alone (palliative) (Thrall 1981; Brewer and Turrel 1982; Theon et al. 1997). Systemic chemotherapy has no known benefit (Gardner et al. 2015a). For histologically low‐grade, biologically high‐grade oral fibrosarcoma, prognosis depends upon early diagnosis and aggressive treatment. Prolonged survival can be achieved in some dogs with surgery, radiotherapy alone, surgery and radiotherapy, and radiotherapy and local hyperthermia (Ciekot et al. 1994).
Oral Melanoma
For local disease, surgery with wide clean margins (Harvey et al. 1981; Bradley et al. 1984; MacEwen et al. 1986; Kosovsky et al. 1991; Schwarz et al. 1991a, 1991b; Wallace et al. 1992; Hahn et al. 1994; Ramos‐Vara et al. 2000; Overly et al. 2001; Kudnig et al. 2003; Esplin 2008; Tuohy et al. 2014; Boston et al. 2014); repeat surgery with wide margins or adjuvant radiation therapy if margins incomplete; radiation therapy alone (Turrel 1987b.; Bateman et al. 1994; Blackwood and Dobson 1996; Theon et al. 1997; Freeman et al. 2003; Proulx et al. 2003; Farrelly et al. 2004; Murphy et al. 2005). ECT using bleomycin was reported in 10 dogs with oral melanoma. The dogs received four weekly sessions. The tumor and a 1 cm margin of grossly normal tissue were injected with bleomycin followed by pulsed electrical bursts of 800 V/cm administered under local or general anesthesia. The overall response rate was 80% with complete remission in 70% and a MST of 6 months (Spugnini et al. 2006a). In a recent study of 67 dogs with oral melanoma treated with ECT, an objective response was seen in 100% (stage 1), 90% (stage 2), 58% (stage 3), and 36% (stage 4) of tumors. The MST was 16.5 months (stage 1), 9 months (stage 2), 7.5 months (stage 3) and 4.5 months (stage 4) dogs (Tellado et al. 2020). A total of 111 dogs with oral melanoma treated with radiation therapy combined with debulking surgery (18 dogs) or chemotherapy (39 dogs), or both (29 dogs). MSTs of stage I, II, III, and IV melanoma were 758 days, 278 days, 163 days, and 80 days, respectively. Dogs with stage III melanoma had a higher risk of death if treated with orthovoltage rather than megavoltage RT (Kawabe et al. 2015). MST for dogs treated with curative intent surgery was 723 days, and the role of adjuvant therapies (chemotherapy, radiation, melanoma vaccine, or interferon treatment) was unclear (Tuohy et al. 2014). Chemotherapy (investigational, several studies fail to show a survival benefit) (Page et al. 1991; Overly et al. 2001; Rassnick et al. 2001; Kudnig et al. 2003; Boria et al. 2004; Murphy et al. 2005; Brockley et al. 2013; Cancedda et al. 2014; Dank et al. 2014; Boston et al. 2014); immunotherapy (investigational) (Moore et al. 1991c; Elmslie et al. 1994, 1995; Quintin‐Colonna et al. 1996; Dow et al. 1998; MacEwen et al. 1999; Bergman et al. 2003a, 2003b, 2004, 2006; Alexander et al. 2006; Grosenbaugh et al. 2011; Finocchiaro and Glikin 2012; Westberg et al. 2013; Ottnod et al. 2013; Riccardo et al. 2014; McLean and Lobetti 2015). Other adjuvant modalities (all investigational) include liposome‐encapsulated muramyl tripeptide phosphatidylethanolamine (L‐MTP‐PE), intralesional cisplatin implants, local hyperthermia combined with intralesional cisplatin (Theon et al. 1991; Kitchell et al. 1994; MacEwen et al. 1999). Itoh et al. (2014) reported a single case of a dog with an oral melanoma treated with high‐temperature hyperthermia, dendritic cell therapy, and lupeol injections with complete remission after 2 months, and no local recurrence or metastasis at 6 months (Itoh et al. 2014). Another two reported cases show benefit of adenovector CD40L immunogene (AdCD40L) treatments (von Euler et al. 2008). Post‐operative lupeol (a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo) was reported in a small number of cases (Yokoe et al. 2015).
Cutaneous Melanoma
Surgical excision is the treatment of choice (Bolon et al. 1990; Aronsohn and Carpenter 1990; Brockley et al. 2013) with median overall survival of 1363 days and MI index prognostic for survival (Laver et al. 2018a); chemotherapy shows little response (Gillick and Spiegle 1987; Ogilvie et al. 1991; Moore 1993; Rassnick et al. 2001 Brockley et al. 2013); hyperthermia and intralesional cisplatin/carboplatin (Theon et al. 1991) and PDT (Dougherty et al. 1981; Cheli et al. 1987) have short‐lived responses. Radiation therapy likely to be of use if melanoma not surgically excisable (Bergman et al. 2013). Immunomodulation is investigational (Quintin‐Colonna et al. 1996; Hajduch et al. 1997; Dow et al. 1998; Hogge et al. 1999; MacEwen et al. 1999; Bianco et al. 2003; Gyorffy et al. 2005; Alexander et al. 2006; Bergman et al. 2006).
