Radiation Oncology/Sarcoma/Angiosarcoma

Overview Rare malignancy of vascular origin Soft tissue sarcoma ~1% of all malignancies Angiosarcoma ~2% of soft tissue sarcomas Clinically heterogenous, and can occur anywhere in the body ~1/3 cutaneous ~1/4 soft tissue Rest miscellaneous locations Thought to arise from vascular endothelium Unlike other sarcomas, may present as multifocal disease, and spread to LNs and distantly Typically have an aggressive course, with difficulty clearing surgical margins, and with frequent local and distant failure Treatment is challenging, and requires multidisciplinary approach Pathogenesis Thought to originate from vascular endothelium Cell marker studies are consistent with lymphocyte differentiation but ultrastructural characteristics are consistent with blood vessel differentiation (3104187) Vascular endothelial factor D (VEGF-D) (14746640) and angiopoietin 2 (15149523) significantly elevated compared to controls Fas ligand (w:Fas_ligand|Fas-L) is detected in >70% tumors (11549589), and number of Fas-L positive cells correlates inversely with survival. This suggests that Fas-L positive tumor cells may induce apoptosis in tumor-infiltrating lymphocytes (TILs) and thus blunt immune response Frequently develops in areas previously treated with radiation (e.g. breast) or with chronic lymphedema Stewart-Treves syndrome Median time from RT 8.6 years in one series (15166970), and risk increases with dose Pathology Distinguished from hemangioma by presence of "collagen dissection patterns", anastomoses, and papillary formation Early lesions may in fact present as benign hemangiomas Most present as intermediate or high grade lesions, but typically have an aggressive course Well differentiated tumors are composed of well-formed, irregular vascular channels (sinusoids) anastomosing together, lined by atypical cells (64%) Poorly differentatied tumors may contain only pleomorphic spindle cells with subtle vascular lumens, or may still contain vaso-formative areas Grade is not a prognostic factor Treatment Mass General Hospital; 2007 (1980-2006) 17356953 -- "Treatment and outcome of 82 patients with angiosarcoma." (Abraham JA, Ann Surg Oncol. 2007 Jun;14(6):1953-67.) Retrospective. 82 patients (32 cutaneous, 22 deep tissue/organs, 10 RT or lymphedema, 8 bone, 7 non-RT breast). Primary disease: 46 patients, all treated with surgery, 67% RT and 27% chemo. 5-year DSS 60%. Negative prognosis: intermediate/high grade, RT- or lymphedema-related Advanced disease: 36 patients, 36 palliative surgery, 78% RT, 58% chemo. Median survival 7 months. Cutaneous tumors better prognosis Conclusion: Aggressive surgical resection with RT for close margins or worrisome pathology can result in long-term survival. Advanced disease poor prognosis UCLA; 1996 (1955-1990) 8635113 -- "Angiosarcoma. A report of 67 patients and a review of the literature." (Mark RJ, Cancer. 1996 Jun 1;77(11):2400-6.) Retrospective. 67 patients. Median F/U 2.5 years) Outcome: 2-year DFS 44% and 5-year DFS 24%. 81% LR component 5-year DFS: surgery + RT 43% vs. surgery +/- CT 17% (SS) Conclusion: Surgery + RT offers best chance for long term control; chemo undefined Cutaneous Angiosarcoma Overview Typically presents on scalp or face Optimal treatment has not been defined due to rarity, but probably includes primary resection with wide margins, followed by adjuvant RT RT recommendations from 17023791 Consider dose 45-50 Gy subclinical disease, 60-65 Gy for adjuvant treatment, and 70-75 Gy for gross disease Risk of LN mets is probably 10-20%, therefore consider elective nodal RT Consider total scalp irradiation due to need for very wide margins Docetaxel and paclitaxel appear to have some activity in palliative setting Presentation Patients tend to be older, white, and male Lesion that resembles a "spreading bruise", variable color from blue, purple, to red May be gravity dependent, and be brought on for example by washing hair in a sink Nodular component often develops with time Usually asymptomatic, but may develop bleeding or ulceration Typically more extensive than suggested by physical findings Diagnosis "Head-Tilt" maneuver, where patient is asked to place his/her head below the level of the heart for 10 seconds. The involved area becomes markedly violaceous and engorged (17224545) MRI to define extent of primary tumor Consider CT to detect regional node mets Biopsy necessary to obtain diagnosis, but grading may be difficult (16359536) There is no specific AJCC Staging; please see Staging for soft tissue sarcoma, with understanding that angiosarcoma grade is not prognostic Hamamatsu; 2005 (Japan) 16272865 -- "Magnetic resonance imaging findings of angiosarcoma of the scalp." (Isoda H, J Comput Assist Tomogr. 