Curettage as first surgery for bone giant cell tumor : adequate surgery is more important than oncology training or surgical management by high volume specialized teams.

We reviewed the files of 203 patients with extremities GCTB treated with curettage as first surgery from 1990 to 2013. Median follow-up was 84.2 months. We evaluated whether the years of practice and training in orthopaedic oncology are associated with local recurrences, function and complications after curettage as first surgery for giant cell tumour of bone (GCTB). Local recurrences were not significantly different between orthopaedic oncology trained and non-trained orthopaedic surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. Function was not significantly different between orthopaedic oncology trained and non-trained surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. The only important univariate and multivariate predictor for local recurrence was PMMA adjuvant. Complications were not significantly different between orthopaedic oncology trained and non-trained orthopaedic surgeons and between orthopaedic surgeons with < 10 years and ≥ 10 years of practice. Curettage may be effectively performed as first surgery for GCTB by early-career (< 10 years of practice) non-trained orthopaedic oncology orthopaedic surgeons. PMMA adjuvant is recommended after appropriate curettage.

Extended intralesional curettage preferred over resection-arthrodesis for giant cell tumour of the distal radius.

BACKGROUND: Distal radius giant cell tumour (GCT) is known to be associated with distinct management difficulties, including high rates of local recurrence and lung metastases compared to other anatomic locations. Multiple treatment options exist, each with different outcomes and complications. QUESTIONS/PURPOSES: To compare oncological and functional outcomes and complications following treatment of patients with distal radius GCT by extended intralesional curettage (EIC) or resection-arthrodesis. METHODS: Patients operated on for distal radius GCT were identified from prospectively collected databases at four Canadian musculoskeletal oncology specialty centres. There were 57 patients with a mean age of 35.4 years (range 17-57). Thirteen tumours were Campanacci grade 2, and 40 were Grade 3 (4 unknown). Twenty patients presented with an associated pathologic fracture. There were 34 patients treated by EIC and 23 by en bloc resection and wrist arthrodesis. All resections were performed for grade 3 tumours. The mean follow-up was 86 months (range 1-280). RESULTS: There were a total of 11 (19%) local recurrences: 10 of 34 (29%) in the EIC group compared to only 1 of 23 (4%) in the resection-arthrodesis group (p = 0.028). For the 10 patients with local recurrence following initial treatment by EIC, 7 underwent repeat EIC, while 3 required resection-arthrodesis. The one local recurrence following initial resection was managed with repeat resection-arthrodesis. Six of the 11 local recurrences followed treatment of Campanacci grade 3 tumours, while 4 were in grade 2 lesions and in one case of recurrence the grade was unknown. There were no post-operative complications after EIC, whereas 7 patients (30%) had post-operative complications following resection-arthrodesis including 4 infections, one malunion, one non-union and one fracture (p = 0.001). The mean post-operative Musculoskeletal Tumor Society score was 33.5 in the curettage group compared to 27 in the resection group (p = 0.001). The mean Toronto Extremity Salvage Score was 98.3% following curettage compared to 91.5% after resection (p = 0.006). No patients experienced lung metastasis or death. CONCLUSIONS: EIC is an effective alternative to wide resection-arthrodesis following treatment of distal radius GCT, with the advantage of preserving the distal radius and wrist joint function, but with a higher risk of local recurrence. Most local recurrences following initial treatment by EIC could be managed with iterative curettage and joint preservation. Wide excision and arthrodesis were associated with a significantly lower risk of tumour recurrence but was technically challenging and associated with more frequent post-operative complications. EIC was associated with better functional scores. Resection should be reserved for the most severe grade 3 tumours and recurrent and complex cases not amenable to treatment with EIC and joint salvage. LEVEL OF EVIDENCE: III, retrospective comparative trial.

Long-term results of the Global Modular Replacement System tumor prosthesis for reconstruction after limb-sparing bone resections in orthopedic oncologic conditions: Results from a national cohort.

