Raffi S. Avedian, MD

All Publications

• Association of Histologic Subtype With Radiation Response and Survival Outcomes in Synovial Sarcoma ADVANCES IN RADIATION ONCOLOGY Matsui, J. K., Jackson, S., Fang, J., Mohler, D. G., Steffner, R. J., Charville, G. W., van de Rijn, M., Million, L., Chin, A. L., Hiniker, S. M., Kalbasi, A., Moding, E. J. 2025; 10 (3)

  View details for DOI 10.1016/j.adro.2025.101718

  View details for Web of Science ID 001436810100001

• Association of Histologic Subtype With Radiation Response and Survival Outcomes in Synovial Sarcoma. Advances in radiation oncology Matsui, J. K., Jackson, S., Fang, J., Mohler, D. G., Steffner, R. J., Avedian, R. S., Charville, G. W., Rijn, M. v., Million, L., Chin, A. L., Hiniker, S. M., Kalbasi, A., Moding, E. J. 2025; 10 (3): 101718

  Abstract

  Synovial sarcoma (SS) is a rare, aggressive soft tissue malignancy that is divided into biphasic and monophasic histologic subtypes. In addition to surgical resection, radiation therapy (RT) improves local control in patients at higher risk of recurrence. This study aimed to investigate the impact of histologic subtype on radiation response and survival outcomes in patients treated with RT as part of definitive management.We retrospectively identified patients with SS treated with RT and surgical resection from 1997 to 2020 at Stanford Medical Center. We assessed the association between histologic subtypes (biphasic vs monophasic) and response to preoperative RT based on imaging and pathology. Volumetric response was calculated using the pre-RT and post-RT/preoperative postcontrast T1-weighted magnetic resonance imaging images. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were conducted using Cox regression models. Variables for univariable and multivariable analyses included age, histologic subtypes, tumor location, tumor size, margin status, chemotherapy, and performance status.In our study, 50 patients met the inclusion criteria. The median age was 34.8 years at diagnosis, and 36% (n = 18) received concurrent chemotherapy. Biphasic (n = 18, 36%) and monophasic (n = 32, 64%) tumors exhibited significant differences in negative margin status (94% vs 66%, P = .036). Of the 22 patients who underwent preoperative RT, 15 patients had pre-RT and post-RT imaging to assess volumetric changes. Biphasic tumors demonstrated less necrosis at the time of surgical resection but a significantly greater volumetric decrease with preoperative RT (42% vs 5%, P = .004). PFS and OS were superior in biphasic tumors (P = .003 and P = .009, respectively). Multivariable analyses identified histologic subtypes (monophasic vs biphasic) as a significant factor impacting PFS (HR, 5.65; 95% CI, 1.78-17.91; P = .003).Biphasic tumors exhibit an improved volumetric response to preoperative RT and improved outcomes. These findings underscore the importance of considering histology when tailoring treatment for patients with SS.

  View details for DOI 10.1016/j.adro.2025.101718

  View details for PubMedID 40092155

  View details for PubMedCentralID PMC11910705

• Evolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response. Cancer research Blomain, E., Soudi, S., Wang, Z., Somani, A., Subramanian, A., Nouth, S. C., Oladipo, E., New, C., Kenney, D. E., Nemat-Gorgani, N., Kindler, T., Avedian, R. S., Steffner, R. J., Mohler, D. G., Hiniker, S. M., Chin, A. L., Kalbasi, A., Binkley, M. S., Fried, M., Gaida, M. M., van de Rijn, M., Moding, E. J. 2025

  Abstract

  Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy. Most unirradiated UPS displayed initial linear evolution followed by subsequent branching evolution with distinct mutational processes during early and late development. Metrics of genetic divergence between regions provided evidence of strong selection pressures during UPS development that further increased during radiotherapy. Subclone abundance changed following radiotherapy with subclone contraction tied to alterations in calcium signaling, and inhibiting calcium transporters radiosensitized sarcoma cells. Finally, ctDNA analysis accurately measured subclone abundance and enabled non-invasive monitoring of subclonal changes. These results demonstrate that radiation exerts selective pressures on UPS and suggest that targeting radioresistant subclonal populations could improve outcomes after radiotherapy.

  View details for DOI 10.1158/0008-5472.CAN-24-3281

  View details for PubMedID 39808162

• IlluminOss photodynamic bone stabilization system improves pain and function in the treatment of humeral metastatic disease. The bone & joint journal Terek, R. M., McGough, R., Fabbri, N., Cheung, F., Brigman, B., Wittig, J., Emory, C., Aboulafia, A., Avedian, R., Mayerson, J., Henshaw, R., Reimer, N., Eward, W., Weiss, K., Healey, J., Mohler, D., Adams, B. 2024; 106-B (12): 1485-1492

  Abstract

  The aim of the LightFix Trial was to evaluate the clinical outcomes for one year after the treatment of impending and completed pathological fractures of the humerus using the IlluminOss System (IS), and to analyze the performance of this device.A total of 81 patients with an impending or completed pathological fracture were enrolled in a multicentre, open label single cohort study and treated with IS. Inclusion criteria were visual analogue scale (VAS) Pain Scores > 60 mm/100 mm and Mirels' Score ≥ 8. VAS pain, Musculoskeletal Tumor Society (MSTS) Upper Limb Function, and The European Organization for Research and Treatment of Cancer QoL Group Bone Metastases Module (QLQ-BM22) scores were all normalized to 100, and radiographs were obtained at baseline and at 14, 30, 90, 180, and 360 days postoperatively.The mean VAS pain score decreased significantly from 84 (SD 15) to 50 (SD 29), 38 (SD 30), 31 (SD 29), 31 (SD 29), and 21 (SD 23) between the baseline and follow-up times (p < 0.001). The mean MSTS function scores significantly increased from 27 (SD 19) to 52 (SD 22), 60 (23), 67 (SD 23), 72 (SD 26), and 83 (SD 14) (p < 0.001). The pain and functional subscales of the QLQ-BM22 also significantly improved at most times. A total of 12 devices broke, giving an unadjusted device fracture rate of 15%.Stabilization with the IS decreased pain and improved function with consistent results during the first postoperative year. IS is a new, minimally invasive type of internal fixation. The use of the IS alone may be better for impending rather than completed pathological fractures, and may be better in completed fractures if an added plate or more than the usual number of locking screws is required. Caution is warranted regarding its use alone in patients with a completed pathological fracture due to the rate of breakage of the device.

  View details for DOI 10.1302/0301-620X.106B12.BJJ-2023-1089.R2

  View details for PubMedID 39615527

• IlluminOss photodynamic bone stabilization system improves pain and function in the treatment of humeral metastatic disease THE ILLUMINO S S LIGHTFIX TRIAL BONE & JOINT JOURNAL Terek, R. M., IlluminOss Study Grp 2024; 106B (12): 1485-1492

  Abstract

  The aim of the LightFix Trial was to evaluate the clinical outcomes for one year after the treatment of impending and completed pathological fractures of the humerus using the IlluminOss System (IS), and to analyze the performance of this device.A total of 81 patients with an impending or completed pathological fracture were enrolled in a multicentre, open label single cohort study and treated with IS. Inclusion criteria were visual analogue scale (VAS) Pain Scores > 60 mm/100 mm and Mirels' Score ≥ 8. VAS pain, Musculoskeletal Tumor Society (MSTS) Upper Limb Function, and The European Organization for Research and Treatment of Cancer QoL Group Bone Metastases Module (QLQ-BM22) scores were all normalized to 100, and radiographs were obtained at baseline and at 14, 30, 90, 180, and 360 days postoperatively.The mean VAS pain score decreased significantly from 84 (SD 15) to 50 (SD 29), 38 (SD 30), 31 (SD 29), 31 (SD 29), and 21 (SD 23) between the baseline and follow-up times (p < 0.001). The mean MSTS function scores significantly increased from 27 (SD 19) to 52 (SD 22), 60 (23), 67 (SD 23), 72 (SD 26), and 83 (SD 14) (p < 0.001). The pain and functional subscales of the QLQ-BM22 also significantly improved at most times. A total of 12 devices broke, giving an unadjusted device fracture rate of 15%.Stabilization with the IS decreased pain and improved function with consistent results during the first postoperative year. IS is a new, minimally invasive type of internal fixation. The use of the IS alone may be better for impending rather than completed pathological fractures, and may be better in completed fractures if an added plate or more than the usual number of locking screws is required. Caution is warranted regarding its use alone in patients with a completed pathological fracture due to the rate of breakage of the device.

  View details for Web of Science ID 001374319900014

  View details for PubMedID 39615527

• Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy. Nature cancer Subramanian, A., Nemat-Gorgani, N., Ellis-Caleo, T. J., van IJzendoorn, D. G., Sears, T. J., Somani, A., Luca, B. A., Zhou, M. Y., Bradic, M., Torres, I. A., Oladipo, E., New, C., Kenney, D. E., Avedian, R. S., Steffner, R. J., Binkley, M. S., Mohler, D. G., Tap, W. D., D'Angelo, S. P., van de Rijn, M., Ganjoo, K. N., Bui, N. Q., Charville, G. W., Newman, A. M., Moding, E. J. 2024

  Abstract

  Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets. We discovered three conserved cellular communities or ecotypes associated with underlying genomic alterations and distinct clinical outcomes. We show that one ecotype defined by tumor-associated macrophages and epithelial-like malignant cells predicts response to immune-checkpoint inhibition but not chemotherapy and validate our findings in an independent cohort. Our results may enable identification of patients with soft tissue sarcomas who could benefit from immunotherapy and help develop new therapeutic strategies.