2005 Nov-Dec;29(6):858-62.) 8 patients with angiosarcoma of the scalp. Outcome: tumors well enhanced on both contrast T1 with fat saturation and T2 with fat saturation. In 4/8 patients tumors were larger than on inspection Conclusion: MRI useful for determining extent Institut Curie; 2003 (France) 12951681 -- "Cytohistologic correlations in angiosarcoma including classic and epithelioid variants: Institut Curie's experience." (Klinanienko J, Diagn Cytopathol. 2003 Sep;29(3):140-5.) Retrospective. FNA and histology review of 29 tumors in 23 patients Conclusion: Accurate tumor typing difficult, particularly in low-grade angiosarcoma Outcomes Japan; 2005 (1988-2002) 15817349 -- "Angiosarcoma of the scalp treated with curative radiotherapy plus recombinant interleukin-2 immunotherapy." (Ohguri T, Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1446-53.) Retrospective. 20 patients treated with RT and recombinant IL-2. RT dose median 70 Gy Outcome: median OS 3 years, 5-year DSS 40%; 70% developed recurrence, 50% local component IL-2 resulted in significantly less DM Conclusion: RT + rIL-2 is effective, need additional studies Multi-institutional; 2004 15153886 -- "Cutaneous angiosarcoma: a case series with prognostic correlation." (Morgan MR, J Am Acad Dermatol. 2004 Jun;50(6):867-74.) Retrospective. 4 institutions. 47 patients with cutaneous angiosarcoma (breast, prior-RT, or prior lymphedema excluded). Average age 75 years, men 3:1, 96% head and neck. Follow up range 0.5-5 years Histology: anastomosing dissecting sinusois lined by atypical cells (64%), diffuse epithelioid/spindle cell proliferation (15%), mixed (21%). Average depth of invasion 2.9 mm (1.8-6 mm), average size 5.3 cm (1-9 cm) 5-year outcome: LR 84%, OS 34%; most patients died with widespread pulmonary, cardiac, and/or brain mets. Negative predictors: large diameter (>5 cm), depth (>3 mm), high mitotic rate, SM+ Conclusion: poor prognosis Michigan; 2003 (1975-2002) 14534889 -- "Cutaneous angiosarcoma of the scalp: a multidisciplinary approach." (Pawlik TM, Cancer. 2003 Oct 15;98(8):1716-26.) Retrospective. 29 patients with scalp lesions only. 75% pT2, 76% high grade. 97% surgery but only 21% SM-. RT given as wide-field in 79% including all patients with SM-. Median F/U 1.5 years Outcome: median OS 2.4 years; negative prognosis: older patients and T2 disease. RT prolonged time to local recurrence Conclusion: surgery first option, post-op RT should be employed routinely MD Anderson; 1995 (1970-1989) 8625109 -- "Cutaneous angiosarcoma of the head and neck. A therapeutic dilemma." (Morrison WH, Cancer. 1995 Jul 15;76(2):319-27.) Retrospective. 14 patients with scalp (n=11) and upper face (n=3). Surgery in 7, chemo in 10. Median RT dose 60 Gy (50-66) microscopic and 55-75 Gy macroscopic 5-year outcome: LR control microscopic 40% vs. 24% macroscopic; infield control 80% vs. 55%; 5-year OS 50% vs. 13% (overall 29%) Conclusion: RT effective for local disease, especially if R0/R1 disease St. John's Hospital; 1987 (London, UK) 3104187 -- "Angiosarcoma of the face and scalp, prognosis and treatment." (Holden CA, Cancer. 1987 Mar 1;59(5):1046-57.) Retrospective. 72 patients with angiosarcoma of face and scalp. 5-year OS: 12%; half died within 15 months of presentation Prognostic factors: larger lesions (>10cm); location, age, gender, appearance not significant Radical RT (wide-field electrons) resulted in good local control; 2 patients developed pulmonary disease 10 years later Chemotherapy Kobe; 2007 (2003-2006) 17582627 -- "Docetaxel: A therapeutic option in the treatment of cutaneous angiosarcoma: report of 9 patients." (Nagano T, Cancer. 2007 Aug 1;110(3):648-51.) Retrospective. 9 patients given docetaxel 25 mg/m2 QW x8 weeks. 6 had RT, 4 surgery, and IL-2 Outcome: 2 CR, 4 PR. Severe radiation dermatitis in 3/9 Conclusion: docetaxel has activity and may suppress lung mets MSKCC; 1999 (1992-1998) 10570428 -- "Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face." (Fata F, Cancer. 1999 Nov 15;86(10):2034-7.) Prospective. 9 patients with AS of scalp or face. 6 prior RT. 3 metastatic, 6 unresectable or recurrent. paclitaxel 175 mg/m2 (also 90 and 250) Q3W Outcome: 4 CR, 4 PR. Median duration of response 5 months Toxicity: neutropenia and peripheral neuropathy Conclusion: paclitaxel as single agent has substantial activity Review Univ Florida; 2006 17023791 -- "Cutaneous angiosarcoma." (Mendenhall WM, Am J Clin Oncol. 2006 Oct;29(5):524-8.)