Search

Soft tissue sarcomas are a relatively rare, heterogeneous group of tumors arising from mesenchymal tissues and occurring almost anywhere in the body. The rate of progression and likelihood of hematogenous dissemination, usually to the lung, is determined primarily by tumor grade. The likelihood of regional spread is low. Pretreatment evaluation includes computed tomography of the primary site and chest and magnetic resonance imaging of the primary tumor. The mainstay of treatment is surgery; wide excision for low-grade lesions and wide or radical (compartmental) resection for high-grade tumors. Often, these procedures cannot be achieved either because of the location and extent of the sarcoma or anticipated functional deficit. Adjuvant preoperative and/or postoperative radiotherapy improves the likelihood of local control and preserves function when adequate margins cannot be achieved with surgery alone. The role of adjuvant chemotherapy is unclear; however, some data suggest the doxorubicin containing regimens may improve the likelihood of cure for high-grade lesions, particularly large tumors arising in the extremities. Prognosis is influenced by a variety of factors, including age, tumor size, histologic grade, depth (superficial or deep), histologic subtype, and site. Approximately 90% and 98% of recurrences are observed within 5 years and 10 years, respectively. Five-year overall survival rates range from approximately 60% to 80%.

Purpose: The management of isolated local recurrence of soft-tissue sarcoma is therapeutically complex, and functional conservative management is preferable to radical or amputative salvage surgery. This study reviews the University of Florida experience using conservative resection and reirradiation to manage isolated local recurrences of soft-tissue sarcoma., Methods and Materials: Between 1976 and 2005, a total of 14 patients who underwent primary conservative resection and irradiation developed isolated local recurrence and were managed with salvage conservative resection and reirradiation. Of the patients treated, 3 had tumors of the distal extremity, 8 had tumors of the proximal extremity, and 3 had tumors of the trunk. At the time of recurrence, 64% of tumors were greater than 5 cm and 79% were high grade. In combination with gross total resection, 13 of 14 patients received external beam radiotherapy with or without brachytherapy, and 1 patient was treated with brachytherapy alone. Two patients received chemotherapy., Results: The median follow-up was 30 months, and no living patients were lost during follow-up. From retreatment, the 5-year actuarial overall survival, cause-specific survival, and local control rates were 40%, 40%, and 18% respectively. There was a 50% incidence of serious complication requiring either reoperation or leading to permanent functional impairment. Of the 14 patients, only 1 has remained disease free and without significant complications. No treatment factors, including achieving wide surgical margins or delivering higher radiation dosages, seemed to confer an advantage in local control., Conclusions: Salvage therapy for management of locally recurrent soft-tissue sarcoma is challenging, and the effects of reoperation and reirradiation can be severe.

Purpose: To review the clinical characteristics and outcomes of adult patients with Ewing family of tumors treated with radiation at the University of Florida., Methods and Materials: Clinical features, treatment, and outcomes of 47 patients older than 18 years with Ewing family of tumors treated with combined radiation therapy and chemotherapy from 1970 to 2005 were retrospectively reviewed. Analysis was stratified by age older or younger than 30 years. Patients with metastatic disease at the time of diagnosis were excluded from the study., Results: The 29 men and 18 women had a median age of 24 years. Thirty-three patients were 18-30 years old and 14 patients were older than 30 years. Median follow-up of living patients was 8.2 years. The 5-year overall survival rate for all patients was 43% (p = 0.8523). The 5-year local control rate for all patients was 75% (p = 0.9326). The 5-year rate of freedom from distant metastasis for all patients was 45% (p = 0.5471). There were no significant differences in 5-year overall survival, local control, and freedom from distant metastasis rates; patterns of distant failure; or toxicity profiles between older adult patients and younger adult patients., Conclusions: We found that the natural history and treatment outcomes of the Ewing family of tumors were consistently similar in adults (young and old) and children. Thus, aggressive combined modality approaches should be considered for adult patients.

Purpose: This retrospective analysis describes our 35-year experience with respect to disease control and functional status., Patients and Methods: Thirty-five patients with localized Ewing tumors of the pelvis and sacral bones were treated from 1970 to 2005. Twenty-six patients were treated with definitive radiotherapy (RT), and 9 patients were treated with combined local therapy in the form of surgery + RT. The median RT dose was 55.2 Gy. The patients who received RT alone were more likely to be older men with larger tumors exhibiting soft-tissue extension. Patients in the definitive RT group were more likely to receive etoposide and ifosfamide or undergo bone marrow transplant. Median potential follow-up was 19.4 years., Results: The 15-year actuarial cause-specific survival, freedom from relapse rate, and local control rates were 26% vs. 76% (p = 0.016), 28% vs. 78% (p = 0.015), and 64% vs. 100% (p = 0.087), respectively, for patients treated with definitive RT and combined therapy. Overall, tumors <8 cm had significantly better cause-specific survival, but this was unrelated to local control. The median Toronto Extremity Salvage Score for the definitive RT and combined therapy groups were 99 and 94, respectively (p = 0.19). Seven definitive RT patients (27%) had serious complications., Conclusion: Combined modality local therapy should be considered if pelvic Ewing tumors are resectable. However, because of the extent of local disease, most patients have unresectable or partially resectable tumors and therefore require RT in some capacity. For this reason, innovative RT strategies are needed to improve long-term disease outcomes and minimize side effects while maintaining an acceptable functional result.

Periosteal chondroma is a slow-growing, cartilaginous, surface tumor that usually occurs in the second and third decades of life. The youngest reported age at diagnosis is 5 years. Marginal excision is the treatment of choice. We report a case of a periosteal chondroma noted at birth and treated conservatively. This report expands the age range of periosteal chondroma to include neonates and suggests a role for observation in its management.

