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Scalp Angiosarcoma Remission with Bevacizumab and Radiotherapy without Surgery: A Case Report and Review of the Literature

Scalp Angiosarcoma Remission with Bevacizumab and Radiotherapy without Surgery: A Case Report and... Hindawi Publishing Corporation Sarcoma Volume 2011, Article ID 160369, 5 pages doi:10.1155/2011/160369 Case Report Scalp Angiosarcoma Remission with Bevacizumab and Radiotherapy without Surgery: A Case Report and Review of the Literature 1, 2 1, 2 2, 3 1, 2 Jocelyn T. De Yao, Danyu Sun, Angela T. Powell, and Esther H. Rehmus Department of Medicine, Akron General Medical Center, 400 Wabash Avenue, Akron, OH 44307, USA Department of Medicine, Northeastern Ohio Universities, College of Medicine and Pharmacy, Rootstown, OH 44272, USA Department of Pathology, Akron General Medical Center, 400 Wabash Avenue, Akron, OH 44307, USA Correspondence should be addressed to Jocelyn T. De Yao, jdeyao@agmc.org Received 18 October 2010; Accepted 27 February 2011 Academic Editor: Marcus Schlemmer Copyright © 2011 Jocelyn T. De Yao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Angiosarcoma (AS) is a rare and aggressive vascular neoplasm with very poor prognosis. Patients with extensive cutaneous AS who are not surgical candidates have very limited options since there is no standard treatment. Treatment options include radiation, chemotherapy, and angiogenesis inhibitor with varying success rates. Here, we report a case an 88 year old patient with extensive scalp angiosarcoma having biopsy proven remission with bevacizumab and radiotherapy without undergoing surgery. 1. Introduction with cutaneous AS who are not surgical candidates due to multiple comorbid conditions have limited treatment Angiosarcoma (AS) is a rare and aggressive vascular neo- options. Due to its rapid progression, achieving local control plasm comprising less than 2% of all soft tissue sarcomas [1– and prevention of metastasis in AS has been a challenge. 3]. Angiosarcomas comprise approximately 15% of all head Few reports have described successful treatment of AS using and neck sarcomas [4–6] and less than 1% of all malignancies adjuvant chemotherapy with radiotherapy [16]. Different in the region [6, 7]. Head and neck ASs are frequently seen treatment modalities used in cutaneous angiosarcoma are in the scalp [1–3, 6–15] and are common in the elderly depicted in Table 1. Here, we report a successful response of population with the mean age greater than 60 years. AS also AS to bevacizumab with concurrent radiation therapy in a has a slight predilection for Caucasian patients and the male patient not eligible for surgical intervention. gender [1, 2, 7–10, 12–14]. PrognosisispoorsinceASis very aggressive with disease-free survival of less than 50% 2. Case Report at five years [1, 4, 5, 8–14] due to its high propensity for local recurrence [4, 5, 8, 11]. However, some studies report An 88-year-old Caucasian male with a 37-pack-year history survival of 10–20% after five years [1, 5, 8–11], which may of smoking noticed purplish lumps on his scalp with scaling indicate lesions that are located in the scalp and face have a and erythema for two months prior to presentation. He lower survival rate and higher rate of recurrence [10]. The had a complicated past medical history of Stage II prostate most important prognostic factors include tumor size and cancer treated with radiation treatments, abdominal aortic ability to achieve negative margins with tumor grade also aneurysm repair, macular degeneration treated with pho- being considered to be a prognostic factor for recurrence todynamic therapy, torn retina, inguinal hernia repair, and [5, 12]and overallsurvival[11]. Patients with facial or four-vessel coronary artery bypass graft. The patient noted scalp AS of less than 5 cm in size tend to do better than the violaceous papules increasing in size and nodularity and those with tumor size greater than 5 cm [6, 10]. Patients extending down to the level of the eyebrows bilaterally. He 2 Sarcoma Table 1: Different treatments used in cutaneous angiosarcoma. Type of Reference Angiosarcoma type Treatment Outcome literature Koontz et al. (1) Nasal area (1) Bevacizumab + XRT + SX (1) CR, 26 mos response duration Case reports 2008 [16] (2) Nasal area (2) Bevacizumab + XRT + SX (2) CR, 8.5 mos response duration XRT alone Gkalpakiotis Well-differentiated Case report Phase 1: 45 Gy 5 yrs remission et al. 2008 [17] exophytic-face Phase 2: 