Yong-Suk Lee

Giant cell tumor of bone (GCTB) typically affects females of reproductive age and may be discovered during pregnancy. Pregnancy entails adaptations that could foster a microenvironment favorable to tumor growth. Although a few case reports have described aggressive features, larger studies in this setting are lacking. Thus, this study aimed to examine the clinical characteristics, obstetrical context, diagnostic process, therapeutic interventions, and prognostic outcomes of patients with GCTBs who presented during pregnancy. Patients were included if they developed pain or swelling during pregnancy at the site subsequently confirmed as primary or recurrent GCTB by pathology. Information on 8 patients was collected. The median age at presentation was 26.5 years (range, 22 to 37 years). One (1/8) patient experienced preterm delivery, and another (1/8) underwent elective termination of pregnancy before GCTB surgery. The first symptom was reported at a median gestational age of 5 + 6 (range, 2 + 3–20 + 2) by obstetric dating, but the first radiologic evaluations were often delayed. The most common location was the distal femur (3/8). Pathologic fracture occurred in one (1/8) patient, and all lesions showed Campanacci grade 3 features. The median lesion volume was 93.6 cm ³ (range, 4.2–3348.6 cm ³ ; interquartile range, 18.8–789.2 cm ³ ). No pulmonary metastases were initially observed. Therapeutic approaches appeared to be tailored to individual clinical circumstances. No local recurrences developed in any patient with GCTB in the extremities. No malignant transformation occurred in any patient. Except for one (1/8) patient who died of another disease at 2.5-year follow-up, the other 7 patients (7/8) survived, and 6 (6/8) have remained continuously disease-free during a median follow-up of 5.3 years (range, 2.6–9.8 years). Clinicians should be aware of diagnostic imaging and treatment considerations to ensure timely and appropriate care for patients with GCTB during pregnancy. When musculoskeletal symptoms lack an obstetric explanation, prompt imaging might be crucial. For patients with tumors in surgically challenging sites, surveillance before pregnancy may be prudent. Further research is warranted to elucidate mechanisms through which pregnancy-related physiological changes may influence the oncologic behavior of GCTB.

Background/Objectives: Denosumab has been considered effective for downstaging giant cell tumor of bone (GCTB), implying that it lowers the Campanacci grade rather than reducing tumor size. Preoperative tumor shrinkage holds therapeutic value by decreasing surgical complications. While previous studies have observed lesion shrinkage in some patients, no study has identified the types of patients likely to show treatment response. Thus, we sought to identify the clinical factors associated with post-denosumab GCTB size reduction. Methods: The data for 45 GCTB patients (29 females [64%], 16 males [36%], median age 32 years [range: 17–65]) who received denosumab were analyzed. Lesions were in the extremities (n = 25, 56%) or spinopelvic region (n = 20, 44%). Ten (22%) were recurrent. Lesion size reduction was assessed using two criteria: a ≥5% and a ≥5 mm decrease in the longest diameter. Univariate analyses were conducted for all variables, and those found to be significant were subjected to multivariate analyses. In addition, multicollinearity was evaluated. Subgroup analyses were performed based on lesion location and recurrence status. Results: Campanacci grade III predicted proportional shrinkage (≥5%) in all patients (OR 4.819, 95% CI 1.121–20.714) and in extremity (OR 11.171, 95% CI 1.023–122.014) and primary lesions (OR 5.781, 95% CI 1.181–28.297), and aneurysmal bone cyst (ABC)-like change was associated with absolute shrinkage (≥5 mm) in all patients (OR 8.734, 95% CI 1.159–65.845) and primary lesions (OR 11.936, 95% CI 1.074–132.69). The longest tumor diameter of ≥7 cm predicted absolute shrinkage in all patients (OR 12.380, 95% CI 1.038–147.694) and for spinopelvic lesions (OR 20, 95% CI 1.676–238.63). Conclusions: ABC-like change, Campanacci grade III, and the longest tumor diameter might predict post-denosumab GCTB shrinkage in all patients, though shrinkage varies with lesion location and recurrence status. These factors could help clinicians tailor treatment strategies in different settings. Further research is needed to explore how clinical factors pharmacologically influence denosumab-induced GCTB shrinkage.

이상욱, et al. J Korean Orthop Assoc. 2025 Dec;60(4):233-240. https://doi.org/10.4055/jkoa.2025.60.4.233

Background/Objectives: Since the initial approach towards the clinical presentation of soft-tissue masses is challenging for frontline physicians, some countries use clinical practice guidelines. Proper imaging work-up is crucial to differentiate between soft-tissue tumors. Recently, ultrasonography and magnetic resonance imaging (MRI) have been widely used. But there is some controversy about whether pre-referral evaluations are being conducted properly. Thus, this study aims to assess whether the ultrasonography investigation of soft-tissue masses prior to referral to the musculoskeletal tumor center is being performed adequately in terms of indications, diagnostic accuracy, and referral interval, and to evaluate whether the pre-referral MRI for soft-tissue masses is being conducted reasonably concerning indications, imaging protocol, reporting, diagnostic accuracy, and cost-effectiveness. Methods: The study protocol was registered. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We performed a database search of the MEDLINE, Embase, and Cochrane Library. Then, two authors reviewed the studies, and the third author resolved any disagreement between them. A total of nine studies were included. The Risk Of Bias In Non-Randomized Studies-of Interventions was applied. Relevant data were extracted by two authors. Results: This review showed that the way that the imaging investigations are performed in non-specialized centers before referral was generally considered inappropriate. Conclusions: Frontline physicians should regard the alarm symptom as an indication for advanced imaging evaluation. Education and certification may be required for ultrasonography. MRI should be performed and interpreted in a specialized center or by a specialist with relevant expertise. Guidance may help reduce inappropriate imaging.

