chondrosarcoma treated with amputation alone, although grade was found to be prognostic (Farese et al. 2009). Hemipelvectomy MST 1232 days (Bray et al. 2014b). Debulking and adjuvant radiation therapy if the location is not amenable to curative resection, or radiation alone (Popovitch et al. 1994, Lana et al. 1997), objective responses to coarse fraction radiation alone (Ehrhart et al. 2013). Metastasis still occurs in about 25%, even after surgical resection. Grade may be prognostic for survival (Waltman et al. 2007; Farese et al. 2009). Laryngeal and tracheal chondrosarcoma have good prognosis with surgical resection alone (Muraro et al. 2013; Ramirez et al. 2015; De Lorenzi et al. 2015).
Cutaneous Hemangiosarcomas (HSA)
Dogs: Dermal (stage I) HSA all firm, raised, dark red papules/nodules, commonly ventral abdomen/preputial area and solar elastosis common (Culbertson 1982; Hargis et al. 1992; Ward et al. 1994; Szivek et al. 2012). Stage II (hypodermal involvement with or without concurrent dermal involvement) or stage III (any primary tumor with underlying muscle involvement) were firm to soft/fluctuant masses with hemorrhagic discoloration, ulceration frequent and many owners thought this was bruising associated with trauma (Ward et al. 1994). The MST for stage I was 780 days, stage II 172 days, and stage III was 307 days (no statistical difference in MST for stage II and III) and all dogs had no evidence of nodal or distant metastasis and all dogs treated with wide surgical resection alone. Surgery alone is treatment of choice for stage I, with no dogs with stage I tumors dying as a consequence of their disease (Ward et al. 1994). Dogs with dermal HSA treated with surgery alone showed MST of 1570 days in predisposed breeds (lightly haired) compared with 593 days in non‐predisposed breeds, dogs with HSA in typical sun‐exposed ventral abdominal locations had a MST of 1085 days compared with 539 days in other locations, and if biopsies showed solar changes MST was 1549 days compared with 545 days in dogs without solar changes. Factors that did not affect survival included multiple masses at presentation, biopsy margin status/completeness of surgical excision, loco‐regional recurrence, and subcutaneous invasion, although dogs with subcutaneous invasion had an increased risk of metastasis compared to dogs with only dermal involvement (Szivek et al. 2012). Yet in another study of non‐visceral hemangiosarcomas in dogs and cats, completeness of excision was the most important factor in predicting clinical outcome (Schultheiss 2004). Adjuvant doxorubicin chemotherapy should be considered for stage II and III diseases (Ward et al. 1994). The addition of adjuvant chemotherapy increases MST from 211 days (Sorenmo et al. 1993) to 425 days (Hammer et al. 1991) for subcutaneous HSA. In another study, 21 dogs with subcutaneous (17) and intramuscular (4) hemangiosarcomas, with adequate local tumor control and no metastasis at presentation, were treated with adjuvant doxorubicin. Five dogs also received adjuvant radiation therapy. The MST for subcutaneous HSA was 1189 days and for intramuscular was 272.5 days (Bulakowski et al. 2008). Doxorubicin‐based chemotherapy used for non‐resectable canine subcutaneous HSA resulted in a response rate of 38–44%, and its use in the neoadjuvant setting to “downstage” tumors to facilitate complete resection appears promising (Wiley et al. 2010). Subcutaneous or intramusuclar HSA was associated with a MST of 246 days for dogs that received chemotherapy, and adequate local control (surgery +/− radiation therapy) with no evidence of metastasis at diagnosis (Shiu et al. 2011). Non‐splenic HSAs in 20 dogs treated with palliative radiation therapy had a MST of 3 months (Hillers et al. 2007).Cats: Wide surgical excision (metastasis occurs less frequently than dogs, but adjuvant chemotherapy may have a role, depending on the case) (Miller et al. 1992; Kraje et al. 1999; Schultheiss 2004; McAbee et al. 2005). Radiation therapy is considered adjuvantly if incompletely resected local disease.
Visceral HSA
Surgery (e.g. splenectomy) (Brown et al. 1985; Spangler and Culbertson 1992; Spangler and Kass 1997; Prymak et al. 1988; Sorenmo et al. 2004a; Wendelburg et al. 2015); adjuvant chemotherapy of various types can be considered for splenic hemangiosarcomas, with median survival times of 141–179 days reported (Hammer et al. 1991; Vail et al. 1995; Sorenmo et al. 1993, 2000a, 2004a, 2005; Ogilvie et al. 1996), although other studies have not shown a significant survival advantage compared to splenectomy alone (Wendelburg et al. 2015; Gardner et al. 2015b). MST splenectomy alone 55–86 days (Brown et al. 1985; Wood et al. 1998; Wendelburg et al. 2015). Reported MST 125 days for non‐resectable disease (Dervisis et al. 2011). Clinical stage influences prognosis, stage I MST 5.5 months, stage II MST 2 months, stage III 0.9 months (Wendelburg et al. 2015). Although in another study of 21 dogs treated with splenectomy and chemotherapy had an overall MST of 150 days and there was no significant difference in survival based upon the stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days (Kahn et al. 2013). Immunotherapy (Vail et al. 1995; U'Ren et al. 2007) and angiogenic therapy are investigational (Sorenmo et al. 2000a). Cardiac hemangiosarcoma treated with doxorubicin had MST 116 days, significantly improved compared to 12 days for untreated dogs (Mullin et al. 2016). Dogs with right atrial HSA that had surgery and adjuvant chemotherapy had a MST of 175 days, compared to dogs treated with surgery alone MST 42 days (Weisse et al. 2005).