Purpose: Retrospective review describing the 35-year University of Florida experience with Ewing's tumors of the lower extremity., Patients and Methods: Fifty-three patients were treated between 1971 and 2006. Thirty patients were treated with radiotherapy (RT) alone and 23 patients were treated with surgery +/- RT. Larger tumors and tumors of the femur were treated more often with definitive RT. Median potential follow-up was 19.2 years. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS)., Results: Before 1985, 24% of patients were treated with surgery; since then, the rate has increased to 61%. The 15-year actuarial overall survival (OS), cause-specific survival (CSS), freedom from relapse, and limb preservation rates were 68% vs. 47% (p = 0.21), 73% vs. 47% (p = 0.13), 73% vs. 40% (p = 0.03), and 43% vs. 40% (p = 0.52), respectively, for patients treated with surgery +/- RT vs. RT alone. Excluding 8 patients who underwent amputation or rotationplasty, the 15-year actuarial local control rate was 100% for the surgery +/- RT group and 68% for the definitive RT group (p = 0.03). The ranges of the TESS for surgery +/- RT vs. RT alone were 70-100 (mean, 94) and 97-100 (mean, 99), respectively. Twenty-six percent (6/23) of patients had complications related to surgery requiring amputation or reoperation., Conclusions: Overall survival and CSS were not statistically compromised, but we observed an increased risk of relapse and local failure in patients treated with RT alone, thereby justifying a transition toward primary surgical management in suitable patients. However, despite an adverse risk profile, patients treated with RT alone had similar long-term amputation-free survival and demonstrated comparable functional outcomes. Poor results observed in Ewing's of the femur mandate innovative surgical and RT strategies.

Disuse atrophy is a common clinical phenomenon that significantly impacts muscle function and activities of daily living. The purpose of this study was to implement genome-wide expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Skeletal muscle biopsies were acquired from the medial gastrocnemius in patients with an ankle fracture and from healthy volunteers subjected to 4-11 days of cast immobilization. We identified 277 misregulated transcripts in immobilized muscles of patients, of which the majority were downregulated. The most broadly affected pathways were involved in energy metabolism, mitochondrial function, and cell cycle regulation. We also found decreased expression in genes encoding proteolytic proteins, calpain-3 and calpastatin, and members of the myostatin and IGF-I pathway. Only 26 genes showed increased expression in immobilized muscles, including apolipoprotein (APOD) and leptin receptor (LEPR). Upregulation of APOD (5.0-fold, P < 0.001) and LEPR (5.7-fold, P < 0.05) was confirmed by quantitative RT-PCR and immunohistochemistry. In addition, atrogin-1/MAFbx was found to be 2.4-fold upregulated (P < 0.005) by quantitative RT-PCR. Interestingly, 96% of the transcripts differentially regulated in immobilized limbs also showed the same trend of change in the contralateral legs of patients but not the contralateral legs of healthy volunteers. Information obtained in this study complements findings in animal models of disuse and provides important feedback for future clinical studies targeting the restoration of muscle function following limb disuse in humans.

Malignant peripheral nerve sheath tumors (MPNST) are the most aggressive cancers associated with neurofibromatosis type 1 (NF1). Here we report a practical and reproducible model of intraneural NF1 MPNST, by orthotopic xenograft of an immortal human NF1 tumor-derived Schwann cell line into the sciatic nerves of female scid mice. Intraneural injection of the cell line sNF96.2 consistently produced MPNST-like tumors that were highly cellular and showed extensive intraneural growth. These xenografts had a high proliferative index, were angiogenic, had significant mast cell infiltration and rapidly dominated the host nerve. The histopathology of engrafted intraneural tumors was consistent with that of human NF1 MPNST. Xenograft tumors were readily examined by magnetic resonance imaging, which also was used to assess tumor vascularity. In addition, the intraneural proliferation of sNF96.2 cell tumors was decreased in ovariectomized mice, while replacement of estrogen or progesterone restored tumor cell proliferation. This suggests a potential role for steroid hormones in supporting tumor cell growth of this MPNST cell line in vivo. The controlled orthotopic implantation of sNF96.2 cells provides for the precise initiation of intraneural MPNST-like tumors in a model system suitable for therapeutic interventions, including inhibitors of angiogenesis and further study of steroid hormone effects on tumor cell growth.

Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder that affects the synovium in young and middle-aged adults. Although most believe that it is an inflammatory process, some believe that it is a benign neoplasm. The optimal treatment is surgery. The local recurrence rate after marginal excision for localized PVNS is low. In contrast, the local recurrence rate after open synovectomy for diffuse PVNS is relatively high. The intra-articular instillation of radioactive isotopes or external beam radiotherapy (approximately 35 Gy in 14-15 fractions over 3 weeks) may significantly improve the likelihood of local control and long-term function in patients with incompletely resected diffuse PVNS. The probability of complications after moderate-dose radiotherapy (RT) is low.

Metabolic factors have been proposed to explain strength deficits observed in skeletal muscle with immobilization that are not completely accounted for by changes in muscle cross-sectional area (CSA) and neural adaptations. The aim of this study was to quantify changes in the resting inorganic phosphate (Pi) concentration from the medial gastrocnemius muscle during immobilization, reloading and rehabilitation. Additionally, we assessed the contributions of CSA, muscle activation and Pi concentration to plantar flexor torque during rehabilitation following immobilization. Eight persons with a surgically stabilized ankle fracture participated. Subjects were immobilized for 6-8 weeks and subsequently participated in 10 weeks of rehabilitation. Localized (31)P-Magnetic resonance spectroscopy, magnetic resonance imaging, isometric torque and activation testing were performed on the immobilized and uninvolved limbs. At 6 weeks of immobilization, significant differences were noted between the immobilized and uninvolved limbs for the Pi concentration and the Pi/PCr ratio (P < 0.05). From 6 weeks of immobilization to 3-5 days of reloading, the increase in Pi concentration (15%, P = 0.26) and Pi/PCr (20%, P = 0.29) was not significant. During rehabilitation, the relative contributions of CSA, muscle activation and Pi concentration to plantarflexor torque were 32, 44 and 40%, respectively. Together, CSA, muscle activation and Pi concentration accounted for 76% of the variance in torque (P < 0.01). In summary, our findings suggest that immobilization, independent of reloading, leads to a significant increase in the resting Pi concentration of human skeletal muscle. Additionally, alterations in resting Pi concentration may contribute to strength deficits with immobilization not accounted for by changes in muscle CSA or neural adaptations.