20 Gy 32 patients Paclitaxel 5/8 PR (mean 5.8 mos) Schlemmer Retrospective 8 scalp and facial ± Sx 1/8 CR (42 mos) et al. 2008 [18] study Rest other sites ± XRT 1/8 PD (3 mos) ± chemotherapy 1/8 NC (2 mos) 6/9: major response (2 CR, 4 PR) Docetaxel with or without 2CR: 2 XRT without SX Nagano et al. Retrospective Cutaneous AS other previous treatment 2007 [19] study 9 patients 4PR: 1XRT +SX, 1XRT without (XRT, SX) SX, 1 SX without XRT, 1 without SX nor XRT Holloway et al. Case report Cutaneous AS (scalp) Liposomal doxorubicin + XRT 4 years response duration 2005 [20] CR with cervical lymph node Eiling et al. Case report Cutaneous AS (scalp) Liposomal doxorubicin + XRT metastasis disappearance 2002 [21] 4 mos response duration Lankester et al. Cutaneous AS (face Liposomal daunorubicin + Case report 15 mos CR 1999 [22] and scalp) XRT CR: complete response, PR: partial response, NC: no change, PD: progression of disease, XRT: radiotherapy, SX: surgery. initially thought the mass was a bruise, but the increase in 46 days. The patient tolerated the treatment well with skin size prompted him to consult a physician. On examination, changes characterized only by erythema and desquamation the patient had multiple irregularly shaped lesions, largest of with residual crusting of the skin. Marked clinical improve- which was a 4 cm × 7 cm on the frontal scalp; these lesions ment was noted. Side effects also included slight swelling were violaceous papules with scaling and erythema as shown of the eyes with yellowish discharge and pruritus from the in Figure 1. A PET scan showed uptake only on the scalp radiation treatment. No hypertension or proteinuria was adjacent to the frontal bone near midline (Stage IIA—T2a noted. A repeat biopsy performed six months after treatment N0 M0). showed fibrosing granulation tissue, fibrosis, hemosiderin deposition, and dilated vessels not reminiscent of the pattern seen in the original angiosarcoma as shown in Figure 3. 3. Histology Seven months after the completion of bevacizumab and radiation therapy, the patient had a biopsy-proven local Biopsy of the lesion showed irregular channels and ectatic recurrence. He was started immediately on an increased dose vascular spaces lined by plump hyperchromatic endothelial of bevacizumab 10 mg/kg IV every two weeks, which he toler- cells. The histology results were most compatible with mod- ated well for three months for a total of 6 doses. He then had erately differentiated angiosarcoma, as shown in Figure 2,in a minor stroke, and bevacizumab was discontinued. Weekly low magnification (L) and high magnification (R). paclitaxel was initiated at 80 mg/m and continued for 15 treatments with stable disease. Progression occurred and 4. Treatment and Followup treatment was changed to pegylated doxorubicin 40 mg/m monthly × 2 treatments without benefit. He expired 23 Due to the extent of the disease and his frail state, the patient months after initial presentation due to disease. was a poor surgical candidate; resection, if performed, would have necessitated the removal of his entire scalp, from ear to ear. The patient was started on one pre-irradiation cycle 5. Discussion of bevacizumab, which was continued through his course of radiation therapy. Bevacizumab was given 5 mg/kg IV Angiosarcoma usually presents as a purple macular ulcerated (with calculated dose of 350 mg) every two weeks while on lesion that is often mistaken for a bruise. Cutaneous radiation therapy, total of four treatments. His tumor total angiosarcoma may be categorized as being idiopathic AS of radiation treatment dose was 6000 rad, in 30 fractions, over the face and scalp, primary AS of the breast, postradiation Sarcoma 3 (a) (b) Figure 1 (a) (b) Figure 2 (a) (b) Figure 3 AS, or AS arising from chronic lymphedema of the extremity support this theory [1, 23]. A combination of surgery [9, 10, 23]. Proposed risk factors for developing cutaneous and radiotherapy offers the best survival and is the most AS include exposure to vinyl chloride, insecticides, tho- common treatment modality used for this very aggressive rium dioxide, and hormones such as anabolic steroids and tumor [9, 12]. Surgery remains the first option for treating synthetic estrogen [5, 12]. It is also postulated that sun- patients with angiosarcoma of the scalp, but due to its damaged skin may be a risk factor due to its predilection rapid progression, patients may present with disseminated for Caucasians; however, there is no direct evidence to or extensive