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Osteosarcoma is a rare primary bone tumor for which no significant therapeutic advancement has been made since the late 1980s despite ongoing efforts. Overall, the five-year survival rate remains about 65%, and is much lower in patients with tumors unresponsive to methotrexate, doxorubicin, and cisplatin therapy. Genetic studies have not revealed actionable drug targets, but our group, and others, have reported that epigenomic biomarkers, including regulatory RNAs, may be useful prognostic tools for osteosarcoma. We tested if microRNA (miRNA) transcriptional patterns mark the transition from a chemotherapy sensitive to resistant tumor phenotype. Small RNA sequencing was performed using 14 patient matched pre-chemotherapy biopsy and post-chemotherapy resection high-grade osteosarcoma frozen tumor samples. Independently, small RNA sequencing was performed using 14 patient matched biopsy and resection samples from untreated tumors. Separately, miRNA specific Illumina DASL arrays were used to assay an independent cohort of 65 pre-chemotherapy biopsy and 26 patient matched post-chemotherapy resection formalin fixed paraffin embedded (FFPE) tumor samples. mRNA specific Illumina DASL arrays were used to profile 37 pre-chemotherapy biopsy and five post-chemotherapy resection FFPE samples, all of which were also used for Illumina DASL miRNA profiling. The National Cancer Institute Therapeutically Applicable Research to Generate Effective Treatments dataset, including PCR based miRNA profiling and RNA-seq data for 86 and 93 pre-chemotherapy tumor samples, respectively, was also used. Paired differential expression testing revealed a profile of 17 miRNAs with significantly different transcriptional levels following chemotherapy. Genes targeted by the miRNAs were differentially expressed following chemotherapy, suggesting the miRNAs may regulate transcriptional networks. Finally, an in vitro pharmacogenomic screen using miRNAs and their target transcripts predicted response to a set of candidate small molecule therapeutics which potentially reverse the chemotherapy resistance phenotype and synergize with chemotherapy in otherwise treatment resistant tumors. Importantly, these novel therapeutic targets are distinct from targets identified by a similar pharmacogenomic analysis of previously published prognostic miRNA profiles from pre chemotherapy biopsy specimens.
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BACKGROUND: Prosthetic joint infections (PJIs) after megaprosthesis implantation are associated with high rates of treatment failure and amputation. Our study analyzed PJI treatment success rates by surgical strategy and assessed risks of reinfection and amputation. METHODS: We retrospectively analyzed the outcomes of patients diagnosed with PJI after undergoing megaprosthesis implantation for oncologic indications. The 2011 Musculoskeletal Infection Society criteria were used to define PJI. Reinfection, reoperation, and amputation for PJI recurrence were assessed. A total of 67 patients with megaprosthesis PJIs were included. There were fourteen patients who were treated with debridement, antibiotics, and implant retention (DAIR), 31 with DAIR plus (DAIR with modular component exchange and stem retention), and 21 with two-stage revisions. Kaplan-Meier estimates were used for survival analyses and Cox proportional hazards for risk factor analyses. RESULTS: The two-year reinfection-free survival was 25% for DAIR and 60% for DAIR plus or two-stage revision (P = .049). The five-year amputation-free survival was 84% for DAIR plus or two-stage revision, and 48% for DAIR (P = .13). Reinfection-free, reoperation-free, and amputation-free survival were similar between DAIR plus and two-stage revision at the 2- and 5-year marks. Body mass index ≥30 (hazard ratio [HR] = 2.65) and chronic kidney disease (HR = 11.53) were risk factors for reinfection. Treatment with DAIR plus or two-stage revision (HR = 0.44) was a protective factor against reinfection. CONCLUSIONS: A DAIR was associated with high rates of treatment failure and higher amputation rates than DAIR plus or 2-stage surgery. A DAIR plus was not inferior to 2-stage revision clearing a PJI and might be performed in patients who cannot withstand two-stage revision surgery.
