Richard J O'Donnell

Memorial Sloan-Kettering Cancer Center, New York City, New York, United States

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Publications (42)140.8 Total impact

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    ABSTRACT: Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.
    Journal of the National Comprehensive Cancer Network: JNCCN 06/2014; 12(6):853-62. · 5.11 Impact Factor
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    ABSTRACT: These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.
    Journal of the National Comprehensive Cancer Network: JNCCN 04/2014; 12(4):473-83. · 5.11 Impact Factor
  • The American journal of surgical pathology 10/2013; 37(10):1627-30. · 4.06 Impact Factor
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    ABSTRACT: The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.
    Journal of the National Comprehensive Cancer Network: JNCCN 08/2012; 10(8):951-60. · 5.11 Impact Factor
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    Andrew E Horvai, Ritu Roy, Dariusz Borys, Richard J O'Donnell
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    ABSTRACT: The molecules Indian hedgehog (IHH), SP7 (also known as osterix), sex-determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and TWIST1 regulate the normal differentiation of osteo- and chondrogenic cells from precursors during skeletal development and remodeling. The aberrant function of the same molecules has been implicated in the pathogenesis of bone tumors. Preliminary studies suggest that antibodies against these molecules have practical, diagnostic or prognostic utility in tumors. However, a comprehensive analysis of the expression of these molecules in a large, diverse set of bone tumors has yet to be reported. The goals of this study were to compare the immunohistochemical profiles of IHH, SP7, SOX9, RUNX2 and TWIST1 among bone tumors and to determine the optimum panel for diagnostic utility. Tissue microarrays prepared from 206 undecalcified tumors (71 osteosarcomas, 26 osteoblastomas/osteoid osteomas, 50 giant cell tumors, 5 chondromyxoid fibromas and 54 chondroblastomas) were stained with antibodies to IHH, SP7, SOX9, RUNX2 and TWIST1. The stains were scored for intensity (0-3+) and distribution. The results were analyzed by cluster analysis. Optimum antibody panels for diagnostic sensitivity and specificity were calculated. Analysis revealed six main clusters that corresponded well to tumor types and suggested a close relationship between the stromal cells of giant cell tumor and the osteoblasts of osteosarcoma. The expression profile of chondromyxoid fibroma and chondroblastoma also suggested related differentiation. The distribution of osteoblastomas and osteoid osteomas was more heterogeneous. RUNX2, SOX9 and TWIST1 represented the most sensitive and specific immunohistochemical panel to distinguish among these diagnoses with the limitation that no result could discriminate between chondroblastoma and chondromyxoid fibroma. IHH and SP7 did not yield additional utility.Modern Pathology advance online publication, 6 July 2012; doi:10.1038/modpathol.2012.110.
    Modern Pathology 07/2012; · 5.25 Impact Factor
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    ABSTRACT: Failure of endoprosthetic reconstruction with conventional stems due to aseptic loosening remains a challenge for maintenance of limb integrity and function. The Compress(®) implant (Biomet Inc, Warsaw, IN, USA) attempts to avoid aseptic failure by means of a unique technologic innovation. Though the existing literature suggests survivorship of Compress(®) and stemmed implants is similar in the short term, studies are limited by population size and followup duration. We therefore compared (1) the rate of aseptic failure between Compress(®) and cemented intramedullary stems and (2) evaluated the overall intermediate-term implant survivorship. We reviewed 26 patients with Compress(®) implants and 26 matched patients with cemented intramedullary stems. The patients were operated on over a 3-year period. Analysis focused on factors related to implant survival, including age, sex, diagnosis, infection, aseptic loosening, local recurrence, and fracture. Minimum followup was 0.32 years (average, 6.2 years; range, 0.32-9.2 years). Aseptic failure occurred in one (3.8%) patient with a Compress(®) implant and three (11.5%) patients with cemented intramedullary stems. The 5-year implant survival rate was 83.5% in the Compress(®) group and 66.6% in the cemented intramedullary stem group. The Compress(®) implant continues to be a reliable option for distal femoral limb salvage surgery. Data regarding aseptic failure is encouraging, with equivalent survivorship against cemented endoprosthetic replacement at intermediate-term followup. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
    Clinical Orthopaedics and Related Research 11/2011; 470(3):735-42. · 2.79 Impact Factor
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    ABSTRACT: To assess the impact of on-site immediate cytologic assessment (ICA) on the diagnostic success rate of computed tomography (CT)-guided percutaneous needle biopsy (PNB) of musculoskeletal lesions and the long-term outcome in inconclusive PNB findings. A total of 299 CT-guided PNBs of musculoskeletal lesions performed between January 1997 and December 2009 were retrospectively reviewed. The lesions were categorized by their morphology, location, and size, and by biopsy type. The diagnostic success rates, impact of ICA, and outcome in inconclusive PNBs were studied, with final histopathologic findings and/or clinical follow-up as a reference. The overall diagnostic success rate of PNBs was 72.9% (218 of 299). The success rate increased with larger lesions (> 2 cm to 4 cm; P = .009). Biopsies performed with ICA had a higher success rate (77.0% vs 63.3%; P = .015). PNBs had inconclusive results in 109 of 299 cases (36.5%). In 66 of these, repeat open biopsy or clinical follow-up demonstrated 19 malignant/aggressive lesions (28.8%) and 47 benign/nonaggressive lesions (71.2%). CT-guided PNB had a satisfactory success rate, which significantly increased when performed with ICA. Inconclusive results in PNB were most frequently associated with benign findings during further workup.
