Neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone and in osteosarcoma located in the extremities: Analogies and differences between the two tumors

Background: Malignant fibrous histiocytoma (MFH) is a rare bone tumor usually treated like osteosarcoma. Studies on analogies and differences between the two tumors have seldom been reported.Patients and methods: Between March 1982 and December 1994, 51 patients with high-grade MFH of bone and 390 with high-grade osteosarcoma were treated with the same regimen of neoadjuvant chemotherapy. All of the tumors in both groups were located in the limbs. Preoperative chemotherapy was performed according to three different, successively activated, regimens consisting of MTX/CDP intraarterially, MTX/CDP/ADM, and MTX/CDP/ADM//IFO.Results: The rate of limb salvage was the same in both the MFH (92%) and osteosarcoma (85%) patients. MFH showed a statistically significantly lower rate of good histologic response, 90% or more tumor necrosis (27% vs. 67%, P = 0.00001) for all three regimens. Despite this low chemosensitivity, the disease-free survivals of the two neoplasms were similar (67% vs. 65%).Conclusions: In terms of histologic response to primary chemotherapy, MFH has a lower chemosensitivity than osteosarcoma. Nevertheless, the two tumors have similar prognoses when treated with chemotherapy regimens based on MTX, CDP, ADM and IFO.     

Bone primary sarcomas undergone unplanned intralesional procedures - the possibility of limb salvage and their oncologic results

BACKGROUND: It is quite rare but some primary sarcomas of the bone can be misdiagnosed as benign and be treated using intralesional procedures. An unplanned surgical excision occurs when tumors are removed without the appropriate preoperative evaluation and consideration for the need to obtain tumor-free margins. Residual tumor tissue as a result of unplanned excision of soft tissue sarcoma is a risk factor for local recurrence. METHODS: Twenty-five patients, undergone unplanned intralesional procedures of lower extremities, were enrolled in this study. There were 22 (88%) cases of osteosarcomas, 2 (8%) MFH of bone and 1 (4%) adamantinoma. Twenty-two (88%) cases had a limb salvage and among them, 4 (18%) cases had local recurrences. Three cases (12%) had amputation without any local event. RESULTS: Lung metastasis developed in 6 (24%) cases. The CDF 5 year survival for 22 osteosarcoma cases was 65%(confidence interval: 52-82%). DISCUSSION: Despite the high recurrence rate, the CDF survival of osteosarcoma cases was comparable to the primary one. Limb salvage procedures are worthwhile in cases whose initial radiographic findings simulate benign lesions, showing favorable response to neoadjuvant chemotherapy. The relative contraindication to the limb salvage is cases with a history of a pathologic fracture and extensive operative fixation.     

Limb salvage surgery for bone and soft tissue sarcoma. A phase II pathologic study of preoperative intraarterial cisplatin.

Preoperative therapy has been tested as part of limb salvage therapy for localized bone and soft tissue sarcoma of the extremities. The activity of cisplatin (CDDP) by intraarterial (IA) infusion was evaluated in 40 cases of which 36 were evaluable for response. All patients had high-grade sarcomas. All but 3 patients received 3 or 4 courses (24 patients received 4 courses) of CDDP at a dosage of 120 to 150 mg/m2 given over 6 hours every 2 weeks by IA infusion. Patients younger than 18 years of age received the higher dose of CDDP. Treatment was well tolerated with combination antiemetics. One patient experienced severe hearing loss with the first cycle of the higher CDDP dose. Pathologic evaluation of resected osteosarcoma showed a favorable response (90% or greater necrosis) in 8 of 20 evaluable cases and in 3 of 4 patients with malignant fibrous histiocytoma (MFH) of bone (without osteoid). In soft tissue sarcomas, minimal (50% to 89%) necrosis was seen in two of nine cases and none had 90% or greater necrosis. Patients received postoperative chemotherapy based on pathologic response, but the value of this postoperative adjuvant therapy requires further follow-up and is uncertain in this small study. IA CDDP can often cause significant tumor necrosis in patients with bone sarcomas, whereas soft tissue sarcomas are less sensitive to this therapy.     