Subject(s)
Anti-Bacterial Agents , Debridement , Prosthesis-Related Infections , Reoperation , Humans , Prosthesis-Related Infections/surgery , Prosthesis-Related Infections/etiology , Male , Female , Retrospective Studies , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Reoperation/statistics & numerical data , Aged , Adult , Treatment Outcome , Amputation, Surgical , Joint Prosthesis/adverse effects , Kaplan-Meier EstimateABSTRACT
INTRODUCTION: Upper extremity (UE) desmoid tumors are locally aggressive neoplasms with high recurrence rates. Our study sought to analyze the demographics and treatment strategies of UE desmoid tumors and identify risk factors for recurrence. MATERIALS AND METHODS: A retrospective review of 52 patients with histologically confirmed UE desmoid tumors treated at our institution between 1990 and 2015 was conducted. Survival was assessed using the Kaplan-Meier method and the Cox proportional hazards model was used for risk factor analysis. RESULTS: For the entire cohort, median age was 40 (29-47) years, 75% were female, and 48% had local recurrence. The median tumor size was 45 (15-111) cm3 on imaging. Twenty-two patients had a previous resection. The most common treatments were surgery alone (50%) and surgery with adjuvant radiotherapy (21%). Tumor size ≥5 cm and tumor volume ≥40 cm3 on imaging were associated with increased recurrence (p = 0.006 and p = 0.005, respectively). Age and sex were not associated with local recurrence. Patients with a tumor size ≥5 cm were 2.6 times more likely to present with recurrence. At the 10-year mark, a lower local recurrence-free survival was seen in patients with tumors ≥5 cm (72.2% vs. 36.3%, p = 0.042) or ≥40 cm3 (67.2% vs. 32.7%, p = 0.034). CONCLUSION: In our study, only tumor dimensions appeared to modify recurrence risk.
Subject(s)
Fibromatosis, Aggressive , Humans , Female , Adult , Male , Fibromatosis, Aggressive/surgery , Fibromatosis, Aggressive/pathology , Upper Extremity/pathology , Radiotherapy, Adjuvant/adverse effects , Combined Modality Therapy , Risk Factors , Retrospective Studies , Neoplasm Recurrence, Local/pathologyABSTRACT
BACKGROUND: Although dual mobility total hip arthroplasty has become increasingly common in recent years, limited remains known on dual mobility in surgical oncology. This university-based investigation compared dislocation and revision rates of DMs, conventional total hip arthroplasty (THA), and hemiarthroplasties (HAs) for oncological hip reconstruction. METHODS: An institutional tumor registry was used to identify 221 patients undergoing 45 DMs, 67 conventional THAs, and 109 HAs, performed for 17 primary hip tumors and 204 hip metastases between 2010 and 2020. The median age at surgery was 65 years, and 52% were female. The mean follow-up was 2.5 years. Kaplan-Meier survivorship curves and log-rank tests were done to compare dislocation and revision rates among all 221 patients, after a one-to-one propensity match, based on age, sex, tumor type (metastasis, primary tumor), and tumor localization (femur, acetabulum). RESULTS: The 5-year survivorship free of dislocation was 98% in DMs, 66% in conventional THAs ( P = 0.03; all P values compared with DMs), and 97% among HAs ( P = 0.48). The 5-year survivorship free of revision was 69% in DMs, 62% in conventional THAs ( P = 0.68), and 92% in HAs ( P = 0.06). After propensity matching, the 5-year survivorship free of dislocation was 42% in 45 conventional THAs ( P = 0.027; compared with all 45 DMs) and 89% in 16 matched HAs ( P = 0.19; compared with 16 DMs with femoral involvement only). The 5-year survivorship free of revision was 40% in matched conventional THAs ( P = 0.91) and 100% in matched HAs ( P = 0.19). CONCLUSIONS: DMs showed markedly lower rates of dislocation than conventional THAs, with overall revision rates remaining comparable among different designs. DMs should be considered the option of choice for oncological hip reconstruction if compared with conventional THAs. HAs are a feasible alternative when encountering femoral disease involvement only. LEVEL OF EVIDENCE: III.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Dislocation , Hip Prosthesis , Joint Dislocations , Neoplasms , Humans , Female , Male , Prosthesis Failure , Prosthesis Design , Reoperation , Joint Dislocations/surgery , Hip Dislocation/etiology , Hip Dislocation/prevention & control , Hip Dislocation/surgery , Retrospective Studies , Risk FactorsABSTRACT