    Journal of vascular and interventional radiology: JVIR 05/2011; 22(7):1024-30. · 1.81 Impact Factor
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    ABSTRACT: The incidence of melanoma in US adults is approximately 1.5 per million, with 2% to 5% of patients developing metastatic disease. In children, melanoma is distinctly uncommon, and metastatic disease occurs even more seldom. This case report, the first of a patellar lesion as the initial presentation of metastatic melanoma in a pediatric patient, highlights use of patellectomy and intraoperative radiation therapy in obtaining palliative local control while avoiding periarticular functional morbidity.
    American journal of orthopedics (Belle Mead, N.J.) 12/2010; 39(12):582-6.
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    ABSTRACT: Osteoid osteoma occurs most commonly in children, adolescents, and young adults between the ages of 5 and 30 years. In the preschool age group, it is quite uncommon, accounting for only 3-8% of all osteoid osteoma cases. We report a case of osteoid osteoma in a 7-month-old infant, who presented with decreased use of the right lower extremity due to pain. Magnetic resonance imaging (MRI) showed an atypical appearance. A biopsy of the lesion, with histopathological examination, confirmed the diagnosis of osteoid osteoma. Radiofrequency ablation (RFA) of the nidus under computed tomography (CT) guidance was performed. The patient developed a recurrence after 3 months, which was treated with a second RFA. On subsequent follow-up, the infant did not show signs of pain after 1 month. In summary, this case report shows that osteoid osteoma can present in early infancy and can be successfully treated with RFA at this age, however, recurrence after the procedure can occur and close follow-up is recommended.
    Skeletal Radiology 11/2010; 39(11):1145-9. · 1.74 Impact Factor
  • Journal of the National Comprehensive Cancer Network: JNCCN 06/2010; 8(6):630-74. · 5.11 Impact Factor
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    ABSTRACT: Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.
    Journal of the National Comprehensive Cancer Network: JNCCN 06/2010; 8(6):688-712. · 5.11 Impact Factor
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    Michael J Cascio, Richard J O'Donnell, Andrew E Horvai
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    ABSTRACT: Epithelioid sarcoma is a rare, malignant, soft tissue neoplasm that can be classified into proximal, distal and fibroma-like subtypes. Regardless of subtype, epithelioid sarcoma often shows morphologic and immunophenotypic evidence of epithelial differentiation. Current therapeutic strategies include surgical resection, amputation, radiation or chemotherapy, although the overall prognosis remains poor. The epidermal growth factor receptor (EGFR) is a novel therapeutic target in carcinomas. In some carcinomas, EGFR kinase domain mutations or gene amplification may correlate with response to specific inhibitors. EGFR expression has been reported in some sarcoma types, but expression, amplification and mutations have not been studied in epithelioid sarcoma. We evaluated 15 cases of epithelioid sarcoma from 14 patients for EGFR expression using immunohistochemistry, EGFR copy number aberration using fluorescence in situ hybridization and screened for mutations in the tyrosine kinase domain of the EGFR gene using direct sequencing. In all, 14 of the 15 epithelioid sarcomas (93%) showed expression of EGFR by immunohistochemistry. A majority of the cases (n=11, 73%) showed strong (2+ to 3+) and homogeneous (>75% of cells) membrane staining. No amplification or polysomy of the EGFR gene or mutations of the tyrosine kinase domain of EGFR (exons 18-21) were detected. These results imply that although EGFR is expressed in most epithelioid sarcomas regardless of subtype, gene amplification and activating mutations in the tyrosine kinase domain appear to be rare or absent. Thus, the benefit of targeted therapy against EGFR in patients with epithelioid sarcoma remains to be determined.
