Edited by: Zongbing You, Tulane University, United States
Reviewed by: Qingsong Zhang, Wuhan Pu'ai Hospital, China; Jiacan Su, Second Military Medical University, China
This article was submitted to Surgical Oncology, a section of the journal Frontiers in Oncology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
A giant cell tumor of bone (GCTB) is a primary bone tumor with potential invasion, local recurrence, and low probability of distant metastasis (
GCTBs grow in an expansive manner and easily penetrate the cortex of the bone or even cause pathological fracture. Although they rarely expand into the articular cavity, they invade the subchondral bone, which seriously affects knee joint function (
There is still controversy about the surgical treatment of GCTB in the around knee joint. How to achieve a balance between completely removal of tumors to reduce recurrence and preservation of knee joint function as much as possible was the linchpin for clinicians to balance. The surgical treatment of GCTB in the around knee joint mainly includes curettage and bone grafting (
Therefore, this study aimed to analyse the correlation between the choice of surgical treatment for GCTB around the knee joint and the prognosis of oncology and limb function through a single-center retrospective cohort study to provide a valuable reference for surgical treatment of GCTB around the knee joint.
Data of 277 GCTB patients who were treated at a single center from March 2007 to March 2017 were retrospectively collected. The inclusion criteria were as follows: GCTB located in the around knee joint, histopathological diagnosis of benign GCTB, surgical treatment with limb salvage, and postoperative follow-up of more than 24 months with integrated data. According to the above criteria, a total of 131 patients with GCTB located around the knee joint were retrieved. Among them, 35 patients lost follow-up, two had amputation due to malignant changes, and one received knee arthrodesis. Finally, 93 patients were enrolled in the present study (
Flow charts of patients included in this study.
This study was approved by Xiangya Hospital Ethics Committee, and written informed consents were obtained from the patients or their legal guardians.
EC was performed as follows. The fenestration from the eccentric cortex of the lesion was sufficiently large to avoid opening the joint capsule (
Specific implementation steps of extended curettage:
SR was performed as follows: The surgical resection margin was determined by preoperative T1-weighted-enhanced images. The tumors were completely resected from normal peripheral tissues, while the common peroneal nerve and important vessels of the lower limbs (femoral and posterior tibial arteries) were protected during the surgery. After resection, bone defects were repaired with artificial prosthesis followed by soft tissue repair, but the fibula was an exception, where only the lateral ligament of knee joint was repaired, and the bone defect was not repaired.
Patients of the EC group were exempted from weight-bearing for 2 weeks, and they gradually began to perform non-weight, semi-weight, and full-weight bearing functional exercises alternately using crutches. Limbs of the patients in the SR group were fixed with plaster or braces for 4–6 weeks, and they gradually began to perform functional exercises, from half-load to full load with crutches.
Patients were followed radiographically every 3 months for the first 2 years after the surgery, every 6 months until the 5th year, and annually until the 10th year. The radiographs of the involved area and CT images of the chest were obtained to evaluate cancer prognosis. The prognosis of limb function was evaluated based on the last follow-up record and those of recurrent patients were based on the best functional records before recurrence. Evaluation tools used were as follows: the Musculoskeletal Tumor Society (MSTS) (
Data were analyzed using SPSS software version 20.0 (IBM Corp., Armonk, NY), and measurement data were expressed as mean ± standard deviation. Multivariate and univariate Cox regressions were used to analyse risk factors of local tumor recurrence. Continuous variables were compared by one-way analysis of variance, and categorical variables were compared by chi-square test.
According to the statistical results of the data (
Patient demographics.
