et al. 2012). Water‐soluble micellar paclitaxel was safer with 30% biologic response rate compared to lomustine (11% biologic response rate) in the treatment of non‐resectable grade II or III MCTs (Vail et al. 2012). In another study of non‐resectable MCT, treated with toceranib phosphate‐lomustine‐prednisone resulted in a response rate of 46% and a median progression‐free survival of 53 days (Burton et al. 2015). Non‐resectable MCT can also be treated with radiation therapy combined with chemotherapy (toceranib‐prednisolone), MST was not reached at a median follow‐up of 374 days (Carlsten et al. 2012). Other adjunctive medical therapies include H1 blocker, H2 blocker, omeprazole, sucralfate, and misoprostol. Pretreatment with prednisone prior to surgery (neoadjuvant) can reduce the size of mast cell tumors, facilitating resection with adequate margins in situations where margins cannot be confidently attained because of mass location or size or both (Stanclift and Gilson 2008). ECT with cisplatin administered intratumorally was used to treat 12 cutaneous MCT nodules in dogs. Electrical pulses were delivered to the tumor and surrounding margin. If the tumor did not respond completely to the first session, additional sessions were performed at 2‐ to 4‐week intervals. The median tumor size was 2.9 cm³, there was a 62.5% complete response with a median follow‐up time of 26 months. Tumors >8 cm³ did not respond. Tumor grade prior to treatment was unknown (Kodre et al. 2009). ECT with bleomycin injected into peritumoral tissue has also been reported as adjuvant treatment for incompletely resected MCT in dogs. The overall response rate was 85% with a mean time to recurrence of 53 ± 6.5 months (Spugnini et al. 2006b) Electrogene therapy with IL‐12 was used in 11 canine cutaneous MCTs, resulting in a 13–83% reduction (median 50%) of the original tumor volume (Pavlin et al. 2011). ECT with cisplatin and peritumoral IL‐12 gene electrotransfer was used to treat 18 dogs with canine MCT. Eleven of 18 dogs had pre‐treatment punch biopsies, and all were grade I or II and the median volume of treated tumors was 2.1 cm³. At a median of 40 months, a complete response was achieved in 72% (Cemezar et al. 2017). Plasma Cell Tumor Multiple myeloma treatment modalities include chemotherapy using melphalan and prednisolone standard, as well as cyclophosphamide, CCNU, chlorambucil, doxorubicin, vincristine (Osborne et al. 1968; MacEwen and Hurvitz 1977; Drazner 1982; Matus et al. 1986; Brunnert et al. 1992; Fan et al. 2002; Hanna 2005; Gentilini et al. 2005; Vail 2007); surgery (stabilization of pathological fractures) (Banks et al. 2003a; Vail 2007) with or without adjuvant radiation therapy, bisphosphonates (Vail 2007); tyrosine kinase–inhibitor therapy (toceranib phosphate) (London et al. 2003), addressing chronic infectious disease/uncontrolled long‐term stimulation of the immune system could be important (Geigy et al. 2013). Extramedullary treatment modalities (cutaneous) include conservative surgical resection (can add chemotherapy if local recurrence or incomplete margins) (Kryiazidou et al. 1989; Rusbridge et al. 1999). Radiation alone for stable solitary osseous plasmacytoma (MacEwen et al. 1984; Meis et al. 1987; Rusbridge et al. 1999). Surgery plus radiation for solitary osseous plasmacytoma resulting in an unstable long‐bone fracture or surgery with or without radiation for solitary osseous vertebral plasmacytoma resulting in neurological compromise (Vail 2007). Lymphoma Various chemotherapy protocols (MacEwen et al. 1981, 1987; Cotter and Goldstein 1983; Carter et al. 1987; Keller et al. 1993; Postorino et al. 1989; Greenlee et al. 1990; Stone et al. 1991; Page et al. 1992; Myers et al. 1997; Valerius et al. 1997a; Khanna et al. 1998; Zemann et al. 1998; Boyce and Kitchell 2000; Chun et al. 2000; Moore et al. 2001; Garrett et al. 2002; Mutsaers et al. 2002; Rassnick et al. 2002, 2007, 2014; Morrison‐Collister et al. 2003; Saba et al. 2007, 2009; Griessmayr et al. 2007, 2009; Sauerbrey et al. 2007; Dervisis et al. 2007; Flory et al. 2008; Bannink et al. 2008; Brodsky et al. 2009; Chun 2009; Northrup et al. 2009; Zenker et al. 2010; Dervisis and Kitchell 2010; Sorenmo et al. 2010; Daters et al. 2010; Beaver et al. 2010; Lori et al. 2010; Fahey et al. 2011; Rebhun et al. 2011; Flory et al. 2011; Tater et al. 2012; Silver et al. 2012; Higginbotham et al. 2013; Gavazza et al. 2013; Burton et al. 2013; Zandvliet et al. 2013; Meier et al. 2013; Elliott et al. 2013; Barnard et al. 2014; Gillem et al. 2015; Collette et al. 2015; Curran and Thamm 2015; Holtermann et al. 2015; Back et al. 2015; Lucas et al. 2015; Wouda et al. 2015); immunotherapy (investigational) (Crow et al. 1977; MacEwen et al. 1985; Jeglum et al. 1988; Rosales et al. 1988; Steplewski et al. 1990; Jeglum 1996; Sorenmo et al. 2011; O'Connor et al. 2012; Marconato et al. 2014, 2015a, 2015b; O'Connor and Wilson‐Robles 2014); radiation therapy for whole body (localize stage I or stage II disease for nasal or CNS or oral lymphoma, palliation of local disease) (Vail and Young 2007; Lurie et al. 2009; Williams et al. 2010; Berlato et al. 2012); bone marrow transplantation and staged half‐body radiation after remission with induction of chemotherapy – both investigational ( Gustafson et al. 2004 ; Williams et al. 2004 ) — or surgery for solitary lymphoma (early stage I) or solitary extranodal, or splenectomy for massive splenomegaly due to lymphoma (Moldovanu et al. 1966; Brooks et al. 1987) or surgery for obstructive or ruptured gastrointestinal lymphoma (Marks 2001).

      

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