    Modern Pathology 04/2010; 23(4):574-80. · 5.25 Impact Factor
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    ABSTRACT: Liposarcoma represents a unique model insofar as some well-differentiated liposarcomas progress to non-lipogenic, so-called 'dedifferentiated,' forms. The well-differentiated and dedifferentiated family of liposarcomas demonstrates amplification of the chromosome subregion 12q13-q15 with resultant amplification of the MDM2 and CDK4 genes. However, the specific genetic changes that distinguish between well-differentiated and dedifferentiated liposarcomas are less well understood. To study the genetic changes in dedifferentiated liposarcomas, paired well-differentiated and dedifferentiated components of 29 tumors were analyzed separately by array-based comparative genomic hybridization. A bacterial artificial chromosome array at approximately 1-Mb resolution was used. The genetic changes were compared with clinical presentation, grade of the dedifferentiated component and overexpression of MDM2 and CDK4. Most tumors (n=21, 72%) were retroperitoneal, with both components present at initial diagnosis (n=25, 86%). Eight tumors (28%) were classified as low-grade dedifferentiation. In four cases (14%), a well-differentiated liposarcoma preceded the presentation of the dedifferentiated tumor by 1-5 years. 12q13-q15 was amplified in all tumors. Using unsupervised hierarchical clustering of copy-number changes, all but two tumors showed close similarities between well-differentiated and dedifferentiated components, and segregated as pairs. Dedifferentiated components had more total amplifications (P=0.008) and a trend for gain at 19q13.2, but no genetic changes were significant in distinguishing between the two components. High-level amplifications of 1p21-32 (n=7, 24%), 1q21-23 (n=9, 31%), 6q23-24 (n=6, 21%) and 12q24 (n=3, 10%) were common, but none significantly correlated with differentiation. Presentation and grade correlated with the frequency of changes at a number of genetic loci (P<0.001), whereas CDK4 immunostaining showed negative correlation with 12q13.13 amplification. The genotypic similarity, at the limit of the array's resolution, between components implies that most genetic changes precede phenotypic 'progression,' early in tumorigenesis. The relationship between genetic changes and presentation or grade may reflect differences in factors that control genomic instability or the background genotype of the tumor.
    Modern Pathology 10/2009; 22(11):1477-88. · 5.25 Impact Factor
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    Richard J O'Donnell
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    ABSTRACT: Compressive osseointegration technology, which provides immediate, mechanically compliant endoprosthetic fixation, has been adapted for massive proximal tibial reconstructions in an attempt to avoid aseptic failure encountered with conventional stems. A retrospective review of 16 patients with resected tumors was undertaken to determine whether compressive osseointegration can provide durable anchorage of tibial implants. Medical records, radiographs, and clinical examinations were reviewed to assess surgical, local disease control, and prosthetic outcomes. The average age was 18 years (range, 12-42 years). Diagnoses included osteosarcoma (12), Ewing sarcoma (two), chondrosarcoma (one), and undifferentiated sarcoma (one). Minimum followup was 2 years (mean, 4.5 years; range, 2-10.3 years); no patient was lost to followup. There were no local recurrences. Four patients developed metastatic disease; one patient died of his primary tumor, and another died from a chemotherapy-related malignancy. Complications included one early deep infection that ultimately resulted in prosthetic loosening and the need for an above-knee amputation. There were two late deep infections; prosthetic retention was achieved with débridement and antibiotics. One patient developed aseptic loosening and underwent revision; the other 15 implants provided stable osseointegration at last followup. Compressive osseointegration technology can thus achieve acceptable short-term endoprosthetic fixation results and may reduce the risk of aseptic loosening reported with conventional tibial stems. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
    Clinical Orthopaedics and Related Research 09/2009; 467(11):2807-12. · 2.79 Impact Factor