Mean age (sd) | 36.3 (12.5) | 34.9 (9.9) |
Gender, |
||
M | 37 (53.6%) | 12 (50.0%) |
F | 32 (46.4%) | 12 (50.0%) |
Lesion length (mm, mean ± SD) | 5.6 ± 1.2 | 7.2 ± 1.3 |
Lesion location, |
||
Femur | 36 (52.2%) | 11 (45.8%) |
Tibia | 32 (46.4%) | 7 (29.2%) |
Fibula | 0 | 6 (25.0%) |
Patella | 1 (1.4%) | 0 |
Campanacci grade, |
||
I | 7 (10.1%) | 0 |
II | 33 (47.8%) | 0 |
III | 29 (42.0%) | 24 (100%) |
Prior surgery, |
12 (17.4%) | 9 (37.5%) |
Pathological fracture, |
18 (26.1%) | 14 (58.3%) |
The SR group included 24 patients (12 men and 12 women), with the mean age of 34.9 (range, 17–52) years. In this group, 11 femurs, 7 tibias, and 6 fibulas were examined. The average length of the lesion was 7.2 cm (4.3–10.2 cm). All cases were of Campanacci grade III. There were 15 primary cases and 9 recurrent cases. There were 14 cases of preoperative pathological fracture and two cases of pulmonary metastasis.
In this study, six cases (6.5%) of recurrence occurred within 18 months after surgery. There were five recurrence cases in the EC group, including three cases in the femur and two cases in the tibia, of which one was far from the articular surface and the four were around to the articular surface. Preoperative pathological fracture occurred in two cases, and two cases were transferred from another hospital as local recurrence. All five patients, including three cases with EC and two cases with SR, were reoperated. No recurrence or metastasis was found at the latest follow-up (
Prognostic comparative statistics.
Duration of follow-up (month) | 67.8 ± 38.7 | 70.9 ± 27.7 | 0.720 |
Mean pre-op VAS (sd) | 4.5 (1.9) | 5.5 (1.8) | 0.033 |
Mean post-op VAS (sd) | 0.3 (0.5) | 1.0 (0.8) | 0.000 |
Mean MSTS score (sd) | 28.2 (1.8) | 26.5 (1.4) | 0.000 |
Local recurrence, |
5 (7.2%) | 1 (4.2%) | 0.597 |
Complication, |
|||
Osteoarthritis | 6 (8.6%) | 0 | |
Rejection reaction | 17 (24.6%) | 0 | |
Joint stiffness | 5 (7.2%) | 4 (16.7%) | 0.006 |
Fracture | 1 (1.4%) | 0 | |
Reoperation, |
5 (7.2%) | 1 (4.2%) | 0.597 |
Typical imaging manifestations of patients with recurrence treated with segmental resection.
A significant difference was found in the mean MSTS score between the two groups (EC group, 28.2 points; range, 24–30 points, 95% CI 27.8–28.5; SR group, 26.5 points; range, 27.7–28.5 points, 95% CI 0.58–0.94;
Nononcologic complications occurred frequently in the EC group than in the SR group (28.0% [29/69] vs. 16.7% [4/24]). In the EC group, six patients had secondary osteoarthritis (five cases with K-L grade 2 and one case with K-L grade 3). Symptoms of osteoarthritis occurred at a mean of 33 months after surgery, but fortunately, these patients did not need surgical treatment for the time being. Seventeen patients developed mild rejection within 1 week after operation, and symptoms disappeared after oral administration of low-dose hormones. Five patients developed joint stiffness, and the patient with patellar lesion developed fracture after complete healing of the lesion. In the SR group, joint stiffness developed in four patients, while other complications were not observed. Postoperative fracture, infection, and failure of internal fixation were not observed in both groups.
GCTBs in the around knee joint were a clinical challenge in orthopedics, as the knee joint is the most important weight-bearing joint with high functional requirements. Furthermore, biologically, GCTB showed expansive growth, which can easily break through the bone cortex and even cause pathological fracture (
Considering that the main surgical methods were EC (
In the present study, we used high-speed burr, electrotome cauterization, and iodine tincture to treat the tumors successively, and we achieved satisfactory oncological prognosis (
Typical imaging manifestations of patients with local recurrence treated with extended curettage.
Although EC can achieve excellent oncological prognosis, we had summed up some experience from recurrent cases: The window must be large enough for curettage under direct vision, and application of sterile oral endoscopy may help in the removal of small lesions in blind visual field. The use of adjuvant therapy should focus on the treatment of articular lateral tumors to preserve the subchondral bone as much as possible and to achieve the goal of EC. For patients with pathological fracture and recurrence, as long as the fracture line or lesion did not involve the articular cartilage, it can still be treated by EC, and the patient's oncological prognosis was still satisfactory.
