Telangiectatic Osteosarcoma Treatment & Management
- Author: Nirag C Jhala, MD, MBBS; Chief Editor: Harris Gellman, MD more...
Advances in diagnosis and chemotherapeutic regimens have improved the prognosis of patients with telangiectatic osteosarcoma.[5, 13, 38, 39, 40] Because of neoadjuvant chemotherapy, the continuous disease-free survival for patients with telangiectatic osteosarcoma is similar to or better than that for persons with conventional osteosarcoma.[13, 38, 41, 42]
Regarding the choice of chemotherapeutic agents, the treatment of telangiectatic osteosarcoma is similar to that of high-grade osteogenic sarcomas. Reported below are two protocols that are used specifically for the treatment of telangiectatic osteosarcoma.
Although no standard recommendations for chemotherapy in telangiectatic osteosarcoma exist, generalizations can be made regarding the modern treatment of this disease, as follows:
Preoperative chemotherapeutic agents can be administered intravenously (IV) or intra-arterially for two to six cycles
Chemotherapy should include at least two of the following drugs: doxorubicin, methotrexate, cisplatin or carboplatin, and ifosfamide 
For adjuvant chemotherapy, two to six cycles of the same drugs are used; however, non–cross-reacting drugs may be selected for use in patients with a poor response to neoadjuvant chemotherapy
As always, and particularly in the case of rare diseases such as telangiectatic osteosarcoma, experimental treatment options that advance scientific knowledge and ensure high-quality patient care should be considered
Chemotherapeutic approach A
Two cycles of IV methotrexate are administered over 6 hours, beginning on days 1 and 21. This agent is followed by citrovorum factor or leucovorin rescue and, after 9 days, by continuous intra-arterial administration of cisplatin for 72 hours. Surgery follows, and depending on the tumor response (good vs poor), further neoadjuvant therapy may be continued.
Postoperative chemotherapy for patients who have a good response may include at least three cycles of IV doxorubicin for 2 days. On day 21, IV methotrexate is infused over 6 hours, followed by citrovorum factor or leucovorin rescue. Continuous intra-arterial cisplatin administration follows this course on day 28 for 72 hours. Such cycles are administered beginning on days 1, 49, and 105, at least.
For patients who have a poor response, (ie, tumor necrosis in <95% of the tumor in the resected specimen), five cycles of IV doxorubicin are administered for 2 days. On day 21, a combination of bleomycin, cyclophosphamide, and IV dactinomycin is administered for 2 days.
Chemotherapeutic approach B
Preoperative chemotherapy involves two cycles of IV methotrexate over 6 hours, followed by citrovorum factor or leucovorin rescue. This is followed by the administration of cisplatin on day 7 for 72 hours. After 48 hours of cisplatin therapy, the patient should receive IV doxorubicin for 8 hours. The second cycle begins on day 28, and surgery follows this cycle.
If the response to chemotherapy is good, as determined by the amount of tumor necrosis in the resected specimens, at least three cycles of IV doxorubicin may be administered for 2 consecutive days in a 4-hour period on each day. This step is followed by IV methotrexate administered over 6 hours on days 21 and 27, followed by citrovorum factor or leucovorin rescue and intra-arterial cisplatin infusion for 72 hours. This course is repeated after 17 days for at least two additional cycles.
For patients with a poor response to the initial neoadjuvant chemotherapy, four cycles of IV doxorubicin are administered for 2 consecutive days in a 4-hour period each day. On day 21, ifosfamide plus mesna is infused for 5 consecutive days in 90 minutes. This step is followed with IV methotrexate administered over 6 hours on day 42 and then citrovorum factor or leucovorin rescue. On day 48, a combination of cisplatin, as given preoperatively, and etoposide (VP16) is administered in 1-hour infusions on 3 days. This cycle is repeated after 19 days for at least two cycles.
The addition of doxorubicin to preoperative neoadjuvant therapy results in a continuous disease-free survival rate of 82% at a follow-up of 2-7 years (mean, 4 years). This rate is significantly better than the continuous disease-free survival rate of 61% reported for conventional osteosarcomas treated with the same chemotherapeutic protocol.