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    ABSTRACT: Periprosthetic fractures after massive endoprosthetic reconstructions pose a reconstructive challenge and jeopardize limb preservation. Compressive osseointegration technology offers the promise of relative ease of prosthetic revision, since fixation is achieved by means of a short intramedullary device. We retrospectively reviewed the charts of 221 patients who had Compress((R)) devices implanted in two centers between December, 1996 and December, 2008. The mean followup was 50 months (range, 1-123 months). Six patients (2.7%) sustained periprosthetic fractures and eight (3.6%) had nonperiprosthetic ipsilateral limb fractures occurring from 4 to 79 months postoperatively. All periprosthetic fractures occurred in patients with distal femoral implants (6/154, 3.9%). Surgery was performed in all six patients with periprosthetic femur fractures and for one with a nonperiprosthetic patellar fracture. The osseointegrated interface was radiographically stable in all 14 cases. All six patients with periprosthetic fracture underwent limb salvage procedures. Five patients had prosthetic revision; one patient who had internal fixation of the fracture ultimately underwent amputation for persistent infection. Periprosthetic fractures involving Compress((R)) fixation occur infrequently and most can be treated successfully with further surgery. When implant revision is needed, the bone preserved by virtue of using a shorter intramedullary Compress((R)) device as compared to conventional stems, allows for less complex surgery, making limb preservation more likely. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
    Clinical Orthopaedics and Related Research 07/2009; 467(11):2800-6. · 2.79 Impact Factor
  • Ryan Gill, Richard J O'Donnell, Andrew Horvai
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    ABSTRACT: Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm of intermediate malignancy. Epithelioid hemangioendothelioma often presents a difficult diagnostic problem, especially in bone, because the epithelioid morphology and radiographic features raise the possibility of metastatic carcinoma. The current trend of small biopsies obtained with computed tomography-guided techniques exacerbates the problem. The markedly different treatment for EHE and metastatic carcinoma underscores the need for specific markers that can differentiate between these 2 entities. To determine the relative utility of endothelial markers in differentiating EHE from metastatic carcinoma, with emphasis on bone biopsies. We used immunohistochemistry in formalin-fixed paraffin-embedded tissue to compare the utility of Fli-1, CD34, CD31, podoplanin, and keratin cocktail in 13 EHEs and 13 morphologically similar carcinomas metastatic to bone. Immunohistochemical data were evaluated using Fisher exact test, and specificity and sensitivity were calculated. Significant proportions of EHEs were positive for Fli-1 (100%), CD34 (85%), and CD31 (100%) compared with metastatic carcinoma (Fli-1, 15%; CD34, 15%; CD31, 38%) (P < .001, P = .005, and P = .01, respectively). However, these markers were not 100% specific for EHE. Cytokeratin cocktail stained significantly more metastatic carcinomas (100%) than EHEs (38%) (P = .01) but was not 100% specific. No significant difference was observed regarding immunostaining for podoplanin between the tumor types. Fli-1 is most helpful in distinguishing EHE from metastatic carcinoma. However, the absence of complete specificity of any of the endothelial markers for EHE, or of keratin cocktail for carcinoma, suggests that these markers are best used in combination.
    Archives of pathology & laboratory medicine 06/2009; 133(6):967-72. · 2.78 Impact Factor
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    ABSTRACT: To evaluate the role of radiation therapy (RT) as a component of multimodality therapy for pediatric desmoids. Twenty-one children diagnosed between 1987 and 2005 were identified. Median age at start of treatment was 13 years (range, 2-21). Primary therapy consisted of resection alone (10), resection + external beam radiation therapy (EBRT) (5), resection + chemotherapy (CT; 3), EBRT alone (1), and CT alone (2). The median follow-up from start of treatment is 75.7 months (range, 16-162). Examining patients with gross total resections (GTRs) (-) margins and those who had GTRs (+) margins followed by EBRT, only 2 of 7 failed primary treatment. Conversely, 13 of 14 patients with other primary treatments failed locally. Of the 15 patients who recurred, only 1 patient had a GTR (-) margins. Seven of these patients had salvage therapy that did not include RT, and of these only 2 have no evidence of disease (NED) at last follow-up. In contrast, the remaining 8 patients received RT as a component of their final salvage therapy and 7 of these are NED at last follow-up. At last follow-up, no patient has died, although toxicities of therapy have occurred. Local control is difficult to achieve in pediatric patients with desmoids. In the setting in which negative surgical margins cannot be achieved, RT plays a key role in achieving NED status. Even after multiple recurrences, successful salvage is achievable, particularly when high-dose focal therapy is incorporated.