Muscle atrophy is clearly related to a loss of muscle torque, but the reduction in muscle size cannot entirely account for the decrease in muscle torque. Reduced neural input to muscle has been proposed to account for much of the remaining torque deficits after disuse or immobilization. The purpose of this investigation was to assess the relative contributions of voluntary muscle activation failure and muscle atrophy to loss of plantarflexor muscle torque after immobilization. Nine subjects (ages 19-23) years with unilateral ankle malleolar fractures were treated by open reduction-internal fixation and 7 weeks of cast immobilization. Subjects participated in 10 weeks of rehabilitation that focused on both strength and endurance of the plantarflexors. Magnetic resonance imaging, isometric plantarflexor muscle torque and activation (interpolated twitch technique) measurements were performed at 0, 5, and 10 weeks of rehabilitation. Following immobilization, voluntary muscle activation (56.8 +/- 16.3%), maximal cross-sectional area (CSA) (35.3 +/- 7.6 cm(2)), and peak torque (26.2 +/- 12.7 N-m) were all significantly decreased ( p < 0.0056) compared to the uninvolved limb (98.0 +/- 2.3%, 48.0 +/- 6.8 cm(2), and 105.2 +/- 27.0 N-m, respectively). During 10 weeks of rehabilitation, muscle activation alone accounted for 56.1% of the variance in torque ( p < 0.01) and muscle CSA alone accounted for 35.5% of the variance in torque ( p < 0.01). Together, CSA and muscle activation accounted for 61.5% of the variance in torque ( p < 0.01). The greatest gains in muscle activation were made during the first 5 weeks of rehabilitation. Both increases in voluntary muscle activation and muscle hypertrophy contributed to the recovery in muscle strength following immobilization, with large gains in activation during the first 5 weeks of rehabilitation. In contrast, muscle CSA showed fairly comparable gains throughout both the early and later phase of rehabilitation.

Objectives: The purpose of this article is to discuss the natural history, treatment, and outcomes for patients with aneurysmal bone cysts (ABC)., Methods: Review of the pertinent literature., Results: ABCs account for 1% to 2% of all primary bone tumors, usually present in the first 2 decades of life, and exhibit a slight female preponderance. The majority of patients are treated with curettage with local control rates ranging from approximately 70% to 90%. Almost all patients with recurrences are salvaged by one or more additional operations. A small subset of patients is treated with marginal or wide excision and almost all are locally controlled. A few patients with incompletely resectable, aggressive, and/or recurrent ABCs are treated with low-dose (26-30 Gy) radiotherapy (RT) and are locally controlled in approximately 90% of cases., Conclusions: The mainstay of treatment is surgery and most patients are cured with one or more operations. A small subset of patients with incompletely resectable, aggressive, and/or recurrent ABCs may be cured with low-dose RT.

Objective: To discuss the treatment and outcomes for giant cell tumor (GCT) of bone., Materials and Methods: Review of the pertinent literature., Results: GCT is a rare benign bone lesion most often found in the extremities of women in the third and fourth decades of life. Surgery is the mainstay of treatment and usually consists of intralesional curettage; local control rates range from 80% to 90% after this procedure. Patients with extensive, recurrent, and/or biologically more aggressive tumors may require wide excision. A small subset of patients with incompletely resectable GCTs or with lesions that are surgically inaccessible may be treated with moderate-dose radiotherapy (45-50 Gy) and have a 65% to 80% likelihood of being locally controlled., Conclusion: The majority of patients with GCTs are effectively treated with intralesional curettage. Wide excision or radiotherapy is necessary to cure a relatively limited subset of patients with extensive, aggressive, and/or incompletely resectable GCTs.

Objective: Treating soft tissue sarcoma (STS) of the distal extremity is challenging in terms of achieving local control and avoiding complications. It is now accepted that a limb conserving approach provides equivalent survival when compared with radical amputation., Methods: Twenty-three patients with STS involving the hand-wrist or foot-ankle complex received adjuvant radiotherapy (RT) for limb conservation and were evaluated to determine if local control, survival, and functional ability were achieved. The median patient age was 64 and median time of follow-up was 11 years. The location of the sarcoma included the hand (n = 12) or foot (n = 11). Seven patients received preoperative RT (median dose, 50.40 Gy) and 16 patients received postoperative RT (median dose, 64.80 Gy). Patients treated preoperatively and 9 treated postoperatively received hyperfractionated RT at 1.2 Gy twice-daily. Seven patients treated postoperatively received conventional daily-fractionated treatment., Results: Twenty of 23 patients received RT at first presentation; 3 were treated for locally recurrent disease. The 5- and 10-year rates of local control were 91%. The 10-year rates of cause-specific and absolute survival were 96% and 91%, respectively. The 5- and 10-year rates of distant metastases-free survival were 87%. The ultimate limb-conservation rate was 91%. No patient required an amputation because of local recurrence or treatment complications. Function of the hand or foot was maintained for all of the 21 patients for whom limb-conserving treatment was achieved., Conclusions: Combined modality therapy with limb-conserving surgery and adjuvant RT achieves excellent local control (91%) and potential overall survival (91%) rates with excellent functional outcome.

Objective: To evaluate the role of postoperative radiotherapy (RT) for patients with dermatofibrosarcoma protuberans (DFSP)., Methods and Materials: Ten patients were treated with surgery and postoperative RT and had follow-up from 21 to 185 months. Nine patients had DFSP and 1 patient had a fibrosarcomatous component (DFSP-FS). No patient had gross disease at the time of RT., Results: Nine patients with DFSP remained disease free after surgery and postoperative RT. The patient with DFSP-FS experienced a local recurrence after surgery, external beam RT, and a brachytherapy boost, and died with disease. There were no severe complications., Conclusion: Postoperative RT may reduce the risk of local recurrence in patients with DFSP who have a high risk of residual disease after surgery.

The purpose of this article is to review the pertinent literature and to define the optimal treatment of patients with aggressive fibromatosis. Data indicate the likelihood of local recurrence after surgery is high, particularly if margins are positive. Moderate-dose radiotherapy alone for gross disease or after a microscopically incomplete resection yields local control rates of approximately 75% to 80%. Treatment with pharmacologic agents results in objective response rates of approximately 40% to 50%; duration of response is variable. Thus, the optimal management for aggressive fibromatosis depends on tumor location and extent. Surgery is indicated if the lesion appears to be completely resectable with acceptable function and cosmesis. Radiotherapy is indicated for patients with unresectable tumors; those with positive margins after resection should be considered for adjuvant radiotherapy depending on the location and extent of the tumor. Pharmacologic treatment should be considered for patients with progressive disease after unsuccessful local-regional therapy.