  View details for DOI 10.1038/s43018-024-00743-y

  View details for PubMedID 38429415

  View details for PubMedCentralID 4486342

• Patterns of local recurrence and risk of skin recurrence in soft tissue sarcomas after surgical resection. Practical radiation oncology Ewongwo, A., Oladipo, E. D., Hui, C., Avedian, R. S., Steffner, R. J., Mohler, D. G., Kalbasi, A., Chin, A. L., Million, L., Hiniker, S. M., Moding, E. J. 2023

  Abstract

  Although there is a theoretical risk of skin seeding during surgical resection of soft tissues sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during RT. However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT.We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007-2021. For patients who developed LR, the depth was evaluated. Progression free survival (PFS) and overall survival (OS) were analyzed from time of first LR using Kaplan-Meier method. Cumulative incidence of distant metastasis (CIDM) was calculated with competing risk analysis from date of LR.Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, five patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had pre-operative RT, 53.3% had post operative RT, and bolus was used in 46.7%. Surgical margins were close (<1mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within RT field in 13 patients (86.7%). At 1 year after LR, PFS was 70.3%, OS was 81.7%, and CIDM was 5.9%.Skin recurrences were rare after surgical resection of STSs, and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

  View details for DOI 10.1016/j.prro.2023.09.006

  View details for PubMedID 37804883

• Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach. Clinical cancer research : an official journal of the American Association for Cancer Research Schott, C. R., Koehne, A. L., Sayles, L. C., Young, E. P., Luck, C., Yu, K., Lee, A. G., Breese, M. R., Leung, S. G., Xu, H., Shah, A. T., Liu, H. Y., Spillinger, A., Behroozfard, I. H., Marini, K. D., Dinh, P. T., Pons Ventura, M. V., Vanderboon, E. N., Hazard, F. K., Cho, S. J., Avedian, R. S., Mohler, D. G., Zimel, M., Wustrack, R., Curtis, C., Sirota, M., Sweet-Cordero, E. A. 2023: OF1-OF16

  Abstract

  Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes.Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model.PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden.The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.

  View details for DOI 10.1158/1078-0432.CCR-23-0873

  View details for PubMedID 37703185

• FUNCTIONAL AND TOXICITY OUTCOMES OF RADIATION THERAPY FOR DUPUYTREN'S CONTRACTURE Oh, J., Wang, Y., Hiniker, S. ELSEVIER IRELAND LTD. 2023: S98

  View details for Web of Science ID 001133676400224

• OUTCOMES OF PEDIATRIC AND ADOLESCENT PATIENTS WITH METASTATIC SARCOMA TREATED WITH SURGICAL RESECTION OR STEREOTACTIC ABLATIVE RADIATION THERAPY Oh, J., Gutkin, P., Wang, Y., Donaldson, S., Steffner, R., Bruzoni, M., Avedian, R., Spunt, S., Pribnow, A., Hiniker, S. ELSEVIER IRELAND LTD. 2023: S98

  View details for Web of Science ID 001133676400225

• MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients. European radiology Düx, D. M., Baal, J. D., Bitton, R., Chen, J., Brunsing, R. L., Sheth, V. R., Rosenberg, J., Kim, K., Ozhinsky, E., Avedian, R., Ganjoo, K., Bucknor, M., Dobrotwir, A., Ghanouni, P. 2023

  Abstract

  To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids.A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded.The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns.MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis.Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely.• Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

  View details for DOI 10.1007/s00330-023-10073-9

  View details for PubMedID 37615768

• Combining Shelf Osteotomy With Proximal Femoral Reconstruction After Oncologic Resection TECHNIQUES IN ORTHOPAEDICS Zhou, J. Y., Lai, C., Pun, S. Y., Richey, A., Leshikar, H. B., Avedian, R., Steffner, R. 2023; 38 (2): 85-89

  View details for DOI 10.1097/BTO.0000000000000610

  View details for Web of Science ID 000992568100005

• Survival and failure modes of the Compress spindle and expandable distal femur endoprosthesis among pediatric patients: A multi-institutional study. Journal of surgical oncology Tanaka, K. S., Andaya, V. R., Thorpe, S. W., Gundle, K. R., Hayden, J. B., Duong, Y., Avedian, R. S., Mohler, D. G., Morse, L. J., Zimel, M. N., O'Donnell, R. J., Fang, A., Randall, R. L., Tran, T. H., New, C., Wustrack, R. L., other members of Study Group FORCE 2022

  Abstract

  BACKGROUND: Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage Systemexpandable distal femur endoprosthesis have not been reported.METHODS: We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis.RESULTS: Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI,5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvagefailures requiring 63 unplanned surgeries. Periprosthetic joint infectionoccurred in six patients (16.7%). Limb preservation rate was 91% at 10years.CONCLUSIONS: There is a high rate of osseointegration of the Compress spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery.LEVEL OF EVIDENCE: Level IV, therapeutic study.

  View details for DOI 10.1002/jso.27094

  View details for PubMedID 36112398

• Outcomes of Pediatric and Adolescent Patients with Metastatic Sarcoma Treated with Surgical Resection or Stereotactic Ablative Radiation Therapy (SABR) Oh, J., Gutkin, P., Donaldson, S., Steffner, R., Bruzoni, M., Avedian, R., Spunt, S., Pribnow, A., Hiniker, S. LIPPINCOTT WILLIAMS & WILKINS. 2022: S42

  View details for Web of Science ID 000847787800089

• Interactions in CSF1-driven Tenosynovial Giant Cell Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research van IJzendoorn, D. G., Matusiak, M., Charville, G. W., Spierenburg, G., Varma, S., Colburg, D. R., van de Sande, M. A., van Langevelde, K., Mohler, D. G., Ganjoo, K. N., Bui, N. Q., Avedian, R. S., Bovee, J. V., Steffner, R., West, R. B., van de Rijn, M. 2022

  Abstract

  A major component of cells in Tenosynovial Giant Cell Tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here we use single cell RNA sequencing to investigate cellular interactions in TGCT.A total of 18,788 single cells from three TGCT and two Giant Cell Tumor of Bone (GCTB) samples underwent singe cell RNAseq. The three TGCTs were additionally analyzed using long read RNA sequencing. Immunofluorescence and immunohistochemistry for a range of markers was used to validate and extend the scRNAseq findings.Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to non-neoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping features between the giant cells in TGCT and GCTB.The neoplastic cells in TGCT are highly similar non-neoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the PDGF receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

  View details for DOI 10.1158/1078-0432.CCR-22-1898

  View details for PubMedID 36007098

• Management of Patients with Newly Diagnosed Desmoid Tumors in a First-Line Setting. Cancers Testa, S., Bui, N. Q., Charville, G. W., Avedian, R. S., Steffner, R., Ghanouni, P., Mohler, D. G., Ganjoo, K. N. 2022; 14 (16)

  Abstract

  The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0-87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease.

  View details for DOI 10.3390/cancers14163907

  View details for PubMedID 36010900

• PET/MR of pediatric bone tumors: what the radiologist needs to know. Skeletal radiology Padwal, J., Baratto, L., Chakraborty, A., Hawk, K., Spunt, S., Avedian, R., Daldrup-Link, H. E. 2022

  Abstract

  Integrated 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/magnetic resonance (MR) imaging can provide "one stop" local tumor and whole-body staging in one session, thereby streamlining imaging evaluations and avoiding duplicate anesthesia in young children. 18F-FDG PET/MR scans have the benefit of lower radiation, superior soft tissue contrast, and increased patient convenience compared to 18F-FDG PET/computerized tomography scans. This article reviews the 18F-FDG PET/MR imaging technique, reporting requirements, and imaging characteristics of the most common pediatric bone tumors, including osteosarcoma, Ewing sarcoma, primary bone lymphoma, bone and bone marrow metastases, and Langerhans cell histiocytosis.

  View details for DOI 10.1007/s00256-022-04113-6

  View details for PubMedID 35804163

• Local control outcomes using stereotactic body radiotherapy or surgical resection for metastatic sarcoma. International journal of radiation oncology, biology, physics Gutkin, P. M., von Eyben, R., Chin, A., Donaldson, S. S., Oh, J., Jiang, A., Ganjoo, K. N., Avedian, R. S., Bruzoni, M., Steffner, R. J., Moding, E. J., Hiniker, S. M. 2022

  Abstract

  Traditional management of metastatic sarcoma primarily relies on systemic therapy, with surgery often used for tumor control. We analyzed the rates of recurrence, overall survival, and treatment complications in patients undergoing either surgical resection or stereotactic body radiotherapy (SBRT) for metastatic sarcoma of the bone and/or soft tissue.The records of patients with metastatic sarcoma between 2009-2020 were reviewed. Local recurrence (LR) was defined as tumor growth or recurrence at the tumor site. Cumulative local recurrence incidence was analyzed accounting for the competing risk of death, and groups were compared using the Gray test. Overall survival (OS) was assessed using the Kaplan Meier method and log-rank test. Hazard ratios were determined using Cox proportional test.A total of 525 metastatic lesions in 217 patients were analyzed. Mean age was 57 years (range 4-88). The lung was the predominant site treated (50%), followed by intra-abdominal (13%), and soft-tissue (11%). Two-year cumulative incidences of LR for surgery and SBRT were 14.8% (95% confidence interval [CI], 11.6-18.5) and 1.7% (95% CI, 0.1-8.2), respectively (p=0.003). LR occurred in 72/437 (16.5%) tumors treated with surgery and 2/88 (2.3%) tumors treated with SBRT. Adjusted hazard ratio for LR of lesions treated surgically was 11.5 (p=0.026) when controlled for tumor size and tumor site. Median OS was 29.8 months (95% CI, 25.6-40.9). There were 47 surgical complications of a total of 275 procedures (18%). Of 58 radiation treatment courses, radiation-related toxicity was reported during the treatment of 7 lesions (12%), and none were higher than grade 2.We observed excellent local control among patients selected for treatment with SBRT for metastatic sarcoma, with no evidence of increase in LR following SBRT when compared to surgical management. Further investigation is necessary to better define the most appropriate local control strategies for metastatic sarcoma.

