Medical Therapy
Advances in diagnosis and chemotherapeutic regimens have improved the prognosis of patients with telangiectatic osteosarcoma. [6, 14, 41, 42, 43] 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. [14, 41, 44, 45]
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:
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Preoperative chemotherapeutic agents can be administered intravenously (IV) or intra-arterially for two to six cycles
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Chemotherapy should include at least two of the following drugs: doxorubicin, methotrexate, cisplatin or carboplatin, and ifosfamide [46]
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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
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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. [47] Because chemotherapeutic protocols are continually evolving, a knowledgeable investigator should always be consulted before such therapy is initiated.
Surgical Therapy
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. [48] 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.
Postoperative Care
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.
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Large blood lakes seen at a low magnification are reminiscent of findings in an aneurysmal bone cyst (hematoxylin and eosin, original magnification X4).
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Careful examination of the lining of blood-filled lakes shows overt malignant cells. Atypical tripolar mitosis is noted in the field (hematoxylin and eosin, original magnification X20).
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Numerous giant cells may be noted in the tumor, which mimics a giant, cell–rich osteosarcoma (hematoxylin and eosin, original magnification X20).
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Areas of necrosis with persistent tumor cells are present after neoadjuvant chemotherapy (hematoxylin and eosin, original magnification X10).
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Anteroposterior radiograph of the distal femur shows a large, aggressive lytic lesion replacing the distal femur with no appreciable intralesional matrix. Courtesy of Robert Lopez-Ben, MD.
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Lateral radiograph of the distal femur shows a large, aggressive lytic lesion that replaces the distal femur with no appreciable intralesional matrix. Courtesy of Robert Lopez-Ben, MD.
Tables
Stage |
Grade |
Location |
Metastasis |
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 |
