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Robert M. Henshaw

Bio: Robert M. Henshaw is an academic researcher from MedStar Washington Hospital Center. The author has contributed to research in topics: Denosumab & Femur. The author has an hindex of 17, co-authored 39 publications receiving 2303 citations. Previous affiliations of Robert M. Henshaw include Washington Cancer Institute & Georgetown University.
Topics: Denosumab, Femur, Prosthesis, Medicine, Chondrosarcoma

Papers
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Journal ArticleDOI
TL;DR: In this article, the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT was investigated.
Abstract: Summary Background Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT. Methods In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov, NCT00396279. Findings Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70–95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3–5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related. Interpretation Further investigation of denosumab as a therapy for GCT is warranted. Funding Amgen, Inc.

575 citations

Journal ArticleDOI
TL;DR: Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB and represents a new treatment option for patients with the rare giant cell tumour of bone.
Abstract: Summary Background Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB. Methods We did an international, open-label, parallel-group, phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease. Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg. We divided patients into three cohorts—those with surgically unsalvageable GCTB (cohort 1), those with salvageable GCTB whose surgery was associated with severe morbidity (cohort 2), and those who transferred from a previous study of denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. Investigator-determined disease status and clinical benefit were assessed every 4 weeks. Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities. Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2. Safety analyses included all patients who received at least one dose of denosumab. Efficacy analyses included all eligible patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, identifier NCT00680992. Findings 282 patients, including ten adolescents, were included between Sept 9, 2008, and March 25, 2011. Of the 281 patients analysable for safety, three (1%) had osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3–4 adverse events were hypophosphataemia, which occurred in nine (3%) patients, and anaemia, back pain, and pain in extremities, each of which occurred in three patients (1%). Serious adverse events were reported in 25 (9%) patients. No treatment-related deaths were reported. On the basis of investigators' assessment of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months (IQR 5·8–21·0). In cohort 2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients who had surgery underwent a less morbid procedure than planned. Median follow-up in cohort 2 was 9·2 months (IQR 4·2–12·9). Interpretation Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB. Funding Amgen.

477 citations

Journal ArticleDOI
TL;DR: Cryosurgery has the advantages of joint preservation, excellent functional outcome, and low recurrence rate when compared with other joint preservation procedures, and it is recommended as an adjuvant to curettage for most giant cell tumors of bone.
Abstract: Between 1983 and 1993, 102 patients with giant cell tumor of bone were treated at three institutions. Sixteen patients (15.9%) presented with already having had local recurrence. All patients were treated with thorough curettage of the tumor, burr drilling of the tumor inner walls, and cryotherapy by direct pour technique using liquid nitrogen. The average followup was 6.5 years (range, 4-15 years). The rate of local recurrence in the 86 patients treated primarily with cryosurgery was 2.3% (two patients), and the overall recurrence rate was 7.9% (eight patients). Six of these patients were cured by cryosurgery and two underwent resection. Overall, 100 of 102 patients were cured with cryosurgery. Complications associated with cryosurgery included six (5.9%) pathologic fractures, three (2.9%) cases of partial skin necrosis, and two (1.9%) significant degenerative changes. Overall function was good to excellent in 94 patients (92.2%), moderate in seven patients (6.9%), and poor in one patient (0.9%). Cryosurgery has the advantages of joint preservation, excellent functional outcome, and low recurrence rate when compared with other joint preservation procedures. For these reasons, it is recommended as an adjuvant to curettage for most giant cell tumors of bone.