Clear cell sarcoma (CCS) is an uncommon malignant mesenchymal neoplasm of young adults with a predilection for tendons and aponeuroses of distal extremities, a distinctive nested growth pattern, melanocytic differentiation, and usually an EWSR1::ATF1 fusion. Distinction from melanoma can be challenging but is critical for clinical management. Rare cases of primary bone CCS have been reported. The purpose of this study was to evaluate the clinicopathologic features of a series of primary bone CCS. Three cases of primary bone CCS were identified out of 140 CCS diagnosed between 2010 and 2021. Two patients were female, and 1 patient was male; ages were 19, 47, and 61 years. All tumors arose in the long bones of the extremities (femur, humerus, fibula). Two tumors also involved regional lymph nodes at presentation. Two showed characteristic histologic features, in the form of nests and fascicles of uniform epithelioid to spindle cells with prominent nucleoli and pale eosinophilic to clear cytoplasm; 1 tumor showed sheet-like growth, unusual focal pleomorphism, and more notable nuclear atypia. By immunohistochemistry, S100 protein was positive in 2/3 cases, SOX10 in 3/3, HMB-45 in 2/3, MiTF in 2/2, and melan A in 1/3. All cases were confirmed to harbor EWSR1 rearrangement and EWSR1::ATF1 fusion or t(12;22). On follow-up, all 3 patients developed metastases and died of disease, 5, 18, and 21 months after diagnosis. In summary, CCS rarely presents in the skeleton. At such locations, distinction from metastatic melanoma is particularly challenging. Clinical and pathologic features are similar to conventional CCS of soft tissue. Primary bone CCS may pursue an aggressive clinical course.
Subject(s)
Melanoma , Sarcoma, Clear Cell , Young Adult , Humans , Male , Female , Sarcoma, Clear Cell/pathology , Melanoma/diagnosis , Immunohistochemistry , S100 Proteins , Biomarkers, Tumor/metabolismABSTRACT
BACKGROUND: This study aimed to investigate whether venous thromboembolic events (VTEs) are clinically relevant predictors of pulmonary metastatic disease in patients with soft tissue sarcomas (STSs). PATIENTS AND METHODS: In this retrospective cohort analysis, we included patients with STS surgically treated for sarcoma between January 2002 and January 2020. The primary outcome of interest was development of pulmonary metastasis after non-metastatic STS diagnosis. Tumor depth, stage, type of surgical intervention, chemotherapy, radiation therapy, body mass index, and smoking status were collected. Episodes of VTEs following STS diagnosis, including deep vein thrombosis, pulmonary embolism, and other thromboembolic events, were also obtained. Univariate analyses and multivariable logistic regression were used to identify potential predictors for pulmonary metastasis. RESULTS: We included 319 patients with mean age of 54.9 ± 16 years. Thirty-seven patients (11.6%) had VTE after STS diagnosis, and 54 (16.9%) developed pulmonary metastasis. Univariate screening revealed pulmonary metastasis, pre- and postoperative chemotherapy, smoking history, and VTE after surgery as potential predictors of pulmonary metastasis. Multivariable logistic regression revealed smoking history [odds ratio (OR) 2.0, confidence interval (CI) 1.1-3.9, P = 0.04] and VTE (OR 6.3, CI 2.9-13.6, P < 0.001) as independent risk factors for predicting pulmonary metastasis in patients with STS, after adjusting for the factors in the univariate screening as well as age, sex, stage of the tumor, and neurovascular invasion. CONCLUSIONS: Patients with VTE after STS diagnosis have an odds ratio of 6.3 for developing metastatic pulmonary disease compared with patients without venous thromboembolic events. Smoking history was also associated with future pulmonary metastases.