Cast immobilization is associated with decreases in muscle contractile area, specific force, and functional ability. The pathophysiological processes underlying the loss of specific force production as well as the role of metabolic alterations are not well understood. The aim of this study was to quantify changes in the resting energy-rich phosphate content and specific force production after immobilization. (31)P-magnetic resonance spectroscopy, three-dimensional magnetic resonance imaging, and isometric strength testing were performed in healthy subjects and patients with an ankle fracture after 7 wk of immobilization and during rehabilitation. Muscle biopsies were obtained in a subset of patients. After immobilization, there was a significant decrease in the specific plantar flexor torque and a significant increase in the inorganic phosphate (P(i)) concentration (P < 0.001) and the P(i)-to-phosphocreatine (PCr) ratio (P < 0.001). No significant change in the PCr content or basal pH was noted. During rehabilitation, both the P(i) content and the P(i)-to-PCr ratio decreased and specific torque increased, approaching control values after 10 wk of rehabilitation. Regression analysis showed an inverse relationship between the in vivo P(i) concentration and specific torque (r = 0.65, P < 0.01). In vitro force mechanics performed on skinned human muscle fibers demonstrated that varying the P(i) levels within the ranges observed across individuals in vivo (4-10 mM) changed force production by approximately 16%. In summary, our findings clearly depict a change in the resting energy-rich phosphate content of skeletal muscle with immobilization, which may negatively impact its force generation.

In the current review, the authors set out to discuss the natural history and treatment of dermatofibrosarcoma protuberans (DFSP), a rare indolent cutaneous tumor. Approximately 10-15% of all DFSPs contain areas of fibrosarcoma (DFSP-FS), and such cases tend to exhibit more aggressive behavior. The optimal treatment for DFSP is resection with wide margins; the likelihood of local control associated with this procedure exceeds 90%. The probability of regional or distant metastases is /= 85% in such patients. Postoperative radiotherapy also is indicated in the rare event that a patient has unresectable macroscopic disease. Experience with the use of radiotherapy alone to treat macroscopic disease is limited., ((c) 2004 American Cancer Society)

This article presents an overview of bone-forming tumors that occur in the upper extremity. Osteoid osteoma, osteoblastoma, osteosarcoma, and Ewing's sarcoma are covered. Each tumor type is described, and suggestions are made for diagnostic workup and differential diagnosis. Locations in the upper extremity where each tumor typically occurs are given. Preferred treatment regimens and incidence of recurrence are also presented.

The optimal treatment of giant cell tumors of the pelvis and sacrum is controversial. Our current patient series was combined with cases identified in a review of the literature published in the past 50 years, yielding a combined group of 239 lesions for study. Recurrence rates were 49% for patients who had radiation therapy alone, 47% for patients who had surgery with intralesional margins, 46% for patients who had surgery with intralesional margins and radiation therapy, and 0% for patients who had surgery with wide margins. Six percent of patients had benign lung metastases develop, 2% of patients had secondary malignancies, 2% of patients died in the perioperative period, and less than 1% of patients had multicentricity. Radiation-induced sarcoma developed in 11% of patients who received radiation for primary or recurrent lesions. Larger doses of radiation therapy did not decrease the rate of local recurrence. Recurrence after surgery and radiation was not lower than after either treatment alone. Local recurrence was more likely in the patients with sacral tumors (48%) than in the patients with pelvic tumors (34%). Disease status was worse in the patients with sacral lesions (23% died of disease) than in the patients with pelvic lesions (6% died of disease).

The biopsy of a musculoskeletal lesion is an important event, the outcome of which guides patient management and helps determine patient prognosis. The principles of biopsy include complete radiologic staging before the biopsy, thorough prebiopsy planning including consultation with the pathologist and radiologist, determining the most appropriate method of biopsy (fine needle, core needle, open surgical biopsy), placing the biopsy tract appropriately, and making sure the biopsy tract can be removed at the time of resection, avoiding contamination of uninvolved structures, avoiding transverse incisions, preventing pathologic fracture, handling biopsy tissue appropriately, and considering referral before biopsy. The common errors of biopsy include sampling errors, postbiopsy hematomas, the use of transverse incisions, tumor implantation, and the treatment of an unsuspected sarcoma with prophylactic fixation. Thoughtful prebiopsy planning and careful completion of the biopsy can result in an expedient and accurate diagnosis. If the treating physician lacks significant expertise in performing biopsy and management of patients with musculoskeletal lesions, then referral to a musculoskeletal oncologist before biopsy should be considered.

We analyzed chondrosarcomas of bone to assess whether Grade 2 tumors are more appropriately grouped with Grade 1 chondrosarcomas or Grade 3 and dedifferentiated chondrosarcomas (Musculoskeletal Tumor Society Stage I or Stage II). A retrospective chart review identified 109 patients who presented with nonmetastatic chondrosarcoma. Data were gathered on each tumor's histologic grade, extent (intracompartmental versus extracompartmental), resection margin status, and site (axial versus appendicular). The cohort included 60 males and 49 females with a mean age of 50 years. Forty tumors were located in the axial skeleton and the remainder were distributed throughout the appendicular skeleton. Fifty-three tumors were Grade 1, 40 tumors were Grade 2, eight tumors were Grade 3, and eight tumors were dedifferentiated. Statistical analysis established grade as the only significant variable for this group of patients; extracompartmental tumor spread also correlated with outcome, but not independent of the grade. Margin status and site were not statistically significant with respect to outcome. Chi-square analysis also established that Grade 2 tumors are grouped more appropriately with the Grade 1 chondrosarcomas as Musculoskeletal Tumor Society Stage I neoplasms. These data should be considered when developing the surgical plan, particularly for patients with Grade 2 appendicular chondrosarcomas.