  View details for DOI 10.1016/j.ijrobp.2022.05.017

  View details for PubMedID 35643255

• Metastatic Pattern of Truncal and Extremity Leiomyosarcoma: Retrospective Analysis of Predictors, Outcomes, and Detection. Journal of personalized medicine Tigchelaar, S. S., Frey, C., Sivaraj, D., Segovia, N. A., Mohler, D. G., Steffner, R. J., Avedian, R. S. 2022; 12 (3)

  Abstract

  Leiomyosarcomas (LMS) are a heterogenous group of malignant mesenchymal neoplasms with smooth muscle origin and are classified as either non-uterine (NULMS) or uterine (ULMS). Metastatic pattern, prognostic factors, and ideal staging/surveillance studies for truncal and extremity LMS have not been defined. A retrospective analysis of patients diagnosed with histopathology-confirmed truncal or extremity LMS between 2009 and 2019 was conducted. Data collected included demographics, tumor characteristics, staging, surveillance, and survival endpoints. The primary site was defined as: (1) extremity, (2) flank/Pelvis, or (3) chest wall/Spine. We identified 73 patients, 23.3% of which had metastatic LMS at primary diagnosis, while 68.5% developed metastatic disease at any point. The mean metastatic-free survival from primary diagnosis of localized LMS was 3.0 ± 2.8 years. Analysis of prognostic factors revealed that greater age (≥50 years) at initial diagnosis (OR = 3.74, p = 0.0003), higher tumor differentiation scores (OR = 12.09, p = 0.002), and higher tumor necrosis scores (OR = 3.65, p = 0.026) were significantly associated with metastases. Older patients (≥50 years, OR = 4.76, p = 0.017), patients with larger tumors (≥5 cm or ≥10 cm, OR = 2.12, p = 0.02, OR = 1.92, p = 0.029, respectively), higher differentiation scores (OR = 15.92, p = 0.013), and higher necrosis scores (OR = 4.68, p = 0.044) show worse survival outcomes. Analysis of imaging modality during initial staging and during surveillance showed greater tumor detection frequency when PET imaging was employed, compared to CT imaging (p < 0.0001). In conclusion, truncal and peripheral extremity LMS is an aggressive tumor with high metastatic potential and mortality. While there is a significant risk of metastases to lungs, extra-pulmonary tumors are relatively frequent, and broad surveillance may be warranted.

  View details for DOI 10.3390/jpm12030345

  View details for PubMedID 35330345

• The US Medical Licensing Examination Step 1 Scoring Change: A Survey of Orthopaedic Surgery Residency Applicants From the 2019 to 2020 Match Cycle. The Journal of the American Academy of Orthopaedic Surgeons Arguello, A. M., Edwards, D. N., Cohn, M. R., Johnson, M. D., Ames, S. E., Avedian, R. S., Ponce, B. A., Kogan, M. 1800

  Abstract

  INTRODUCTION: The USMLE Step 1 examination has been used as an objective measure for comparing residency applicants. Recently, the National Board of Medical Examiners and the Federation of State Medical Boards decided that the USMLE Step 1 examination will transition to a pass/fail result starting no earlier than 2022. The purpose of this study was to investigate the perspective of medical students who applied for orthopaedic surgery residency positions during the 2019 to 2020 interview cycle on the USMLE scoring change, and the potential effect this change may result in for future applicants and the residency selection process.METHODS: A 15-item anonymous web-based survey was sent to 1,090 orthopaedic surgery residency applicants from four regionally diverse residency programs. The survey elicited attitudes toward the transition of the Step 1 examination to pass/fail and perspectives this change may or may not have on the residency selection process.RESULTS: Responses were received from 356 applicants (32.7%). The majority (61.6%) disagreed with the change to pass/fail scoring, and 68.5% do not believe that the change will decrease stress levels in medical students. For interview invitations, respondents chose Step 2 clinical knowledge, letters of recommendation, and performance on away rotations as the most influential factors in the absence of a Step 1 score.CONCLUSION: Most of the students surveyed who applied for an orthopaedic surgery residency position during the most recent application cycle disagreed with the National Board of Medical Examiner/Federation of State Medical Board decision to change Step 1 to pass/fail and feel that this change may have disadvantage in certain student groups while either increasing or having no effect on medical student stress.LEVEL OF EVIDENCE: IV.

  View details for DOI 10.5435/JAAOS-D-21-00615

  View details for PubMedID 35025821

• Postinterview Communication in Orthopaedic Surgery Residency Interviews: A Survey of Match Applicants. JB & JS open access Arguello, A. M., Love, B., Ponce, B. A., McGwin, G., Patt, J. C., Johnson, M. D., Ames, S. E., Avedian, R., Kogan, M. 2022; 7 (1)

  Abstract

  Background: To maintain the integrity of the match, postinterview communication (PIC) from programs to applicants is monitored and discouraged. The most recent report on the prevalence of PIC in orthopaedics found that 64% of surveyed applicants in 2014 and 2015 had received some form of PIC during their match cycle. In July 2019, the American Orthopaedic Association's Council of Orthopaedic Residency Directors (AOA/CORD) released a guideline recommending the elimination of all PIC in any form. The goal of this follow-up study was to determine the current prevalence of PIC with orthopaedic surgery applicants and assess the perspectives of medical students who recently applied for orthopaedic surgery residency positions.Methods: A 35-question survey was e-mailed to all orthopaedic surgery residency applicants of 4 geographically diverse residency programs in postmatch March 2020. The survey was open for 1 month, and the responses were reported using descriptive statistics.Results: Of the 229 respondents (21% response rate), 91 (39.7%) received PIC during the 2019 to 2020 residency match cycle. The program director was most commonly identified (80.2%) as the person who communicated with the applicants. At the interview day, 198 respondents (86.5%) were told that programs would not be contacting the applicants with PIC. However, over a quarter of respondents (25.3%) who received PIC answered that those programs contacted applicants after announcing they would not. Nearly half of the respondents (48.5%) agreed or strongly agreed that PIC causes added stress on applicants, and over half (52.9%) agreed or strongly agreed that all programs should stop participating in any form of PIC.Conclusions: Although the prevalence of PIC seems to have decreased since the 2014 and 2015 match, there is still room for improvement toward eliminating PIC. The AOA/CORD position statement from July 2019 should be disseminated to all members of the residency selection team to ensure consistency from all programs. The primary limitation of this study was the 21% response rate.Level of Evidence: Level IV (survey study).

  View details for DOI 10.2106/JBJS.OA.20.00140

  View details for PubMedID 35261934

• Education research - Understanding the factors involved in inpatient communication for orthopedic trainees. Annals of medicine and surgery (2012) Daniel, D., Avedian, R., Johnson, T., Michaud, J. B., Weimer-Elder, B., Kline, M., Nassar, A. K. 2021; 72: 103079

  Abstract

  Background: "Interpersonal and Communication Skills" (ICS) is a core competency set forth by the ACGME. No structured curriculum exists to train orthopedics residents in ICS.Methods: Twenty-four out of thirty-five orthopedics residents completed the survey (69%). The survey had the following domains: [1] Demographics, [2] Communication Needs/Goals, and [3] Communication Barriers.Results: Eighty-three percent of respondents wanted to improve their communication skills and their patient's experience. Interns-PGY4s wanted to improve on similar specific communication skills. All residents desired training in conflict management.Conclusion: There is a need among orthopedics residents for a communication skills curriculum early in residency training, specifically in conflict management.

  View details for DOI 10.1016/j.amsu.2021.103079

  View details for PubMedID 34876980

• Distal femoral fine wire traction assisted retrograde nailing of the femur. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Chen, M. J., Avedian, R. S., Gardner, M. J., Bishop, J. A. 2021

  Abstract

  Here we describe the surgical technique for using distal femoral fine wire traction during retrograde femoral nailing and present case examples. This technique allows for hands-free distraction across the fracture site to restore length and alignment, while not interfering with the preparation and insertion of the retrograde femoral nail. Distal femoral fine wire traction is a useful adjunctive technique to restore length and effect an indirect reduction in femur fractures being stabilized with a retrograde nail.

  View details for DOI 10.1007/s00590-021-02897-2

  View details for PubMedID 33575843

• Ferumoxytol magnetic resonance imaging detects joint and pleural infiltration of bone sarcomas in pediatric and young adult patients. Pediatric radiology Theruvath, A. J., Rashidi, A., Nyalakonda, R. R., Avedian, R. S., Steffner, R. J., Spunt, S. L., Daldrup-Link, H. E. 2021

  Abstract

  The diagnosis of joint infiltration by a malignant bone tumor affects surgical management. The specificity of standard magnetic resonance imaging (MRI) for diagnosing joint infiltration is limited. During our MRI evaluations with ferumoxytol nanoparticles of pediatric and young adult patients with bone sarcomas, we observed a surprising marked T1 enhancement of joint and pleural effusions in some patients but not in others.To evaluate if nanoparticle extravasation differed between joints and pleura with and without tumor infiltration.We retrospectively identified 15 pediatric and young adult patients (mean age: 16±4 years) with bone sarcomas who underwent 18 MRI scans at 1 h (n=7) or 24 h (n=11) after intravenous ferumoxytol infusion. Twelve patients also received a gadolinium-enhanced MRI. We determined tumor invasion into the joint or pleural space based on histology (n=11) and imaging findings (n=4). We compared the signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) of the joint or pleural fluid for tumors with and without invasion using a Mann-Whitney U test.MRI scans 24 h after intravenous ferumoxytol infusion demonstrated a positive T1 enhancement of the effusion in all joints and pleural spaces with tumor infiltration and no joint or pleural space without infiltration. Corresponding SNR (P=0.004) and CNR (P=0.004) values were significantly higher for joints and pleural spaces with tumor infiltration than without. By contrast, unenhanced MRI, gadolinium-enhanced MRI and 1-h post-contrast ferumoxytol MRI did not show any enhancement of the joint or pleural effusion, with or without tumor infiltration.This pilot study suggests that 24-h post-contrast ferumoxytol MRI scans can noninvasively differentiate between joints with and without tumor infiltration.