Extra-abdominal desmoid-type fibromatosis (EADTF) is a rare neoplastic condition of monoclonal fibroblastic proliferation characterized by local aggressiveness with a distinct tendency to recur. Although EADTF is a benign disease entity, these tumors have a tendency to infiltrate surrounding normal tissues, making it difficult to completely eliminate them without adjacent healthy tissue injury. Surgical excision of these locally aggressive tumors without clear resection margins often leads to local recurrence. The aim of this thorough review was to assess the current treatment concepts for these rare tumors. A comprehensive search of articles published in the Cochrane Library, MEDLINE (PubMed), and EMBASE databases between January 2008 and February 2023 was conducted. Surgical intervention is no longer the first-line approach for most cases; instead, strategies like active surveillance or systemic therapies are used as initial treatment options. With the exception of EADTFs situated near vital structures, a minimum of 6–12 months of active surveillance is currently advocated for, during which some disease progression may be considered acceptable. Non-surgical interventions such as radiation or cryoablation may be employed in certain patients to achieve local control. The currently preferred systemic treatment options include tyrosine kinase inhibitors, low-dose chemotherapy, and gamma-secretase inhibitors, while hormone therapy is not advised. Nonsteroidal anti-inflammatory drugs are utilized primarily for pain management.

Joo MW, et al. Clin Orthop Surg. 2024 Feb;16(1):157-167. https://doi.org/10.4055/cios23186

Background: Improvement in survival in patients with advanced cancer is accompanied by an increased probability of bone metastasis and related pathologic fractures (especially in the proximal femur). The few systems proposed and used to diagnose impending fractures owing to metastasis and to ultimately prevent future fractures have practical limitations; thus, novel screening tools are essential. A CT scan of the abdomen and pelvis is a standard modality for staging and follow-up in patients with cancer, and radiologic assessments of the proximal femur are possible with CT-based digitally reconstructed radiographs. Deep-learning models, such as convolutional neural networks (CNNs), may be able to predict pathologic fractures from digitally reconstructed radiographs, but to our knowledge, they have not been tested for this application. Questions/purposes: (1) How accurate is a CNN model for predicting a pathologic fracture in a proximal femur with metastasis using digitally reconstructed radiographs of the abdomen and pelvis CT images in patients with advanced cancer? (2) Do CNN models perform better than clinicians with varying backgrounds and experience levels in predicting a pathologic fracture on abdomen and pelvis CT images without any knowledge of the patients’ histories, except for metastasis in the proximal femur? Methods: A total of 392 patients received radiation treatment of the proximal femur at three hospitals from January 2011 to December 2021. The patients had 2945 CT scans of the abdomen and pelvis for systemic evaluation and follow-up in relation to their primary cancer. In 33% of the CT scans (974), it was impossible to identify whether a pathologic fracture developed within 3 months after each CT image was acquired, and these were excluded. Finally, 1971 cases with a mean age of 59 ± 12 years were included in this study. Pathologic fractures developed within 3 months after CT in 3% (60 of 1971) of cases. A total of 47% (936 of 1971) were women. Sixty cases had an established pathologic fracture within 3 months after each CT scan, and another group of 1911 cases had no established pathologic fracture within 3 months after CT scan. The mean age of the cases in the former and latter groups was 64 ± 11 years and 59 ± 12 years, respectively, and 32% (19 of 60) and 53% (1016 of 1911) of cases, respectively, were female. Digitally reconstructed radiographs were generated with perspective projections of three-dimensional CT volumes onto two-dimensional planes. Then, 1557 images from one hospital were used for a training set. To verify that the deep-learning models could consistently operate even in hospitals with a different medical environment, 414 images from other hospitals were used for external validation. The number of images in the groups with and without a pathologic fracture within 3 months after each CT scan increased from 1911 to 22,932 and from 60 to 720, respectively, using data augmentation methods that are known to be an effective way to boost the performance of deep-learning models. Three CNNs (VGG16, ResNet50, and DenseNet121) were fine-tuned using digitally reconstructed radiographs. For performance measures, the area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, precision, and F1 score were determined. The area under the receiver operating characteristic curve was used to evaluate three CNN models mainly, and the optimal accuracy, sensitivity, and specificity were calculated using the Youden J statistic. Accuracy refers to the proportion of fractures in the groups with and without a pathologic fracture within 3 months after each CT scan that were accurately predicted by the CNN model. Sensitivity and specificity represent the proportion of accurately predicted fractures among those with and without a pathologic fracture within 3 months after each CT scan, respectively. Precision is a measure of how few false-positives the model produces. The F1 score is a harmonic mean of sensitivity and precision, which have a tradeoff relationship. Gradient-weighted class activation mapping images were created to check whether the CNN model correctly focused on potential pathologic fracture regions. The CNN model with the best performance was compared with the performance of clinicians. Results: DenseNet121 showed the best performance in identifying pathologic fractures; the area under the receiver operating characteristic curve for DenseNet121 was larger than those for VGG16 (0.77 ± 0.07 [95% CI 0.75 to 0.79] versus 0.71 ± 0.08 [95% CI 0.69 to 0.73]; p = 0.001) and ResNet50 (0.77 ± 0.07 [95% CI 0.75 to 0.79] versus 0.72 ± 0.09 [95% CI 0.69 to 0.74]; p = 0.001). Specifically, DenseNet121 scored the highest in sensitivity (0.22 ± 0.07 [95% CI 0.20 to 0.24]), precision (0.72 ± 0.19 [95% CI 0.67 to 0.77]), and F1 score (0.34 ± 0.10 [95% CI 0.31 to 0.37]), and it focused accurately on the region with the expected pathologic fracture. Further, DenseNet121 was less likely than clinicians to mispredict cases in which there was no pathologic fracture than cases in which there was a fracture; the performance of DenseNet121 was better than clinician performance in terms of specificity (0.98 ± 0.01 [95% CI 0.98 to 0.99] versus 0.86 ± 0.09 [95% CI 0.81 to 0.91]; p = 0.01), precision (0.72 ± 0.19 [95% CI 0.67 to 0.77] versus 0.11 ± 0.10 [95% CI 0.05 to 0.17]; p = 0.0001), and F1 score (0.34 ± 0.10 [95% CI 0.31 to 0.37] versus 0.17 ± 0.15 [95% CI 0.08 to 0.26]; p = 0.0001). Conclusion: CNN models may be able to accurately predict impending pathologic fractures from digitally reconstructed radiographs of the abdomen and pelvis CT images that clinicians may not anticipate; this can assist medical, radiation, and orthopaedic oncologists clinically. To achieve better performance, ensemble-learning models using knowledge of the patients’ histories should be...

