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Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells. There have been few guidelines or consensus statements on how to optimally collect and manage biospecimens and source material being used for immunotherapy and related research. The Society for Immunotherapy of Cancer Surgery Committee has brought together surgical experts from multiple subspecialty disciplines to identify best practices and to provide consensus on how best to access and manage specific tissues for immuno-oncology treatments and clinical investigation. In addition, the committee recommends early integration of surgeons and other interventional physicians with expertise in biospecimen collection, especially in clinical trials, to optimize the quality of tissue and the validity of correlative clinical studies in cancer immunotherapy.

The presence of Alternative lengthening of telomeres (ALT) and/or ATRX loss, as well as the role of other telomere abnormalities, have not been formally studied across the spectrum of NF1-associated solid tumors. Utilizing a telomere-specific FISH assay, we classified tumors as either ALT-positive or having long (without ALT), short, or normal telomere lengths. A total of 426 tumors from 256 NF1 patients were evaluated, as well as 99 MPNST tumor samples that were sporadic or of unknown NF1 status. In the NF1-glioma dataset, ALT was present in the majority of high-grade gliomas: 14 (of 23; 60%) in contrast to only 9 (of 47; 19%) low-grade gliomas (p = 0.0009). In the subset of ALT-negative glioma cases, telomere lengths were estimated and we observed 17 (57%) cases with normal, 12 (40%) cases with abnormally long, and only 1 (3%) case with short telomeres. In the NF1-associated malignant nerve sheath tumor (NF1-MPNST) set (n = 75), ALT was present in 9 (12%). In the subset of ALT-negative NF1-MPNST cases, telomeres were short in 9 (38%), normal in 14 (58%) and long in 1 (3%). In the glioma set, overall survival was significantly decreased for patients with ALT-positive tumors (p

BackgroundPatients with recurrent or refractory osteosarcoma have a poor prognosis with less than 30% surviving two years. Eribulin is a synthetic analog of halichondrin B, has a novel mechanism of action when compared with other microtubule inhibitors, and may have antitumor activity in osteosarcoma.MethodsA prospective study was designed to assess the disease control success at four months and objective response rates in patients with recurrent or refractory osteosarcoma treated with eribulin. Eligible patients were between 12 and 50 years of age, had measurable tumor, and met standard organ function requirements. Patients were given eribulin 1.4 mg/m2 /dose on days 1 and 8 of each 3-week cycle for up to 24 months if there was no progressive disease. Response to therapy was assessed using RECIST 1.1 criteria after cycles 2 and 5 and every fourth cycle thereafter.ResultsNineteen patients enrolled on the AOST1322 study. The median age of enrollment was 16 years (range, 12-25 years). Twelve patients were male and seven female. Eribulin was well tolerated, with neutropenia identified as the most common toxicity. The median progression-free survival was 38 days and no patients reached the four-month time point without progression. No objective responses were seen in any patient.ConclusionThis study rapidly assessed the clinical activity of a novel agent in this patient population. Eribulin was well tolerated, but there were no patients who demonstrated objective response, and all patients had progression prior to four months.

BackgroundComplete surgical resection of primary tumors is critical for long-term control of high-grade osteosarcoma. Uniform assessment of the extent of surgical resection is important in clinical trials, though the accuracy of this reporting has been poorly studied.MethodsWe conducted a retrospective cohort study of patients 5-40 years of age with newly diagnosed high-grade resectable osteosarcoma treated as part of the AOST0331 clinical trial at Children's Oncology Group institutions. The extent of surgical resection of the primary tumor was graded as wide or radical by the treating institution. Central assessment of the extent of resection by two orthopedic oncologists was compared with institutional assessment by reviewing pathology and operative reports.ResultsWe included 956 patients who had data available for central review. The extent of resection reported by treating institutions was 536/956 (56%) radical and 420/956 (44%) wide. The extent of resection assessed by central review was 162/956 (17%) radical and 794/956 (83%) wide. The overall discordance rate for the cohort was 43%.ConclusionsInstitutional reports of radical resection in high-grade osteosarcoma significantly over-estimate the proportion of patients undergoing radical resection. This highlights the need for centralized review and improved accuracy of reporting of the extent of resection. J. Surg. Oncol. 2016;113:351-354. © 2016 Wiley Periodicals, Inc.