  View details for DOI 10.1007/s00247-021-05156-y

  View details for PubMedID 34410452

• Simulation-Based Mastery Learning to Teach Distal Radius Fracture Reduction. Simulation in healthcare : journal of the Society for Simulation in Healthcare Toal, G. G., Gisondi, M. A., Miller, N. M., Sebok-Syer, S. S., Avedian, R. S., Dixon, W. W. 2020; Publish Ahead of Print

  Abstract

  Distal radius fractures are common orthopedic injuries managed in emergency departments. Simulation-based mastery learning is widely recognized to improve provider competence for bedside procedures but has not been studied to teach fracture management. This study evaluated the effectiveness of a simulation-based mastery learning curriculum to teach distal radius fracture reduction to novice orthopedic surgery and emergency medicine residents.We created a novel mastery learning checklist using the Mastery Angoff method of standard setting, paired with a new simulation model designed for this project, to teach orthopedic surgery and emergency medicine interns (N = 22) at the study site. Orthopedic surgery and emergency medicine faculty members participated in checklist development, curriculum design, and implementation. Training included just-in-time asynchronous education with a readiness assessment test, in-classroom expert demonstration, and deliberate practice with feedback. Residents completed a pretest/posttest skills examination and a presurvey/postsurvey assessing procedural confidence.Standard setting resulted in a 41-item checklist with minimum passing score of 37/41 items. All participants met or surpassed the minimum passing score on postexamination. Postsurvey confidence levels were significantly higher than presurvey in all aspects of the distal radius fracture procedure (P < 0.05).This study demonstrated that a simulation-based mastery learning curriculum improved skills and confidence performing distal radius fracture reductions for orthopedic surgery and emergency medicine interns. Future planned studies include curriculum testing across additional institutions, examination of clinical impact, and application of mastery learning for other orthopedic procedures.

  View details for DOI 10.1097/SIH.0000000000000534

  View details for PubMedID 33337726

• An anatomic classification for heterotopic ossification about the hip. Journal of orthopaedics DeBaun, M. R., Ziino, C. n., LaPrade, C. n., Pun, S. n., Avedian, R. S., Bellino, M. J. 2020; 21: 228–31

  Abstract

  Retrospective cohort.Heterotopic ossification (HO) about the hip is a debilitating condition that can occur after fixation for acetabular fractures, total hip replacement, or polytrauma with closed head injuries. No classification exists that informs surgical treatment.To establish a classification system for HO about the hip by reviewing a consecutive series of HO at a single institution. It was hypothesized that HO about the hip could be grouped into a novel classification scheme based upon the location and involved structures of the hip.Retrospective chart review of single center's case log for HO excision from 2004 to 2018 was performed. Inclusion criteria included all patients undergoing excision of heterotopic bone excision about the hip. Demographic data, pre and post hip range of motion, surgical approach for each surgery, index surgery date and interval to excision are reported as well as presence and location of HO and Brooker classification.A total of 36 patients (21 men and 15 women) and 40 hips were identified meeting inclusion criteria. The mean age at the time of the index surgery was 47 (range, 16-77 years). Traumatic injury with fracture (35%) included 9 acetabular fractures (22%), 2 long bone fractures (5%) treated with intramedullary devices, one displaced femoral neck fracture (2%), and one pelvic ring injury (2%). Total hip arthroplasty accounted for 32% of patients. Brooker classification was type 4 (35%), 3 (25%), 2 (23%), 1(17%) which translated to 55% anterior, 48% posterior, 3% medial with respect to location. Average improvement in hip flexion and abduction was 22 and 8°, respectively.This study identified discrete locations for heterotopic ossification following hip or acetabulum surgery. Both posterior and anterior structures are implicated in the formation of HO, and this investigation presents a novel classification to guide surgical approach for HO excision based upon location.

  View details for DOI 10.1016/j.jor.2020.03.038

  View details for PubMedID 32273662

  View details for PubMedCentralID PMC7132042

• Comparison of ferumoxytol- and gadolinium chelate-enhanced MRI for assessment of sarcomas in children and adolescents. European radiology Siedek, F., Muehe, A. M., Theruvath, A. J., Avedian, R., Pribnow, A., Spunt, S. L., Liang, T., Farrell, C., Daldrup-Link, H. E. 2019

  Abstract

  OBJECTIVES: We compared the value of ferumoxytol (FMX)- and gadolinium (Gd)-enhanced MRI for assessment of sarcomas in paediatric/adolescent patients and hypothesised that tumour size and morphological features can be equally well assessed with both protocols.METHODS: We conducted a retrospective study of paediatric/adolescent patients with newly diagnosed bone or soft tissue sarcomas and both pre-treatment FMX- and Gd-MRI scans, which were maximal 4 weeks apart. Both protocols included T1- and T2-weighted sequences. One reader assessed tumour volumes, signal-to-noise ratios (SNR) of the primary tumour and adjacent tissues and contrast-to-noise ratios (CNR) ofFMX- and Gd-MRI scans. Additionally, four readers scored FMX- and Gd-MRI scansaccording to15 diagnostic parameters, using a Likert scale. The results were pooled across readers and compared between FMX- and Gd-MRI scans. Statistical methods included multivariate analyses with different models.RESULTS: Twenty-two patients met inclusion criteria (16 males, 6 females; mean age 15.3 ± 5.0). Tumour volume was not significantly different on T1-LAVA (p = 0.721), T1-SE (p = 0.290) and T2-FSE (p = 0.609)sequences. Compared to Gd-MRI, FMX-MRI demonstrated significantly lower tumour SNR on T1-LAVA (p < 0.001), equal tumour SNR on T1-SE (p = 0.104) and T2-FSE (p = 0.305), significantly higher tumour-to-marrow CNR (p < 0.001) on T2-FSE as well as significantly highertumour-to-liver (p = 0.021) and tumour-to-vessel (p = 0.003) CNR on T1-LAVAimages. Peritumoural and marrow oedema enhancedsignificantly more on Gd-MRIcompared to FMX-MRI (p < 0.001/p = 0.002, respectively). Tumour thrombi and neurovascular bundle involvement were assessed with a significantly higher confidence on FMX-MRI (both p < 0.001).CONCLUSIONS: FMX-MRI provides equal assessment of the extent of bone and soft tissue sarcomas compared to Gd-MRI with improvedtumour delineation and improved evaluation of neurovascular involvement and tumour thrombi. Therefore,FMX-MRI is a possiblealternative to Gd-MRIfor tumour staging in paediatric/adolescent sarcoma patients.KEY POINTS: Ferumoxytol can be used as an alterative to gadolinium chelates for MRI staging ofpaediatric sarcomas. Ferumoxytol-enhanced MRI provides equal assessment of tumour size and other diagnostic parameters compared to gadolinium chelate-enhanced MRI. Ferumoxytol-enhanced MRI provides improved delineation of sarcomas from bone marrow, liver and vessels compared to gadolinium chelate-enhanced MRI.

  View details for DOI 10.1007/s00330-019-06569-y

  View details for PubMedID 31844962

• Anti-rotation pins for the compress implant do not increase risk of mechanical failure or impair osseointegration ANNALS OF JOINT Campbell, S. T., Steffner, R. J., Finlay, A., Mohler, D. G., Avedian, R. S. 2019; 4 (8)

  View details for DOI 10.21037/aoj.2019.08.02

  View details for Web of Science ID 000485117900002

• A technique for anchor plug salvage in the setting of a cold welded taper adapter following compress implant failure ANNALS OF JOINT Campbell, S. T., Roe, A. K., Avedian, R. S. 2019; 4 (8)

  View details for DOI 10.21037/aoj.2019.08.01

  View details for Web of Science ID 000485117900003

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2019; 42 (2): 166–71

  View details for DOI 10.1097/COC.0000000000000496

  View details for Web of Science ID 000465420000010

• Ferumoxytol Does Not Impact Standardized Uptake Values on PET/MR Scans. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Muehe, A. M., Yerneni, K. n., Theruvath, A. J., Thakor, A. S., Pribnow, A. n., Avedian, R. n., Steffner, R. n., Rosenberg, J. n., Hawk, K. E., Daldrup-Link, H. E. 2019

  Abstract

  Tumor response assessments on positron emission tomography (PET)/magnetic resonance imaging (MRI) scans require correct quantification of radiotracer uptake in tumors and normal organs. Historically, MRI scans have been enhanced with gadolinium (Gd)-based contrast agents, which are now controversial due to brain deposition. Recently, ferumoxytol nanoparticles have been identified as an alternative to Gd-based contrast agents because they provide strong tissue enhancement on MR images but are not deposited in the brain. However, it is not known if the strong T1- and T2-contrast obtained with iron oxide nanoparticles such as ferumoxytol could affect MR-based attenuation correction of PET data. The purpose of our study was to investigate if ferumoxytol administration prior to a 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG PET/MR scan would change standardized uptake values (SUV) of normal organs.Thirty pediatric patients (6-18 years) with malignant tumors underwent [18F]FDG-PET/MR scans (dose 3 MBq/kg). Fifteen patients received an intravenous ferumoxytol injection (5 mg Fe/kg) prior to the [18F]FDG-PET/MR scans (group 1). Fifteen additional age- and sex-matched patients received unenhanced [18F]FDG-PET/MR scans (group 2). For attenuation correction of PET data, we used a Dixon-based gradient echo sequence (TR 4.2 ms, TE 1.1, 2.3 ms, FA 5), which accounted for soft tissue, lung, fat, and background air. We used a mixed linear effects model to compare the tissue MRI enhancement, quantified as the signal-to-noise ratio (SNR), as well as tissue radiotracer signal, quantified as SUVmean and SUVmax, between group 1 and group 2. Alpha was assumed at 0.05.The MRI enhancement of the blood and solid extra-cerebral organs, quantified as SNR, was significantly higher on ferumoxytol-enhanced MRI scans compared to unenhanced scans (p < 0.001). However, SUVmean and SUVmax values, corrected based on the patients' body weight or body surface area, were not significantly different between the two groups (p > 0.05).Ferumoxytol administration prior to a [18F]FDG PET/MR scan did not change standardized uptake values (SUV) of solid extra-cerebral organs. This is important, because it allows injection of ferumoxytol contrast prior to a PET/MRI procedure and, thereby, significantly accelerates image acquisition times.