local disease which make surgery inappropriate 4 Sarcoma [1, 8–15]. Postoperative radiotherapy is employed routinely similar to the case reported by Gkalpakiotis et al. [17] as it improves survival [5, 7, 8], although there is still an or if bevacizumab improved our patient’s response since extremely high rate of recurrence and local failure [12]. The vascular endothelial growth factor was overexpressed in 80% role of chemotherapy, however, is not well established and of angiosarcoma cases [27]. To our knowledge, this case is hasnot been proven to increasesurvival[12]. the only one to report remission of AS after treatment with As a result of the above-mentioned challenges, treatment bevacizumab and radiotherapy without surgical interven- options are limited, especially since AS is often found in tion. In two case reports from the Duke University, 5 mg/kg elderly patients who may have many comorbidities and of bevacizumab was used in one patient and 10 mg/kg for are more prone to adverse treatment reactions. Prospective the other in conjunction with radiotherapy as postsurgical studies with regard to adjuvant chemotherapy and other treatment [16]. Our patient was given four treatments of treatment combinations are also limited due to the rarity of 5 mg/kg of bevacizumab with radiation therapy as a primary the disease so there are no specific guidelines with regards treatment without surgical resection and achieved complete to treatment. Radiation therapy dose response has been clinical response with a negative pathology on biopsy suggested wherein those receiving greater than 5000 rad have remission. Due to the lack of resection, we cannot report a better local control, though larger case numbers are required complete pathologic response. A second course involving a to validate initially reported successes [5]. There are case higher dose of bevacizumab for his recurrence led to clinical reports of remission with radiotherapy alone; these cases response after three months but had to be discontinued when tend to be well-differentiated and exophytic forms of AS [17]. patient had a stroke, a known risk of bevacizumab though a The addition of another therapy to radiation therapy has meta-analysis done based on 5 randomized controlled trials seen some support over the years; different cases showed AS among 2,288 patients receiving bevacizumab showed no responding to radiation when biological, angiomodulation, statistical difference of stroke incidence compared to control and/or tubulin-affinic substances are given in conjunction [28]. with radiation therapy [5, 16, 18–20, 23–26]. Nevertheless, With AS being very aggressive and having a very low five- the overwhelming opinion about chemotherapy is that year survival rate, therapy with bevacizumab in conjunction its utility remains largely undefined [5]. Major responses with radiation therapy or as a primary therapy may be one have also been reported with paclitaxel, but side effects option to improve survival outcomes especially in patients are dose limiting [24, 25]. A retrospective study done on who are not surgical candidates. Currently, there are two 32 advanced angiosarcoma patients by the soft tissue and phase II clinical trials studying the use of bevacizumab for bone sarcoma EORTC group has 62% response rate in AS which were not available during our patient’s initial advanced angiosarcomas with paclitaxel, with 6 out of 8 scalp diagnosis. One is an open-label multicenter phase II trial and face angiosarcomas responding [18]. There are 6 scalp assessing the median disease-free progression of AS with angiosarcoma patients in the EORTC study, with 3 previously the treatment of bevacizumab alone [29]. The other is the treated with radiation therapy (2 with partial response and study of adding bevacizumab to the combined chemotherapy 1 with progression of disease) and 1 previously treated with of gemcitabine and docetaxel in the treatment of different doxorubicin (no change with paclitaxel). However, there has types of sarcoma including AS [30]. Both trials are currently been a complete response for 42 months on one patient recruiting patients. A prospective clinical trial regarding with scalp angiosarcoma without previous therapy and no neoadjuvant therapy with bevacizumab possibly also includ- previous surgery. Another taxane drug, docetaxel, has been ing chemotherapy would be an interesting approach. In the used for cutaneous AS; a retrospective study of nine patients absence of specific treatment