Subject(s)
Lung Neoplasms , Pulmonary Embolism , Sarcoma , Soft Tissue Neoplasms , Venous Thromboembolism , Venous Thrombosis , Humans , Adult , Middle Aged , Aged , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Retrospective Studies , Venous Thrombosis/etiology , Pulmonary Embolism/diagnosis , Pulmonary Embolism/etiology , Risk Factors , Sarcoma/complications , Lung Neoplasms/complicationsABSTRACT
Dedifferentiated chondrosarcoma is rare, aggressive, and microscopically bimorphic. How pathologic features such as the amounts of dedifferentiation affect prognosis remains unclear. We evaluated the percentages and sizes of dedifferentiation in a consecutive institutional series of dedifferentiated chondrosarcomas from 1999 to 2021. The statistical analysis included cox proportional hazard models and log-rank tests. Of the 67 patients (26 women, 41 men; age, 39 to >89 [median 61] years; 2 with Ollier disease), 58 presented de novo; 9 were identified with conventional chondrosarcomas 0.6-13.2 years (median, 5.5 years) prior. Pathologic fracture and distant metastases were noted in 27 and 7 patients at presentation. The tumors involved the femur (n = 27), pelvis (n = 22), humerus (n = 7), tibia (n = 4), scapula/ribs (n = 4), spine (n = 2), and clivus (n = 1). In the 56 resections, the tumors ranged in size from 3.5 to 46.0 cm (median, 11.5 cm) and contained 1%-99.5% (median, 70%) dedifferentiated components that ranged in size from 0.6 to 24.0 cm (median, 7.3 cm). No correlation was noted between total size and percentage of dedifferentiation. The dedifferentiated components were typically fibrosarcomatous or osteosarcomatous, whereas the associated cartilaginous components were predominantly grade 1-2, rarely enchondromas or grade 3. The entire cohort's median overall survival and progression-free survival were 11.8 and 5.4 months, respectively. In the resected cohort, although the total size was not prognostic, the percentage of dedifferentiation ≥20% and size of dedifferentiation >3.0 cm each predicted worse overall survival (9.9 vs 72.5 months; HR, 3.76; 95% CI, 1.27-11.14; P = .02; 8.7 vs 58.9 months; HR, 3.03; 95% CI, 1.21-7.57; P = .02, respectively) and progression-free survival (5.3 vs 62.1 months; HR, 3.05; 95% CI, 1.13-8.28; P = .03; 5.3 vs 56.6 months; HR, 2.50; 95% CI, 1.06-5.88; P = .04, respectively). In conclusion, both the percentages and sizes of dedifferentiation were better prognostic predictors than total tumor sizes in dedifferentiated chondrosarcomas, highlighting the utility of their pathologic evaluations.
Subject(s)
Bone Neoplasms , Chondrosarcoma , Fibrosarcoma , Male , Humans , Female , Adult , Bone Neoplasms/pathology , Prognosis , Chondrosarcoma/pathology , Progression-Free SurvivalABSTRACT
BACKGROUND: Tibial turnup-plasty is a rarely performed surgical option for large bone defects of the distal or entire femur and can serve as an alternative to hip disarticulation or high above-knee amputation. It entails pedicled transport of the ipsilateral tibia with or without the proximal hindfoot for use as a vascularized autograft. It is rotated 180° in the coronal or sagittal plane to the remaining proximal femur or pelvis, augmenting the functional length of the thigh. Prior reports consist of small case series with heterogeneous surgical techniques. Patient-reported outcome measures after the procedure have not been reported, and ambulatory status after the procedure is also unknown. QUESTIONS/PURPOSES: (1) What proportion of patients underwent reoperation after tibial turnup-plasty? (2) What is the ambulatory status and what proportion of patients used a prosthesis after tibial turnup-plasty? (3) What are the Patient-Reported Outcome Measurement Information System (PROMIS) Global-10 mental and physical function scores after tibial turnup-plasty? METHODS: A retrospective analysis was performed of 11 patients who underwent tibial turnup-plasty between 2003 and 2021 by a single orthopaedic oncology division in collaboration with a reconstructive plastic surgery team. Nine patients were men, with a median age of 55 years (range 34 to 75 years). All had chronic infections after arthroplasty or oncologic reconstructions, with a median number of 13 surgeries before turnup-plasty. All were considered to have no other surgical options other than hip disarticulation or high transfemoral amputation. All patients who were offered this possibility accepted it. Data of interest included patient demographics and comorbidities, surgical history that led to limb compromise, medical and surgical perioperative complications, date of prosthesis fitting, and functional capacity at the most recent follow-up interval based on ambulatory status and PROMIS Global-10 mental and physical function scores. The statistical analysis was descriptive. RESULTS: The median number of reoperations after turnup-plasty was one (range 0 to 11). Of the six patients who underwent at least one reoperation, indications for surgery included wound infection (four patients), nonunion of the osteosynthesis site (two), heterotopic ossification (one), tumor recurrence (one), and flap hypoperfusion treated with local tissue revision (one). One patient underwent conversion to external hemipelvectomy for tumor recurrence. Ten of the 11 patients were ambulatory at the final follow-up interval with standard above-knee amputation prostheses. Two ambulated unassisted, four used a single crutch or cane, and four used two crutches or a walker. Of the nine patients for whom scores were available, the median PROMIS Global-10 physical and mental health scores were 48 (range 30 to 68) and 53 (range 41 to 68), both within the standard deviation of the population mean of 50. CONCLUSION: The tibial turnup-plasty is a complex surgical option for patients with large bone defects of the femur for whom there are no alternative surgeries capable of producing residual extremities with acceptable functional length. This should be viewed as a procedure of last resort to avoid a hip disarticulation or a high transfemoral amputation in patients who have typically undergone numerous prior operations. Although ambulation with a prosthesis within 1 year can be expected, almost all patients will require an assistive device to do so, and reoperations are frequent. LEVEL OF EVIDENCE: Level IV, therapeutic study.