The Children's Oncology Group and its precursor organizations, the Pediatric Oncology Group (POG) and the Cancer Strategies Group (CSG), have been pioneers with regard to studies aimed at establishing standardized neoadjuvant chemotherapeutic protocols for the treatment of osteosarcomas. Because chemotherapeutic protocols are continually evolving, a knowledgeable investigator should always be consulted before such therapy is initiated.
Surgical management of telangiectatic osteosarcoma depends on the tumor's location, the stage of the disease, and the tumor's response to neoadjuvant chemotherapy.
The primary goal of surgery is the complete resection of the tumor, using wide margins. With the success of current neoadjuvant chemotherapeutic protocols, this goal is usually achieved. However, cases in which the major neurovascular structures are involved or a pathologic fracture has occurred usually require wide excision or radical amputation to completely resect the primary tumor. Intraoperatively, the margins of surgical excision may be evaluated with intraoperative frozen-section examination as indicated.
Margins that are intralesional, marginal, or less than wide result in unacceptably high local recurrence rates that may indicate lower disease-free survival rates. In limb-salvage procedures, the type of reconstruction depends on the primary tumor's location, the structures being resected, the patient's age and activity level, and the surgeon's experience. The resultant function of the patient with a salvaged limb should be determined by using standard Musculoskeletal Tumor Society (MSTS) functional outcome assessments. The local recurrence of disease after limb-salvage procedures is usually treated with wide excision or radical amputation to achieve local control of the disease.
Initial staging studies should include standard radiography, whole-body technetium-99m (99mTc) methylene diphosphonate (MDP) bone scanning, computed tomography (CT) of the chest, and magnetic resonance imaging (MRI) of the primary tumor. MRI scans should include not only the tumor but also the joint proximal to and the one distal to the tumor to detect any skip metastases.
After these studies, biopsy is performed in close consultation with the musculoskeletal oncologic surgeon and the radiologist, as well as with the surgical pathologist, the cytopathologist, or both. A sample can be obtained by means of open biopsy, fine-needle aspiration biopsy, or core-needle biopsy, with image guidance used as indicated. The biopsy incision or tract must be placed so that its site can be resected en bloc at the time of definitive surgery. Therefore, the musculoskeletal oncologic surgeon must be involved in the initial biopsy.
After the preoperative portion of neoadjuvant chemotherapy, the tumor stage is reassessed to determine the effect of the chemotherapy on the local extent of the disease and the presence of any distant metastatic disease. The staging system used by musculoskeletal oncologic surgeons is the surgical system introduced by Enneking, which is advocated by the MSTS. According to this staging system, most telangiectatic osteosarcomas are stage IIB—that is, high-grade, extracompartmental lesions. Some patients present with distant metastatic disease; their tumors are stage IIIB.
After successful resection with limb-salvage methods or amputation, the patient should be closely monitored for recurrence of the tumor and for distant metastatic disease. Standard radiographs should be obtained to assess local recurrence. CT scans of the chest and bone scans are periodically obtained to assess distant metastatic disease.
Ewing J. A review and classification of bone sarcomas. Arch Surg. 1922. 485-533.
Huvos AG, Rosen G, Bretsky SS. Telangiectatic osteogenic sarcoma: a clinicopathologic study of 124 patients. Cancer. 1982 Apr 15. 49(8):1679-89. [Medline].
Larsson SE, Lorentzon R, Wedren H, et al. Osteosarcoma. A multifactorial clinical and histopathological study with special regard to therapy and survival. Acta Orthop Scand. 1978 Dec. 49(6):571-81. [Medline].
Larsson SE, Lorentzon R, Boquist L. Telangiectatic osteosarcoma. Acta Orthop Scand. 1978 Dec. 49(6):589-94. [Medline].
Mervak TR, Unni KK, Pritchard DJ, et al. Telangiectatic osteosarcoma. Clin Orthop Relat Res. 1991 Sep. (270):135-9. [Medline].
Berner K, Johannesen TB, Berner A, Haugland HK, Bjerkehagen B, Bøhler PJ, et al. Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma. Acta Oncol. 2014 Jun 24. 1-9. [Medline].
Sangle NA, Layfield LJ. Telangiectatic osteosarcoma. Arch Pathol Lab Med. 2012 May. 136(5):572-6. [Medline].