guidelines for AS, the addition in Japan reported a major response in six patients with of bevacizumab to radiation may be one option to offer hope reduced neutropenia and peripheral neuropathy compared to patients who are deemed nonsurgical candidates. to paclitaxel [19]. Published case reports have cited a partial response without surgery [26] and a sustained complete response after surgery in a patient four years later [20] References following the addition of liposomal doxorubicin [20, 21, [1] W. M. Lydiatt, A. R. Shaha, and J. P. Shah, “Angiosarcoma of 26]. Eiling et al. reported a case of confirmed histological the head and neck,” American Journal of Surgery, vol. 168, no. tumor regression of a nonresectable radioresistant scalp 5, pp. 451–454, 1994. angiosarcoma and cervical lymph node metastasis treated [2] M. R. Aust, K. D. Olsen, J. E. Lewis et al., “Angiosarcomas with pegylated liposomal doxorubicin [21]. Complete remis- of the head and neck: clinical and pathologic characteristics,” sion with liposomal daunorubicin with radiotherapy in Annals of Otology, Rhinology and Laryngology, vol. 106, no. 11, unresectable AS has also been published [22]. pp. 943–951, 1997. Although our patient had a moderately differentiated AS, [3] M. G. Fury, C. R. Antonescu, K. J. van Zee, M. F. Brennan, and the tumor location, the extent of disease, the patient’s age, R. G. Maki, “A 14-year retrospective review of angiosarcoma: and his comorbidities all pointed to a very poor prognosis. clinical characteristics, prognostic factors, and treatment Due to the extent of our patient’s disease, it would have outcomes with surgery and chemotherapy,” Cancer Journal, been difficult to achieve a tumor-free margin surgically vol. 11, no. 3, pp. 241–247, 2005. without any disfiguring effects, and radiotherapy alone was [4] H. J. Wanebo, R. J. Koness, J. K. MacFarlane et al., “Head and initially thought to be insufficient. It is difficult to assess neck sarcoma: report of the head and neck sarcoma registry,” whether our patient’s response is due to radiotherapy alone Head and Neck, vol. 14, no. 1, pp. 1–7, 1992. Sarcoma 5 [5] R.J.Mark, J. C. Poen,L.M.Tran, Y. S. Fu,and G. F. Juillard, [22] K. J. Lankester, R. S. D. Brown, and M. F. Spittle, “Complete “Angiosarcoma: a report of 67 patients and a review of the resolution of angiosarcoma of the scalp with liposomal literature,” Cancer, vol. 77, no. 11, pp. 2400–2406, 1996. daunorubicin and radiotherapy,” Clinical Oncology, vol. 11, no. 3, pp. 208–210, 1999. [6] R. S. Weber, R. S. Benjamin, L. J. Peters et al., “Soft tissue sarcomas of the head and neck in adolescents and adults,” [23] K. M. Benbenisty, P. G. Lang, and J. C. 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Ilson et al., “Paclitaxel in the treatment [9] C.A.Holden,M.F.Spittle, andE.W.Jones,“Angiosarcoma of of patients with anglosarcoma of the scalp or face,” Cancer, vol. the face and scalp, prognosis and treatment,” Cancer, vol. 59, 86, no. 10, pp. 2034–2037, 1999. no. 5, pp. 1046–1057, 1987. [26] U. Wollina, J. Ful ¨ ler, T. Graefe, M. Kaatz, and E. Lopatta, [10] J. C. Maddox and H. L. Evans, “Angiosarcoma of skin and soft tissue: a study of forty-four cases,” Cancer,vol. 48, no.8,pp. “Angiosarcoma of the scalp: treatment with liposomal dox- orubicin and radiotherapy,” Journal of Cancer Research and 1907–1921, 1981. Clinical Oncology, vol. 127, no. 6, pp. 396–399, 2001. [11] H. Willers, E. B. Hug, I. J. Spiro, J. T. Efird, A. E. Rosenberg, and C. C. Wang, “Adult soft tissue sarcomas of the head [27] C. Zietz, M. Rossle, ¨ C. 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Scalp Angiosarcoma Remission with Bevacizumab and Radiotherapy without Surgery: A Case Report and Review of the Literature

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Copyright © 2011 Jocelyn T. De Yao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Publishing Corporation Sarcoma Volume 2011, Article ID 160369, 5 pages doi:10.1155/2011/160369 Case Report Scalp Angiosarcoma Remission with Bevacizumab and Radiotherapy without Surgery: A Case Report and Review of the Literature 1, 2 1, 2 2, 3 1, 2 Jocelyn T. De Yao, Danyu Sun, Angela T. Powell, and Esther H. Rehmus Department of Medicine, Akron General Medical Center, 400 Wabash Avenue, Akron, OH 44307, USA Department of Medicine, Northeastern Ohio Universities, College of Medicine and Pharmacy, Rootstown, OH 44272, USA Department of Pathology, Akron General Medical Center, 400 Wabash Avenue, Akron, OH 44307, USA