Keywords
giant-cell tumor - treatment - resection - polymethyl metacrylate
Introduction
Giant cell tumor (GCT) of the bone is a neoplasm of mesenchymal origin that commonly
presents as an osteolytic lesion at the epiphysial-metaphyseal region of long bones.
It accounts for more than 20% of all primary bone neoplasms and 5% of primary bone
tumors in adults. It typically affects patients aged from 20 to 50 years, with no
gender-related differences.[1]
[2] It is locally aggressive in skeletally-mature patients in more than 80% of cases,
and it occurs around the knee in 75% of patients.[2] The distal radius is affected in 10% of 15% of the cases,[3] and this is a site particularly prone to recurrence.[4]
Local recurrence is commonly due to narrow surgical margins.[3]
Several modalities have been used to treat GCTs. However, recurrence rates range from
10% to 54%, reflecting therapeutic efficacy.[5] The optimal treatment for GCTs remains controversial.[6]
The present study aims to identify the recurrence rate of CGT in patients treated
with curettage and cementation during a minimum follow-up of 3 years ([Figure 1]).
Fig. 1 Trans- and postsurgical exemplification: (A) Transoperative radiograph after intralesional curettage and preparation of the Campanacci
stage-II giant-cell tumor cementing bed associated with a pathological fracture of
the tibial plateau. (B) Radiograph at 15 years of follow-up with no cement loosening and 6.5-mm screws,
without radiographic data indicating recurrence.
Material and Methods
Retrospective and observational cohort of a registry of patients diagnosed with GCT
of any gender and age treated with intralesional curettage and cementation from 1981
to 2011. The cases eligible for this treatment were those in Enneking stages 1 and
2 (with no soft-tissue invasion). Age, gender, anatomical region, recurrence, and
mean time until recurrence were identified.
The sampling technique was convenience of consecutive cases.
Descriptive statistics were used with measures of central tendency (mean, median,
and mode) for non-grouped quantitative variables, in addition to dispersion measures
(standard deviation). We used descriptive statistics with frequency measures, that
is, percentages for qualitative variables. Incidence calculations were performed.
The present article is in accordance with the ethical standards for scientific research
on human beings of the Nüremberg Declaration and its amendments. In addition, it is
in full compliance with the Regulations of the Mexican General Health Law on Health
Research and institutional ethical standards. Informed consent letters were not required
since information was obtained from secondary sources.
The research team did not receive third party contributions or sponsorships.
Results
In total, 375 cases of GCT were reviewed. The mean age at presentation was 27 years,
(mean: 27 ± 11.9 years; range: 12 to 80 years), with a peak of incidence in the third
decade of life (45.33%, n = 233). Regarding gender, 190 cases (50.6%) occurred in men, and 185 (49.4%), in
women, with a male-to-female ratio of 1.03:1 ([Figure 2]).
Fig. 2 Distribution of cases of giant-cell tumor regarding age and gender.
A total of 141 cases (37.6%) were treated by curettage and cementation ([Figure 3]). The mean follow-up was of 144 months, ranging from 48 to 240 months. In subjects
treated with this method, the mean age was 27 ± 9 years (range: 13 to 64 years); regarding
gender, 77 (54.6%) cases occurred in men, and 64 (45.4%), in women.
Fig. 3 Treatment modality for giant-cell tumor. PMMA (polymethyl methacrylate): Curettage
and cementation. Other: other treatment modalities.
All treated cases occurred in the appendicular skeleton, including 38.3% (54 cases)
in the tibia, 32.6% (46 cases) in the femur, 11.3% (16 cases) in the humerus, 8.5%
(12 cases) in the radius, 3.5% (5 cases) in short bones, 2.8% (4 cases) in the ulna,
1.4% (2 cases) in the clavicles, and 1.4% (2 cases) in the fibula. Pathological fracture
was observed in 22 (15.7%) cases ([Figure 4]).
Fig. 4 Sites of anatomical involvement with giant-cell tumor treated by curettage and cementation.
Note the higher number of cases in the long bones of the lower limb.
Recurrence occurred in 12.7% (18) of the cases ([Figure 5]). In total, 16 patients underwent en bloc resection as the surgical treatment, and
reconstruction was carried out with resection arthrodesis with an endomedullary nail
in 6 cases, tumor prosthesis in 9 cases, and external fixation in 1 case; another
case underwent a new marginal resection and cementation, and 1 case was not treated
due to hematological complications (coagulopathy).
Fig. 5 Recurrence rate in giant-cell tumor treated with curettage and cementation. No case
was submitted to revision curettage and cementation. One case was not treated due
to hematological complications.