For giant cell tumors of bone, does radiotherapy provide a safe and effective treatment? This retrospective review includes 24 patients with 26 histologically diagnosed tumors treated with megavoltage radiotherapy between March 1972 and July 1996. Of the 10 recurrent tumors, five had an intralesional resection, two had a biopsy, and three had no biopsy before radiotherapy. Of the 16 previously untreated tumors, one was irradiated after a marginal resection, five after an intracapsular resection, and 10 after biopsy alone. The total doses ranged from 35 to 55 Gy (median, 43 Gy) in fractions of 1.67 to 2.33 Gy per day. Twenty of 26 tumors (77%) were controlled locally. All of the local recurrences occurred within the irradiated field. Five of six patients with local recurrence were treated successfully with additional surgery. Salvage surgery after local recurrence required amputation of an extremity in three patients and a total knee replacement in one patient. The ultimate local control rate was 96% with one patient alive with progressive disease. Lung metastases in one patient were treated successfully with surgery, chemotherapy, and radiotherapy. In one patient a radiation-induced sarcoma developed 22 years after treatment. The authors conclude that radiation therapy is a safe and effective treatment option for benign giant cell tumors of bone. A total dose greater than 40 Gy is the only variable found to significantly influence local control.

The results of treatment of 28 patients with Stage IE primary lymphoma of bone were evaluated. Nine patients were treated with curative intent with irradiation alone and 19 patients received radiotherapy combined with adjuvant chemotherapy. Local control was 100%. The 10-year freedom-from-relapse rate was 53%; all relapses were distant metastases, and the median time to failure was 1 year. All patients with relapses succumbed to their disease. The 10-year cause-specific survival rate was 48%. The 10-year survival rate was 53%. Multivariate analysis of survival suggested that pathologic fracture before treatment, age greater than 60 years, no aggressive chemotherapy, and lesions that were not in long bones may influence these end points. Two patients (7%) sustained moderate or severe late toxicity. Although the likelihood of local control after treatment of Stage IE primary lymphoma of bone is very high with radiotherapy, more effective systemic regimens are needed. A significant proportion of patients with this disease die of distant metastases, despite the use of what are considered standard doxorubicin-based chemotherapy regimens.

Purpose: To review a large single-institution experience in the management of aggressive fibromatosis to determine the effectiveness of external beam radiotherapy (EBRT) and identify the presentation and treatment variables predictive of locoregional control., Methods and Materials: Between 1975 and 2000, 72 patients were treated with EBRT for a pathologically confirmed diagnosis of aggressive fibromatosis. Thirty patients were treated at the primary presentation and 42 at the time of a locoregional recurrence. Minimal 2-year follow-up data were available for 65 patients (median 6 years). Megavoltage irradiation with 60Co to 20 MV photons or electron therapy was used for all patients. Most patients were treated after attempted complete surgical resection; 16 patients underwent pretreatment biopsy alone. The prescribed treatment was standard (1.8 Gy) daily fractions in 42 cases and 1.2 Gy fractions b.i.d. in 23 cases. The median prescribed dose was 54 Gy. The prognostic variables and treatment results were evaluated by Kaplan-Meier actuarial analysis., Results: Locoregional control was achieved in 52 of 65 patients. The 5-year actuarial locoregional control was 83%. Locoregional failure occurred in 13 patients (11 in patients with recurrent tumors). Only two failures occurred within the irradiation fields; nine failures occurred at the field margins. Eleven patients were salvaged by surgery: wide excision in nine and amputation in two. The only prognostic factor significant for locoregional control was primary vs. recurrent presentation (p = 0.0193). The 5-year locoregional control rates for irradiation at initial presentation and at recurrence were 96% and 75%, respectively. The variables without significance for locoregional control included primary tumor location, surgical procedures performed, resection margins, and gross vs. microscopic residual tumor at irradiation. Lymphedema was the most common late effect, occurring in 7 patients, 5 with prior treatment. Bone fracture occurred in 3 patients; all 3 had fibromatosis involving the bone at presentation but without recurrence at the time of fracture., Conclusion: EBRT is effective treatment for aggressive fibromatosis. The probability of locoregional control decreases with multiple prior recurrences.

Three patients initially diagnosed with benign giant cell tumors of bone who had lung metastases develop were treated with whole-lung radiotherapy as part of the therapeutic treatment of their distant disease. External beam therapy to 16 Gy in 10 fractions was delivered to the whole lung, with a boost of 35 to 45 Gy to sites of gross metastatic disease. One patient's lung metastases progressed after treatment, and the patient soon died. The two other patients were long-term survivors (7.5 years and 13 years) with complete resolution of detectable disease. One of the two patients required two additional courses of local radiation to metastatic sites. The authors therefore recommend whole lung radiotherapy to 16 Gy with an additional boost to 35 to 45 Gy to gross disease as an option for patients with pulmonary metastases who are poor surgical candidates, who refuse thoracic surgery, whose disease is technically unresectable, or whose disease recurs or progresses after surgery or chemotherapy.

The goal of the current study was to analyze the oncologic results and wound complications in patients with soft tissue sarcomas treated with preoperative radiation therapy and en bloc resection. A standard protocol of preoperative radiotherapy was administered followed by en bloc resection in 209 patients. The protocol included needle or incisional biopsy, prospective staging, a consistent dose of radiotherapy, standardized prospective evaluation of surgical margins, and long-term followup. The target radiotherapy dose was 50.4 cGy. Twenty-nine patients had low-grade lesions, and 180 had high-grade lesions. The mean followup was 55 months. The significant wound complication rate was 22% (moderate 14%, major 7%, and amputation 1%). Wound complications were significantly higher in patients with lower extremity lesions when compared with patients with upper extremity or axial lesions, and in patients with lesions larger than 5 cm. The local recurrence rate was 11% in patients who did not have prior surgery, and 37% in patients who had prior surgery at an outside institution (17% overall). Local recurrence was increased significantly in patients who had prior surgery. At latest followup, 78 patients (47%) were continuously disease-free, six (4%) were alive with no evidence of disease, nine (5%) were alive with disease, 63 (38%) died of disease, and 11 (7%) died of another cause. The 2- and 5-year disease-specific survival rates were 77% and 67%, respectively. Overall survival was 56%. A significant decrease in survival was seen in patients who had a local recurrence, and in patients with high-grade lesions. Preoperative radiotherapy can be given safely with a wound complication rate not significantly higher than that reported for other forms of radiotherapy delivery. Local recurrence tends to be higher if surgical intervention is done before tertiary center referral. Distant disease continues to be the cause of the high mortality in these patients.