Correspondence should be addressed to Jocelyn T. De Yao, jdeyao@agmc.org Received 18 October 2010; Accepted 27 February 2011 Academic Editor: Marcus Schlemmer Copyright © 2011 Jocelyn T. De Yao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Angiosarcoma (AS) is a rare and aggressive vascular neoplasm with very poor prognosis. Patients with extensive cutaneous AS who are not surgical candidates have very limited options since there is no standard treatment. Treatment options include radiation, chemotherapy, and angiogenesis inhibitor with varying success rates. Here, we report a case an 88 year old patient with extensive scalp angiosarcoma having biopsy proven remission with bevacizumab and radiotherapy without undergoing surgery. 1. Introduction with cutaneous AS who are not surgical candidates due to multiple comorbid conditions have limited treatment Angiosarcoma (AS) is a rare and aggressive vascular neo- options. Due to its rapid progression, achieving local control plasm comprising less than 2% of all soft tissue sarcomas [1– and prevention of metastasis in AS has been a challenge. 3]. Angiosarcomas comprise approximately 15% of all head Few reports have described successful treatment of AS using and neck sarcomas [4–6] and less than 1% of all malignancies adjuvant chemotherapy with radiotherapy [16]. Different in the region [6, 7]. Head and neck ASs are frequently seen treatment modalities used in cutaneous angiosarcoma are in the scalp [1–3, 6–15] and are common in the elderly depicted in Table 1. Here, we report a successful response of population with the mean age greater than 60 years. AS also AS to bevacizumab with concurrent radiation therapy in a has a slight predilection for Caucasian patients and the male patient not eligible for surgical intervention. gender [1, 2, 7–10, 12–14]. PrognosisispoorsinceASis very aggressive with disease-free survival of less than 50% 2. Case Report at five years [1, 4, 5, 8–14] due to its high propensity for local recurrence [4, 5, 8, 11]. However, some studies report An 88-year-old Caucasian male with a 37-pack-year history survival of 10–20% after five years [1, 5, 8–11], which may of smoking noticed purplish lumps on his scalp with scaling indicate lesions that are located in the scalp and face have a and erythema for two months prior to presentation. He lower survival rate and higher rate of recurrence [10]. The had a complicated past medical history of Stage II prostate most important prognostic factors include tumor size and cancer treated with radiation treatments, abdominal aortic ability to achieve negative margins with tumor grade also aneurysm repair, macular degeneration treated with pho- being considered to be a prognostic factor for recurrence todynamic therapy, torn retina, inguinal hernia repair, and [5, 12]and overallsurvival[11]. Patients with facial or four-vessel coronary artery bypass graft. The patient noted scalp AS of less than 5 cm in size tend to do better than the violaceous papules increasing in size and nodularity and those with tumor size greater than 5 cm [6, 10]. Patients extending down to the level of the eyebrows bilaterally. He 2 Sarcoma Table 1: Different treatments used in cutaneous angiosarcoma. Type of Reference Angiosarcoma type Treatment Outcome literature Koontz et al. (1) Nasal area (1) Bevacizumab + XRT + SX (1) CR, 26 mos response duration Case reports 2008 [16] (2) Nasal area (2) Bevacizumab + XRT + SX (2) CR, 8.5 mos response duration XRT alone Gkalpakiotis Well-differentiated Case report Phase 1: 45 Gy 5 yrs remission et al. 2008 [17] exophytic-face Phase 2: 20 Gy 32 patients Paclitaxel 5/8 PR (mean 5.8 mos) Schlemmer Retrospective 8 scalp and facial ± Sx 1/8 CR (42 mos) et al. 2008 [18] study Rest other sites ± XRT 1/8 PD (3 mos) ± chemotherapy 1/8 NC (2 mos) 6/9: major response (2 CR, 4 PR) Docetaxel with or without 2CR: 2 XRT without SX Nagano et al. Retrospective Cutaneous AS other previous treatment 2007 [19] study 9 patients 4PR: 1XRT +SX, 1XRT without (XRT, SX) SX, 1 SX without XRT, 1 without SX nor XRT Holloway et al. Case report Cutaneous AS (scalp) Liposomal doxorubicin + XRT 4 years response duration 2005 [20] CR with cervical lymph node Eiling et al. Case report Cutaneous AS (scalp) Liposomal doxorubicin + XRT metastasis disappearance 2002 [21] 4 mos response duration Lankester et al. Cutaneous AS (face Liposomal daunorubicin + Case report 15 mos CR 1999 [22] and scalp) XRT CR: complete response, PR: partial response, NC: no change, PD: progression