BACKGROUND AND OBJECTIVES: We investigated implant revision, implant failure, and amputation risk after limb-sparing bone tumor surgery using the Global Modular Replacement System (GMRS) tumor prosthesis in patients suffering from bone sarcomas (BS), giant cell tumors (GCT), or metastatic bone disease (MBD). MATERIAL AND METHODS: A retrospective study of a nationwide consecutive cohort (n = 119, 47 [12-81] years, M/F = 65/54) having limb-sparing surgery and reconstruction using the GMRS tumor prosthesis due to bone tumors (BS/GCT/MBD = 70/8/41) from 2005 to 2013. Anatomical locations were as followed: distal femur (n = 49), proximal femur (n = 41), proximal tibia (n = 26), or total femur (n = 3). Kaplan-Meier survival analysis and competing risk analysis with death as a competing risk were used for statistical analysis. RESULTS: For BS and GCT patients, 5-year patient survival was 72% (95% confidence interval [CI]: 59-85%) and for MBD 33% (95% CI: 19-48%). Thirty-two patients underwent revision surgery (5-year revision incidence 14%; 95% CI: 8-21%). Twelve patients had revision of bone-anchored parts (implant failure) with a 5-year revision incidence 6% (95% CI: 2-10%). Ten amputations were performed due to local relapse (n = 9) or recurrent infections (n = 1) with a 5-year incidence of amputation: 8% (95% CI: 3-13%). CONCLUSIONS: We identified a low risk of revision and amputation when using the GMRS tumor prosthesis for limb-sparing bone tumor.

The prognostic significance of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio in giant cell tumor of the extremities.

BACKGROUND: In this study, the influence of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of giant cell tumor (GCT) of the extremities were investigated. METHODS: The clinical parameters of 163 patients who were diagnosed with GCT of the extremities between July 2008 and January 2018 were retrospectively analyzed. Optimal cutoff values of NLR and PLR were determined using receiver operating characteristic (ROC) analysis. According to optimal cutoff values, patients were divided into high NLR and low NLR groups or high PLR and low PLR groups. Kaplan-Meier and log-rank methods were used to compare the recurrence-free survival (RFS) between the high and low NLR groups, and between the high and low PLR groups. Univariate analysis was performed to determine the influence of age, gender, neutrophil count, lymphocyte count, platelet count, white blood cell count, tumor size, surgical approach and Campanacci stage on the prognosis of giant cell tumor of bone. The main predictors of RFS were determined by Cox multivariate regression analysis. RESULTS: The optimal cutoff value of NLR in giant cell tumor of the extremities was 2.32, which was used to classify patients into high and low NLR groups. The optimal cutoff value of PLR was 116.81, and was used to classify patients into high and low PLR groups. Campanacci stage, tumor maximum diameter, alkaline phosphatase, and C-reactive protein (CRP) were significantly associated with the high NLR and PLR. Cox multivariate regression analysis revealed that the Campanacci stage (HR = 3.28, 95% CI: 1.24~8.69) and NLR (HR = 4.18, 95% CI: 1.83~9.57) were independent prognostic factors for giant cell tumor of the extremities. CONCLUSION: As a novel inflammatory index, NLR has some predictive power for the prognosis of patients with giant cell tumor of the extremities.

Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial.

BACKGROUND: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers. METHODS: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery. RESULTS: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw. CONCLUSION: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases.

Diagnostic value of histone 3 mutations in osteoclast-rich bone tumors.

Differentiating osteoclast-rich lesions of bone (giant cell tumor of bone [GCTB], chondroblastoma [CBA], and aneurysmal bone cyst [ABC]) can be challenging, especially in small biopsies or fine-needle aspirations. Mutations affecting codons 34 and 36 of either H3 Histone Family Member 3A (H3F3A) and/or 3B (H3F3B) are characteristically seen in GCTB and CBAs. We devised a simple assay to identify these mutations and evaluated its applicability for routine clinical diagnosis. One hundred twenty-four tissue specimens from 108 patients (43 GCTBs, 38 CBAs and 27 ABCs) were collected from the archives of the Calgary Laboratory Services/University of Calgary and Vanderbilt University Medical Center. Histology was reviewed by an expert orthopedic pathologist. A single base extension assay (SNaPshot) is used to interrogate each nucleotide in codons 34 and 36 of H3F3A and codon 36 of H3F3B. Final diagnoses were generated after re-reviewing cases and incorporating molecular findings. Of 43 GCTBs, 38 (88%) had an H3F3A G34W mutation; 35 of 38 CBAs (92%) had a K36M mutation in either H3F3B (N = 31; 82%) or H3F3A (N = 4; 11%); none of 27 ABCs had a tested mutation. Molecular findings changed the histomorphologic diagnosis in 5 cases (3 GCTB changed to ABC, and 2 ABC changed to GCTB). These findings support the diagnostic utility of mutational analysis for this differential diagnosis in certain challenging cases when clinicoradiologic and histomorphologic features are not definitive, particularly for distinguishing cellular ABC versus GCTB with secondary ABC.

