Giant cell tumor of bone Raskin, Kevin A; Schwab, Joseph H; Mankin, Henry J ...
Journal of the American Academy of Orthopaedic Surgeons
21, Številka:
2
Journal Article
Recenzirano
Giant cell tumor (GCT) of bone is one type of giant cell-rich lesion of bone. This benign mesenchymal tumor has characteristic multinuclear giant cells. Mononuclear stromal cells are the ...physiologically active and diagnostic cell type. Most GCTs are located in the epiphyseal regions of long bones. The axial skeleton-primarily the sacrum-is a secondary site of involvement. Most patients present with pain, swelling, joint effusion, and disability in the third and fourth decades of life. Imaging studies are important for tumor staging and radiographic grading. Typically, these clinically active but slow-growing tumors are confined to bone, with relatively well-defined radiographic borders. Monostotic disease is most common. Metastatic spread to the lungs is rare. Extended intralesional curettage with or without adjuvant therapy is the primary treatment choice. Local recurrence is seen in ≤ 20% of cases, and a second local intralesional procedure is typically sufficient in cases that are detected early. Medical therapies include diphosphonates and denosumab. Denosumab has been approved for use in osteoporosis as well as breast and prostate cancer metastatic to bone. Medical therapy and radiotherapy can alter the management of GCT of bone, especially in multifocal disease, local recurrences, and bulky central/axial disease.
A preoperative estimation of survival is critical for deciding on the operative management of metastatic bone disease of the extremities. Several tools have been developed for this purpose, but there ...is room for improvement. Machine learning is an increasingly popular and flexible method of prediction model building based on a data set. It raises some skepticism, however, because of the complex structure of these models.
The purposes of this study were (1) to develop machine learning algorithms for 90-day and 1-year survival in patients who received surgical treatment for a bone metastasis of the extremity, and (2) to use these algorithms to identify those clinical factors (demographic, treatment related, or surgical) that are most closely associated with survival after surgery in these patients.
All 1090 patients who underwent surgical treatment for a long-bone metastasis at two institutions between 1999 and 2017 were included in this retrospective study. The median age of the patients in the cohort was 63 years (interquartile range IQR 54 to 72 years), 56% of patients (610 of 1090) were female, and the median BMI was 27 kg/m (IQR 23 to 30 kg/m). The most affected location was the femur (70%), followed by the humerus (22%). The most common primary tumors were breast (24%) and lung (23%). Intramedullary nailing was the most commonly performed type of surgery (58%), followed by endoprosthetic reconstruction (22%), and plate screw fixation (14%). Missing data were imputed using the missForest methods. Features were selected by random forest algorithms, and five different models were developed on the training set (80% of the data): stochastic gradient boosting, random forest, support vector machine, neural network, and penalized logistic regression. These models were chosen as a result of their classification capability in binary datasets. Model performance was assessed on both the training set and the validation set (20% of the data) by discrimination, calibration, and overall performance.
We found no differences among the five models for discrimination, with an area under the curve ranging from 0.86 to 0.87. All models were well calibrated, with intercepts ranging from -0.03 to 0.08 and slopes ranging from 1.03 to 1.12. Brier scores ranged from 0.13 to 0.14. The stochastic gradient boosting model was chosen to be deployed as freely available web-based application and explanations on both a global and an individual level were provided. For 90-day survival, the three most important factors associated with poorer survivorship were lower albumin level, higher neutrophil-to-lymphocyte ratio, and rapid growth primary tumor. For 1-year survival, the three most important factors associated with poorer survivorship were lower albumin level, rapid growth primary tumor, and lower hemoglobin level.
Although the final models must be externally validated, the algorithms showed good performance on internal validation. The final models have been incorporated into a freely accessible web application that can be found at https://sorg-apps.shinyapps.io/extremitymetssurvival/. Pending external validation, clinicians may use this tool to predict survival for their individual patients to help in shared treatment decision making.
Level III, therapeutic study.
Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of >or=66 Gy are recommended. A Phase II ...clinical trial evaluated high-dose photon/proton XRT for spine sarcomas.
Eligible patients had nonmetastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or postoperative photon/proton XRT with or without radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (Gy RBE) to subclinical disease, 70.2 Gy RBE to microscopic disease in the tumor bed, and 77.4 Gy RBE to gross disease at 1.8 Gy RBE qd. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 Gy RBE to surface/center. Intraoperative boost doses of 7.5 to 10 Gy could be given by dural plaque.