Histiocytic Sarcomas (HS)
Localized (skin/subcutis) is treated with aggressive surgery with clean margins (Affolter and Moore 2000); adjuvant radiation therapy if incomplete resection; adjuvant chemotherapy is indicated, following surgery and/or radiation therapy for localized (Skorupski et al. 2009; Liptak and Forrest 2013; Cannon et al. 2015), aggressive local therapy combined with adjuvant CCNU chemotherapy in dogs with localized HS resulted in a MST of 568 days in 16 dogs (Skorupski et al. 2009). Chemotherapy also indicated for primary treatment for disseminated or metastatic disease (Cannon et al. 2015), MST with lomustine‐doxorubicin ± cyclophosphamide was 185 days in 17 cases (6 of which had local therapy as part of treatment) (Cannon et al. 2015). In another study, 59 dogs were treated with lomustine chemotherapy, 20 dogs had received prior local therapy, the MST 106 days. Thrombocytopenia and hypoalbuminemia were negative prognostic factors (<1 month survival) (Skorupski et al. 2007). In another study, anemia, thrombocytopenia, hypoalbuminemia, hypoproteinemia were associated with shorter survival times (Takahashi et al. 2014). Other negative prognostic factors include use of prednisone during therapy and metastatic disease at the time of diagnosis (Klahn et al. 2011). Periarticular HS may have a better prognosis than non‐periarticular HS. Dogs with periarticular HS without evidence of metastasis at diagnosis had a MST of 980 days (Klahn et al. 2011). In another study, dogs that received no/or symptomatic treatment MST was 12 days, and dogs that were treated with surgery and/or chemotherapy had a MST of 85 days (Takahashi et al. 2014). Survival times in other studies are similar in the range of 3–4 months (Skorupski et al. 2007; Rassnick et al. 2010; Higuchi et al. 2010; Klahn et al. 2011). Outcomes may be better in dogs with localized HS treated with local therapy and adjuvant chemotherapy (Skorupski et al. 2009; Klahn et al. 2011). Negative prognostic factors include splenic involvement (Skorupski et al. 2007; Constantino‐Casas et al. 2011), hypoalbuminemia, anemia, thrombocytopenia (Skorupski et al. 2007), use of prednisone during therapy, and metastatic disease at the time of diagnosis (Klahn et al. 2011). Lomustine ± corticosteroids are the most commonly used protocol although other options include doxorubicin, combination protocols, vinorelbine and bisphosphonates (Skorupski et al. 2007, 2009; Rassnick et al. 2010; Higuchi et al. 2010; Hafeman et al. 2010, 2012; Klahn et al. 2011; Clifford et al. 2012; Wouda et al. 2015).
Uterine Leiomyoma and Leiomyosarcoma in Dogs
Prognosis good with complete surgical resection.
Since doxorubicin is one of the most common chemotherapy agents used and is a severe vesicant, extravasations of this agent are of significant concern and will be the main focus of this section. Most perivascular doxorubicin leaks are noticed immediately if careful monitoring is implemented during infusion. Signs may include a focal “bleb,” regional swelling, or erythema over or around the catheter site, and the patient may react as if in discomfort upon extravasation. If signs of a doxorubicin extravasation should occur, then immediate action needs to be taken.
Multiple protocols that describe proper handling of chemotherapy extravasations have been advocated. In general, the initial step of such protocols – aspirating any residual drug back from the extravasation site via the catheter/needle
chondrosarcoma treated with amputation alone, although grade was found to be prognostic (Farese et al. 2009). Hemipelvectomy MST 1232 days (Bray et al. 2014b). Debulking and adjuvant radiation therapy if the location is not amenable to curative resection, or radiation alone (Popovitch et al. 1994, Lana et al. 1997), objective responses to coarse fraction radiation alone (Ehrhart et al. 2013). Metastasis still occurs in about 25%, even after surgical resection. Grade may be prognostic for survival (Waltman et al. 2007; Farese et al. 2009). Laryngeal and tracheal chondrosarcoma have good prognosis with surgical resection alone (Muraro et al. 2013; Ramirez et al. 2015; De Lorenzi et al. 2015).