Metcalf DJ, Nightingale TD, Zenner HL, et al. Formation and function of Weibel-Palade bodies. J Cell Sci. 2008 Jan 1. 121(Pt 1):19-27. [Medline].
Roessner A, Hobik HP, Immenkamp M, et al. Ultrastructure of telangiectatic osteosarcoma. J Cancer Res Clin Oncol. 1979 Oct. 95(2):197-207. [Medline].
Nishida J, Abe M, Shiraishi H, et al. Familial occurrence of telangiectatic osteosarcoma: cousin cases. J Pediatr Orthop. 1994 Jan-Feb. 14(1):119-22. [Medline].
Bell W, Siegal GP. Osteosarcoma. Cullinane C, Burchill S, Squire J, et al, eds. Molecular Biology and Pathology of Paediatric Cancer. London, England: Oxford University Press; 2003.
Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2010. 152:3-13. [Medline].
Bacci G, Picci P, Ferrari S. Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patients. Eur J Cancer. 1994. 30A(5):620-6. [Medline].
Fechner R, Mills S. Tumors of the bone and joints. Rosai J, Sobin L, eds. Atlas of Tumor Pathology. Washington, DC: Armed Forces Institute of Pathology; 1993. 51-4.
Xie L, Guo W, Li Y, Ji T, Sun X. Pathologic fracture does not influence local recurrence and survival in high-grade extremity osteosarcoma with adequate surgical margins. J Surg Oncol. 2012 Jun 27. [Medline].
Papagelopoulos PJ, Mavrogenis AF, Savvidou OD, et al. Pathological fractures in primary bone sarcomas. Injury. 2007 Nov 29. [Medline].
Raymond AK, Jaffe N. Osteosarcoma Multidisciplinary Approach to the Management from the Pathologist's Perspective. Cancer Treat Res. 2010. 152:63-84. [Medline].
Kunze B, Bürkle S, Kluba T. Multifocal osteosarcoma in childhood. Chir Organi Mov. 2009 May. 93(1):27-31. [Medline].
Brown MJ, Logan PM, O'Connell JX. Diaphyseal telangiectatic osteosarcoma as a second tumor after bilateral retinoblastomas. Skeletal Radiol. 1996 Oct. 25(7):685-8. [Medline].
Chan CW, Kung TM, Ma L. Telangiectatic osteosarcoma of the mandible. Cancer. 1986 Nov 1. 58(9):2110-5. [Medline].
Naik LK, Shetty P, Teerthanath S, Jagadeesh HM. Telangiectatic osteosarcoma affecting the mandible. J Oral Maxillofac Pathol. 2014 Sep. 18 (Suppl 1):S143-6. [Medline]. [Full Text].
Donato G, Lavano A, Volpentesta G. Telangiectatic osteosarcoma of the skull. A post-Paget case. Clin Neuropathol. 1997 Jul-Aug. 16(4):201-3. [Medline].
Merino S, Arrazola J, Saiz A, et al. Post-Paget telangiectatic osteosarcoma of the skull. Skeletal Radiol. 1999 Aug. 28(8):470-2. [Medline].
Wick MR, Siegal GP, Unni KK, et al. Sarcomas of bone complicating osteitis deformans (Paget''s disease): fifty years'' experience. Am J Surg Pathol. 1981 Jan. 5(1):47-59. [Medline].
Wines A, Bonar F, Lam P. Telangiectatic dedifferentiation of a parosteal osteosarcoma. Skeletal Radiol. 2000 Oct. 29(10):597-600. [Medline].
Radhi JM, Loewy J. Dedifferentiated chondrosarcoma with features of telangiectatic osteosarcoma. Pathology. 1999 Nov. 31(4):428-30. [Medline].
Adler CP. Case report 111. Skeletal Radiol. 1980 Feb. 5(1):56-60. [Medline].
Kyriakos M, Hardy D. Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. Cancer. 1991 Oct 15. 68(8):1770-80. [Medline].
Janevska V, Spasevska L, Samardziski M, Nikodinovskai V, Zhivadinovik J, Trajkovskai E. FROM ANEURYSMAL BONE CYST TO TELANGIECTATIC OSTEOSARCOMA WITH METASTASIS IN INGUINAL LYMPH NODES - CASE REPORT. Med Pregl. 2015 Mar-Apr. 68 (3-4):127-32. [Medline].