Discussion
The classic treatment for CGTs has been curettage and bone grafting to preserve the
function of the adjacent joint.[7] In 1969, Vidal et al.[8] treated 2 cases of GCT with acrylic cement in an attempt to create stability after
surgical curettage. Persson et al.[7] treated 14 patients using this method, with a recurrence rate of 15%. This technique
is simple, with no need for bone grafting. In addition, it provides immediate fixation
and stabilization, and spares joint function. Disease control is improved, and local
recurrence is easy to detect.[5]
Regarding cementation, heat treatment lowers cell viability.[5] Wilkins et al.[9] demonstrated bone necrosis at 60° C. Leeson[10] showed that the polymerization reaction produces necrosis, extending the macroscopic
surgical margin and decreasing the probability of recurrence; on the other hand, it
releases a toxic monomer.[11] The margins obtained with this technique are between 1.5 mm to 2 mm in cancellous
bone and of 0.5 mm in cortical bone.[12]
Another advantage of cementation is the possibility of immediate fixation and stabilization
of large defects, especially in load-bearing bones.[5] In contrast, if the construct fails, methyl methacrylate does not prevent other
forms of treatment, such as bone grafting or total joint reconstruction.[6]
Currently, there is no consensus on the optimal curettage surgical technique, including
adjuvants to limit recurrence, and possibly combined with high-speed reaming to improve
the effectiveness of the curettage.[3]
[13]
[14]
Most recurrences occur within 2 years of the initial surgery, but can be observed
up to 7 years after the surgical treatment.[13]
O'Donnell et al.[16] studied 69 patients and noted a local recurrence rate of 25%, with a mean time until
onset of 2 years, regardless of age and gender; the recurrence rate was higher in
patients not treated with high-speed ream or phenol application. For Jamshidi et al.,[2] recurrence occurred after a mean time of 30 months (range: 6 to 54 months), with
higher rates after simple curettage (33.3%) compared to high-speed reaming (16.6%);
there were no differences regarding cementation, confirming the findings from O'Donnell
et al.[16] Zuo et al.[3] demonstrated that this method reduces the risk of recurrence. Bini et al.[6] observed a recurrence rate of 8% in 38 patients. In one case, recurrence was in
soft tissues, while the remaining were local, suggesting that the low primary recurrence
depends on meticulous and aggressive debridement and on the local adjunctive effects
of acrylic cementation.[6] Boons et al.[12] described one case of recurrence in four patients. Becker et al.[14] reported a higher risk of local recurrence in extracompartmental tumors, and this
method reduces the risk of local recurrence by 22% compared to simple curettage and
bone graft provision. Recurrence-free outcomes were observed in 87% of intracompartmental
tumors treated with this method compared to 64% of extracompartmental lesions.[14] Kivioja et al.[17] reported a rate of 19% of local recurrence, including 75% of cases diagnosed within
the first 2 years after surgery, and none after 5 years. Gitelis et al.[18] reported recurrences in 12.5% (5) of their patients during a mean follow-up of 58.2
months.[18] Labs et al.[19] reported a local recurrence rate of 13.3% (2 patients), with only one case treated
with methyl methacrylate adjuvant. Fraquet et al.[20] studied 30 patients and reported a recurrence rate of 30%, including 77% within
the first 2 years of follow-up, and 66% in the distal femur. According to these authors,[20] the cytotoxic properties of the cement can reduce recurrence from 25% to 17%. Zhang
et al.[21] evaluated 101 patients with a recurrence of 12.7%, and concluded that the key aspect
is aggressive curettage and the use of cement as an adjuvant. In 91 patients, Balke
et al.[22] described recurrences in 27.6% of the patients treated with this method, reducing
this possibility by a factor of 8 when compared with isolated intralesional curettage.
Portabella et al.[23] treated 10 cases of GCTs with curettage and cementation during a mean follow-period
up of 11 years without observing recurrences; these outcomes were attributed to the
surgical technique.[24]
In the Mexican population, Moreno-Wright et al.[11] found a recurrence rate of 25.7% from 6 to 16 months of follow-up, and 1 (2.8%)
patient died due to tumor activity, and the remaining subjects were treated with en
bloc resection.[11]
Regarding the treatment consisting of intralesional curettage and phenol and methyl
methacrylate as adjuvants.[25] Klenke et al.[26] evaluated 41 patients submitted to intralesional curettage treatment, and observed
a recurrence rate of 25% and a mean interval of recurrence of 16 ± 12 months; subjects
treated with local methyl methacrylate and phenol had a better recurrence-free survival
rate (85%) compared to those submitted to a bone graft with the application of phenol
(66%); as such, the use of phenol did not improve the recurrence-free rate.[26] Lackman et al.[27] evaluated 63 patients, and reported a local recurrence rate ranging from 5.4% to
7.7%. Saiz et al.[28] evaluated 40 patients submitted to this type of treatment, and described a recurrence
rate of 12.5% in a mean period of 11 months.