Subject(s)
Artificial Limbs , Bone Neoplasms , Male , Humans , Adult , Middle Aged , Aged , Female , Tibia , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Persistent Infection , Treatment Outcome , Foot , Bone Neoplasms/pathologyABSTRACT
In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature. We consider therapeutic strategies and raise the hypothesis that CDK4/6 inhibition (CDK4/6i) may be effective against ESR1-FUS with functional ligand-binding domain swaps. These cases highlight the importance of screening for ESR1-FUS in patients with HR+ MBC while continuing investigation of precision treatments for these genomic rearrangements.
Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Estrogen Receptor alpha/genetics , MutationABSTRACT
BACKGROUND CONTEXT: Local control remains a vexing problem in the management of chordoma despite advances in operative techniques and radiotherapy (RT) protocols. Existing studies show satisfactory local control rates with different treatment modalities. However, those studies with minimum follow-up more than 4 years demonstrate increasing rates of local failure. Therefore, mid-term local survival rates may be inadvertently elevated by studies with less than 4 years follow-up. PURPOSE: The purpose of this study is to report the mid-term results of primary spinal chordoma treated with en bloc resection and proton-based RT with minimum 5 years of follow-up. STUDY DESIGN/SETTING: Retrospective, single-center, cohort study. PATIENT SAMPLE: Patients undergoing primary surgical excision of a spine or sacral chordoma tumor between 1990 and 2016 at a single-institution were included. Patients were included if they had a local failure at any time, or they had a minimum of 5 years of follow up with no local failure. Patients were excluded if a prior surgical excision was performed or metastases were present at the time of referral. OUTCOME MEASURES: The outcome measures were local recurrence-free interval (LRFI) and overall survival (OS). METHODS: Demographic, clinical, oncologic and surgical variables, including margin status, as well as radiation doses and schedule (neoadjuvant, adjuvant, or both) were compared using Wilcoxon rank-sum or chi-squared testing. The goal RT dose was 70 Gray (total) and patients were stratified based on completing (C70) or receiving incomplete (I70) dosing. Overall survival (OS) and local-recurrence free interval (LRFI) were calculated using the Kaplan-Meier method. FUNDING STATEMENT: No funding was obtained for this work. RESULTS: Seventy-six patients were included in the final analysis. All patients had a minimum of 5-year follow-up (median 9.3 years, range 5.1-24.7 years). There were no significant clinical differences between the C70 and I70 RT groups. OS was greater for the C70 RT group (5-year OS 82% vs. 63%, p=.001). There was similar OS for the positive margin group (5-year OS 70% vs. 61%, p=.266). LRFI was greater for the C70 RT group (5-year OS 93% vs. 78%, p=.017). There was similar LRFI for the positive margin group (5-year OS 90% versus 87%, p=.810). CONCLUSION: Chordoma outcomes trend towards diminishing LRFI rates in the literature. Here we report the results of the operative management of primary spinal chordoma with minimum five year follow-up, the addition of C70 RT to surgical excision conferred a benefit to OS and local recurrence.