  View details for DOI 10.1007/s11307-019-01409-3

  View details for PubMedID 31325083

• Patient Preferences for Shared Decision Making: Not All Decisions Should Be Shared. The Journal of the American Academy of Orthopaedic Surgeons E Lindsay, S. n., Alokozai, A. n., Eppler, S. L., Fox, P. n., Curtin, C. n., Gardner, M. n., Avedian, R. n., Palanca, A. n., Abrams, G. D., Cheng, I. n., Kamal, R. N. 2019

  Abstract

  To assess bounds of shared decision making in orthopaedic surgery, we conducted an exploratory study to examine the extent to which patients want to be involved in decision making in the management of a musculoskeletal condition.One hundred fifteen patients at an orthopaedic surgery clinic were asked to rate preferred level of involvement in 25 common theoretical clinical decisions (passive [0], semipassive [1 to 4], equally shared involvement between patient and surgeon [5], semiactive [6 to 9], active [10]).Patients preferred semipassive roles in 92% of decisions assessed. Patients wanted to be most involved in scheduling surgical treatments (4.75 ± 2.65) and least involved in determining incision sizes (1.13 ± 1.98). No difference exists in desired decision-making responsibility between patients who had undergone orthopaedic surgery previously and those who had not. Younger and educated patients preferred more decision-making responsibility. Those with Medicare desired more passive roles.Despite the importance of shared decision making on delivering patient-centered care, our results suggest that patients do not prefer to share all decisions.

  View details for DOI 10.5435/JAAOS-D-19-00146

  View details for PubMedID 31567900

• Tissue-engineered 3D Models for Elucidating Primary and Metastatic Bone Cancer Progression. Acta biomaterialia González Díaz, E. C., Sinha, S. n., Avedian, R. S., Yang, F. n. 2019

  Abstract

  Malignant bone tumors are aggressive neoplasms which arise from bone tissue or as a result of metastasis. The most prevalent types of cancer, such as breast, prostate, and lung cancer, all preferentially metastasize to bone, yet the role of the bone niche in promoting cancer progression remains poorly understood. Tissue engineering has the potential to bridge this knowledge gap by providing 3D in vitro systems that can be specifically designed to mimic key properties of the bone niche in a more physiologically relevant context than standard 2D culture. Elucidating the crucial components of the bone niche that recruit metastatic cells, support tumor growth, and promote cancer-induced destruction of bone tissue would support efforts for preventing and treating these devastating malignancies. In this review, we summarize recent efforts focused on developing in vitro 3D models of primary bone cancer and bone metastasis using tissue engineering approaches. Such 3D in vitro models can enable the identification of effective therapeutic targets and facilitate high-throughput drug screening to effectively treat bone cancers. STATEMENT OF SIGNIFICANCE: Biomaterials-based 3D culture have been traditionally used for tissue regeneration. Recent research harnessed biomaterials to create 3D in vitro cancer models, with demonstrated advantages over conventional 2D culture in recapitulating tumor progression and drug response in vivo. However, previous work has been largely limited to modeling soft tissue cancer, such as breast cancer and brain cancer. Unlike soft tissues, bone is characterized with high stiffness and mineral content. Primary bone cancer affects mostly children with poor treatment outcomes, and bone is the most common site of cancer metastasis. Here we summarize emerging efforts on engineering 3D bone cancer models using tissue engineering approaches, and future directions needed to further advance this relatively new research area.

  View details for DOI 10.1016/j.actbio.2019.08.020

  View details for PubMedID 31419564

• Outcomes for pediatric patients with osteosarcoma treated with palliative radiotherapy. Pediatric blood & cancer Chen, E. L., Yoo, C. H., Gutkin, P. M., Merriott, D. J., Avedian, R. S., Steffner, R. J., Spunt, S. L., Pribnow, A. K., Million, L. n., Donaldson, S. S., Hiniker, S. M. 2019: e27967

  Abstract

  Few studies have addressed the efficacy of palliative radiotherapy (RT) for pediatric osteosarcoma (OS), a disease generally considered to be radioresistant. We describe symptom relief, local control, and toxicity associated with palliative RT among children with OS.Patients diagnosed with OS at age 18 and under and treated with RT for palliation of symptomatic metastases or local recurrence at the primary site from 1997 to 2017 were included. We retrospectively reviewed details of RT, symptom improvement, local control, survival, and toxicity.Thirty-two courses of palliative RT were given to 20 patients with symptomatic metastatic and/or locally recurrent primary disease. The median equivalent dose in 2 Gy fractions (EQD2) was 40.0 Gy (range, 20.0-60.4). The median number of fractions per course was 15 (range, 5-39). Symptom improvement occurred in 24 (75%) courses of RT at a median time of 15.5 days (range, 3-43). In nine courses (37.5%), symptoms recurred after a median duration of symptom relief of 140 days (range, 1-882). Higher EQD2 correlated with longer duration of response (r = 0.39, P = 0.0003). Imaging revealed local failure in 3 of 14 courses followed with surveillance imaging studies (21.4%). The median time to progression was 12.9 months (range, 4.4-21.8). The median follow-up time following the first course of palliative RT was 17.5 months (range, 1.74-102.24), and median time to overall survival was 19.4 months. Toxicity was mild, with grade 2 toxicity occurring in one course (3.1%).RT is an effective method of symptom palliation for patients with recurrent or metastatic OS, with higher delivered dose correlating with longer symptom relief and with little associated toxicity.

  View details for DOI 10.1002/pbc.27967

  View details for PubMedID 31407520

• Genome-Informed Targeted Therapy for Osteosarcoma CANCER DISCOVERY Sayles, L. C., Breese, M. R., Koehne, A. L., Leung, S. G., Lee, A. G., Liu, H., Spillinger, A., Shah, A. T., Tanasa, B., Straessler, K., Hazard, F. K., Spunt, S. L., Marina, N., Kim, G. E., Cho, S., Avedian, R. S., Mohler, D. G., Kim, M., DuBois, S. G., Hawkins, D. S., Sweet-Cordero, E. 2019; 9 (1): 46–63

  View details for DOI 10.1158/2159-8290.CD-17-1152

  View details for Web of Science ID 000455598900022

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University. American journal of clinical oncology Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2018

  Abstract

  BACKGROUND: As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure.METHODS: We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins.RESULTS: 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009).CONCLUSIONS: Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

  View details for PubMedID 30557163

• Genome-Informed Targeted Therapy for Osteosarcoma. Cancer discovery Sayles, L. C., Breese, M. R., Koehne, A. L., Leung, S. G., Lee, A. G., Liu, H., Spillinger, A., Shah, A. T., Tanasa, B., Straessler, K., Hazard, F. K., Spunt, S. L., Marina, N., Kim, G. E., Cho, S., Avedian, R. S., Mohler, D. G., Kim, M., Dubois, S. G., Hawkins, D. S., Sweet-Cordero, E. A. 2018

  Abstract

  Osteosarcoma (OS) is a highly aggressive cancer for which treatment has remained essentially unchanged for over 30 years. OS is characterized by widespread and recurrent somatic copy-number alterations (SCNAs) and structural rearrangements. In contrast, few recurrent point mutations in protein-coding genes have been identified, suggesting that genes within SCNAs are key oncogenic drivers in this disease. SCNAs and structural rearrangements are highly heterogeneous across OS cases, suggesting the need for a genome-informed approach to targeted therapy. To identify patient-specific candidate drivers, we used a simple heuristic based on degree and rank order of copy number amplification (identified by Whole Genome Sequencing) and changes in gene expression as identified by RNAseq. Using patient-derived tumor xenografts, we demonstrate that targeting of patient-specific somatic copy number alterations leads to significant decrease in tumor burden, providing a roadmap for genome-informed treatment of OS.

  View details for PubMedID 30266815

• Treatment of Low-Flow Vascular Malformations of the Extremities Using MR-Guided High Intensity Focused Ultrasound: Preliminary Experience JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Ghanouni, P., Kishore, S., Lungren, M. P., Bitton, R., Chan, L., Avedian, R., Bazzocchi, A., Pauly, K., Napoli, A., Hovsepian, D. M. 2017; 28 (12): 1739–44

  Abstract

  Five patients with painful vascular malformations of the extremities that were refractory to standard treatment and were confirmed as low-flow malformations on dynamic contrast-enhanced magnetic resonance (MR) imaging were treated with MR imaging-guided high intensity focused ultrasound. Daily maximum numeric rating scale scores for pain improved from 8.4 ± 1.5 to 1.6 ± 2.2 (P = .004) at a median follow-up of 9 months (range, 4-36 mo). The size of the vascular malformations decreased on follow-up MR imaging (median enhancing volume, 8.2 mL [0.7-10.1 mL] before treatment; 0 mL [0-2.3 mL] after treatment; P = .018) at a median follow-up of 5 months (range, 3-36 mo). No complications occurred.

  View details for PubMedID 29157478

  View details for PubMedCentralID PMC5726422

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study EUROPEAN RADIOLOGY Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2017; 27 (2): 732-740

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for DOI 10.1007/s00330-016-4376-5

  View details for Web of Science ID 000392142000034

• Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma Moding, E. J., Million, L., Avedian, R., Ghanouni, P., Kunder, C., Ganjoo, K. N. 2017; 2017: 2316839

  Abstract

  Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

  View details for PubMedID 28761389

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study. European radiology Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2016: -?

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for PubMedID 27147222

• The Effect of Applicant Publication Volume on the Orthopaedic Residency Match. Journal of surgical education Campbell, S. T., Gupta, R., Avedian, R. S. 2016; 73 (3): 490-495

  Abstract

  Research is an important factor used in evaluating applicants to orthopaedic training programs. Current reports regarding the publication rate among prospective residents are likely inaccurate. It is unknown whether research productivity is weighted more heavily at programs affiliated with research-driven institutions.To establish accurate baseline data on publication rate among matched applicants to orthopaedic residency programs and to compare publication rates between applicants who matched at research-focused institutions and those who matched elsewhere.We performed a literature search for each U.S. resident in the 2013-2014 intern class. Number of publications: (1) in total, (2) in orthopaedic journals, and (3) as first/last author were recorded. Publication rate at the top 25 programs (according to medical school and departmental National Institutes of Health [NIH] funding and U.S. News ranking) was compared statistically against all others.Average number of publications per intern for all programs was 1.28 ± 0.15. Number of total and first/last author publications was significantly greater for programs affiliated with medical schools and departments in the top 25 for NIH funding, and at schools in the top 25 U.S. News rankings. Publication rate in orthopaedic journals was significantly higher for programs affiliated with departments in the top 25 for NIH funding and at top 25 U.S. News medical schools.The average matched applicant to an orthopaedic residency program publishes in the peer-reviewed literature less frequently than previously reported. Matched applicants at research-focused institutions tended to have more publications than those who matched at other programs.