Gao et al.[29] reported local recurrence in 12.9% of the cases treated with curettage and cementation,
including 81.3% within the first 2 years of follow-up.
In 677 cases treated with intralesional resection and various adjuvants, Rock[30] observed a total recurrence rate of 25.5% in a mean period of 21 months, including
81% of recurrences within the first 3 years of follow-up. McDonald et al.[31] identified the surgical margin as the only factor influencing the risk of local
recurrence.
Dreinhöfer et al.[32] reported 10 cases of fracture upon presentation which were treated with curettage
and cementation. These authors[32] described a recurrence rate of 20% within the first year of follow-up, and a total
recurrence rate of 40%. They recommend this method for pathological fractures.[32] However, O'Donnell et al.[17] reported a recurrence rate of 50% in patients with pathological fractures ([Table 1]).
Table 1
|
AUTHOR
|
YEAR
|
CASES
|
FOLLOW-UP (months)
|
TREATMENT
|
RECURRENCE
|
|
Persson et al.[7]
|
1984
|
14
|
−
|
MR and PMMA
|
15.0%
|
|
Rock[30]
|
1990
|
677
|
−
|
Variable
|
25.5%
|
|
O'Donnell et al.[16]
|
1994
|
69
|
48
|
MR, PMMA, phenol
|
25.0%
|
|
Bini et al.[6]
|
1995
|
38
|
63
|
MR, PMMA
|
8.0%
|
|
Dreinhöffer et al.[32]
|
1995
|
10
|
−
|
MR, PMMA
|
40.0%
|
|
Portabella et al.[23]
|
1998
|
10
|
132
|
MR, PMMA
|
0.0%
|
|
Zhang et al.[21]
|
1999
|
101
|
96
|
MR, PMMA
|
12.7%
|
|
Labs et al.[19]
|
2001
|
11
|
56
|
MR, PMMA
|
13.3%
|
|
Boons et al.[12]
|
2002
|
4
|
84
|
MR, PMMA
|
25.0%
|
|
Moreno-Wright et al.[11]
|
2003
|
31
|
56.5
|
MR, PMMA
|
27.5%
|
|
Saiz et al.[28]
|
2004
|
40
|
−
|
MR, PMMA, phenol
|
12.5%
|
|
Gitelis et al.[18]
|
2005
|
40
|
58.2
|
MR, PMMA
|
12.5%
|
|
Lackman et al.[27]
|
2005
|
63
|
108
|
MR, PMMA, phenol
|
5.4%-7.7%
|
|
Jamshidi et al.[2]
|
2008
|
82
|
74
|
MR, PMMA
|
16.6%
|
|
Becker et al.[14]
|
2008
|
102
|
64.2
|
MR, PMMA
|
22.0%
|
|
Kivioja et al.[17]
|
2008
|
194
|
2.4-216
|
MR, PMMA
|
19.0%
|
|
Balke et al.[22]
|
2008
|
91
|
12.4
|
MR, PMMA
|
27.6%
|
|
Fraquet et al.[20]
|
2009
|
30
|
76
|
MR, PMMA
|
30.0%
|
|
Klenke et al.[26]
|
2011
|
41
|
108
|
MR, PMMA, phenol
|
25.0%
|
|
Zuo et al.[3]*
|
2013
|
374
|
60-108
|
MR, PMMA
|
−
|
|
Gao et al.[29]
|
2014
|
31
|
38.8
|
MR, PMMA
|
12.9%
|
|
Abat et al.[24]
|
2015
|
71
|
144
|
MR, BG
|
28.2%
|
According to Lackman et al.,[27] Dreinhöfer et al.,[32] and other authors, the extraosseous extension of a GCT is not a contraindication
to intralesional curettage and adjuvant treatment with methylmethacrylate.[26]
[32]
Using adjuvants, the recurrence rate ranges from 27% to 15% compared to 49% with isolated
intralesional curettage.[15] Turcotte[33] reported similar recurrence rates without methyl methacrylate or other adjuvants,
contradicting this premise. However, Abat et al.[24] observed a recurrence rate of 28.2% in 71 cases treated with resection and bone
grafting in the residual defect, with a mean follow-up time of 12 years.
Gambini et al.[34] reported the use of adjuvant therapy as part of the treatment for GCT. In addition,
they described a lower risk of recurrence due to thorough tumor excision, since adjuvants
alone cannot prevent recurrence if the tumor is not properly removed.
Some of the recommendations of surgical techniques made by other authors for GCT treatment
include adequate exposure, tumor isolation, careful manipulation to avoid soft-tissue
contamination, thorough curettage, intracavitary reaming, adjuvant use, and proper
bone reconstruction.[35]
Conclusion
According to the available evidence, in our environment, intracompartmental resection
combined with acrylic cementation for the treatment of GCT is a viable option, with
recurrence rates consistent with those reported by other authors.