285 citations

Journal ArticleDOI
15 Dec 2000-Cancer
TL;DR: The purpose of this study was to analyze the role of percutaneous core needle biopsy in the diagnosis of musculoskeletal sarcomas.
Abstract: BACKGROUND The purpose of this study was to analyze the role of percutaneous core needle biopsy in the diagnosis of musculoskeletal sarcomas. METHODS One hundred eighty-five biopsy procedures were performed on 161 musculoskeletal tissue masses suspected of being a sarcoma in 155 patients who underwent subsequent tumor resection. A percutaneous core needle biopsy was performed on all masses either in the clinic or under radiologic guidance. If an adequate diagnosis could not be made on the basis of this biopsy specimen, an open incisional biopsy was performed. RESULTS One hundred seventy-three core needle biopsy procedures were performed: 90 without radiologic guidance, 55 computed tomography guided, and 28 fluoroscopically guided. Twelve open incisional biopsies were performed. Eighty-three sarcomas, 67 benign mesenchymal tumors, and 11 metastatic epithelial tumors were identified. Analysis of the data reveals that only 7.4% of the masses required open biopsy. In 88.2% of the masses, a single percutaneous biopsy procedure was adequate, and no additional biopsy was necessary. There was a 1.1% rate of complications; none caused a change in the patient's treatment plan. There was a 1.1% rate of major diagnostic errors, none of which ultimately impacted on the patient's outcome. There were no unnecessary amputations. Percutaneous needle biopsy showed a positive predictive value of 100%, a negative predictive value of 82%, a sensitivity of 81.8%, and a specificity of 100%. The accuracy of a single-needle biopsy procedure to identify benign versus malignant lesions, exact grade, and exact pathology was 92.4%, 88.6%, and 72.7%, respectively. CONCLUSIONS The percutaneous needle biopsy was found to be extremely effective and safe for the diagnosis of musculoskeletal masses. This method allowed 88% of patients with suspected sarcomas to undergo a single-needle biopsy procedure before the initiation of definitive treatment. Patients undergoing percutaneous needle biopsy had lower rates of major diagnostic errors and complications than previously described for open biopsy. Open biopsy offered limited additional information when preceded by a needle biopsy, given that these tumors were difficult to identify even after final resection. Cancer 2000;89:2677–86. © 2000 American Cancer Society.

200 citations

Journal ArticleDOI
TL;DR: Percutaneous biopsy of primary bone tumors is safe and accurate for diagnosis and grade of specific tumor, in cases with nondiagnostic biopsy.
Abstract: PURPOSE: To determine the diagnostic accuracy of image-guided percutaneous biopsy in 110 primary bone tumors of varying internal compositions. MATERIALS AND METHODS: One hundred ten consecutive patients with primary bone tumors underwent biopsy with computed tomography (CT) or fluoroscopy. Ninety-one patients underwent surgical follow-up and 19 received medical treatment and underwent subsequent imaging studies. Final analysis of bone biopsy results included tumor type, malignancy, final tumor grade, biopsy complications, and effect on eventual treatment outcome. RESULTS: Seventy-seven tumors were malignant and 33 were benign. Most common tumors at biopsy were osteosarcoma (n = 20), lymphoma (n = 18), chondrosarcoma (n = 16), and giant cell tumor (n = 16). Correct final diagnosis was attained in 97 (88%) patients. Sixty-three lesions were solid nonsclerotic; 26, sclerotic; and 21, lytic with cystic centers containing internal areas of fluid, hemorrhage, or necrosis. In six of 21 lesions with a predominant...

191 citations


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TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.

1,988 citations

Journal ArticleDOI
TL;DR: The following recommendations apply to adult-type soft tissue sarcomas arising from limbs and superficial trunk and Extraskeletal Ewing sarcoma, which is excluded from this chapter.