A total of 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). With 48 month median follow-up, 5-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence (p < 0.001). Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared after 77.12 to 77.4 Gy RBE.
Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 Gy RBE are at risk for late toxicity.
•Both radiation-induced and neurofibromatosis-associated MPNSTs have poorer prognosis than sporadic MPNSTs.•Complete resection of the tumor is a significant prognostic factor for MPNST.•Surgery with ...adjuvant radiotherapy is related to improved local control in patients with positive surgical margins.
Malignant peripheral nerve sheath tumors (MPNST) may be sporadic or associated with neurofibromatosis or prior radiation. MPNST may behave aggressively with a high rate of local recurrence and distant metastasis.
In an IRB approved protocol, we reviewed the clinical characteristics, treatment, and outcomes of 280 patients treated for MPNST at Massachusetts General Hospital (MGH) between 1960 and 2016.
There were 138 men and 142 women with a median age of 41 (range: 3–95) years. Tumors were classified as neurofibromatosis-associated (nfMPNST, n = 77), radiation-induced (rMPNST, n = 21), or sporadic (sMPNST, n = 182) MPNST. The median time to development of rMPNST from prior radiation was 15 years. With a median follow-up of 43.1 months, the median overall survival (OS) was 65.3 months. Older age, nfMPNST, rMPNST, increased tumor size, lymph node involvement, metastatic disease, intermediate to high grade, radiotherapy alone, and R2 resection were related to worse OS, whereas surgery with radiotherapy was associated with improved OS. Among the 251 patients without metastasis, nfMPNST, rMPNST, and increased tumor size were correlated with worse metastasis-free survival; nfMPNST, radiotherapy alone, and R1/R2 resection were associated with local recurrence, whereas surgery with adjuvant radiotherapy was related to improved local control in patients with R1/R2 resection.
Both radiation-induced and neurofibromatosis-associated MPNSTs have poorer prognosis than sporadic MPNSTs. Complete resection of the tumor is a significant prognostic factor for MPNST. The addition of radiotherapy after surgery should be considered especially when the surgical margins are positive.
Heterologous differentiation has only been previously reported twice in metastatic uterine leiomyosarcomas. We report herein the first case of metastatic uterine leiomyosarcoma with ...rhabdomyosarcomatous differentiation. A 67-yr-old woman presented with femur, abductor magnus, and lymph node metastases 9 yr after the primary diagnosis. The metastatic sites showed rhabdomyosarcomatous morphologic features, and immunohistochemical studies confirmed skeletal muscle differentiation. Molecular testing revealed the same loss-of-function TP53 mutation in the uterine leiomyosarcoma and metastatic sites supporting heterologous differentiation of the primary tumor. Our case highlights the morphologic shifts metastatic tumors may manifest and the potential diagnostic problems that may arise.
Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to ...reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA).
This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009.
A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure.
Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.
Several studies have identified prognostic factors for patients with chondrosarcoma, but there are few studies investigating the accuracy of computationally intensive methods such as machine ...learning. Machine learning is a type of artificial intelligence that enables computers to learn from data. Studies using machine learning are potentially appealing, because of its possibility to explore complex patterns in data and to improve its models over time.
The purposes of this study were (1) to develop machine-learning algorithms for the prediction of 5-year survival in patients with chondrosarcoma; and (2) to deploy the best algorithm as an accessible web-based app for clinical use.
All patients with a microscopically confirmed diagnosis of conventional or dedifferentiated chondrosarcoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2010. SEER covers approximately 30% of the US population and consists of demographic, tumor characteristic, treatment, and outcome data. In total, 1554 patients met the inclusion criteria. Mean age at diagnosis was 52 years (SD 17), ranging from 7 to 102 years; 813 of the 1554 patients were men (55%); and mean tumor size was 8 cm (SD 6), ranging from 0.1 cm to 50 cm. Exact size was missing in 340 of 1544 patients (22%), grade in 88 of 1544 (6%), tumor extension in 41 of 1544 (3%), and race in 16 of 1544 (1%). Data for 1-, 3-, 5-, and 10-year overall survival were available for 1533 (99%), 1512 (98%), 1487 (96%), and 977 (63%) patients, respectively. One-year survival was 92%, 3-year survival was 82%, 5-year survival was 76%, and 10-year survival was 54%. Missing data were imputed using the nonparametric missForest method. Boosted decision tree, support vector machine, Bayes point machine, and neural network models were developed for 5-year survival. These models were chosen as a result of their capability of predicting two outcomes based on prior work on machine-learning models for binary classification. The models were assessed by discrimination, calibration, and overall performance. The c-statistic is a measure of discrimination. It ranges from 0.5 to 1.0 with 1.0 being perfect discrimination and 0.5 that the model is no better than chance at making a prediction. The Brier score measures the squared difference between the predicted probability and the actual outcome. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. The Brier scores of the models are compared with the null model, which is calculated by assigning each patient a probability equal to the prevalence of the outcome.
