Analyzing the hazard ratios associated with recurrence, we found intralesional surgery had a greater risk (p = 0.042) of local recurrence compared with wide resection (hazard ratio, 8.71) (Table 4). Among patients undergoing intralesional procedures, those treated with polymethylmethacrylate and local phenol application had a smaller risk (p = 0.030) for local recurrence than patients treated with bone grafting and local phenol application (hazard ratio, 3.232). For patients treated with bone grafting, additional phenol application did not decrease the risk (p = 0.799) of recurrence (hazard ratio, 1.129).
Among the disease-related and demographic factors analyzed for their impact on recurrence, only age at the time of diagnosis was associated with risk (p = 0.019) of local recurrence. Subgroup analysis revealed patients 25 years and younger at diagnosis had the greatest hazard of local recurrence. Age at diagnosis was an independent risk factor for recurrence regardless of the status of the disease and the chosen treatment. The increased risk of recurrence in young patients was not biased by other variables such as type of surgery (p = 0.089), adjuvants (p = 0.22), tumor grade (p = 0.67), tumor extension (p = 0.72), and pathologic fractures (p = 0.63).
Pulmonary metastases occurred in five patients. In three, pulmonary metastases were associated with recurrent disease; two patients had pulmonary metastases develop without local recurrence. Treatment of pulmonary metastases consisted of a multidisciplinary approach, including wedge resection, chemotherapy, and radiotherapy. With this approach, a status of no evidence of disease or stable disease was achieved in two and three patients, respectively.
Intralesional curettage has been established as the preferred treatment for most GCTs. Wide resection is reserved for tumors with extensive destruction, impossible joint salvage, and when expendable bones (ie, fibular head or distal ulna) are affected [14, 16, 23, 27, 31, 32, 51]. We analyzed the recurrence-free survival after treatment of GCT with an emphasis on the impact of surgical approach, adjuvant therapy, tumor presentation, and demographic factors on the risk of recurrence in 118 patients.
Although this investigation benefits from a large group of patients with extended followup, there are several clear limitations to this retrospective study. First, data were gathered from clinical files, and patients were not contacted to assess ultimate outcomes. Second, although the total sample size is relatively large, the number of patients in each treatment group becomes relatively small and limits our ability to draw conclusions. Finally, we limited patients to those treated primarily at our institution. However, this study design did allow us to analyze a large cohort of patients consistently treated. We also had access to a complete set of data for the patients included in this study.
Phenol is a commonly used adjuvant for GCT treatment. Phenol induces tumor necrosis [24, 41] with few adverse effects [35, 47]. However, tissue penetration is poor and limits tumor necrosis to superficial cell layers . Yun et al. found a negligible necrotizing effect of phenol and discounted it as an adjuvant after curettage of bone tumors . Others also have reported little effect of phenol on recurrence [1, 47, 49]. However, Durr et al. did report decreased local recurrence with the use of phenol . In the current study, we did not find any effect of adjuvant phenol treatment on GCT recurrence.
Age at diagnosis independently predicted recurrence regardless of the status of the disease and the aggressiveness of the chosen treatment: recurrence rate decreased as the patient’s age increased. The greater risk of young patients having recurrence develop has been reported  and may be associated with increased bone turnover in young people [21, 34]. This hypothesis is supported by studies showing inhibition of bone turnover with bisphosphonates reduced the risk of recurrence of GCT [7, 9, 17, 48].
Other demographic and disease-related variables (gender, location, tumor grade, soft tissue extension, and pathologic fracture) had no influence on local recurrence in our patients included in this study. Previous studies also have shown that gender, location, and tumor grade did not influence recurrence [1, 3, 43, 50]. The prognostic relevance of soft tissue expansion and pathologic fractures is controversial [1, 3, 15, 22, 31, 38, 40, 50]. Becker et al. found the prevalence of soft tissue extension influenced the risk of local recurrence  and O’Donnell et al. reported pathologic fractures were associated with an increased recurrence rate . The aggressiveness of the treatment should be considered when interpreting the correlation of soft tissue expansion or pathologic fractures and local recurrence. In the current study, wide resection was performed in 18% and 20% of T1 and T2 tumors, respectively, indicating the recurrence rates of T1 and T2 tumors were not biased by differences in the aggressiveness of surgical treatment. In tumors with and without pathologic fractures, wide resections were performed in 47% and 14%, respectively. Thus, patients with pathologic fractures more commonly received resections. In this retrospective study, this may underestimate the risk of recurrence in patients with pathologic fractures.
The rate of pulmonary metastases in our study patients was 4%, similar to previous reports reporting ranges from 0% to 4% [3, 4, 8, 10, 15, 20, 30, 39, 42, 44, 49]. Two of five patients were diagnosed with metastases at presentation, showing patients with GCT are at risk for development of synchronous pulmonary metastases. Although GCT is classified as a benign lesion , few patients develop progressive lung metastases with poor outcomes [2, 6, 44]. Our treatment approach, including wedge resections, radiotherapy, and chemotherapy, achieved disease eradication or stability in all patients with pulmonary metastases.
It is difficult to quantify the real morbidity (physical and emotional) of patients who experience recurrence and require repeat surgery. Based on the results of this study, we recommend intralesional surgery for treating most GCTs; the selection of bone graft versus polymethylmethacrylate remains individualized. Because young age is a risk factor for local recurrence, we favor the use of polymethylmethacrylate in young patients as the best way to minimize recurrence and preserve the native joint. Similarly, when little bone stock remains or for patients with questionable compliance for a limited weightbearing rehabilitation, methylmethacrylate is favored for its immediate stability. Local phenol treatment did not reduce the risk of recurrence, and we no longer consider phenol an effective adjuvant. Finally, patients with adverse presentations or an adamant desire for one surgery may be best suited for resection at the time of presentation. However, because the treatment of pulmonary metastases in patients with GCT usually controls the disease and metastases may occur independent of recurrence, we believe the potential risk for development of pulmonary metastases should not by itself create an indication for wide resection of primary tumors.
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