BackgroundPatients with failed distal femoral megaprostheses often have bone loss that limits reconstructive options and contributes to the high failure rate of revision surgery. The Compress(®) Compliant Pre-stress (CPS) implant can reconstruct the femur even when there is little remaining bone. It differs from traditional stemmed prostheses because it requires only 4 to 8 cm of residual bone for fixation. Given the poor long-term results of stemmed revision constructs, we sought to determine the failure rate and functional outcomes of the CPS implant in revision surgery.Questions/purposes(1) What is the cumulative incidence of mechanical and other types of implant failure when used to revise failed distal femoral arthroplasties placed after oncologic resection? (2) What complications are characteristic of this prosthesis? (3) What function do patients achieve after receiving this prosthesis?MethodsWe retrospectively reviewed 27 patients who experienced failure of a distal femoral prosthesis and were revised to a CPS implant from April 2000 to February 2013. Indications for use included a minimum 2.5 mm cortical thickness of the remaining proximal femur, no prior radiation, life expectancy > 10 years, and compliance with protected weightbearing for 3 months. The cumulative incidence of failure was calculated for both mechanical (loss of compression between the implant anchor plug and spindle) and other failure modes using a competing risk analysis. Failure was defined as removal of the CPS implant. Followup was a minimum of 2 years or until implant removal. Median followup for patients with successful revision arthroplasty was 90 months (range, 24-181 months). Functional outcomes were measured with the Musculoskeletal Tumor Society (MSTS) functional assessment score.ResultsThe cumulative incidence of mechanical failure was 11% (95% confidence interval [CI], 4%-33%) at both 5 and 10 years. These failures occurred early at a median of 5 months. The cumulative incidence of other failures was 18% (95% CI, 7%-45%) at 5 and 10 years, all of which were deep infection. Three patients required secondary operations for cortical insufficiency proximal to the anchor plug in bone not spanned by the CPS implant and unrelated to the prosthesis. Median MSTS score was 27 (range, 24-30).ConclusionsRevision distal femoral replacement arthroplasty after a failed megaprosthesis is often difficult as a result of a lack of adequate bone. Reconstruction with the CPS implant has an 11% failure rate at 10 years. Our results are promising and demonstrate the durable fixation provided by the CPS implant. Further studies to compare the CPS prosthesis and other reconstruction options with respect to survival and functional outcomes are warranted.Level of evidenceLevel IV, therapeutic study.

Percent necrosis (PN) following chemotherapy is a prognostic factor for survival in osteosarcoma. Pathologists estimate PN by calculating tumor viability over an average of whole‐slide images (WSIs). This non‐standardized, labor‐intensive process requires specialized training and has high interobserver variability. Therefore, we aimed to develop a machine‐learning model capable of calculating PN in osteosarcoma with similar accuracy to that of a musculoskeletal pathologist. In this proof‐of‐concept study, we retrospectively obtained six WSIs from two patients with conventional osteosarcomas. A weakly supervised learning model was trained by using coarse and incomplete annotations of viable tumor, necrotic tumor, and nontumor tissue in WSIs. Weakly supervised learning refers to processes capable of creating predictive models on the basis of partially and imprecisely annotated data. Once "trained," the model segmented areas of tissue and determined PN of the same six WSIs. To assess model fidelity, the pathologist also estimated PN of each WSI, and we compared the estimates using Pearson's correlation and mean absolute error (MAE). MAE was 15% over the six samples, and 6.4% when an outlier was removed, for which the model inaccurately labeled cartilaginous tissue. The model and pathologist estimates were strongly, positively correlated (r = 0.85). Thus, we created and trained a weakly supervised machine learning model to segment viable tumor, necrotic tumor, and nontumor and to calculate PN with accuracy similar to that of a musculoskeletal pathologist. We expect improvement can be achieved by annotating cartilaginous and other mesenchymal tissue for better representation of the histological heterogeneity in osteosarcoma. [ABSTRACT FROM AUTHOR]

Periprosthetic fractures after massive endoprosthetic reconstructions pose a reconstructive challenge and jeopardize limb preservation. Compressive osseointegration technology offers the promise of relative ease of prosthetic revision, since fixation is achieved by means of a short intramedullary device. We retrospectively reviewed the charts of 221 patients who had Compress® devices implanted in two centers between December, 1996 and December, 2008. The mean followup was 50 months (range, 1–123 months). Six patients (2.7%) sustained periprosthetic fractures and eight (3.6%) had nonperiprosthetic ipsilateral limb fractures occurring from 4 to 79 months postoperatively. All periprosthetic fractures occurred in patients with distal femoral implants (6/154, 3.9%). Surgery was performed in all six patients with periprosthetic femur fractures and for one with a nonperiprosthetic patellar fracture. The osseointegrated interface was radiographically stable in all 14 cases. All six patients with periprosthetic fracture underwent limb salvage procedures. Five patients had prosthetic revision; one patient who had internal fixation of the fracture ultimately underwent amputation for persistent infection. Periprosthetic fractures involving Compress® fixation occur infrequently and most can be treated successfully with further surgery. When implant revision is needed, the bone preserved by virtue of using a shorter intramedullary Compress® device as compared to conventional stems, allows for less complex surgery, making limb preservation more likely. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.