    International journal of radiation oncology, biology, physics 05/2009; 75(1):177-82. · 4.59 Impact Factor
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    ABSTRACT: Dedifferentiated liposarcoma can be readily diagnosed by the juxtaposition of a well-differentiated liposarcoma to a nonlipogenic sarcoma. However, if the lipogenic component is not abundant due to surgical sampling or small biopsy, dedifferentiated liposarcoma can be difficult to distinguish from other poorly different sarcomas. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a nuclear hormone receptor that plays a critical role in adipocyte differentiation. Prior studies have not only demonstrated PPAR-gamma mRNA in various subtypes of liposarcoma but have also shown that adipocyte differentiation can be induced in some liposarcomas by a PPAR-gamma agonist. In the present study, we investigated whether immunostaining for PPAR-gamma can be used to distinguish dedifferentiated liposarcoma from other retroperitoneal sarcomas. We examined a series of 40 dedifferentiated liposarcoma and compared the staining for PPAR-gamma to a series of 24 retroperitoneal sarcomas that lacked lipogenic differentiation. A monoclonal antibody against PPAR-gamma was used to stain formalin-fixed paraffin-embedded tissue. Specific nuclear immunostaining was present in 37/40 (93%) of the dedifferentiated liposarcoma and 6/24 (25%) of the other sarcomas (two leiomyosarcomas and four undifferentiated sarcomas). Interestingly, immunostaining for CDK4 and/or MDM2 was identified in three of the four PPAR-gamma-positive undifferentiated sarcomas, raising the possibility that these may represent dedifferentiated liposarcoma. This is the first study demonstrating the utility of PPAR-gamma immunohistochemistry in the diagnosis of dedifferentiated liposarcoma in tissue sections. Although not completely specific, the presence of PPAR-gamma staining, in combination with histologic findings and other markers, can aid in the diagnosis of dedifferentiated liposarcoma, particularly on small biopsies that may not sample the well-differentiated component.
    Modern Pathology 06/2008; 21(5):517-24. · 5.25 Impact Factor
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    ABSTRACT: Giant-cell tumor of bone is considered a benign, locally aggressive and rarely metastasizing neoplasm of bone. Specific microscopic or radiographic findings that reliably predict behavior have remained elusive. However, recent evidence suggests that activity of the telomerase enzyme complex correlates with recurrence in giant-cell tumor, although the subset of cells with telomerase activity in these heterogeneous tumors has not been defined. In the present study, we investigated whether immunostaining for human telomerase reverse transcriptase, a component of the telomerase complex, correlates with outcome in giant-cell tumor and the distribution of telomerase reverse transcriptase staining in these tumors. We analyzed 58 cases of giant-cell tumor for the presence and pattern of telomerase reverse transcriptase immunostaining, presence of soft tissue involvement and the type of initial surgery, and correlated these findings with recurrence-free survival and metastasis-free survival. Specific staining with telomerase reverse transcriptase was present in 20 out of 58 tumors (35%) in the nuclei of mononuclear cells and, occasionally, osteoclast-like giant cells. Furthermore, positive telomerase reverse transcriptase immunohistochemistry correlated with recurrence-free survival (P=0.02), whereas the presence of soft tissue extension (P=0.3) and the type of initial surgery (P=0.2) did not. Only soft-tissue extension significantly correlated with metastasis-free survival (P=0.003). Therefore, telomerase reverse transcriptase expression may predict recurrence in giant-cell tumor insofar as positive immunostaining correlates with shorter recurrence-free survival and may be a useful prognostic marker to stratify patients to more aggressive treatment protocols.
    Modern Pathology 05/2008; 21(4):423-30. · 5.25 Impact Factor
  • Pamela M Aubert, Richard J O'Donnell
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    ABSTRACT: Hundreds of thousands of Americans are affected every year by skeletal complications of oncologic disease. Recent developments in medical oncology, radiation oncology and radiology, particularly with respect to the use of bisphosphonate medication and radiofrequency techniques, have served to greatly lessen the morbidity associated with metastatic skeletal disease. Similarly, there has been significant advancement in the field of orthopaedic oncology in the areas of internal fixation, endoprosthetic implant design, and minimally invasive kyphoplasty technology. Given the palliative intent of intervention in this patient population, the goal of treatment of skeletal metastases must be optimization of limb function and ultimately, quality of life.
    Surgical Oncology 01/2008; 16(4):311-30. · 2.14 Impact Factor

Publication Stats

276 Citations
140.80 Total Impact Points

Institutions

  • 2009–2013
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 2001–2012
    • University of California, San Francisco
      • • Department of Pathology
      • • Department of Radiation Oncology
      San Francisco, CA, United States
  • 2010
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2007–2008
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
    • Royal National Orthopaedic Hospital NHS Trust
      Londinium, England, United Kingdom