Subject(s)
Chordoma , Spinal Neoplasms , Humans , Chordoma/radiotherapy , Chordoma/surgery , Chordoma/pathology , Retrospective Studies , Cohort Studies , Follow-Up Studies , Sacrum/surgery , Sacrum/pathology , Spinal Neoplasms/radiotherapy , Spinal Neoplasms/surgery , Spinal Neoplasms/pathology , Treatment Outcome , Neoplasm Recurrence, Local/pathologyABSTRACT
AIMS: Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture. METHODS: This single tertiary-institutional, retrospectively matched case-control study included 72 patients who underwent prophylactic or therapeutic fixation for pathological fracture of the humerus, femur, or tibia with either a titanium (control group, n = 36) or carbon fibre (case group, n = 36) intramedullary nail between 2016 to 2020. Patients were excluded if intramedullary fixation was combined with any other surgical procedure/fixation method. Outcomes included operating time, blood loss, fluoroscopic time, and complications. Fisher's exact test and Mann-Whitney U test were used for categorical and continuous outcomes, respectively. RESULTS: Patients receiving carbon nails as compared to those receiving titanium nails had higher blood loss (median 150 ml (interquartile range (IQR) 100 to 250) vs 100 ml (IQR 50 to 150); p = 0.042) and longer fluoroscopic time (median 150 seconds (IQR 114 to 182) vs 94 seconds (IQR 58 to 124); p = 0.001). Implant complications occurred in seven patients (19%) in the titanium group versus one patient (3%) in the carbon fibre group (p = 0.055). There were no notable differences between groups with regard to operating time, surgical wound infection, or survival. CONCLUSION: This pilot study demonstrates a non-inferior surgical and short-term clinical profile supporting further consideration of carbon fibre nails for pathological fracture fixation in orthopaedic oncology patients. Given enhanced accommodation of imaging methods important for oncological surveillance and radiation therapy planning, as well as high tolerances to fatigue stress, carbon fibre implants possess important oncological advantages over titanium implants that merit further prospective investigation. Level of evidence: III, Retrospective study Cite this article: Bone Jt Open 2022;3(8):648-655.
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Background: Patellar tumors are rare but certainly must be considered in the differential diagnosis in patients with knee pain. Diagnosis can be challenging as often patellar neoplasms are confused with benign conditions and their clinical presentation is usually not specific. We performed an institutional and a literature review to determine what are the most common tumors affecting the patella and what is the best management. Methods: This is a case series from our institution including all patients with benign, malignant, and metastatic patellar neoplasms. Charts were reviewed for patient demographics, clinical presentation, pathology characteristics, radiographic classification, and oncologic and functional outcomes. Results: Twenty-four patients were identified; twelve patients had benign lesions, 10 metastatic and 2 primary malignant tumors. Chondroblastoma and Giant Cell Tumor were the most common tumors. Management of benign lesions with intralesional curettage and packing with bone graft or cement demonstrated excellent results with no local recurrence. In terms of malignant tumors, the spectrum of treatment is variable; it could range from medical management alone or in combination with surgical procedures to total patellectomy with reconstruction of the extensor mechanism. Conclusion: Patellar tumors should be part of the differential in patients with chronic knee pain that does not respond to initial conservative interventions. Recurrence rate with intralesional curettage and bone grafting or cement packing is very low and therefore should be the treatment of choice for benign intraosseous neoplasms. Resection with negative margins in malignant neoplasms or bone metastasis decreases local recurrence but only in the former group there is a potential impact in survival.
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BACKGROUND: Giant cell tumor of bone (GCTB) is a destructive lesion with a high potential for recurrence. RANK-ligand targeted therapy has provided promising, yet mixed results. Sclerostin (SOST) inhibition results in a net anabolic response and is currently used in the treatment of osteoporosis. The application to GCTB is unknown. OBJECTIVES: We sought to determine if GCTB stained for SOST on immunohistochemistry and correlate its expression with predictor variables. METHODS: All patients at a single institution undergoing surgery for GCTB between 1993 and 2008 with a minimum of 6 months follow-up were included. Primary outcomes included the presence of SOST staining, secondary outcomes included the correlation of patient and tumor-specific predictor variables. RESULTS: SOST antibody staining of any cell type was present in 47 of 48 cases (97.9%). Positivity of the stromal cells was present in 39 of 48 cases (81.3%) and was associated with radiographic aggressiveness (p = 0.023), symptomatic presentation (p = 0.032), prior surgery (p = 0.005), and patient age (p = 0.034). Positivity of giant cells was present in 41 of 48 cases (85.4%) and was not significant with predictive factors. CONCLUSIONS: Sclerostin staining in GCTB is a novel finding and warrants further research to define the role of sclerostin as a prognostic factor and therapeutic target.