Sarcomas of soft tissue and bone

Sarcomas arise primarily from mesenchymal structures at any site in the body, even within visceral stroma and neurovascular bundles. Sarcomas have been associated with prior radiation therapy, toxic exposures, and genetic conditions and soft tissue sarcomas have been distinguished from bone sarcomas. For localized soft tissue sarcoma, tumor grade is the most important prognostic variable. Low-grade tumors are generally cured by wide surgical excision, but there is a significant rate of both local recurrence and development of distant metastasis in high-grade lesions. The treatment of soft tissue sarcoma histologic subtypes is generally similar grade-for-grade, with the exception of rhabomyosarcoma, Kaposi's sarcoma, and mesothelioma. Tumor location strongly influences resectability. Radiation therapy has been used successfully in conjunction with conservative surgery to improve local control rates for soft tissue sarcomas, particularly in extremity lesions. Currently, adjuvant chemotherapy remains unproven for most adult soft tissue sarcomas, but is established in the treatment of rhabdomyosarcomas, osteosarcomas, and Ewing's sarcomas.     

Sarcomas of the head and neck

With the exception of pediatric RMS, soft tissue sarcomas only rarely arise in the head and neck region. Soft tissue sarcomas include a diverse array of histologic types because of the variety of mesenchymal tissues from which they originate. The combination of infrequent occurrence, varied pathologic features, and the many potential sites of presentation makes these tumors a challenge for the head and neck oncologist and underscore the need for review by a pathologist experienced with soft tissue tumors. Classification schemes that group sarcomas according to grade have been helpful in providing prognostic information. Although local control of the primary tumor is critical to successful treatment of both high- and low-grade lesions, the high rate of distant metastases in high-grade tumors supports the role of combined modality therapy. Compared with other types of head and neck neoplasms, such as squamous cell carcinoma, soft tissue sarcomas have low rates of regional metastases. Surgery generally has been recommended as the primary method of treatment for achieving local control, except in those high-grade tumors arising in sites not amenable to resection. Exceptions to this principle include RMSs of the orbit, paranasal sinuses, and masticator space in children; these are usually treated with radiotherapy and combined multiagent chemotherapy, thereby avoiding the functional and cosmetic impact of surgery. Also, extensive angiosarcomas of the scalp should be treated with multimodality therapy combining surgery and wide-field radiation therapy in an attempt to achieve local control. Adjuvant radiotherapy is generally recommended for high-grade sarcomas, large tumors, close or positive surgical margins, and certain histologic variants. Systemic chemotherapy is recommended for those tumors with a significant risk of distant metastases. Increasingly, neoadjuvant chemotherapy is being used to determine responsiveness to chemotherapy, which can help physicians select patients who may benefit from systemic postoperative therapy. Traditional predictors of treatment failure for soft tissue sarcomas include larger tumor size, high-grade histology, and positive surgical margins. The advent of more advanced reconstructive techniques, including free tissue transfer, has made more aggressive surgical resection of these tumors possible. Nevertheless, a considerable number of ancillary support staff are critical to the patient's postoperative rehabilitation and eventual return to a satisfactory level of function and quality of life. In the future, the discovery of the molecular pathogenesis of specific tumor types, such as the cytogenetic findings in synovial sarcoma, will improve physicians' prognostic abilities and selection of patients who are most likely to benefit from emerging adjuvant therapies.     

The activity of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group

The Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical Oncology Group (JCOG) was established in 2002. At present, 26 institutions are participating as active members of the BSTTSG of the JCOG. In 2004, the first BSTTSG trial, JCOG 0304, was initiated. JCOG 0304 was a Phase II study of perioperative chemotherapy with doxorubicin and ifosfamide for patients with operable, high-grade, non-round cell soft tissue sarcomas (T2bN0M0) arising in the extremities. The results of JCOG 0304 suggested the efficacy of the perioperative chemotherapy on operable soft tissue sarcoma in the extremities and led to planning of the subsequent clinical trial for the disease. The BSTTSG has currently been conducting a Phase III trial, JCOG 0905, to investigate the superiority of the addition of ifosfamide to the standard chemotherapy with methotrexate, cisplatin and doxorubicin for operable, high-grade osteosarcoma. The BSTTSG is also conducting a JCOG ancillary study, JCOG 0905-A1, to evaluate the gene expression profiles of osteosarcoma treated in the JCOG 0905 study. The BSTTSG will further try to develop new standard therapy for bone and soft tissue tumors.     