Giant cell tumor of the pelvis: a systematic review.

This is a systematic review of articles concerning the morbidity, recurrence rate, treatment and treatment complications of pelvic giant cell tumors (GCTs). The key words "giant cell tumor, pelvis" were used to identify articles which included data on patients with pelvic GCTs in English and Chinese databases of published reports from 1949-2012. The articles were filtered by title, abstract and full text. Thirty-eight articles and 165 patients were identified for this review. Data on all identified patients were studies; data in different articles on the same patients was not used repeatedly. The following patient data were collected where possible and subjected to systematic analysis; age, location of GCT, treatment, follow-up, complications, recurrence and whether alive or dead. The mean age of onset was 33.2 years (range, 14-73 years), the peak ages of onset being between 21 and 40 years. A pronounced sex difference was identified, the male : female ratio being 1:1.7. The acetabulum was the commonest area for pelvic GCTs. Forty-eight tumors were primarily located in the iliac, 60 in the acetabular and 31 in the ischiopubic area. Twenty-seven patients experienced complications of treatment. Patients who had been treated by wide resection had the most complications; these included incisional infection and delayed healing of incisions. Local recurrence was common, having occurred in 39/158 patients (24.6%), comprising 24/72 (33.3%) who had undergone intralesional surgery only; 9/20 (45.0%) who had undergone radiotherapy only; 1/51 (2.0%) who had undergone wide resection; and 5/14 patients (35.7%) who had undergone radiation therapy or cryotherapy plus intralesional surgery. Mortality was low (3.2%, 5/158). Pelvic GCT is not common, the acetabular area appears to the most frequent site and the peak age is the third and fourth decades. Although the recurrence rate is high for all pelvic GCTs, the mortality is low. Treatment has a critical influence on recurrence. In spite of the associated complications, the lower local recurrence rate makes wide resection a reasonable option for patients with extensive and/or aggressive GCTs.

Treatment and outcome of malignant giant cell tumor in the spine.

Malignant giant cell tumor (MGCT) in the spine is extremely rare and there is little published information regarding this subject in the literature. We attempted to correlate different treatment options and outcomes over time. A retrospective study of patients with spinal MGCT who were surgically treated in our center between 2006 and 2012 was performed. Overall, three surgical management strategies, including subtotal resection, piecemeal total resection, and total en bloc spondylectomy were applied. Postoperative radiotherapy was carried out in 4 cases. Clinical data and efficacy of surgical treatment strategy were analyzed via chart review. A total of 14 patients with spinal MGCT were included in the study. Three cases were diagnosed as primary MGCT (PMGCT), while the other 11 patients were secondary MGCT (SMGCT). The mean follow-up period was 41 (range 3-75) months. Recurrence was found in 7 patients after surgery in our center, while distant metastasis and death occurred in 4 and 6 cases, respectively. MGCT of bone is always a high-grade sarcoma with a poor prognosis and complete excision, while also preserving neural function, is recommended. In our study, patients who underwent total en bloc spondylectomy had significantly lower local recurrence rate for MGCT in the spine.

Expression of ezrin, CD44, and VEGF in giant cell tumor of bone and its significance.