  View details for DOI 10.1016/j.jsurg.2015.11.011

  View details for PubMedID 26861584

• Effect of Patellar Resurfacing on Distal Femoral Replacements: Commentary on an article by Mauricio Etchebehere, MD, PhD, et al.: "Patellar Resurfacing. Does It Affect Outcomes of Distal Femoral Replacement After Distal Femoral Resection?". journal of bone and joint surgery. American volume Avedian, R. S. 2016; 98 (7)

  View details for DOI 10.2106/JBJS.15.01316

  View details for PubMedID 27053593

• Is MR-guided High-intensity Focused Ultrasound a Feasible Treatment Modality for Desmoid Tumors? CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Avedian, R. S., Bitton, R., Gold, G., Butts-Pauly, K., Ghanouni, P. 2016; 474 (3): 697-704

  Abstract

  MR-guided high-intensity focused ultrasound is a noninvasive treatment modality that uses focused ultrasound waves to thermally ablate tumors within the human body while minimizing side effects to surrounding healthy tissues. This technology is FDA-approved for certain tumors and has potential to be a noninvasive treatment option for extremity soft tissue tumors. Development of treatment modalities that achieve tumor control, decrease morbidity, or both might be of great benefit for patients. We wanted to assess the potential use of this technology in the treatment of extremity desmoid tumors.(1) Can we use MR-guided high-intensity focused ultrasound to accurately ablate a predetermined target volume within a human cadaver extremity? (2) Does MR-guided high-intensity focused ultrasound treatment stop progression and/or cause regression of extremity desmoid tumors?Simulated tumor volumes in four human cadavers, created by using plastic markers, were ablated using a commercially available focused ultrasound system. Accuracy was determined in accordance with the International Organization of Standards location error by measuring the farthest distance between the ablated tissue and the plane corresponding to the target. Between 2012 and 2014, we treated nine patients with desmoid tumors using focused ultrasound ablation. Indications for this were tumor-related symptoms or failure of conventional treatment. Of those, five of them were available for MRI followup at 12 months or longer (mean, 18.2 months; range, 12-23 months). The radiographic and clinical outcomes of five patients who had desmoid tumors treated with focused ultrasound were prospectively recorded. Patients were assessed preoperatively with MRI and followed at routine intervals after treatment with MRI scans and clinical examination.The ablation accuracy for the four cadaver extremities was 5 mm, 3 mm, 8 mm, and 8 mm. Four patients' tumors became smaller after treatment and one patient has slight progression at the time of last followup. The mean decrease in tumor size determined by MRI measurements was 36% (95% confidence interval, 7%-66%). No patient has received additional adjuvant systemic or local treatment. Treatment-related adverse events included first- and second-degree skin burns occurring in four patients, which were managed successfully without further surgery.This preliminary investigation provides some evidence that MR-guided high-intensity focused ultrasound may be a feasible treatment for desmoid tumors. It may also be of use for other soft tissue neoplasms in situations in which there are limited traditional treatment options such as recurrent sarcomas. Further investigation is necessary to better define the indications, efficacy, role, and long-term oncologic outcomes of focused ultrasound treatment.Level IV, therapeutic study.

  View details for DOI 10.1007/s11999-015-4364-0

  View details for Web of Science ID 000370150000018

  View details for PubMedID 26040967

  View details for PubMedCentralID PMC4746191

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study ANNALS OF SURGERY Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632-640

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion.Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

  View details for DOI 10.1097/SLA.0000000000001455

  View details for Web of Science ID 000367999800009

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study. Annals of surgery Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632-40

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion.Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

  View details for DOI 10.1097/SLA.0000000000001455

  View details for PubMedID 26366542

• Prophylactic antibiotic regimens in tumour surgery (PARITY) A PILOT MULTICENTRE RANDOMISED CONTROLLED TRIAL BONE & JOINT RESEARCH Ghert, M., Bhandari, M., Deheshi, B., Guyatt, G., Holt, G., O'Shea, T., Randall, R. L., Thabane, L., Wunder, J., Evaniew, N., McKay, P., Schneider, P., Turcotte, R., Madden, K., Scott, T., Sprague, S., Simunovic, N., Swinton, M., Racano, A., Heels-Ansdell, D., Buckingham, L., Rose, P., Brigman, B., Pullenayegum, E., Ghert, M., Evaniew, N., McKay, P., Schneider, P., Sobhi, G., Chan, R., Biljan, M., Ferguson, P., Wunder, J., Griffin, A., Mantas, I., Wylie, A., Han, A., Grewal, G., Turcotte, R., Goulding, K., Dandachli, F., Matte, G., Werier, J., Abdelbary, H., Paquin, K., Cosgrove, H., Dugal, A., Fetzer, S., Aikens, W., Clarkson, P., Wang, B., Kondo, L., Yip, J., Isler, M., Mottard, S., Barry, J., St Yves, H., Quach, M., Assayag, H., DAOUST, K., Goyette, K., Projean, D., Dion, N., Arteau, A., Turmel, S., Bertrand, A., Gagnon, N., Labbe, V., Holt, G., Halpern, J., Schwartz, H., Atkinson, A., Daniels, J., Moore, M. S., Anderson, M., Gebhardt, M., Wagner, K., Patel, H., Jolin, H., Anderson, M., Gebhardt, M., ALLAR, B., Naqvi, M., Bennett, J., Albuquerque, S., Randall, R. L., Jones, K., Crabtree, S., Davis, R., Sorenson, S., Healey, J. H., Galle, J., O'Neill, G., Del Corral, B., Lopez, S., Galli Serra, M., Parizzia, W., Podrzaj, A., Foa Torres, M., Clayer, M., CHAI, Y., Slobodian, P., Balach, T., COYLE, K., Lacasse, R., Abraham, J., Morrison, T., Angelos, M., SAILOR, L., Sadaka, R., Miller, B., Milhem, M., MCCURDY, N., Kain, J., Nohr, J., Johnson, K., Merriss, A., Cheng, E., LUKE, D. G., Scharschmidt, T. J., Crist, M. K., DiMeo, A., MARMON, L., Reimer, N., Monson, D., Oskouei, S., Lomba, C., Rogers, S., Avedian, R., Jordan, L., Chinn, S., Hamilton, M., Ghert, M., Evaniew, N., McKay, P., Schneider, P., Sobhi, G., Chan, R., Bil-Jan, M., Ferguson, P., Wunder, J., Griffin, A., Mantas, I., Wylie, A., Han, A., Grewal, G., Turcotte, R., Goulding, K., Dandachli, F., Matte, G., Werier, J., Abdelbary, H., Paquin, K., Cosgrove, H., Dugal, A., Fetzer, S., Aikens, W., Clarkson, P., Wang, B., Kondo, L., Yip, J., Isler, M., Mottard, S., Barry, J., Yves, H. S., Quach, M., Assayag, H., DAOUST, K., Goyette, K., Projean, D., Dion, N., Arteau, A., Turmel, S., Bertrand, A., Gagnon, N., Labbe, V., Holt, G., Halpern, J., Schwartz, H., Atkinson, A., Daniels, J., Moore, M. S., Anderson, M., Gebhardt, M., Wagner, K., Patel, H., Jolin, H., Anderson, M., Gebhardt, M., ALLAR, B., Naqvi, M., Bennett, J., Albuquerque, S., Randall, R. L., Jones, K., Crabtree, S., Davis, R., Sorenson, S., Healey, J. H., Galle, J., O'Neill, G., Del Corral, B., Lopez, S., Galli Serra, M., Parizzia, W., Podrzaj, A., Foa Torres, M., Clayer, M., Tran, N., Slobodian, P., Balach, T., COYLE, K., Lacasse, R., Abraham, J., Morrison, T., Angelos, M., SAILOR, L., Sadaka, R., Miller, B., Milhem, M., MCCURDY, N., Kain, J., Nohr, J., Johnson, K., Merriss, A., Cheng, E., LUKE, D. G., Scharschmidt, T. J., Crist, M. K., DiMeo, A., MARMON, L., Reimer, N., Monson, D., Oskouei, S., Lomba, C., Rogers, S., Geller, D., Hoang, B., Tingling, J., Solorzano, C., Avedian, R., Jordan, L., Chinn, S., Hamilton, M., Puloski, S., Monument, M., Carcary, K., Cameron, C., Aboulafia, A., Loo-Mis, M., Bosley, J., Bonvegna, R., Kassa, M., Damron, T., Craig, T., Reale, M., Goodman, H. J., Culbertson, M. D., Caruso, P., GARLING, E., Schwab, J., Fiore, A., Phukan, R., PARK, C., Joshi, L., Aboulafia, A., Wallace, M., Flack, J., Vaughan, K., Avergas, A., Brady, M., Brown, S., Schadie, N., Battersby, R., Weiss, K., Goodman, M., Heyl, A., Yeschke, C. A., Sumic, P., DUDGEON, M., Prosser, R., Korenoski, C., DiCaprio, M., Palmer, B., Cioppa, E., Schaeffer, T. M., Paul, P., TORESON, J., Cummings, J., Schwartz, L., Zahner, B., Morris, C., Laljani, V., Mesko, N., Joyce, M., Lietman, S., Wustrack, R., O'Donnell, R., Stevenson, C., Carmody, E., Tyler, W., McIntyre, A., Spiguel, A., Scarborough, M., Gibbs, C. P., Steshyn, J., NUNN, B., Rosenthal, H., Haynes, K., LEDDY, L., Walton, Z., Doung, Y., Hayden, J., Velez, R., AGUIRRE, M., Perez, M., Barrera, S., Garca Lopez, A., Grimer, R., Dunn, K., VIRDEE, H., Rankin, K., Beckingsale, T., Gerrand, C., Campbell, I., Allen, M., Khan, S. A., Bakshi, S., Rastogi, S., Poudel, R., Kumar, V. S., Rai, A., Baptista, A. M., de Camargo, O. P., Marais, L., Rodseth, R., Ferreira, N., RAJAH, C., Gumede, S., Gortzak, Y., STERNHEIM, A., Bickels, J., KOLANDER, Y., Lev, S., Hettwer, W., Petersen, M. M., Grum-Schwensen, T., Jutte, P., Ploegmakers, J. J., Stevens, M., Mahendra, A., Gupta, S., Bergovec, M., Leithner, A., Funovics, P., Dijkstra, P. D., van de Sande, M., Hoogenstraaten, A., Leijerzapf, N., Steadman, P., Steadman, P., BOFFANO, M., Piana, R., Marone, S., Albertini, U., Boux, E., Maiello, A., Repsa, L., Zile, S., Aston, W., Pollock, R., Cool, P., Gibbons, M., Whit-Well, D., Cosker, T., Hemingway, J., Porter, D., Patton, S., Navia, J., Betancur, A. F., Laitenen, M., Pakarinen, K., Nieminen, J., Yla-Mononen, S., RAUTIAINEN, S., Fiorenza, F. 2015; 4 (9): 154-162