Preoperative adjuvant therapy for primary malignant bone tumors

In primary bone sarcomas, the efficacy of chemotherapy varies according to the histological types. Prognoses are poor in patients with osteosarcoma or Ewing's sarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses have been improved with adjuvant chemotherapy. Nowadays, in highgrade bone sarcomas, especially in osteosarcoma, Ewing.s sarcoma and malignant fibrous histiocytoma of bone, adjuvant chemotherapy including neoadjuvant or preoperative chemotherapy is usually performed. The purpose of the neoadjuvant chemotherapy is (I) to prevent distant metastases, (II) to reduce the size of the primary tumor and (III) to evaluate the efficacy of the chemotherapeutic agents. Reducing the tumor size facilitates easier excision with less risk of local recurrence. In addition, not only limb-saving but also function-preserving surgery is made possible. Evaluating the efficacy of the chemotherapeutic agents in preoperative chemotherapy facilitates rational selection of postoperative chemotherapeutic agents. Several kinds of anticancer agents are used, and many authors have reported various kinds of protocols and their clinical results. Commonly used drugs include adriamycin, ifosfamide, cisplatin, methotrexate and vincristine in osteosarcoma, and vincristine, adriamycin, cyclophosphamide, ifosfamide, actinomycin-D and etoposide in Ewing's sarcoma. In contrast, chondrosarcomas are chemoresistant, and chemotherapy is rarely performed. Low-grade bone sarcomas, e. g., parosteal osteosarcoma, central low-grade osteosarcoma, are well cured only by surgical excision, and adjuvant chemotherapy is not performed for these low-grade sarcomas. To enhance the efficacy of preoperative chemotherapy, various modalities have been used e. g., intraarterial infusion, caffeine-assisted chemotherapy, and local perfusion with hyperthermia. Good clinical results have been reported.     

Current strategy of chemotherapy for reflactory bone and soft tissue sarcomas

Pulmonary metastases have been curative in some patients of osteosarcoma with aggressive surgical excision and intensive chemotherapy. But several retrospective studies and randomized II studies did not prove survival advantages of advanced cases with bone and soft tissue sarcoma. In treatment for refractory and advanced osteosarcoma after conventional treatments, clinical phase II trials showed 20-30% response ratio of high-dose ifosfamide and etoposide combination or carboplatin combination. In soft tissue sarcomas, high-dose ifosfamide and doxorubicin have over 50% response rate to advanced soft tissue sarcoma and total surgical excision of residual lung metastases prolong the survival. But new drugs active to refractory sarcoma had not reported in a recent decade.     

Large, deep, high-grade extremity sarcomas: treating tumors of the flexor fossae

Limb salvage is now possible for the majority of patients with extremity sarcomas. Although overall prognosis is primarily based on tumor size and histologic grade, complete surgical excision and local control is essential for cure. There are, however, certain anatomic locations such as the flexor fossae in which a complete surgical margin is difficult to attain, and surgery without adjuvant therapy has a high local failure and amputation rate. We have found that preoperative adjuvant therapy consisting of chemotherapy and radiation followed by surgical excision with tumor-free margins has been successful in treating flexor fossa sarcomas with high limb salvage (96%), local control (89%) and overall survival rates (70%). These results are comparable to patients with similar large, high-grade extremity tumors in other compartmental locations.     

Adjuvant therapy for sarcomas.

Adjuvant therapy is currently established in the treatment of osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma. Of the 12 reported randomized studies of adjuvant chemotherapy for soft tissue sarcoma, only 2 show a significant overall survival advantage for chemotherapy (the most important endpoint). In three randomized trials, the survival of the observation arm exceeds that of the chemotherapy arm. In two additional studies, subset analyses currently indicate a significant DFS advantage for adjuvant chemotherapy in extremity lesions, but no significant improvement in survival. Although initial NCI reports showed significantly prolonged survival for the subset of chemotherapy-treated extremity primaries, survival on longer follow-up is no longer significantly different. In the subset analysis of retroperitoneal sarcomas in the same NCI study, the survival of the control group is superior to the treatment group. Doxorubicin associated cardiotoxicity has occurred in about 10% of treated patients, occasionally contributing to treatment-related deaths. Based on these data, adjuvant chemotherapy should be considered investigational for adult soft-tissue sarcomas of any primary site. Future randomized trials should include patients at high risk for metastases (large, high-grade lesions) with a reasonable likelihood of local control by radical resection, or resection with uninvolved margins and subsequent radiotherapy. Low-grade sarcomas are currently cured by surgical resection in 80% of cases, and thus should not be included in adjuvant trials.     

Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma.

BACKGROUND: The purpose of this study was to retrospectively analyze the relationship between neo-adjuvant chemotherapy (NAC) and outcome in patients with high-grade extremity sarcomas. PATIENTS AND METHODS: Inclusion criteria were high-grade, deep, >5 cm extremity soft tissue sarcomas. Patients diagnosed between 1990 and 2001 were treated with surgery only (n=282) or NAC containing doxorubicin/ifosfamide/mesna (AIM) (n=74). The stratified Cox proportional hazards model was used to test the effect of NAC on disease-specific survival and recurrence while adjusting for known prognostic factors. RESULTS: NAC was associated with improved disease-specific survival for this cohort of patients (P=0.02). This overall improvement appears to be driven by the benefit of NAC on disease-specific survival for patient with tumors >10 cm. The 3-year disease-specific survival for tumors >10 cm was 0.62 (95% CI: 0.53-0.71) for patients not receiving NAC and 0.83 (95% CI: 0.72-0.95) for patients receiving NAC. CONCLUSION: NAC with AIM was associated with a significant improvement in disease-specific survival in patients with high-grade extremity soft tissue sarcomas >10 cm. These data emphasize the need for further prospective clinical studies of neo-adjuvant or adjuvant chemotherapy for patients with large high-grade extremity sarcomas.     

SEOM Clinical Guideline of management of soft-tissue sarcoma (2016)

Soft-tissue sarcomas are uncommon and heterogeneous tumors of mesenchymal origin. A soft-tissue mass that is increasing in size, greater than 5 cm, or located under deep fascia are criteria for suspicion of sarcoma. Diagnosis, treatment, and management should preferably be performed by a multidisciplinary team in reference centers. MRI and lung CT scan are mandatory for local and distant assessment. A biopsy indicating histological type and grade is needed previous to the treatment. Wide surgical resection with tumor-free tissue margin is the primary treatment for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not likely of being improved with reexcision. Neoadjuvant and adjuvant chemotherapy improve survival in selected cases, usually in high-grade sarcomas of the extremities. In the case of metastatic disease, patients with exclusive lung metastasis could be considered for surgery. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. New drugs have shown activity in second-line therapy and in specific histological subtypes.     

Bone sarcomas of the head and neck in children: the St Jude Children's Research Hospital experience

BACKGROUND: Bone sarcomas of the head and neck are difficult to resect. The authors reviewed their institutional experience with these tumors to characterize patients' clinical findings and to assess the impact of surgical resection on outcome. METHODS: The records of the 28 patients with bone sarcomas originating in the head and neck treated at St. Jude Children's Research Hospital between March 1962 and January 1998 were reviewed. RESULTS: There were 10 males and 18 females (median age, 12.6 years) each with a single sarcoma: osteosarcoma (18), Ewing sarcoma (7), malignant fibrous histiocytoma (MFH) (2), and fibrosarcoma (1). Primary tumor sites included the maxilla (13), skull (10), mandible (2), and other sites (3). All but one patient with Ewing sarcoma had localized disease at the time of diagnosis. All patients underwent surgery: complete resection, 8; gross total resection, 4; incomplete resection, 14; and biopsy only, 2; 22 also received chemotherapy. Radiotherapy was given to all patients with Ewing sarcoma and to four patients with primary osteosarcoma. Twelve patients survived a median of 8.4 years after diagnosis, 14 died of disease, and 2 died of unrelated causes. Local disease progression was evident in 12 patients (9 with osteosarcoma, 2 with MFH, and 1 with Ewing sarcoma) who died of disease, 9 of whom had the initial treatment of biopsy alone or incomplete resection. Patients with osteosarcoma who had the initial treatment of incomplete resection or biopsy alone were more likely to experience local failure (P = 0.001) and had poorer survival (P = 0.014) than those who underwent complete or gross total resection. CONCLUSIONS: Bone sarcomas of the head and neck are rare among children and most often are localized at the time of diagnosis. Incomplete resection of osteosarcoma is associated with local failure and poor outcome. Although aggressive surgery is essential for the cure of osteosarcoma, its necessity in the treatment of Ewing sarcomas remains controversial.     