of disease, XRT: radiotherapy, SX: surgery. initially thought the mass was a bruise, but the increase in 46 days. The patient tolerated the treatment well with skin size prompted him to consult a physician. On examination, changes characterized only by erythema and desquamation the patient had multiple irregularly shaped lesions, largest of with residual crusting of the skin. Marked clinical improve- which was a 4 cm × 7 cm on the frontal scalp; these lesions ment was noted. Side effects also included slight swelling were violaceous papules with scaling and erythema as shown of the eyes with yellowish discharge and pruritus from the in Figure 1. A PET scan showed uptake only on the scalp radiation treatment. No hypertension or proteinuria was adjacent to the frontal bone near midline (Stage IIA—T2a noted. A repeat biopsy performed six months after treatment N0 M0). showed fibrosing granulation tissue, fibrosis, hemosiderin deposition, and dilated vessels not reminiscent of the pattern seen in the original angiosarcoma as shown in Figure 3. 3. Histology Seven months after the completion of bevacizumab and radiation therapy, the patient had a biopsy-proven local Biopsy of the lesion showed irregular channels and ectatic recurrence. He was started immediately on an increased dose vascular spaces lined by plump hyperchromatic endothelial of bevacizumab 10 mg/kg IV every two weeks, which he toler- cells. The histology results were most compatible with mod- ated well for three months for a total of 6 doses. He then had erately differentiated angiosarcoma, as shown in Figure 2,in a minor stroke, and bevacizumab was discontinued. Weekly low magnification (L) and high magnification (R). paclitaxel was initiated at 80 mg/m and continued for 15 treatments with stable disease. Progression occurred and 4. Treatment and Followup treatment was changed to pegylated doxorubicin 40 mg/m monthly × 2 treatments without benefit. He expired 23 Due to the extent of the disease and his frail state, the patient months after initial presentation due to disease. was a poor surgical candidate; resection, if performed, would have necessitated the removal of his entire scalp, from ear to ear. The patient was started on one pre-irradiation cycle 5. Discussion of bevacizumab, which was continued through his course of radiation therapy. Bevacizumab was given 5 mg/kg IV Angiosarcoma usually presents as a purple macular ulcerated (with calculated dose of 350 mg) every two weeks while on lesion that is often mistaken for a bruise. Cutaneous radiation therapy, total of four treatments. His tumor total angiosarcoma may be categorized as being idiopathic AS of radiation treatment dose was 6000 rad, in 30 fractions, over the face and scalp, primary AS of the breast, postradiation Sarcoma 3 (a) (b) Figure 1 (a) (b) Figure 2 (a) (b) Figure 3 AS, or AS arising from chronic lymphedema of the extremity support this theory [1, 23]. A combination of surgery [9, 10, 23]. Proposed risk factors for developing cutaneous and radiotherapy offers the best survival and is the most AS include exposure to vinyl chloride, insecticides, tho- common treatment modality used for this very aggressive rium dioxide, and hormones such as anabolic steroids and tumor [9, 12]. Surgery remains the first option for treating synthetic estrogen [5, 12]. It is also postulated that sun- patients with angiosarcoma of the scalp, but due to its damaged skin may be a risk factor due to its predilection rapid progression, patients may present with disseminated for Caucasians; however, there is no direct evidence to or extensive local disease which make surgery inappropriate 4 Sarcoma [1, 8–15]. Postoperative radiotherapy is employed routinely similar to the case reported by Gkalpakiotis et al. [17] as it improves survival [5, 7, 8], although there is still an or if bevacizumab improved our patient’s response since extremely high rate of recurrence and local failure [12]. The vascular endothelial growth factor was overexpressed in 80% role of chemotherapy, however, is not well established and of angiosarcoma cases [27]. To our knowledge, this case is hasnot been proven to increasesurvival[12]. the only one to report remission of AS after treatment with As a result of the above-mentioned challenges, treatment bevacizumab and radiotherapy without surgical interven- options are limited, especially since AS is often found in tion. In two case reports from the Duke University, 5 mg/kg elderly patients who may have many comorbidities