BACKGROUND: This research aimed to study the role of ezrin, CD44, and VEGF in invasion, metastasis, recurrence, and prognosis of giant cell tumor of bone (GCTB) and its association with the clinical and pathological features of GCTB. METHODS: Expression status of ezrin, CD44, and VEGF in 80 GCTB tissues and its adjacent noncancerous tissue samples were measured with immunohistochemical and Elivison staining. Their correlation with the clinical and pathologic factors was statistically analyzed by chi-square test. RESULTS: The expression status of ezrin, CD44, and VEGF were significantly higher in GCTB tissue samples than in its adjacent noncancerous tissue samples and in GCTB at Campanacci stage III than in Campanacci stages I and II (P < 0.05). No significant difference was found in age and sex of the patients and locations of the tumor (P > 0.05). Survival analysis showed that the expression status of ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB were positively associated with the survival rate of GCTB patients and negatively associated with ezrin and Campanacci stages of GCTB, indicating that ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB are the independent factors for GCTB. CONCLUSIONS: Ezrin, CD44, and VEGF are over-expressed in GCTB tissue and its adjacent noncancerous tissue samples and may play an important role in the occurrence, invasion, metastasis, and recurrence of GCTB. Measurement of ezrin, CD44, and VEGF expression status may contribute to the judgment of prognosis of GCTB patients.

Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study.

Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow-up. The impact of tumor-host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP-2 and to pro-survival proteins NFIB and c-Fos. Kaplan-Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co-overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12-44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor-host endpoints for new biological treatments.

Is intralesional treatment of giant cell tumor of the distal radius comparable to resection with respect to local control and functional outcome?

BACKGROUND: A giant cell tumor is a benign locally aggressive tumor commonly seen in the distal radius with reported recurrence rates higher than tumors at other sites. The dilemma for the treating surgeon is deciding whether intralesional treatment is adequate compared with resection of the primary tumor for oncologic and functional outcomes. More information would be helpful to guide shared decision-making. QUESTIONS/PURPOSES: We asked: (1) How will validated functional scores, ROM, and strength differ between resection versus intralesional excision for a giant cell tumor of the distal radius? (2) How will recurrence rate and reoperation differ between these types of treatments? (3) What are the complications resulting in reoperation after intralesional excision and resection procedures? (4) Is there a difference in functional outcome in treating a primary versus recurrent giant cell tumor with a resection arthrodesis? METHODS: Between 1985 and 2008, 39 patients (39 wrists) were treated for primary giant cell tumor of the distal radius at two academic centers. Twenty patients underwent primary intralesional excision, typically in cases where bony architecture and cortical thickness were preserved, 15 underwent resection with radiocarpal arthrodesis, and four had resection with osteoarticular allograft. Resection regardless of reconstruction type was favored in cases with marked cortical expansion. A specific evaluation for purposes of the study with radiographs, ROM, grip strength, and pain and functional scores was performed at a minimum of 1 year for 21 patients (54%) and an additional 11 patients (28%) were available only by phone. We also assessed reoperations for recurrence and other complications via chart review. RESULTS: With the numbers available, there were no differences in pain or functional scores or grip strength between groups; however, there was greater supination in the intralesional excision group (p=0.037). Tumors recurred in six of 17 wrists after intralesional excision and none of the 15 after en bloc resection (p=0.030). There was no relationship between tumor grade and recurrence. There were 12 reoperations in eight of 17 patients in the intralesional excision group but only one of 11 patients (p=0.049) who underwent resection arthrodesis with distal radius allograft had a reoperation. There were no differences in functional scores whether resection arthrodesis was performed as the primary procedure or to treat recurrence after intralesional excision. CONCLUSIONS: Resection for giant cell tumor of the distal radius with distal radius allograft arthrodesis showed a lower recurrence rate, lower reoperation rate, and no apparent differences in functional outcome compared with joint salvage with intralesional excision. Because an arthrodesis for recurrence after intralesional procedures seems to function well, we believe that intralesional excision is reasonable to consider for initial treatment, but the patient should be informed about the relative benefits and risks of both options during the shared decision-making process. Because arthrodesis after recurrence functions similar to the initial resection and arthrodesis, an initial treatment with curettage remains a viable, and likely the standard, mode of treatment for most giant cell tumors of the distal radius unless there is extensive bone loss. LEVEL OF EVIDENCE: Level III, therapeutic study.

[Giant cell tumour of bone: a series of 97 cases with a mean follow-up of 12 years]. / Tumor de células gigantes óseo. Noventa y siete casos con seguimiento medio de 12 años.