One hundred eight patients with low-grade soft tissue sarcoma treated at the authors' institution from 1984 to 1999 were reviewed retrospectively. Low-grade sarcomas were defined as those designated as Grade I of III or Grade I or II of IV. Patients who presented with recurrent tumors or who had multiple procedures at outside institutions were excluded. The patient's gender, age at diagnosis, histologic diagnosis, site and depth of primary involvement, and specimen size at resection were noted. Involvement of periosteum, bone, and neurovascular structures also was recorded. The decision to use radiation therapy was made case-by-case. Indications for preoperative radiation therapy included tumor adjacent to the neurovascular bundle or bone where a marginal surgical margin was anticipated. Indications for postoperative radiation therapy included followup resection of an unsuspected malignancy. Patients were evaluated according to treatment rendered. Sixty-six patients were treated with surgery alone, whereas 42 patients had excision of the tumor in conjunction with radiation therapy. The overall local control rate was 97.2% (105 of 108). There were no statistically significant differences in local recurrence, wound complication, fibrosis, or survival between the two groups. Patients treated with radiation therapy had an increased incidence of postoperative lymphedema. Kaplan-Meier 10-year survival rates were approximately 90% for both groups.

The current study was done to assess the oncologic outcomes after inadvertent intraoperative contamination in the treatment of musculoskeletal sarcomas, to determine the prognostic significance of these events. Forty-three patients with malignant lesions and either positive margins or intraoperative tumor penetration are included in the study. There were 12 bone lesions and 31 soft tissue lesions. The final margin was intracapsular in 11 patients, contaminated marginal in 13 patients, and contaminated wide in 19 patients. Thirty-two patients received radiation therapy with doses from 4560 to 7000 cGy. The mean followup was 69 months (range, 24-179 months). In patients in whom the surgical margin was contaminated, additional tissue was removed with the goal being to obtain tumor-free surgical margins. Local recurrence occurred in four of 32 patients (12.5%) with no gross residual tumor. There was a significant difference in the recurrence rate between a wide (0 of 19) versus a marginal or intracapsular margin (nine of 24) based on the final surgical margin. High-grade lesions were more likely to recur than low-grade lesions, and soft tissue lesions were more likely to recur than bone lesions. Similar to previous reports, treatment of inadvertent contamination with reexcision and irrigation of the wound results in a similar recurrence rate to cases without contamination. Efforts should be made to achieve a wide final margin. Adjuvant therapies should be used whenever feasible.

Since 1969, 144 patients with previously untreated Ewing's sarcoma of bone were entered in prospective protocols at the University of Florida. From 1969 through 1981, three institutional protocols were used, and some patients were entered into the First Intergroup Ewing's Sarcoma Study. Starting in 1982, an attempt was made to intensify treatment, with patients divided according to their primary tumor size into standard-risk (< or = 8 cm in maximum diameter) and high-risk groups. Patients with metastases at diagnosis also were considered high risk. The standard-risk protocols (Number 1 and Number 2 specified treatment with chemotherapy considered to be standard for the era; the patients who were high risk had standard chemotherapy followed by end-intensification. Treatment for patients with metastases at diagnosis was intensified additionally in 1993 with a protocol (high-risk protocol Number 5) specifically designed just for these patients. The absolute survival rate of all patients treated before 1982 was 50% at 5 years for patients without metastases at diagnosis and 18% for patients with metastases. Patients with small primary lesions had a better survival rate than patients with large primary lesions. After 1982, the 5-year survival rate for patients treated on the standard-risk protocols was 53% (1985-1998), whereas for high-risk protocols the 5-year survival rate was 63%. Survival rates were better for younger patients at diagnosis and for patients who responded well to induction chemotherapy, indicating that future trials may need to tailor therapy based on the response to induction chemotherapy.

Although continuous infusion of local anesthetic through nerve sheath catheters provides excellent pain control after amputation, the influence of this technique on the incidence of phantom limb pain is controversial. The current retrospective study examined the influence of continuous nerve sheath catheter analgesia and primary anesthetic technique (general or regional anesthesia) on the incidence of phantom limb pain. After institutional review board approval, data were gathered on patients who had amputation from 1990 to 1999. Medical records were reviewed to determine the level of and indication for amputation, age at time of amputation, current disease status, date of diagnosis and surgery, and primary anesthetic technique. Six months after amputation, preoperative pain, phantom limb sensations, and phantom limb pain were assessed using a verbal scale ranging from 0 (no pain) to 10 (worst pain) and methods of pain control also were evaluated. Thirty-nine patients completed the study. The incidence of phantom limb pain (visual analog scale score > or = 3) was 67% and was lower than the historic incidence (80%) before the use of this analgesia technique. Incidence of phantom limb pain was higher for patients requiring proximal versus distal amputations. The primary anesthetic technique (general versus regional) did not affect the incidence of phantom limb pain. Long-term followup showed that the incidence of phantom limb pain in patients receiving continuous nerve sheath catheter infusion is lower than previously reported for patients who had amputation for oncologic indications.

Twenty pathologic fractures occurred in 285 patients with soft tissue tumors that were treated with radiation therapy and surgery. Twelve of these fractures occurred in 11 patients from a subpopulation of 163 patients with 168 soft tissue tumors of the thigh (155 soft tissue sarcomas and 13 aggressive fibromatosis). The fractures occurred at a mean of 40.5 months after treatment and were not associated with significant trauma. Risk factors associated with the development of fracture included tumor location within the anterior compartment of the thigh, extensive surgical periosteal stripping, and a marginal or intralesional margin of resection. The dose, timing, and fractionation of radiation therapy were not related to the risk of fracture. A high rate of complications was seen with this series, including fracture nonunion (45%) and deep infection (20%). Prophylactic intramedullary fixation of the femur should be considered for patients undergoing resection of large tumors in the anterior compartment of the thigh requiring extensive periosteal stripping and adjuvant radiation therapy.