Lung resection for metastatic sarcomas: total survival from primary treatment

The results of surgical management of 63 cases of pulmonary metastases from bone and soft tissue sarcomas, admitted at the Istituto Nazionale Tumori of Milan, between 1970 and 1987, are reviewed in this paper. To estimate the relative impact of metastasectomy on the overall performance of treatment, survival curves were calculated from the time of first thoracotomy, as well as from the initial treatment of primary sarcoma. In the present series, total actuarial survival at 10 years was 37% for osteosarcoma, 27% for soft tissue sarcomas, and 24% for the other bone sarcomas, with a median survival of 48, 56, and 36 months, respectively. Five-year survival from the first pulmonary resection was influenced by the number of metastases and the length of the first disease-free interval only in osteosarcoma, while in soft tissue sarcomas a major untoward factor was represented by local recurrence at the site of the primary tumor. These data support the concept of pulmonary metastasectomy as effective salvage therapy for radically treated sarcomas; this management can rescue a significant proportion of all relapsed patients.     

腹部恶性纤维组织细胞瘤47例临床和预后分析

目的探讨腹部恶性纤维组织细胞瘤(MHF)的临床病理特点、治疗策略及预后相关因素。方法回顾性分析1970年1月至2000年1月间天津医科大学附属肿瘤医院47例腹部恶性纤维组织细胞瘤患者手术切除治疗情况。所有患者均经手术病理证实,病变单一。结果术后随访中共有32例患者出现复发、转移,术后单纯局部复发13例(29.5%),出现肺及胸膜转移7例(15.9%),肝转移4例(9.0%),骨转移6例(13.6%),肾脏转移2例(4.5%),复发 转移5例(11.4%)。术后1,3,5年无瘤生存率分别为65.9%、40.9%和29.5%,累计生存率分别为70.5%、52.3%和31.8%,中位生存期为18个月。影响预后的主要因素为肿瘤发生的部位、治疗方式、病理类型、肿瘤的局部复发等。以手术为主的综合治疗较单纯手术及放化疗预后好,术后辅以放疗可降低局部复发率,尤其对那些切端阳性患者。结论腹部MHF侵袭性强,复发率高,病理分级差,以手术切除为主辅以放疗有助于提高患者的远期生存率。     

Spontaneous tumors in dogs and cats: Models for the study of cancer biology and treatment

Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology. The pet population is a vastly underutilized resource of animals available for study. Dogs and cats develop spontaneous tumors with histopathologic and biologic behavior similar to tumors that occur in humans. The tumors with potential relevance for human cancer biology include osteosarcoma, mammary carcinoma, oral melanoma, oral squamous cell carcinoma, nasal tumors, lung carcinoma, soft tissue sarcomas, and malignant non-Hodgkin's lymphoma.Canine osteosarcoma is a malignant aggressive bone tumor with a 90% matastasis rate after surgical amputation. Its predictable metastatic rate and pattern and its relative resistance to chemotherapy make this tumor particularly attractive for studying anti-metastasis approaches. Canine and feline malignant mammary tumors are fairly common in middle-aged animals and have a metastatic pattern similar to that in women; that is, primarily to regional lymph nodes and lungs. Chemotherapy has been minimally effective, and these tumors may be better models for testing biological response modifiers.Oral tumors, especially melanomas, are the most common canine malignant tumor in the oral cavity. Metastasis is frequent, and the response to chemotherapy and radiation has been disappointing. This tumor can be treated with anti-metastatic approaches or biological response modifiers. Squamous cell carcinomas, especially in the gum, are excellent models for radiation therapy studies.Nasal carcinomas are commonly treated with radiation therapy. They tend to metastasize slowly, but have a high local recurrence rate. This tumor is suitable for studying radiation therapy approaches.Primary lung tumors and soft tissue sarcomas are excellent models for studying combined modality therapy such as surgery with chemotherapy or biological response modifiers.Finally, non-Hodgkin's lymphoma is a common neoplastic process seen in the dog. These tumors respond to combination chemotherapy and have great potential as a model for newer chemotherapeutic agents and biological response modifiers.This paper will further elaborate on the relative merits of each tumor type as a model for human cancer therapy and biology.     