PURPOSE: To describe our series of patients with giant cell tumour of bone with a long-term follow-up to show the results obtained with our treatment protocol. MATERIAL AND METHODS: A total of 97 histologically confirmed giant cell tumour of bone were treated in our center between 1982 and 2009. The mean follow-up period was 12 years (2-27 years). The treatment received was determined by the radiological grade based on the Campanacci classification. The series consisted of 53 women (54.6%) and 44 men (54.4%) with a median age of 34.16 years (15-71 years). The data collected was focused on the clinical presentation, location, phase, extension, recurrences, and complications. RESULTS: The treatment most used in Campanacci grades i and ii was intralesional excision with high velocity drilling and filling with a graft. In grades iii that could not be treated with the aforementioned method, it was decided to perform en bloc resection. An overall recurrence rate of around 25.8% was observed. Seven cases (7.2%) presented with a recurrence of the malignancy. The death rate at the end of follow-up was 2.1% (2 cases). CONCLUSIONS: Curettage with a high-velocity drill and a bone graft in giant cell tumour of bone Campanacci grades i and ii obtain good results after long-term follow-up. Some grade iii giant cell tumour of bone that cannot be treated with this therapeutic option require en bloc resection and reconstruction.

Giant cell tumors of the sacrum--a nationwide study on midterm results in 26 patients after intralesional excision.

PURPOSE: Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). METHODS: We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All patients underwent intralesional excision, 21 with local adjuvants, 5 radiotherapy, 3 IFN-α, 1 bisphosphonates. Functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) score. Statistics were performed with Kaplan-Meier, Cox regression, log rank and Mann-Whitney U. RESULTS: Recurrence rate was 14/26 after median 13 (3-139) months and was highest after isolated curettage (4/5). Soft tissue masses >10 cm increased recurrence risk (HR = 3.3, 95 % CI = 0.81-13, p = 0.09). Complications were reported in 12/26 patients. MSTS was superior in patients without complications (27 vs. 21; p = 0.024). CONCLUSION: Recurrence rate for sacral GCT was highest after isolated curettage, indicating that (local) adjuvant treatment is desired to obtain immediate local control. Complications were common and impaired function.

Ankle fusion with centralisation of the fibula after distal tibia bone tumour resection.

BACKGROUND: Management of distal tibial tumours with limb salvage surgery poses a challenge for the orthopaedic surgeon. This study was done to evaluate the results of fibular centralisation as a technique to reconstruct defects that occurred after resection at this site. MATERIALS AND METHODS: Nine patients with a mean age of 23.2 years (range 17-34) with diagnosis of osteosarcoma in four patients, Ewing's sarcoma in two, giant cell tumour in two and chondrosarcoma in one patient underwent surgical treatment for tumour in the distal tibia. All patients had wide resection of the tumour and ankle arthrodesis with centralisation of the fibula. Patients were assessed clinico-radiologically for bone union, infection and complications. The final functional outcome was estimated according to Musculoskeletal Tumor Society (MSTS) scores. RESULTS: The mean age at the time of surgery was 23.2 years (17-34). There were five females and four males. The mean follow-up was 37 months (range 28-54 months). One of the patients with osteosarcoma had a recurrence a year after limb salvage surgery, underwent above-knee amputation, and died 18 months later due to metastasis. One patient developed leg length discrepancy. The mean MSTS score was 22.75 (range 17-27). CONCLUSION: Fibular centralisation is a durable reconstruction tool for defects of the distal tibial metaphysis with an acceptable functional outcome. It is an inexpensive and simple procedure, with a low rate of late complications, and reproducible results. LEVEL OF EVIDENCE: IV Retrospective case series.

Giant cell tumor with pathologic fracture: should we curette or resect?