Vascular reconstruction and limb salvage surgery has been the authors' preferred approach when malignancy involves major vessels of the extremities. Treatment of 16 patients involved resection, with vascular grafting in 14 patients and rotationplasty in two patients. The major vessels were surrounded by tumor in six patients, nearly encased in three patients, invaded by tumor in four patients, and widely contaminated by intralesional surgery in three patients. The tumor stage included one Stage IB, 12 Stage IIB, two Stage IIIB sarcomas, and one multiply recurrent carcinoma. The largest average tumor dimension was 9.5 cm, and the length of grafting was 14 cm. Major nerves were sacrificed in eight (50%) patients, flaps or muscle transfers were done in seven (44%), chemotherapy was administered in nine (56%), radiation therapy was used in four (25%), and pulmonary metastasectomy was done in two (12%). At a mean followup of 56 months, 50% (eight of 16) of patients were alive without disease. Local recurrence was 12% (two of 16 patients), and infection was 12% (two of 16 patients). Limb salvage was achieved in 88% (14 of 16 patients), and functional status was judged good or excellent in 81% (13 of 16 patients). The complication rate observed in this subset of patients is significant, yet local control and the incidence of major complications was acceptable. Results observed from this series and data gathered from the literature clearly indicate that patients can avoid amputation, despite malignant involvement of major vessels to their extremities.

The treatment of soft-tissue sarcomas has undergone significant changes over the past several decades. Previously, patients were often treated with surgery alone, which frequently necessitated amputation of the affected extremity. Less extensive, limb-sparing operations combined with adjuvant irradiation are now feasible for most patients without compromising the likelihood of cure.

Purpose: An aneurysmal bone cyst (ABC) is a rapidly expansile and destructive benign tumor of bone that is usually treated by curettage and bone graft, with or without adjuvant treatment. For recurrent tumors, or tumors for which surgery would result in significant functional morbidity, does radiotherapy (RT) provide a safe and effective alternative for local control?, Patients and Methods: Nine patients with histologically diagnosed aneurysmal bone cysts without other associated benign or malignant tumors were treated at the University of Florida with megavoltage RT between February 1964 and June 1992. The patients received local radiotherapy doses between 20 and 60 Gy, with 6 patients receiving 26--30 Gy. In 6 patients the diagnosis was made by biopsy alone; 3 underwent intralesional curettage before RT. Minimum follow-up was 20 months; 7 of 9 patients (77%) had follow-up greater than 11 years., Results: No patient experienced a local recurrence (median follow-up, 17 years). One patient required stabilization of the cervical spine 10 months after RT because of dorsal kyphosis from vertebral body collapse. No other significant side effects were experienced, and no patients developed secondary malignancies. Four patients were lost to follow-up: at 20 months, 11.5 years, 17 years, and 20 years after the initiation of treatment, none with any evidence of local recurrence. All of the patients who had significant pain before RT had relief of their symptoms within 2 weeks of completion of therapy., Conclusions: Using modern-day RT, patients with recurrent or inoperable aneurysmal bone cysts can be treated effectively (with minimal toxicity) using a prescribed tumor dose of 26--30 Gy.

Adamantinoma of long bones is a rare neoplasm predominantly involving the tibia. Cytogenetic studies of adamantinoma are few. Cytogenetic or molecular cytogenetic analysis of four adamantinomas, and a review of eleven cases in the literature reveals extra copies of chromosomes 7, 8, 12, 19, and 21 as recurrent in this neoplasm. Adamantinoma may be confused with a variety of primary and metastatic epithelial and mesenchymal neoplasms. Observation of these aneuploidies may be useful in establishing the diagnosis of adamantinoma.

Two cases are presented in which an allograft was inserted to salvage a previous allograft bone reconstruction that had followed resection for osteosarcoma. In each instance an allograft-allograft junction was created and, with time, healed. In the first case, a fracture of a distal femoral osteoarticular allograft was salvaged by adding a second allograft and a total knee arthroplasty. This construct preserved the majority of the allograft and allowed rapid rehabilitation. In the second case, an allograft arthrodesis of the knee was salvaged after fracture by replacing the distal portion of the fractured allograft with a new allograft. Again, an allograft-allograft junction was created and healed within 6 months. Allograft fractures pose challenging reconstructive problems. In these two cases, the addition of more allograft facilitated continued limb salvage and function.

Osteoid osteoma is a benign bone tumor. Patients usually require surgical treatment for reliable pain relief. Difficulties with intraoperative localization of the tumor and anatomic locations that carry a high morbidity with en bloc resection complicate open surgery. Various methods have been developed to lessen the invasiveness of surgery including computed tomography-guided percutaneous radiofrequency thermal ablation. Eleven patients in three different centers were evaluated and diagnosed with osteoid osteoma based on typical histories, physical examinations, and imaging studies. All patients were treated with computed tomography-guided percutaneous radiofrequency thermal ablation after medical treatment failed. Excellent pain relief was reported in 10 patients. One patient suffered recurrence of a femoral neck lesion despite an initial 7-month period without pain. Patients were given a questionnaire to quantify the effectiveness of percutaneous radiofrequency ablation in terms of pain relief and return to function. The current study shows that percutaneous radiofrequency thermal ablation provides reliable, excellent pain relief and early return to function with minimal morbidity as compared with traditional open techniques. The authors suggest that this technique be used for all patients with extraspinal osteoid osteomas that are not immediately adjacent to neurovascular structures.

Aims: Dermatofibrosarcoma protuberans is a rare condition which is frequently misdiagnosed at presentation, resulting in a high incidence of local recurrence due to inadequate resection. The archives of the Department of Orthopaedics at the University of Florida were analysed to investigate the natural history and results of treatment for this tumour., Methods: Between 1975 and 1996, 35 cases of DFSP were treated at the University of Florida. Of these, one was treated primarily, five were treated for local recurrence, 17 had tumour bed excisions following inadequate primary excisions elsewhere and 12 had tumour bed excisions following inadequate resection of local recurrences elsewhere. The data were analysed to assess the impact of age, gender, duration of symptoms, tumour site and size, surgical margin, number of operations and adjuvant treatments on survival and local recurrence outcomes., Results: Complete follow-up was available for 34 patients. Mean follow-up was 58 months (range 12-144 months). Thirty-three patients remain alive and disease-free. One patient died of unrelated causes. The margins obtained were wide in 28 patients, marginal in six and intralesional in one. Of the seven patients with inadequate surgical margins, four received adjuvant radiation therapy and remain disease-free. No patient with an adequate margin developed a local recurrence, but there were three local recurrences in the patients with an inadequate margin who did not receive adjuvant radiation therapy (local recurrence rate: 8%). No patient developed lymphatic or distant metastasis. Local recurrences were more likely to be classified Stage IB (17/17) than primary tumours (1/18) (P<0.001). Local recurrence was more likely where the surgical margin was less than 2.5 cm from the lesion., Conclusions: Dermatofibrosarcoma protuberans is a low-grade tumour that has a high potential for local recurrence unless it can be completely excised. The overall rate of local recurrence in referred patients in this series was 20/35 cases (57%). All occurred after inadequate margins at previous surgery in other institutions. Revision surgery in these patients showed a local recurrence rate of 8%. To avoid extensive surgery for recurrences, initial treatment should be by wide excision incorporating the underlying deep fascia and a cuff of 2.5-3 cm of normal skin tissue. Radiation therapy provides a useful adjunct where adequate margins cannot be obtained., (Copyright 1999 W.B. Saunders Company Ltd.)

