Search

Introduction: Increasingly, national accrediting bodies and professional societies for musculoskeletal oncology recognize the need for more standardized training. This study elucidates recent trends in reported case volume during Accreditation Council for Graduate Medical Education (ACGME)-accredited musculoskeletal oncology fellowship training relative to case minimum requirements., Methods: We conducted a retrospective cross-sectional analysis of fellows at ACGME-accredited musculoskeletal oncology fellowships (2017 to 2022). Percentiles in reported case volumes were calculated across ACGME-defined case categories and temporal changes assessed by linear regression. Variability between the highest (90th percentile) and lowest (10th percentile) deciles was calculated as fold differences. Sensitivity analyses were conducted to estimate the number of fellows not meeting ACGME-defined case minimum requirements., Results: Case logs from 95 musculoskeletal oncology fellows were analyzed. From 2017 to 2022, total relevant oncology procedures increased from 191 ± 49 to 228 ± 73 (P = 0.066). Pediatric oncology accounted for a minority of cases (range, 6 to 8%). A mean of 222 total relevant oncology procedures were reported. Most were in management of metastatic disease (21%), soft-tissue resection/reconstruction (20%), and limb salvage (13%). Variability in total relevant oncology procedures was 2.6 and greatest in spine/pelvis (4.6), pediatric oncologic cases (4.4), and surgical management of complications (4.4). No clear trends were observed in case volume variability over the study period (P > 0.05). Analysis of case volume percentiles identified at least 30% of musculoskeletal oncology fellows not achieving minimum requirements for pediatric oncologic cases (n = 29 fellows) and 10% of fellows not achieving minimum requirements for total relevant oncology procedures (n = 10 fellows)., Discussion: Results from this study may help future musculoskeletal oncology fellows and faculty identify potential areas to increase case exposure and reduce variability during fellowship training. More investigation is needed to determine evidence-based case minimum requirements including surgical learning curves and other competency-based assessment tools in musculoskeletal oncology., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Tumor antigen-specific T cells rapidly lose energy and effector function in tumors. The cellular mechanisms by which energy loss and inhibition of effector function occur in tumor-infiltrating lymphocytes (TILs) are ill-defined, and methods to identify tumor antigen-specific TILs that experience such stress are unknown. Processes upstream of the mitochondria guide cell-intrinsic energy depletion. We hypothesized that a mechanism of T-cell-intrinsic energy consumption was the process of oxidative protein folding and disulfide bond formation that takes place in the endoplasmic reticulum (ER) guided by protein kinase R-like endoplasmic reticulum kinase (PERK) and downstream PERK axis target ER oxidoreductase 1 (ERO1α). To test this hypothesis, we created TCR transgenic mice with a T-cell-specific PERK gene deletion (OT1 + Lck cre + PERK f/f , PERK KO). We found that PERK KO and T cells that were pharmacologically inhibited by PERK or ERO1α maintained reserve energy and exhibited a protein profile consistent with reduced oxidative stress. These T-cell groups displayed superior tumor control compared with T effectors. We identified a biomarker of ER-induced mitochondrial exhaustion in T cells as mitochondrial reactive oxygen species (mtROS), and found that PD-1 + tumor antigen-specific CD8 + TILs express mtROS. In vivo treatment with a PERK inhibitor abrogated mtROS in PD-1 + CD8 + TILs and bolstered CD8 + TIL viability. Combination therapy enabled 100% survival and 71% tumor clearance in a sarcoma mouse model. Our data identify the ER as a regulator of T-cell energetics and indicate that ER elements are effective targets to improve cancer immunotherapy., (©2019 American Association for Cancer Research.)

Carcinoma of the lung is the most common lethal form of cancer in both men and women worldwide. Orthopedic manifestations of lung cancer frequently include bony metastasis, most commonly the vertebrae (42%), ribs (20%), and pelvis (18%). Acral metastatic disease is defined as metastasis distal to the elbow or the knee. Metastases to the bones of the hand are extremely rare. Only 0.1% of metastatic disease resulting from any type of carcinoma or sarcoma manifests as metastasis in the hand. There are only a few reports in the literature of soft-tissue or muscular metastasis to the hand from a carcinoma. Of these cases, the majority are caused by metastatic lung carcinoma. However, there are no reports in the literature of metastatic disease of squamous cell origin affecting the soft tissues of the hand. We present a case of a man with known metastatic squamous cell carcinoma of the lung who presented with acral soft-tissue metastatic disease. This report highlights a rare clinical scenario that has not been reported in the literature. This report also highlights a rare but important consideration for clinicians who encounter acral soft-tissue lesions in patients with a history of a primary carcinoma.