and of bevacizumab was used in one patient and 10 mg/kg for are more prone to adverse treatment reactions. Prospective the other in conjunction with radiotherapy as postsurgical studies with regard to adjuvant chemotherapy and other treatment [16]. Our patient was given four treatments of treatment combinations are also limited due to the rarity of 5 mg/kg of bevacizumab with radiation therapy as a primary the disease so there are no specific guidelines with regards treatment without surgical resection and achieved complete to treatment. Radiation therapy dose response has been clinical response with a negative pathology on biopsy suggested wherein those receiving greater than 5000 rad have remission. Due to the lack of resection, we cannot report a better local control, though larger case numbers are required complete pathologic response. A second course involving a to validate initially reported successes [5]. There are case higher dose of bevacizumab for his recurrence led to clinical reports of remission with radiotherapy alone; these cases response after three months but had to be discontinued when tend to be well-differentiated and exophytic forms of AS [17]. patient had a stroke, a known risk of bevacizumab though a The addition of another therapy to radiation therapy has meta-analysis done based on 5 randomized controlled trials seen some support over the years; different cases showed AS among 2,288 patients receiving bevacizumab showed no responding to radiation when biological, angiomodulation, statistical difference of stroke incidence compared to control and/or tubulin-affinic substances are given in conjunction [28]. with radiation therapy [5, 16, 18–20, 23–26]. Nevertheless, With AS being very aggressive and having a very low five- the overwhelming opinion about chemotherapy is that year survival rate, therapy with bevacizumab in conjunction its utility remains largely undefined [5]. Major responses with radiation therapy or as a primary therapy may be one have also been reported with paclitaxel, but side effects option to improve survival outcomes especially in patients are dose limiting [24, 25]. A retrospective study done on who are not surgical candidates. Currently, there are two 32 advanced angiosarcoma patients by the soft tissue and phase II clinical trials studying the use of bevacizumab for bone sarcoma EORTC group has 62% response rate in AS which were not available during our patient’s initial advanced angiosarcomas with paclitaxel, with 6 out of 8 scalp diagnosis. One is an open-label multicenter phase II trial and face angiosarcomas responding [18]. There are 6 scalp assessing the median disease-free progression of AS with angiosarcoma patients in the EORTC study, with 3 previously the treatment of bevacizumab alone [29]. The other is the treated with radiation therapy (2 with partial response and study of adding bevacizumab to the combined chemotherapy 1 with progression of disease) and 1 previously treated with of gemcitabine and docetaxel in the treatment of different doxorubicin (no change with paclitaxel). However, there has types of sarcoma including AS [30]. Both trials are currently been a complete response for 42 months on one patient recruiting patients. A prospective clinical trial regarding with scalp angiosarcoma without previous therapy and no neoadjuvant therapy with bevacizumab possibly also includ- previous surgery. Another taxane drug, docetaxel, has been ing chemotherapy would be an interesting approach. In the used for cutaneous AS; a retrospective study of nine patients absence of specific treatment guidelines for AS, the addition in Japan reported a major response in six patients with of bevacizumab to radiation may be one option to offer hope reduced neutropenia and peripheral neuropathy compared to patients who are deemed nonsurgical candidates. to paclitaxel [19]. Published case reports have cited a partial response without surgery [26] and a sustained complete response after surgery in a patient four years later [20] References following the addition of liposomal doxorubicin [20, 21, [1] W. M. Lydiatt, A. R. Shaha, and J. P. Shah, “Angiosarcoma of 26]. Eiling et al. reported a case of confirmed histological the head and neck,” American Journal of Surgery, vol. 168, no. tumor regression of a nonresectable radioresistant scalp 5, pp. 451–454, 1994. angiosarcoma and cervical lymph node metastasis treated [2] M. R. Aust, K. D. Olsen, J. E. 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