Intraoperative evaluation of bone marrow margins by frozen section analysis is a common practice in the surgical treatment of osteogenic sarcoma. The purpose of this study was to assess the clinical use of intraoperative marrow margin evaluation to rule out occult intramedullary tumor extension in osteosarcoma surgery. One hundred twenty-eight consecutive patients with high grade osteosarcoma diagnosed between 1988 and 1996 (Group 1) were reviewed retrospectively and compared with 92 consecutive patients treated from 1979 to 1984 (Group 2). Eighty-five patients in Group 1 met the inclusion criteria of having high grade intramedullary lesions of the long bones observed on preoperative magnetic resonance imaging evaluation of the lesion and intraoperative frozen section analysis of the bone marrow margin. Thirty-three patients in Group 2 met the same inclusion criteria with the exception of having preoperative magnetic resonance imaging. Ninety-two marrow margins in Group 1 and 33 marrow margins in Group 2 were evaluated by frozen section. All 92 marrow margins in patients in Group 1 were negative by frozen section analysis and permanent histologic analysis. Of the 33 marrow margins in patients in Group 2, three (9.1%) were reported positive for tumor. Of these, one was found to be a false positive result on permanent pathologic examination. In addition, one false negative frozen section result was found, which was positive for tumor on permanent pathologic examination. The difference in true positive results of marrow margins between Group 1 and Group 2 was statistically significant. Intraoperative marrow margin evaluation by frozen section is not mandatory with modern imaging techniques. Preoperative evaluation of tumor extent using magnetic resonance imaging and intraoperative evaluation of the specimen by the pathologist (done by bivalving the specimen) are reliable methods to ensure adequate surgical margins in most cases of conventional osteosarcoma of the long bones.

Arthrodesis of the knee may be indicated for the reconstruction after resection of tumor around the knee. Since the introduction of this technique, resection arthrodesis using segmental autogenous grafts has been the principal method of reconstruction. From August 1967 to February 1985, 73 patients underwent resection arthrodesis using autogenous grafts. All procedures were performed for malignant or potentially malignant lesions. Ten-year followup was available on 40 patients. The reconstructive procedure was performed using an intramedullary rod and hemicortical femoral or tibial grafts with a single autogenous nonvascularized fibula or with dual nonvascularized fibulae. Despite a high surgical complication rate, the majority of patients achieved successful limb salvage. Independent ambulation was achieved by 86% of the patients. A Musculoskeletal Tumor Society functional evaluation in 32 available patients at a mean of 17 years showed the majority of patients functioning satisfactorily. Long-term followup of these patients shows continued durability of the reconstruction and a persistent high level of function and patient satisfaction. Resection arthrodesis using massive autogenous grafts should continue to be in the armamentarium of the orthopaedic oncologist.

Objective: We prospectively compared the ability of two techniques--bone scintigraphy with single-photon emission computed tomography (SPECT) of the chest and CT of the chest--to reveal potential osteosarcoma metastases of the lung., Subjects and Methods: Our study included 27 patients with osteosarcoma who prospectively underwent both bone scintigraphy with SPECT of the chest and CT of the chest. The imaging results were compared with outcome or pathologic analysis of any lung lesions found., Results: Eight (30%) of the 27 patients had pulmonary metastases. Four of these eight patients had positive results on both CT studies and bone SPECT studies, with additional lesions detected with bone SPECT in two of these four patients. The other four patients with pulmonary metastases had positive results on CT studies, whereas the results of bone SPECT studies remained negative. The results of bone SPECT studies were negative in the 19 patients without pulmonary metastases. CT, however, showed abnormalities in seven (37%) of the 19 patients, which were eventually attributed to benign conditions., Conclusion: Negative results on a bone SPECT study of the chest should not be used to exclude the possibility of lung metastases. However, if the results are positive, a bone SPECT study can be used to confirm abnormalities seen on CT scans and may also reveal subtle lesions missed on CT scans.

Purpose: The necrotic effect of chemotherapy on primary osteosarcoma has been shown to be predictive of the final outcome. Little attention has been paid to the local response of the host (LHR), which reflects the tumour-host relationship., Design: A four-step grading system was developed based on distinct histological patterns of the LHR around the lesion. These responses were correlated with the chemotherapy-induced necrosis or chemosensitivity and analysed in an attempt to ascertain their influence on the patient prognosis. The ability of conventional radiographs and computed tomography to measure LHR was studied., Methods: The grading system was applied to macroslides of specimens obtained from 72 patients with stage II B primary osteosarcoma in various limbs after wide resection and complete courses of pre- and postoperative chemotherapy who were treated between 1985 and 1991 with a median follow-up of 5 years and 9 months. The histological specimens were blindly reviewed by two pathologists and two experienced musculoskeletal oncologists to assign a grade of response. The results were correlated with tumour necrosis, patient survival and response features on conventional radiographs and CT images., Results: Significant correlation was found between LHR and tumour necrosis or chemosensitivity (r=0.55) and between LHR and CT response (r=0.56). There was no correlation between LHR and the findings on conventional radiographs. A grade 4 LHR was predictive of long-term survival., Conclusions: The LHR to preoperative chemotherapy has a prognostic influence on patient survival and can be predicted by CT.