  Abstract

  Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours.We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens.We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol.It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154-162.

  View details for DOI 10.1302/2046-3758.49.2000482

  View details for Web of Science ID 000364596500002

  View details for PubMedID 26423584

  View details for PubMedCentralID PMC4602191

• What Is the Use of Imaging Before Referral to an Orthopaedic Oncologist? A Prospective, Multicenter Investigation CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Miller, B. J., Avedian, R. S., Rajani, R., Leddy, L., White, J. R., Cummings, J., Balach, T., Macdonald, K. 2015; 473 (3): 868-874

  Abstract

  Patients often receive advanced imaging before referral to an orthopaedic oncologist. The few studies that have evaluated the value of these tests have been single-center studies, and there were large discrepancies in the estimated frequencies of unnecessary use of diagnostic tests.(1) Is there regional variation in the use of advanced imaging before referral to an orthopaedic oncologist? (2) Are these prereferral studies helpful to the treating orthopaedic oncologist in making a diagnosis or treatment plan? (3) Are orthopaedic surgeons less likely to order unhelpful studies than other specialties? (4) Are there any tumor or patient characteristics that are associated with the ordering of an unhelpful study?We performed an eight-center prospective analysis of patients referred for evaluation by a fellowship-trained orthopaedic oncologist. We recorded patient factors, referral details, advanced imaging performed, and presumptive diagnosis. The treating orthopaedic oncologist determined whether each study was helpful in the diagnosis or treatment of the patient based on objective and subjective criteria used in prior investigations. We analyzed the data using bivariate methods and logistic regression to determine regional variation and risk factors predictive of unhelpful advanced imaging. Of the 371 participants available for analysis, 301 (81%) were referred with an MRI, CT scan, bone scan, ultrasound, or positron emission tomography scan.There were no regional differences in the use of advanced imaging (range of patients presenting with advanced imaging 66%-88% across centers, p = 0.164). One hundred thirteen patients (30%) had at least one unhelpful study; non-MRI advanced imaging was more likely to be unhelpful than MRIs (88 of 129 [68%] non-MRI imaging versus 46 of 263 [17%] MRIs [p < 0.001]). Orthopaedic surgeons were no less likely than nonorthopaedic surgeons to order unhelpful studies before referral to an orthopaedic oncologist (56 of 179 [31%] of patients referred by orthopaedic surgeons versus 35 of 119 [29%] referred by primary care providers and 22 of 73 [30%] referred by nonorthopaedic specialists, p = 0.940). After controlling for potential confounding variables, benign bone lesions had an increased odds of referral with an unhelpful study (59 of 145 [41%] of benign bone tumors versus 54 of 226 [24%] of soft tissue tumors and malignant bone tumors; odds ratio, 2.80; 95% confidence interval, 1.68-4.69, p < 0.001).We found no evidence that the proportion of patients referred with advanced imaging varied dramatically by region. Studies other than MRI were likely to be considered unhelpful and should not be routinely ordered by referring physicians. Diligent education of orthopaedic surgeons and primary care physicians in the judicious use of advanced imaging in benign bone tumors may help mitigate unnecessary imaging.Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

  View details for DOI 10.1007/s11999-014-3649-z

  View details for Web of Science ID 000349242200019

  View details for PubMedID 24777726

  View details for PubMedCentralID PMC4317449

• Antirotation Pins Improve Stability of the Compress Limb Salvage Implant: A Biomechanical Study CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Avedian, R. S., Chen, T., Lindsey, D., Palanca, A., Mohler, D. 2014; 472 (12): 3982-3986

  Abstract

  Limb salvage implants that rely on compliant compression osseointegration to achieve bone fixation may achieve longer survivorship rates compared with traditional cemented or press-fit stemmed implants; however, failures resulting from rotational instability have been reported. The effect of using antirotation pins on the rotational stability of the fixation has not been well studied.We asked the following question: When tested in a cadaver model, does the use of antirotation pins increase the torque required to cause implant failure or rotation?Thirty-two cadaver femurs were divided into four groups of eight femurs. We compared the torque to failure among groups containing zero, one, two, three, and four pins using a servohydraulic testing device.Adding antirotation pins increased the torque required to cause failure (R(2) = 0.77; p < 0.001). This increase was most notable in groups comparing zero pins with one pin (14 N-m, [95% CI, 10.9-17.1] versus 23 N-m, [95% CI 22.5-23.48]; p = 0.01) and two compared with three pins (29 N-m, [95% CI, 21.7-36.3] versus 42 N-m, [95% CI, 37.8-46.2]; p = 0.35).It appears that the use of antirotation pins improves rotational stability of the compliant compression endoprosthesis. Although these findings need to be verified in a clinical study, the addition of antirotation pins may improve osteointegration and we have changed our practice to use a minimum of three antirotation pins when implanting this device.Improvements in implant technology and surgical techniques may lead to improved clinical outcomes and patient quality of life. Addition of antirotation pins appears to improve implant stability and may decrease the need for revision surgery.

  View details for DOI 10.1007/s11999-014-3899-9

  View details for Web of Science ID 000344647200052

  View details for PubMedCentralID PMC4397809

• Antirotation pins improve stability of the compress limb salvage implant: a biomechanical study. Clinical orthopaedics and related research Avedian, R. S., Chen, T., Lindsey, D., Palanca, A., Mohler, D. 2014; 472 (12): 3982-3986

  Abstract

  Limb salvage implants that rely on compliant compression osseointegration to achieve bone fixation may achieve longer survivorship rates compared with traditional cemented or press-fit stemmed implants; however, failures resulting from rotational instability have been reported. The effect of using antirotation pins on the rotational stability of the fixation has not been well studied.We asked the following question: When tested in a cadaver model, does the use of antirotation pins increase the torque required to cause implant failure or rotation?Thirty-two cadaver femurs were divided into four groups of eight femurs. We compared the torque to failure among groups containing zero, one, two, three, and four pins using a servohydraulic testing device.Adding antirotation pins increased the torque required to cause failure (R(2) = 0.77; p < 0.001). This increase was most notable in groups comparing zero pins with one pin (14 N-m, [95% CI, 10.9-17.1] versus 23 N-m, [95% CI 22.5-23.48]; p = 0.01) and two compared with three pins (29 N-m, [95% CI, 21.7-36.3] versus 42 N-m, [95% CI, 37.8-46.2]; p = 0.35).It appears that the use of antirotation pins improves rotational stability of the compliant compression endoprosthesis. Although these findings need to be verified in a clinical study, the addition of antirotation pins may improve osteointegration and we have changed our practice to use a minimum of three antirotation pins when implanting this device.Improvements in implant technology and surgical techniques may lead to improved clinical outcomes and patient quality of life. Addition of antirotation pins appears to improve implant stability and may decrease the need for revision surgery.

  View details for DOI 10.1007/s11999-014-3899-9

  View details for PubMedID 25209342

• Principles of musculoskeletal biopsy. Cancer treatment and research Avedian, R. S. 2014; 162: 1-7

  Abstract

  The appropriate treatment of any musculoskeletal tumor is based on a correct diagnosis. In some instances, a patient's history and imaging studies provide sufficient information to guide definitive treatment. However, in many cases, a biopsy may be necessary. A biopsy, although technically simple, must be conducted in a thoughtful manner in order to obtain an accurate tissue sample while avoiding complications. Some potential complications include inaccurate sampling, improperly placed incision that complicates future surgeries, and healthy tissue contamination that can add morbidity to the definitive surgery or preclude the chance of limb salvage. This chapter will review the considerations for planning and performing a biopsy of musculoskeletal tumors.

  View details for DOI 10.1007/978-3-319-07323-1_1

  View details for PubMedID 25070228

• Successful Limb Salvage of a "Too-Short Segment" of the Proximal Part of the Femur with Use of a Compression Osseointegration Implant: A Case Report. JBJS case connector Avedian, R. S., Giori, N. J., Mohler, D. n. 2014; 4 (3): e63–e6

  View details for PubMedID 29252502

• Changes in health status among aging survivors of pediatric upper and lower extremity sarcoma: a report from the childhood cancer survivor study. Archives of physical medicine and rehabilitation Marina, N., Hudson, M. M., Jones, K. E., Mulrooney, D. A., Avedian, R., Donaldson, S. S., Popat, R., West, D. W., Fisher, P., Leisenring, W., Stovall, M., Robison, L. L., Ness, K. K. 2013; 94 (6): 1062-1073

  Abstract

  To evaluate health status and participation restrictions in survivors of childhood extremity sarcomas.Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003, or 2007 were included.Cohort study of survivors of extremity sarcomas.Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5% white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986.Not applicable.Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age.In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation.Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age.