BACKGROUND: Approximately one in five patients with giant cell tumor of bone presents with a pathologic fracture. However, recurrence rates after resection or curettage differ substantially in the literature and it is unclear when curettage is reasonable after fracture. QUESTIONS/PURPOSES: We therefore determined: (1) local recurrence rates after curettage with adjuvants or en bloc resection; (2) complication rates after both surgical techniques and whether fracture healing occurred after curettage with adjuvants; and (3) function after both treatment modalities for giant cell tumor of bone with a pathologic fracture. METHODS: We retrospectively reviewed 48 patients with fracture from among 422 patients treated between 1981 and 2009. The primary treatment was resection in 25 and curettage with adjuvants in 23 patients. Minimum followup was 27 months (mean, 101 months; range, 27-293 months). RESULTS: Recurrence rate was higher after curettage with adjuvants when compared with resection (30% versus 0%). Recurrence risk appears higher with soft tissue extension. The complication rate was lower after curettage with adjuvants when compared with resection (4% versus 16%) and included aseptic loosening of prosthesis, allograft failure, and pseudoarthrosis. Tumor and fracture characteristics did not increase complication risk. Fracture healing occurred in 24 of 25 patients. Mean Musculoskeletal Tumor Society score was higher after curettage with adjuvants (mean, 28; range, 23-30; n = 18) when compared with resection (mean, 25; range, 13-30; n = 25). CONCLUSIONS: Our observations suggest curettage with adjuvants is a reasonable option for giant cell tumor of bone with pathologic fractures. Resection should be considered with soft tissue extension, fracture through a local recurrence, or when structural integrity cannot be regained after reconstruction. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Radiotherapy in the management of giant cell tumor of bone.

OBJECTIVES: To evaluate the long-term treatment outcomes for patients with giant cell tumor of bone (GCTB) treated with radiotherapy with or without surgical resection. METHODS: This retrospective review includes 34 patients with GCTB treated with megavoltage radiotherapy between January 1973 and January 2008 at the University of Florida. Patients' ages ranged from 16 to 85 years (median, 29). Tumor sizes ranges from 2.5 to 12 cm (median, 4.8 cm) in the maximum dimension. Twenty-one patients received radiation for gross disease, either de novo (22 patients) or recurrent (12 patients). Thirteen patients were treated with postoperative radiation after gross total resection. The median dose was 45 Gy in both the definitive and adjuvant settings. RESULTS: The median follow-up was 16.8 years. The 5- and 10-year local-control (LC) rates were 85% and 81%, respectively. Six patients developed an isolated local recurrence (2/13 treated postoperatively and 4/21 who were treated for gross disease). All 6 patients who developed a local recurrence were successfully salvaged with surgery; therefore, the ultimate LC rate was 100%. Both the 5- and 10-year freedom from distant metastasis rates were 91%. Three patients developed lung metastases, including 1 patient who experienced GCTB transformation into a high-grade sarcoma. The 5- and 10-year progression-free survival rates were both 78%. CONCLUSIONS: Moderate-dose radiotherapy for GCTB provides a long-term LC >80%, justifying its role as an alternative to morbid surgery.

Soft tissue extension increases the risk of local recurrence after curettage with adjuvants for giant-cell tumor of the long bones.

BACKGROUND AND PURPOSE: Risk factors for local recurrence of giant-cell tumor of bone (GCTB) have mostly been studied in heterogeneous treatment groups, including resection and intralesional treatment. The aim of the study was the identification of individual risk factors after curettage with adjuvants in GCTB. METHODS: Of 147 patients treated for primary GCTB between 1981 and 2009, 93 patients were included in this retrospective single-center study. All patients were treated with curettage and polymethylmethacrylate (PMMA) with (n = 75) or without (n = 18) phenol. Mean follow-up was 8 (2-24) years. Recurrence-free survival was assessed for treatment modalities. Age, sex, tumor location, soft tissue extension, and pathological fractures were scored for every patient and included in a Cox regression analysis. RESULTS: The recurrence rate after the first procedure was 25/93. Recurrence-free survival for PMMA and phenol and for PMMA alone was similar. Eventually, local control was achieved using 1 or multiple intralesional procedures in 85 patients. Resection was required in 8 patients. A higher risk of local recurrence was found for soft tissue extension (HR = 5, 95% CI: 2-12), but not for age below 30, sex, location (distal radius vs. other), or pathological fracture. INTERPRETATION: Curettage with adjuvants is a feasible first-choice treatment option for GCTB, with good oncological outcome and joint preservation. Soft tissue extension strongly increased the risk of local recurrence, whereas age, sex, location, and pathological fractures did not.

Radiotherapy for giant cell tumors of the bone: a safe and effective treatment modality.