Appendicular Osteosarcoma
Surgery (amputation/limb‐spare) (Vasseur 1987; Mauldin et al. 1988b; LaRue et al. 1989; Thrall et al. 1990; Straw et al. 1991b; Berg et al. 1992; Spodnick et al. 1992; Withrow et al. 1993; Kuntz et al. 1998; Tomamassini et al. 2000; Huber et al. 2000; Morello et al. 2001, 2003; Buracco et al. 2002; Rovesti et al. 2002; Seguin et al. 2003; Pooya et al. 2004; Liptak et al. 2004b, 2005, 2006; Ehrhart 2005a; Irvine‐Smith and Lobetti 2006; Boston et al. 2007; MacDonald and Schiller 2010; Hodge et al. 2011; Boston et al. 2011; Venzin et al. 2012; Gasch et al. 2013; Renwick and Scurrell 2013; Covey et al. 2014; Seguin et al. 2017); hemipelvectomy (Straw et al. 1992; Bray et al. 2014b); partial or total scapulectomy (Kirpensteijn et al. 1994; Trout et al. 1995; Montinaro et al. 2013); ulnectomy (Straw et al. 1991a; Sivacolundhu et al. 2013); limb shortening (investigational) (Boston and Skinner 2018). Local chemotherapy as adjuvant to limb‐sparing (OPLA‐Pt) reduced local recurrence rate (Straw et al. 1994; Withrow et al. 2004). Local chemotherapy (isolated limb perfusion) (Van Ginkel et al. 1995) as adjuvant to limb‐sparing (investigational); radioisotopes (Milner et al. 1998; Aas et al. 1999); radiation therapy to the primary site (palliative as an alternative to amputation/limb‐spare) (Heidner et al. 1991; McEntee et al. 1993; Ramirez et al. 1999; Green et al. 2002; Mueller et al. 2005); adjunctive to limb‐spare (Thrall et al. 1990; Withrow et al. 1993); stereotactic radiation therapy (SRT) with surgical stabilization in dogs with pathologic fracture or at high risk of pathologic fracture showed varying results but high risk of complications (Covey et al. 2014; Boston et al. 2017), SRT +/− adjuvant radiation therapy resulted in a MST of 363 days and was ideally suited in dogs with small tumors with minimal bone destruction (Farese et al. 2004). In 46 dogs with appendicular OSA treated with SRT, the MST was 9.7 months, with a median time to fracture of 4.2 months in dogs with subchondral bone involvement and versus 16.3 months in dogs without subchondral bone involvement (Kubicek et al. 2016). Various chemotherapy protocols have been reported, as adjuvant to limb‐spare or amputation (clear benefit) (Thompson and Fugent 1992; Berg et al. 1995; Bergman et al. 1996; Berg et al. 1997; Kent et al. 2004; Chun et al. 2005; Bacon et al. 2008; Phillips et al. 2009; McMahon et al. 2011; Saam et al. 2011; Simcock et al. 2012; Lane et al. 2012; Skorupski et al. 2013; Bracha et al. 2014; Selmic et al. 2014; Alvarez et al. 2014; Kozicki et al. 2015; London et al. 2015); Toceranib did not improve survival combined with metronomic chemotherapy after carboplatin (London et al. 2015), and metronomic chemotherapy did not increase survival after carboplatin (Matsuyama et al. 2018); chemotherapy neoadjuvant to limb‐sparing to downstage disease pre‐surgery (Withrow et al. 1993; O’Brien et al. 1996); chemotherapy as an adjuvant to palliative radiation (Walter et al. 2005; Fan et al. 2009; Oblak et al. 2012); bisphosphonates (Tomlin et al. 2000; Fan et al. 2005, 2007, 2008, 2009, Fan, 2009, 2007; Batschinski et al. 2014); immunotherapy (investigational) (reviewed by Wycislo and Fan 2015) (Wycislo and Fan 2015), toceranib in dogs with macroscopic pulmonary metastasis of OSA resulted in a clinical benefit in 10% of dogs (Kim et al. 2017), the median progression‐free survival time was 57 days with a median overall survival time of 89 day (Laver et al. 2018b); Radionucleide therapy for palliation (Barnard et al. 2007; Chakraborty et al. 2016). In 51 small‐breed dogs with appendicular OSA, 9 dogs treated non‐surgically had a MST of 112 days, 16 treated with amputation only had a MST of 257 days, and 26 treated with limb‐spare/ amputation and chemotherapy had a MST of 415 days (Amsellem et al. 2014).
Multi‐lobular Osteochondrosarcoma
Surgery as cure of local disease, prolonged survival if local disease cured (MST 14 months even if metastasis present at diagnosis) (Dernell et al. 1998a). If surgical removal not possible, consider surgical debulk plus adjuvant radiation therapy (Straw et al. 1989). Radionuclide therapy (investigational) (Vancil et al. 2012).
Chondrosarcoma
Wide surgical excision significantly improves survival. Median survival time is 540 days treated with amputation alone (Popovitch et al. 1994); chest wall resection MST 1080 days (Pirkey‐Ehrhart et al. 1995); wide surgical excision for non‐nasal sites MST of 3097 days and did not reach MST (Waltman et al.
alone (palliative) (Thrall 1981; Brewer and Turrel 1982; Theon et al. 1997). Systemic chemotherapy has no known benefit (Gardner et al. 2015a). For histologically low‐grade, biologically high‐grade oral fibrosarcoma, prognosis depends upon early diagnosis and aggressive treatment. Prolonged survival can be achieved in some dogs with surgery, radiotherapy alone, surgery and radiotherapy, and radiotherapy and local hyperthermia (Ciekot et al. 1994).