617 citations

Journal ArticleDOI
TL;DR: This Review chronicles the events that led to an increased understanding of bone resorption, the elucidation of the signalling pathway mediated by osteoprotegerin, receptor activator of NF-κB and RANK ligand (RANKL) and its role in osteoclast biology, as well as the evolution of recombinant RankL antagonists, which culminated in the development of the therapeutic RANKL-targeted antibody denosumab.
Abstract: Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a complex interplay between bone-forming cells termed osteoblasts and bone-resorbing cells termed osteoclasts, and is guided physiologically by a diverse set of hormones, cytokines and growth factors. The balance between these processes changes over time, causing an elevated risk of fractures with age. Osteoclasts may also be activated in the cancer setting, leading to bone pain, fracture, spinal cord compression and other significant morbidities. This Review chronicles the events that led to an increased understanding of bone resorption, the elucidation of the signalling pathway mediated by osteoprotegerin, receptor activator of NF-κB (RANK) and RANK ligand (RANKL) and its role in osteoclast biology, as well as the evolution of recombinant RANKL antagonists, which culminated in the development of the therapeutic RANKL-targeted antibody denosumab.

509 citations

Journal ArticleDOI
TL;DR: Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB and represents a new treatment option for patients with the rare giant cell tumour of bone.
Abstract: Summary Background Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB. Methods We did an international, open-label, parallel-group, phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease. Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg. We divided patients into three cohorts—those with surgically unsalvageable GCTB (cohort 1), those with salvageable GCTB whose surgery was associated with severe morbidity (cohort 2), and those who transferred from a previous study of denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. Investigator-determined disease status and clinical benefit were assessed every 4 weeks. Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities. Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2. Safety analyses included all patients who received at least one dose of denosumab. Efficacy analyses included all eligible patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, identifier NCT00680992. Findings 282 patients, including ten adolescents, were included between Sept 9, 2008, and March 25, 2011. Of the 281 patients analysable for safety, three (1%) had osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3–4 adverse events were hypophosphataemia, which occurred in nine (3%) patients, and anaemia, back pain, and pain in extremities, each of which occurred in three patients (1%). Serious adverse events were reported in 25 (9%) patients. No treatment-related deaths were reported. On the basis of investigators' assessment of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months (IQR 5·8–21·0). In cohort 2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients who had surgery underwent a less morbid procedure than planned. Median follow-up in cohort 2 was 9·2 months (IQR 4·2–12·9). Interpretation Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB. Funding Amgen.

477 citations

Journal ArticleDOI
TL;DR: There are five primary modes of endoprosthetic failure, and their relative incidences are significantly different and dependent on anatomic location.
Abstract: Background: Massive endoprostheses provide orthopaedic oncologists with many reconstructive options after tumor resection, although failure rates are high. Because the number of these procedures is limited, failure of these devices has not been studied or classified adequately. This investigation is a multicenter review of the use of segmental endoprostheses with a focus on the modes, frequency, and timing of failure. Methods: Retrospective reviews of the operative databases of five institutions identified 2174 skeletally mature patients who received a large endoprosthesis for tumor resection. Patients who had failure of the endoprosthesis were identified, and the etiology and timing of failure were noted. Similar failures were tabulated and classified on the basis of the risk of amputation and urgency of treatment. Statistical analysis was performed to identify dependent relationships among mode of failure, anatomic location, and failure timing. A literature review was performed, and similar analyses were done for these data. Results: Five hundred and thirty-four failures were identified. Five modes of failure were identified and classified: soft-tissue failures (Type 1), aseptic loosening (Type 2), structural failures (Type 3), infection (Type 4), and tumor progression (Type 5). The most common mode of failure in this series was infection; in the literature, it was aseptic loosening. Statistical dependence was found between anatomic location and mode of failure and between mode of failure and time to failure. Significant differences were found in the incidence of failure mode Types 1, 2, 3, and 4 when polyaxial and uniaxial joints were compared. Significant dependence was also found between failure mode and anatomic location in the literature data. Conclusions: There are five primary modes of endoprosthetic failure, and their relative incidences are significantly different and dependent on anatomic location. Mode of failure and time to failure also show a significant dependence. Because of these relationships, cumulative reporting of segmental failures should be avoided because anatomy-specific trends will be missed. Endoprosthetic design improvements should address failure modes specific to the anatomic location. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

471 citations