BACKGROUND: Giant cell tumor of the bone (GCTB) is a benign or sometimes semi-malignant neoplasm accounting for 5% of all primary bone tumors. This type of tumor has been historically considered as radioresistant, but nowadays radiotherapy (RT) is used in unresectable, recurrent or incompletely resected cases. Since the value of RT is not well defined, a national cohort study was conducted. PATIENTS AND METHODS: Six German institutions collected data from 35 patients treated during the last 35 years and analyzed them. RESULTS: From 1975-2010 16 male and 19 female patients with 39 lesions were irradiated for GCTB. The median age was 30 years and the median follow-up 65 months. Nineteen patients had undergone RT for recurrent or unresectable disease and 16 patients for non-in-sano resection. The actuarial 5-year overall and disease-free survival rates were 90% and 59%, respectively. CONCLUSION: RT is an easy, safe and effective method for the treatment of GCTB. It may provide an attractive alternative to mutilating surgery.

Giant cell tumor of the mobile spine: a review of 49 cases.

STUDY DESIGN: This is a retrospective review of 49 cases of giant cell tumor (GCT) of the mobile spine treated surgically. OBJECTIVE: Our goal was to determine which factors influenced local recurrence. SUMMARY OF BACKGROUND DATA: GCT is a benign, locally aggressive tumor that rarely occurs in the spine. The management of local recurrence can be challenging. METHODS: We performed a retrospective analysis of GCTs of the mobile spine managed between 1970 and 2005. Median follow-up was 145 months with a minimum of 2 years or until death. We used the Kaplan-Meier method to test whether Enneking stage, surgery type, and surgical margin had statistically significant impact on local recurrence. The log rank test was used for comparison, and a P value of less than 0.05 was deemed significant. RESULTS: Of the 49 patients, 11 (22%) local recurrences occurred. The latest recurrence occurred at 60 months. Age less than 25 years was associated with a worse relapse-free survival (P = 0.03). En bloc resection was associated with better local control with Enneking stage III tumors (P = 0.01); however, intralesional resection provided adequate control of Enneking stage II tumors. There were 6 (12%) cases of metastasis, and 2 patients died from the progression of their disease. One patient died from the complications of the surgery. CONCLUSION: En bloc resection should be considered for Enneking stage III GCTs of the mobile spine. The choice of en bloc resection must be balanced with the inherent risks of the procedure. Intralesional resection of Enneking stage II tumors provides adequate local control. Patients should be followed for at least 5 years because local relapse can occur late.

Similar local control between phenol- and ethanol-treated giant cell tumors of bone.

BACKGROUND: Giant cell tumors (GCTs) of bone often are treated with curettage, adjuvant therapy, and cementation. Phenol is a commonly used adjuvant associated with local control rates ranging from 9% to 25%. However, it is corrosive to the eyes, skin, and respiratory tract. Ethanol is readily available and does not cause chemical burns on contact, but it is unclear whether ethanol can achieve similar local control rates as phenol for treating GCTs. QUESTIONS/PURPOSES: We evaluated (1) the recurrence rate and recurrence-free Kaplan-Meier survival function, (2) Musculoskeletal Tumor Society (MSTS) functional score (1993 version), and (3) complications of two groups of patients with GCTs treated with extensive curettage, local adjuvant therapy with phenol or ethanol, and cement reconstruction, to determine if ethanol was a reasonable alternative to phenol. PATIENTS AND METHODS: We retrospectively reviewed all 26 patients with GCTs in the long bones of extremities treated with curettage, high-speed burring, phenolization, and cementation between May 1995 and November 2001, and 35 patients treated with the same protocol, except phenol was replaced with 95% ethanol, between November 2001 and November 2007. The recurrence rates, Kaplan-Meier recurrence-free survival curves, and MSTS functional scores of these two treatment groups were compared with Fisher's exact test, Tarone-Ware test, and Mann-Whitney U test, respectively. The minimum followup was 36 months (mean, 58 months; range, 36-156 months). RESULTS: Local recurrence rates were similar in the two groups: 11% in the ethanol group and 12% in the phenol group. The survival curves (using local recurrence as an endpoint) of the two groups were similar. The mean MSTS functional score was 27.3 (91%) for the ethanol group and 26.9 (90%) for the phenol group. CONCLUSIONS: Ethanol is a reasonable alternative to phenol when adjuvant therapy is considered in the treatment of GCTs of long bones. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.