Four models for 5-year survival were developed with c-statistics ranging from 0.846 to 0.868 and Brier scores ranging from 0.117 to 0.135 with a null model Brier score of 0.182. The Bayes point machine was incorporated into a freely available web-based application. This application can be accessed through https://sorg-apps.shinyapps.io/chondrosarcoma/.
Although caution is warranted, because the prediction model has not been validated yet, healthcare providers could use the online prediction tool in daily practice when survival prediction of patients with chondrosarcoma is desired. Future studies should seek to validate the developed prediction model.
Level III, prognostic study.
Aims
Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although ...the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. EWSR1–NFATC2 or FUS–NFATC2 fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts.
Methods and results
Using RNA‐based next‐generation sequencing and/or fluorescence in‐situ hybridisation, we investigated the presence of EWSR1 or FUS rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3–23 years (median, 14 years); the tumours ranged from 19 mm to 160 mm (median, 46 mm) in size, and involved the femur (n = 3), humerus (n = 2), fibula (n = 2), tibia (n = 1), and iliac wing (n =1). We identified three cases with EWSR1–NFATC2 fusion (showing identical breakpoints to those in EWSR1–NFATC2 sarcomas) and one additional case with FUS rearrangement. Unlike in EWSR1–NFATC2 sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested.
Conclusions
More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of EWSR1 and/or FUS rearrangement may help to distinguish simple bone cysts from mimics, and NFATC2 rearrangement is not pathognomonic of malignancy.
EWSR1‐NFATC2 fusion in simple bone cyst.
Surface osteosarcoma: Predictors of outcomes Lee, Stella J.; Lans, Jonathan; Cook, Samuel D. ...
Journal of surgical oncology,
09/2021, Letnik:
124, Številka:
4
Journal Article
Recenzirano
Background and Objectives
The subtypes of surface osteosarcomas include well‐differentiated, low‐grade parosteal osteosarcoma (POS), intermediate‐grade periosteal osteosarcoma (PerOS), high‐grade ...surface osteosarcoma (HGSO), and high‐grade, dedifferentiated POS (dPOS). We aimed to determine disease progression, defined as local recurrence and metastatic disease, and overall (OS) and disease‐specific survival (DSS). We identify outcome predictive factors and report functional results.
Methods
This retrospective study evaluated patients with primary surface osteosarcoma at our hospital from 1992 to 2019. Fifty‐one patients had a median follow‐up of 6.1 years (range: 0.1–25.2). Histologic subtypes included 32 POS, 11 PerOS, 4 HGSO, and 3 dPOS. Bone and soft tissue margins were classified using the American Joint Committee on Cancer residual tumor classification (Rx = Not evaluable; R0 = negative margin; R1 = microscopic positive margin; and R2 = macroscopic positive margin) and the modified R classification (mRx = not evaluable; mR0 = negative margin >1 mm; mR1 = negative margin ≤1 mm; mR1‐dir: Positive microscopic margin locally; mR2a: Positive macroscopic margin locally; mR2b: positive macroscopic margin distally; and mR2C: positive macroscopic margin locally and distally). Forty‐one patients had functional outcomes.
Results
Three POS patients developed recurrence: two had R0 margins and one an intralesional resection. Five patients developed lung metastases (POS: 3, dPOS: 2). Four patients died. The only significant disease progression predictor was age. OS at 10 years was 97%. 48 patients had negative bone margins (R0 or mR0 and mR1) and 47 patients had negative soft‐tissue margins (R0 or mR0 and mR1). The average MSTS score was 88.43 (range: 34.29–100).
Conclusions
We advocate surgery for POS and believe R0 (mR0 and mR1 resections) or planned R1 (mR1‐dir) to preserve function are acceptable. We favor chemotherapy and surgery for PerOS, though a chemotherapeutic response is highly variable. High‐grade tumors are the most infrequent subtype, but HGSO and dPOS seem to portend a poorer prognosis. Good function can be obtained.
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