Flap reconstruction and interstitial brachytherapy in nonextremity soft tissue sarcoma

Radiotherapy is an integral component of management of high-grade soft tissue sarcomas. Interstitial brachytherapy is used to deliver a boost or radical dose with several advantages over external beam radiotherapy. There has always been a concern to use brachytherapy with flap reconstruction of skin defects after wide excision. We preset our initial experience with interstitial brachytherapy in two patients of recurrent high-grade non-extremity sarcomas treated with surgical excision and soft tissue reconstruction of surgical defect.     

Retroperitoneal sarcomas

Opinion statement The approach to the management of retroperitoneal tumors begins with a complete history and physical examination. Imaging of the abdomen and pelvis by computed tomography (CT) provides both an imaging modality and a method by which to obtain tissue for diagnosis. Because a histologic diagnosis is essential in treatment planning, adequate tissue can usually be obtained by a CT-guided core biopsy. If the diagnosis is sarcoma, additional tests necessary for staging include plain chest radiography and evaluation of the liver by either CT scan or magnetic resonance imaging (MRI). The treatment options for primary retroperitoneal sarcomas include chemotherapy, radiation therapy, surgery, or a combination of these modalities; therefore, a multidisciplinary group best manages treatment planning. Primary radiation therapy for cure is seldom effective for retroperitoneal sarcomas but can provide palliation in select cases. Systemic chemotherapy for chemosensitive lesions, such as poorly differentiated liposarcoma, malignant fibrous histiocytoma (MFH), synovial cell sarcoma, and primitive neuroectodermal tumors (PNET), can be useful when used in a neoadjuvant manner. Consequently, surgical resection continues to be the mainstay of treatment for retroperitoneal sarcomas and requires en bloc resection of the primary tumor. Frequently this includes adjacent organs such as colon, small bowel, kidney, adrenal, and pancreas. Postoperative adjuvant therapy with chemotherapy or radiation has not been proven to be of any additional benefit. Overall treatment results are predominantly influenced by tumor stage, grade, size, and margins of surgical resection. Follow-up CT scans at 6-month intervals and surgical resection of recurrences can be valuable.     

Malignant fibrous histiocytoma: a retrospective study of 109 cases

The purpose of this report is to assess the prognostic factors that could influence management and clinical outcome of malignant fibrous histiocytoma (MFH) of soft tissues. Between 1975 and 1998, 109 patients diagnosed with MFH of the soft tissues, seen at King Faisal Specialist Hospital and Research Center, have been reviewed. Of the 109 patients, 75 were men and 34 were women. The median age at presentation was 48 years (range: 3-94). Seven patients (6%) had regional nodal disease and 10 other patients (9%) with distant metastases were excluded from survival analysis. The remaining 92 patients had localized disease and had surgery as the primary treatment modality with or without radiotherapy and/or chemotherapy. Extremities were the most common location (58%). Tumors less than 5 cm represented 32%, whereas 68% had tumors 5 cm or more. Low-grade tumors constituted 46%, and the remaining 54% were high grade. Thirty-seven percent of patients had positive surgical margins histologically after complete gross resection. The 5- and 10-year relapse-free survival (RFS) rates were 39% and 36%, respectively. Isolated local recurrence occurred in 20 patients (22%), isolated metastatic disease without local recurrence in 9 patients (10%), and combined local and metastatic disease occurred in 20 patients (22%). The overall 5- and 10-year overall survival (OS) rates were 50% and 43%, respectively. On multivariate analysis, tumor size and radiation dose were significant factors for RFS (p = 0.04 and 0.0005, respectively). In terms of OS, size, histologic grade, and surgical margins were significant factors on multivariate analysis (p = 0.001. 0.006, and 0.0001, respectively). Complete surgical resection at the time of primary tumor presentation is likely to afford the best chance for RFS and OS. Radiation therapy plays an important role, in combination with surgery for better local control, particularly in high-grade lesions, and in cases with positive surgical margins after wide complete gross excision. The role of adjuvant chemotherapy remains investigational.