  View details for DOI 10.1016/j.apmr.2013.01.013

  View details for PubMedID 23380347

• Successful Surgical and Medical Treatment of Rhizopus Osteomyelitis Following Hematopoietic Cell Transplantation ORTHOPEDICS Vashi, N., Avedian, R., Brown, J., Arai, S. 2012; 35 (10): E1556-E1561

  Abstract

  Mucormycosis has been reported in otherwise healthy individuals; however, it is primarily seen in immunocompromised patients, such as those with diabetes mellitus, malignancy, or chronic graft-versus-host disease, and has a high mortality rate. Because most cases of mucormycosis are associated with contiguous rhinocerebral infection, only 5 cases of isolated musculoskeletal Rhizopus infection have been reported in the literature. One patient underwent hematopoietic cell transplant, which resulted in a fatal outcome.This article describes the successful treatment of isolated Rhizopus osteomyelitis in a patient who underwent hematopoietic cell transplant using a combined surgical and medical approach. A 33-year-old woman with pre-B cell acute lymphoblastic leukemia underwent hematopoietic cell transplant with few complications but developed chronic graft-versus-host disease 8 months posttransplant. She was treated with high-dose steroids for 6 weeks before she was admitted for severe right tibial pain in the absence of trauma. Early detection, aggressive therapies, and a multidisciplinary surgical and medical team allowed for the microbiologically confirmed resolution of the infection. Treatment included multiagent antimicrobial therapy with amphotericin B, daptomycin, and ertapenem. Several surgical irrigation and debridement procedures were also performed, with the eventual placement of amphotericin-impregnated polymethylmethacrylate cement beads and small fragment titanium screws. The patient continued taking postoperative antifungal treatment for 7 months after discharge. Six months following the discontinuation of antifungal therapy, the team's multidisciplinary approach achieved a continued resolution of the patient's infection and a return to a fully ambulatory and radiographically proven recovery without limb loss.

  View details for DOI 10.3928/01477447-20120919-30

  View details for Web of Science ID 000309814600019

  View details for PubMedID 23027498

• Surgical Technique: Methods for Removing a Compress (R) Compliant Prestress Implant CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Abrams, G. D., Gajendran, V. K., Mohler, D. G., Avedian, R. S. 2012; 470 (4): 1204-1212

  Abstract

  The Compress® device uses a unique design using compressive forces to achieve bone ingrowth on the prosthesis. Because of its design, removal of this device may require special techniques to preserve host bone. DESCRIPTION OF TECHNIQUES: Techniques needed include removal of a small amount of bone to relieve compressive forces, use of a pin extractor and/or Kirschner wires for removal of transfixation pins, and creation of a cortical window in the diaphysis to gain access to bone preventing removal of the anchor plug.We retrospectively reviewed the records of 63 patients receiving a Compress® device from 1996 to 2011 and identified 11 patients who underwent subsequent prosthesis removal. The minimum followup was 1 month (average, 20 months; range, 1-80 months). The most common reason for removal was infection (eight patients) and the most common underlying diagnosis was osteosarcoma (five patients). Three patients underwent above-knee amputation, whereas the others (eight patients) had further limb salvage procedures at the time of prosthesis removal.Five patients had additional unplanned surgeries after explantation. Irrigation and débridement of the surgical wound was the most common unplanned procedure followed by latissimus free flap and hip prosthesis dislocation. At the time of followup, all patients were ambulating on either salvaged extremities or prostheses.Although removal of the Compress® device presents unique challenges, we describe techniques to address those challenges.

  View details for DOI 10.1007/s11999-011-2128-z

  View details for PubMedID 22002827

• Surgical Intervention of Nonvertebral Osseous Metastasis CANCER CONTROL Attar, S., Steffner, R. J., Avedian, R., Hussain, W. M. 2012; 19 (2): 113-121

  Abstract

  Nonvertebral osseous metastases can result in pain and disability. The goals of surgical intervention are to reduce pain and to improve function if nonsurgical treatment fails. The indications for proceeding with surgical intervention depend on anatomic location, amount of local destruction, extent of skeletal and visceral disease and, most important, the patient's performance status and life expectancy.This article reviews the evaluation and treatment of metastatic nonvertebral osseous lesions from the perspective of the orthopedic surgeon, based mainly on an assessment of the surgical literature.This article summarizes the approaches to preoperative evaluation, patient selection, and medical optimization. Guidelines for estimating osseous stability and fracture risk are discussed, and surgical implants and their relation to postoperative outcomes are examined. This review also describes less invasive ablative procedures currently available.The surgical management of nonvertebral osseous metastases involves multidisciplinary collaboration. The surgical construct must be a stable, reliable, and durable intervention that is individually tailored and matched to a patient's prognosis and performance status.

  View details for Web of Science ID 000307969100005

  View details for PubMedID 22487973

• COMPARISON OF HEALTH STATUS BETWEEN UPPER AND LOWER EXTREMITY SARCOMA SURVIVORS: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY Marina, N., Hudson, M., Mulrooney, D. A., Avedian, R., Donaldson, S., Fisher, P., Leisenring, W., Stovall, M., Robison, L. L., Ness, K. WILEY PERIODICALS, INC. 2011: 714

  View details for Web of Science ID 000295239600029

• Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors. Current orthopaedic practice Avedian, R. S., Gold, G., Ghanouni, P., Pauly, K. B. 2011; 22 (4): 303-308

  Abstract

  This article reviews the fundamental principles and clinical experimental uses of magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) ablation of musculoskeletal tumors. MRgHIFU is a noninvasive treatment modality that takes advantage of the ability of magnetic resonance to measure tissue temperature and uses this technology to guide high-intensity focused ultrasound waves to a specific focus within the human body that results in heat generation and complete thermal necrosis of the targeted tissue. Adjacent normal tissues are spared because of the accurate delivery of thermal energy, as well as, local blood perfusion that provides a cooling effect. MRgHIFU is approved by the Food and Drug Administration for the treatment of uterine fibroids and is used on an experimental basis to treat breast, prostate, liver, bone, and brain tumors.

  View details for PubMedID 26120376

• Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors CURRENT ORTHOPAEDIC PRACTICE Avedian, R. S., Gold, G., Ghanouni, P., Pauly, K. 2011; 22 (4): 303–8

  View details for DOI 10.1097/BCO.0b013e318220dad5

  View details for Web of Science ID 000217802900004

• Curettage and Cryosurgery for Low-grade Cartilage Tumors Is Associated with Low Recurrence and High Function CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Mohler, D. G., Chiu, R., McCall, D. A., Avedian, R. S. 2010; 468 (10): 2765-2773

  Abstract

  Chondrosarcomas of bone traditionally have been treated by wide or radical excision, procedures that may result in considerable lifelong disability. Grade 1 chondrosarcomas have little or no metastatic potential and are often difficult to distinguish from painful benign enchondromas. Curettage with adjuvant cryosurgery has been proposed as an alternative therapy for Grade 1 chondrosarcomas given the generally better function after the procedure. However, because it is an intralesional procedure, curettage and cryosurgery may be associated with higher rates of recurrence.We asked whether Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery are associated with low recurrence rates and high functional scores.We retrospectively reviewed the records of 46 patients with Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery. Forty-one patients had tumors of the long bones. Patients were followed a minimum of 18 months (average, 47.2. months; range, 18-134 months) for evidence of recurrence and for assessment of Musculoskeletal Tumor Society (MSTS) functional score.Two of the 46 patients had recurrences in the original tumor site (4.3% recurrence rate), which subsequently were removed by wide excision, and both patients were confirmed to be disease-free 36 and 30 months, respectively, after the second surgery. The mean MSTS score was 27.2 of 30 points (median, 29 points).Our observations show curettage with cryosurgery is associated with low recurrence of Grade 1 chondrosarcoma and high functional scores. Curettage with cryosurgery is a reasonable alternative to wide or radical excision as the treatment for Grade 1 chondrosarcomas, and allows for more radical surgery in the event of local recurrence.Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  View details for DOI 10.1007/s11999-010-1445-y

  View details for PubMedID 20574801

• Multiplanar Osteotomy with Limited Wide Margins: A Tissue Preserving Surgical Technique for High-grade Bone Sarcomas CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Avedian, R. S., Haydon, R. C., Peabody, T. D. 2010; 468 (10): 2754-2764

  Abstract

  Limb-salvage surgery has been used during the last several decades to treat patients with high-grade bone sarcomas. In the short- and intermediate-term these surgeries have been associated with relatively good function and low revision rates. However, long-term studies show a high rate of soft tissue, implant, and bone-related complications. Multiplanar osteotomy with limited wide margins uses angled bone cuts to resect bone tumors with the goal of complete tumor removal while sparing host tissue although its impact on local recurrence is not known.We determined whether multiplanar osteotomy was associated with local recurrences, reconstruction failures, and allograft nonunions.We retrospectively reviewed the charts of six patients. Four patients had an osteosarcoma, one had a Ewing's sarcoma, and one had a chondrosarcoma. Patient and treatment factors such as age, diagnosis, percent of tumor necrosis (if applicable), margin status, and time to allograft union were recorded. In all patients, reconstruction was performed with an intercalary allograft cut to fit the residual defect. The minimum followup was 25 months (average, 39 months; range, 24-66 months).No patient experienced a local recurrence or metastasis, and all patients were alive and disease-free at the most recent followup. All allografts healed during the study period.With careful patient selection, the multiplanar osteotomy resection technique may be considered an option for treating patients with high-grade bone sarcomas, and, when compared with traditional surgical techniques, may lead to improved healing and function of the involved extremity.Level IV, therapeutic study. See the guidelines online for a complete description of levels of evidence.

  View details for DOI 10.1007/s11999-010-1362-0

  View details for Web of Science ID 000281843200027

  View details for PubMedID 20419483

  View details for PubMedCentralID PMC3049617