Daniel M. Lerman

Tumoral TP53 and/or CDKN2A Alterations are Not Reliable Prognostic Biomarkers in Patients with Localized Ewing Sarcoma: A Report from the Children’s Oncology Group

A growing collection of retrospective studies have suggested that TP53 mutations and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to evaluate these variables in patients with localized disease treated prospectively on a single Childrens Oncology Group protocol.

Has the Level of Evidence of Podium Presentations at the Musculoskeletal Tumor Society Annual Meeting Changed Over Time

BackgroundLevel of evidence (LOE) framework is a tool with which to categorize clinical studies based on their likelihood to be influenced by bias. Improvements in LOE have been demonstrated throughout orthopaedics, prompting our evaluation of orthopaedic oncology research LOE to determine if it has changed in kind.Questions/purposes(1) Has the LOE presented at the Musculoskeletal Tumor Society (MSTS) annual meeting improved over time? (2) Over the past decade, how do the MSTS and Orthopaedic Trauma Association (OTA) annual meetings compare regarding LOE overall and for the subset of therapeutic studies?MethodsWe reviewed abstracts from MSTS and OTA annual meeting podium presentations from 2005 to 2014. Three independent reviewers evaluated a total of 1222 abstracts for study type and LOE; there were 577 abstracts from MSTS and 645 from OTA. Changes in the distributions of study type and LOE over time were evaluated by Pearson chi-square test.ResultsThere was no change over time in MSTS LOE for all study types (p = 0.13) and therapeutic (p = 0.36) study types during the reviewed decade. In contrast, OTA LOE increased over this time for all study types (p < 0.01). The proportion of Level I therapeutic studies was higher at the OTA than the MSTS (3% [14 of 413] versus 0.5% [two of 387], respectively), whereas the proportion of Level IV studies was lower at the OTA than the MSTS (32% [134 of 413] versus 75% [292 of 387], respectively) during the reviewed decade. The proportion of controlled therapeutic studies (LOE I through III) versus uncontrolled studies (LOE IV) increased over time at OTA (p < 0.021), but not at MSTS (p = 0.10).ConclusionsUncontrolled case series continue to dominate the MSTS scientific program, limiting progress in evidence-based clinical care. Techniques used by the OTA to improve LOE may be emulated by the MSTS. These techniques focus on broad participation in multicenter collaborations that are designed in a comprehensive manner and answer a pragmatic clinical question.

Are two plates necessary for extraarticular fractures of the distal humerus

Background:We compared the biomechanical stability of a standard precontoured two-plate locked construct with that of a single laterally placed locked plate for extraarticular supracondylar distal humeral fractures. Methods:Extraarticular supracondylar humeral fractures were created in matched pairs of nonosteoporotic cadaver humeri. Specimens were plated with a single locked plate placed posterolaterally or two precontoured locked plates placed orthogonally. Both constructs were instrumented in a hybrid manner with locking and nonlocking screws. Each sample underwent cyclic loading in flexion and varus to failure. Average cycles to failure, force to failure, displacement, and mechanical stiffness were compared. Results:Stiffness was 1072 N/mm for the single-plate construct and 722 N/mm for the two-plate construct (P=0.06). Average number of cycles to failure was 3586 for the single-plate and 2772 for the two-plate construct (P=0.42). Force to failure averaged 428 N for the single-plate and 380 N for the two-plate construct (P=0.56). All constructs failed through the plate-bone interface without failure of the devices. Conclusions:A single plate designed specifically for fractures of the distal humerus is biomechanically equivalent to two precontoured plates also designed for the distal humerus. The finding might be clinically significant because the single-plate technique potentially reduces surgical time and exposure to the posterior and medial aspects of the elbow. Decreased exposure, especially to the medial elbow, might reduce iatrogenic injury.

PROMIS® scores in operative metastatic bone disease patients: A multicenter, prospective study: BLANK et al.

The prevalence of metastatic bone disease (MBD) grows each year as treatments improve. Little has been published about functional and pain outcomes in this group after surgery. Patient‐Reported Outcomes Measurement Information System (PROMIS®) can collect information, in just minutes, about patients physical, mental, and social health. This study evaluated PROMIS® pain and functional scores in surgically treated patients with MBD.

Erratum to: Use of Compressive Osseointegration Endoprostheses for Massive Bone Loss From Tumor and Failed Arthroplasty: A Viable Option in the Upper Extremity

A financial disclosure statement was improperly reported in the published study, ‘‘Use of Compressive Osseointegration Endoprostheses for Massive Bone Loss From Tumor and Failed Arthroplasty: A Viable Option in the Upper Extremity.’’ The study should have included the following statement: ‘‘The institution of one of the authors (DL) has received, during the study period, funding from NCATS/NI1H (UL1 TR000445) for the utilization of the REDCap (Research Electronic Data Capture) database.’’ We apologize for the error.

The Impact of Microenvironment on the Synovial Sarcoma Transcriptome

Synovial sarcoma (SS) is initiated by a t(X;18) chromosomal translocation and resultant SS18-SSX fusion oncogene. Only a few SS cell lines exist. None has been compared to its source tumor. In order to compare matched tumor and cell line pairs, we performed RNAseq on 3 tumor/cell line pairs from a genetically engineered mouse model of SS, as well as 2 pairs from human SS tumors. Transcriptomes of mouse tumors and derivative cell lines deviated significantly. Differentially expressed genes highlighted inflammatory infiltrates and metabolism. The same was found for the human tumor and cell line pairs. More was shared between different tumors than between any tumor and its cell line. Direct xenografting generated transcriptomes that more closely resembled the primary tumor than did its derivative cell line. SS tumor transcriptomes are powerfully impacted by the environment wherein they reside, especially with regard to immune interaction and metabolism.

Consideration of the Temporal Relationship Between Surgery and Radiation Therapy

Patients with an impending or realized pathologic fracture from metastatic bone disease often benefit from surgical intervention in combination with radiation therapy. Although this bimodality therapy improves patient outcomes and implant survival, the addition of radiotherapy has the potential to increase the risk for postoperative complications.

Pitfalls to avoid when treating patients with metastatic bone disease

The surgical management of patients with impending or realized pathologic fractures is fraught with multiple potential pitfalls. Many of these are unique to patients with metastatic bone disease and therefore warrant additional attention. An ordered systemic preoperative evaluation helps to prevent diagnostic omissions. A whole body bone scan and subsequent radiographic evaluation of all active lesions allows the identification of additional sites of concern that were not apparent on presentation. Determination of the tissue of origin, which is typically made with a thorough diagnostic evaluation, has implications for perioperative management and projected patient longevity that may influence operative planning. Before surgical intervention a histologic confirmation of metastatic disease must be obtained to prevent incidental intervention for a nonmetastatic lesion. Lastly, serum calcium levels should be assessed to rule out malignancy-associated hypercalcemia, a potentially fatal complication with nonspecific symptoms and an indolent progression. Both skeletal disease burden and projected patient longevity may influence whether skeletal fixation or arthroplasty is performed. Regardless of which modality is employed, a few general principles are constant. Surgical intervention should provide a durable reconstruction that allows immediate weight bearing and whose success is independent of osseous healing, which is unlikely to occur. As standard practice, long-stem, full-length implants are used to prophylactically splint the uninvolved segments of the operated bone, protecting against further disease progression. Optimal postoperative management requires use of localized and systemic therapies to limit metastatic disease progression and improve patient outcomes.