Subject(s)
Bone Neoplasms , Giant Cell Tumor of Bone , Bone Neoplasms/pathology , Bone and Bones/pathology , Giant Cell Tumor of Bone/pathology , Giant Cell Tumor of Bone/surgery , Humans , Immunohistochemistry , Staining and LabelingABSTRACT
Aberrant methylation of genomic DNA has been reported in many cancers. Specific DNA methylation patterns have been shown to provide clinically useful prognostic information and define molecular disease subtypes with different response to therapy and long-term outcome. Osteosarcoma is an aggressive malignancy for which approximately half of tumors recur following standard combined surgical resection and chemotherapy. No accepted prognostic factor save tumor necrosis in response to adjuvant therapy currently exists, and traditional genomic studies have thus far failed to identify meaningful clinical associations. We studied the genome-wide methylation state of primary tumors and tested how they predict patient outcomes. We discovered relative genomic hypomethylation to be strongly predictive of response to standard chemotherapy. Recurrence and survival were also associated with genomic methylation, but through more site-specific patterns. Furthermore, the methylation patterns were reproducible in three small independent clinical datasets. Downstream transcriptional, in vitro, and pharmacogenomic analysis provides insight into the clinical translation of the methylation patterns. Our findings suggest the assessment of genomic methylation may represent a strategy for stratifying patients for the application of alternative therapies.
Subject(s)
Bone Neoplasms , Osteosarcoma , Bone Neoplasms/genetics , Bone Neoplasms/pathology , DNA , DNA Methylation , Humans , Osteosarcoma/genetics , Osteosarcoma/pathology , PrognosisABSTRACT
CASE: Two patients with cancer involving their proximal tibia required proximal tibial replacement (PTR). One had a soft-tissue sarcoma that involved her posterior cortex, and the other had extensive metaphyseal destruction from metastatic breast cancer. Their anterolateral cortex and tibial tubercle were uninvolved, permitting tubercle-sparing PTR. A plate was applied to the bone bridge in the latter patient in anticipation of radiotherapy. Both healed uneventfully and had minimal extensor lag 2 weeks postoperatively. CONCLUSION: Tubercle-sparing PTR preserves extensor mechanism function with minimal lag. It should be considered in patients with cancer when sparing the anterolateral cortex is oncologically safe.
Subject(s)
Bone Neoplasms , Sarcoma , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Bone Plates , Female , Humans , Sarcoma/surgery , Tibia/pathology , Tibia/surgery , Treatment OutcomeABSTRACT
BACKGROUND: The outcome differences following surgery for an impending versus a completed pathological fracture have not been clearly defined. The purpose of the present study was to assess differences in outcomes following the surgical treatment of impending versus completed pathological fractures in patients with long-bone metastases in terms of (1) 90-day and 1-year survival and (2) intraoperative blood loss, perioperative blood transfusion, anesthesia time, duration of hospitalization, 30-day postoperative systemic complications, and reoperations. METHODS: We retrospectively performed a matched cohort study utilizing a database of 1,064 patients who had undergone operative treatment for 462 impending and 602 completed metastatic long-bone fractures. After matching on 22 variables, including primary tumor, visceral metastases, and surgical treatment, 270 impending pathological fractures were matched to 270 completed pathological fractures. The primary outcome was assessed with the Cox proportional hazard model. The secondary outcomes were assessed with the McNemar test and the Wilcoxon signed-rank test. RESULTS: The 90-day survival rate did not differ between the groups (HR, 1.13 [95% CI, 0.81 to 1.56]; p = 0.48), but the 1-year survival rate was worse for completed pathological fractures (46% versus 38%) (HR, 1.28 [95% CI, 1.02 to 1.61]; p = 0.03). With regard to secondary outcomes, completed pathological fractures were associated with higher intraoperative estimated blood loss (p = 0.03), a higher rate of perioperative blood transfusions (p = 0.01), longer anesthesia time (p = 0.04), and more reoperations (OR, 2.50 [95% CI, 1.92 to 7.86]; p = 0.03); no differences were found in terms of the rate of 30-day postoperative complications or the duration of hospitalization. CONCLUSIONS: Patients undergoing surgery for impending pathological fractures had lower 1-year mortality rates and better secondary outcomes as compared with patients undergoing surgery for completed pathological fractures when accounting for 22 covariates through propensity matching. Patients with an impending pathological fracture appear to benefit from prophylactic stabilization as stabilizing a completed pathological fracture seems to be associated with increased mortality, blood loss, rate of blood transfusions, duration of surgery, and reoperation risk. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Subject(s)