The repair of bone defect after EC was also a focus of current clinical controversy. Previous studies have confirmed that cement has many benefits in repairing bone defects after EC of GCTB: The heat released during cement solidification can kill the residual tumor cells in the cavity to achieve the effect of extended curettage (
SR, as an excellent surgical method for oncological prognosis, was recommended for GCTB of the proximal fibula (
Typical imaging features of a 38-year-old man with GCT in the distal femur on the right side. Anteroposterior and lateral radiographs
Prosthetic replacement can make patients recover joint function early without affecting appearance and provide good joint stability and range of motion, but long-term complications may engender a heavier burden on patients (
Through this study, we found that the treatment of GCTB around the knee joint seems to be appropriately conservative, giving more patients a joint salvage opportunity. Considering that GCTB mostly occurred in individuals aged 20–40 years, long-term function cannot be guaranteed by SR and prosthesis replacement. For patients with Campanacci grade III, we also recommended EC (unless a large mass of peripheral soft tissue was involved or a pathological fracture involves the articular surface). Even if the patient unfortunately relapses, we can use SR to make up for it. Both SR and EC can effectively reduce the recurrence rate (
The cumulative recurrence-free survival in the Kaplan–Meier curve was based on local recurrence and 93 cases according to the type of surgery.
We have also acquired some unique insights into the treatment of GCTB through this study: Oncological and functional prognosis should be regarded both as equally important in the treatment of GCTB around the knee joint. Complete removal of the lesion was the fundamental guarantee for oncology prognosis, and subchondral bone grafting was a good choice to avoid secondary early osteoarthritis. SR was recommended for patients with pathological fracture involving the articular surface and lesion that extensively invades the surrounding tissue. EC was still preferred for recurrence as long as the articular surface and peripheral tissue are not involved.
Our study should be interpreted in light of its limitations. Similar to many orthopedic oncology studies, our study was retrospective, the number of patients was limited, and the follow-up time of patients was inadequate for assessment of long-term complications. Additionally, the number of patients in the two groups varies greatly, so there are some biases in the statistical results, which may weaken the real validity of the results. Overall, this study comprehensively analyzed the efficacy of the two methods in the treatment of GCTB around the knee joint, confirmed the excellent oncological prognosis of EC and SR, and compared the functional prognosis of the two methods, which could provide correct guidance for the surgical treatment of GCTB around the knee joint.
In conclusion, EC and SR for GCTB around the knee joint can achieve satisfactory oncological prognosis, but we should individually select the most suitable surgical method according to Campanacci grade, age, and long-term complications of patients and take into account the functional prognosis to ensure excellent oncological prognosis.
The datasets generated for this study are available on request to the corresponding author.
The studies involving human participants were reviewed and approved by the Research Ethics Committee of Xiangya Hospital. The patients/participants provided their written informed consent to participate in this study.
HH: conceptualization and design of the study, performed the surgical procedures, collected and analyzed the data, prepared the manuscript, and approved final version of the manuscript. HZ: analyzed the actigraphy data and approved final version of the manuscript. WL: performed the surgical procedures, critical revision the manuscript, and approved final version of the manuscript. YL: performed the surgical procedures, screened and included eligible patients, and approved final version of the manuscript. CZ: performed the surgical procedures, analyzed the data, and approved final version of the manuscript. QL: conceptualization and design of the study, data collection, statistical analysis, manuscript drafting and revision, and approved final version of the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We would like to give our sincere thanks to Dr. Zhan Liao, Dr. Jun wan, Dr. Feng Long, and Dr. Jian Tian for assistance in data collection and Miss. Qi Qiu (the wife of QL) for her selfless support during the study.
giant cell tumor of bone
computed tomography
magnetic resonance imaging
extended curettage
segmental resection
Musculoskeletal tumor Society
Visual Analog Scale
Kellgren-Lawrence.