Lee YS, et al. Clin Orthop Surg. 2023 Mar;15(2):318-326. https://doi.org/10.4055/cios22223

Giant cell tumor of bone (GCTB) undergoes a sarcomatous transformation. Secondary malignancy in giant cell tumor (MGCT) is associated with radiotherapy and has a dismal prognosis. We reviewed medical records to investigate the clinicopathological characteristics and prognosis of MGCT patients. The enrollment criterion was high-grade spindle-cell sarcoma, which developed at the site of prior GCTB treatment. Twelve patients were analyzed: six females and six males. The median age was 42.5 years. Benign recurrence occurred in five GCTB patients not treated with radiotherapy. No pulmonary implants were observed. The median latency to the malignant transformation was 63 months. Nine patients were AJCC stage IIB, and three were stage IVA. The median follow-up period after malignant transformation was 62.5 months. Five patients developed local recurrence, and six had distant metastasis. Five-year overall recurrence and metastasis-free survival rates were 61.9%, 66.7%, and 58.3%, respectively. Initial metastasis was a predictive factor for overall survival. Benign local recurrence of GCTB was also a negative factor for metastasis-free survival of MGCT patients. Differences in overall survival according to benign recurrence also showed a tendency toward significance. In our series, secondary MGCT did not occur after radiotherapy. The prognosis was better than previous findings. Benign recurrence of GCTB could reflect the prognosis of MGCT.

Background. Although it is generally agreed that vitamin D is important for bone health, the role of vitamin D in preventing fractures in children and adolescents remains unclear. Therefore, this study aimed to investigate the prevalence of vitamin D deficiency and insufficiency in healthy Korean children with fractures. Our secondary aim was to compare serum vitamin D levels before and during the coronavirus disease 2019 (COVID‐19) outbreak. Methods. We evaluated 334 patients with fractures who were surgically treated at our institution between 2018 and 2019 before the onset of COVID‐19 (group I). In addition, we collected data on the serum 25(OH)D levels of 210 patients who visited our pediatric department for evaluation of short stature (group II) and the serum 25(OH)D levels of the patients with fractures during the COVID‐19 pandemic period (group III). A serum 25(OH)D level of Results. The mean age was 8.1 ± 3.5 years in group I, 8.2 ± 3.7 years in group II, and 8.6 ± 3.5 years in group III. The prevalence of vitamin D deficiency was 53.0% in group I and 32.9% in group II. The mean serum 25(OH)D level was lower in group I than in group II (20.0 ± 7.3 ng/ml vs. 23.2 ± 6.9 ng/ml, p < 0.001). The mean serum 25(OH)D level of younger patients (p = 0.037). Conclusions. We observed a high prevalence of vitamin D deficiency/insufficiency in children with fractures who required surgical treatment. During the COVID‐19 pandemic, the serum vitamin D levels became even lower, especially in younger children.