Bone Neoplasms/surgery , Fractures, Spontaneous/surgery , Aged , Bone Neoplasms/complications , Bone Neoplasms/mortality , Cohort Studies , Databases, Factual , Female , Fractures, Spontaneous/etiology , Fractures, Spontaneous/mortality , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Local recurrence of microinvasive sarcoma or benign aggressive pathologies can be limb- and life-threatening. Although frozen pathology is reliable, tumor microinvasion can be subtle or missed, having an impact on surgical margins and postoperative radiation planning. The authors' service has begun to temporize the tumor bed after primary tumor excision with a wound vacuum-assisted closure (VAC) pending formal margin analysis, with coverage performed in the setting of final negative margins. METHODS: This retrospective analysis included all patients managed at a tertiary referral cancer center with VAC temporization after soft tissue sarcoma or benign aggressive tumor excision from 1 January 2000 to 1 January 2019 and at least 2 years of oncologic follow-up evaluation. The primary outcome was local recurrence. The secondary outcomes were distant recurrence, unplanned return to the operating room for wound/infectious indications, thromboembolic events, and tumor-related deaths. RESULTS: For 62 patients, VAC temporization was performed. The mean age of the patients was 62.2 ± 22.3 years (median 66.5 years; 95% confidence interval [CI] 61.7-72.5 years), and the mean age-adjusted Charlson Comorbidity Index was 5.3 ± 1.9. The most common tumor histology was myxofibrosarcoma (51.6%, 32/62). The mean volume was 124.8 ± 324.1 cm3, and 35.5% (22/62) of the cases were subfascial. Local recurrences occurred for 8.1% (5/62) of the patients. Three of these five patients had planned positive margins, and 17.7% (11/62) of the patients had an unplanned return to the operating room. No demographic or tumor factors were associated with unplanned surgery. CONCLUSIONS: The findings showed that VAC-temporized management of microinvasive sarcoma and benign aggressive pathologies yields favorable local recurrence and unplanned operating room rates suggestive of oncologic and technical safety. These findings will need validation in a future randomized controlled trial.
Subject(s)
Negative-Pressure Wound Therapy , Sarcoma , Soft Tissue Neoplasms , Adult , Aged , Aged, 80 and over , Humans , Margins of Excision , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Sarcoma/pathology , Sarcoma/surgery , Soft Tissue Neoplasms/pathology , Treatment OutcomeABSTRACT
INTRODUCTION: Maxillofacial (MF) giant cell lesions (GCLs) are benign, often locally aggressive lesions with potential for recurrence. Systemic treatments have included interferon alpha, calcitonin, bisphosphonates, and denosumab. Sclerostin (SOST) is typically thought to be a negative regulator of bone metabolism and anti-SOST agents have been used to treat osteoporosis; however, its role in central giant cell granuloma is unknown. The purpose of this study was to evaluate the expression of SOST in MF GCLs. MATERIALS AND METHODS: This was a retrospective study of patients with MF GCLs treated at a single institution between 1993 and 2008 with a minimum follow-up of 6âmonths. Representative tissue was used to create a tissue microarray and SOST immunohistochemical (IHC) staining and grading was performed. The primary outcomes were IHC staining of the stromal cells and giant cells. The secondary outcomes included correlation of IHC staining and patient predictor variables including clinically benign and aggressive lesions. All analyses were completed using univariate statistical tests. RESULTS: A total of 37 subjects were included (29 clinically aggressive and 8 clinically benign). Sclerostin staining was present in 30 of 37 subjects (81%). Of these, 22 (60%) had stromal cell staining and 28 (76%) had giant cell staining. The presence or absence of staining, of either cell type, was not associated with aggressiveness, presence of clinical symptoms, tumor size, previous interferon therapy, previous surgery, or the race or age of the patient. DISCUSSION: Maxillofacial GCLs have an overall high level of SOST staining; however, the role of SOST in treatment and prognosis is unknown and warrants further study.