Mirra JM, Fain JS, Ward WG, et al. Extraskeletal telangiectatic osteosarcoma. Cancer. 1993 May 15. 71(10):3014-9. [Medline].
Graadt van Roggen JF, Zonderland HM, Welvaart K, Peterse JL, Hogendoorn PC. Local recurrence of a phyllodes tumour of the breast presenting with widespread differentiation to a telangiectatic osteosarcoma. J Clin Pathol. 1998 Sep. 51(9):706-8. [Medline]. [Full Text].
Hirakawa T, Tsuneyoshi M, Enjoji M, et al. Ovarian sarcoma with histologic features of telangiectatic osteosarcoma of the bone. Am J Surg Pathol. 1988 Jul. 12(7):567-72. [Medline].
Azura M, Vanel D, Alberghini M, Picci P, Staals E, Mercuri M. Parosteal osteosarcoma dedifferentiating into telangiectatic osteosarcoma: importance of lytic changes and fluid cavities at imaging. Skeletal Radiol. 2009 Jul. 38(7):685-90. [Medline].
White VA, Fanning CV, Ayala AG, et al. Osteosarcoma and the role of fine-needle aspiration. A study of 51 cases. Cancer. 1988 Sep 15. 62(6):1238-46. [Medline].
Vanel D, Tcheng S, Contesso G. The radiological appearances of telangiectatic osteosarcoma. A study of 14 cases. Skeletal Radiol. 1987. 16(3):196-200. [Medline].
Khuu H, Moore D, Young S. Examination of tumor and tumor-like conditions of bone. Ann Diagn Pathol. 1999 Dec. 3(6):364-9. [Medline].
Cui Q, Li D, Liu C, Guo J, Liu S, Liu Y, et al. The significance of MGMT protein detection in evaluation of osteosarcoma necrosis rate after cisplatin chemotherapy. Bosn J Basic Med Sci. 2011 May. 11(2):80-3. [Medline].
Rosen G, Huvos AG, Marcove R, et al. Telangiectatic osteogenic sarcoma. Improved survival with combination chemotherapy. Clin Orthop Relat Res. 1986 Jun. (207):164-73. [Medline].
Weiss A, Khoury JD, Hoffer FA, et al. Telangiectatic osteosarcoma: the St. Jude Children's Research Hospital's experience. Cancer. 2007 Apr 15. 109(8):1627-37. [Medline].
Liu JJ, Liu S, Wang JG, Zhu W, Hua YQ, Sun W, et al. Telangiectatic osteosarcoma: a review of literature. Onco Targets Ther. 2013. 6:593-602. [Medline]. [Full Text].
Rosen G, Caparros B, Huvos AG. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982 Mar 15. 49(6):1221-30. [Medline].
Eftekhari F. Imaging assessment of osteosarcoma in childhood and adolescence: diagnosis, staging, and evaluating response to chemotherapy. Cancer Treat Res. 2010. 152:33-62. [Medline].
Basaran M, Bavbek ES, Saglam S, et al. A phase II study of cisplatin, ifosfamide and epirubicin combination chemotherapy in adults with nonmetastatic and extremity osteosarcomas. Oncology. 2008 Jan 10. 72(3-4):255-260. [Medline].
Ferguson WS, Harris MB, Goorin AM, et al. Presurgical window of carboplatin and surgery and multidrug chemotherapy for the treatment of newly diagnosed metastatic or unresectable osteosarcoma: Pediatric Oncology Group Trial. J Pediatr Hematol Oncol. 2001 Aug-Sep. 23(6):340-8. [Medline].
Rashid M, Hafeez S, Zia Ul Islam M, et al. Limb salvage in malignant tumours of the upper limb using vascularised fibula. J Plast Reconstr Aesthet Surg. 2007 Dec 22. [Medline].
|IA||Low grade, G1||T1||M0, intracompartmental|
|IB||Low grade, G1||T2||M0, intracompartmental|
|IIA||High grade, G2||T1||M0, intracompartmental|
|IIB||High grade, G2||T2||M0, extracompartmental|
|IIIA||Low or high grade, G1 or G2||T1||M1, intracompartmental with metastasis|
|IIIB||Low or high grade, G1 or G2||T2||M1, extracompartmental with metastasis|