No abstract

No abstract

In 2004, nearly 120 000 fragility fractures of the humerus were reported. As the US population ages, this number is expected to increase. Fractures of the distal humerus can be treated in a closed or open fashion. Open treatment includes open reduction and internal fixation or total elbow arthroplasty. Open reduction and internal fixation typically involves dual plating for increased stability and early mobility. We present a case in which dual plating failed due to lack of screw purchase in osteoporotic bone. This patient's fracture was then revised with the use of a fibular strut allograft for improved stability and screw purchase. This method of fixation has not previously been described in the distal humerus and may prove useful in open fixation of osteoporotic distal humerus fractures.

2599 Background: Pembrolizumab was recently approved in tumors with TMB ≥10 mut/Mb. FSM can complement TMB in predicting ICI responses. We obtained a real-world dataset of genomic alterations from 250,813 samples to examine the distribution of TMB and FSM across a variety of malignancies. We then conducted a multi-institutional retrospective review of pts treated with ICI. Methods: Database samples were sequenced by Foundation Medicine using hybrid capture genomic profiling to evaluate all classes of genomic alterations in at least 315 genes. The clinical cohort included pts with metastatic solid malignancies who received ICI and had undergone commercial next-generation sequencing (NGS). Pts were classified into four distinct groups: TMB-L ( < 10mut/Mb)/ FS-A (absent FSM), TMB-H (≥10mut/Mb)/ FS-A, TMB-L /FS-P (present, ≥1 FSM) and TMB-H/FS-P. Progression-free survival (PFS), overall survival (OS), and response rate (RR) were compared between the groups. Results: 246,252 MSS and 4,561 MSI-High samples were segregated by histology and divided into four distinct groups based on the TMB and FSM. For the MSS cohort the distribution was: TMB-L/FS-A (N = 111,065, 45%), TMB-H/FS-A(N = 15,313, 6%), TMB-L /FS-P (N = 98,389, 40%) and TMB-H/FS-P (N = 21,485, 9%). In the ICI-treated clinical cohort, there were 230 pts in 12 histology groups; 212 had information on TMB and FSM. The most common primary sites were GI (N = 39), melanoma (N = 37), GU (N = 32) and H&N cancer (N = 21). 159 pts received single ICI and 53 dual ICI. 196 tumors were MSS, 11 MSI, and 5 unknown. Group distribution: TMB-L/FS-A 80 pts (38%), TMB-L/FS-P 57pts (27%), TMB-H/FS-A 36pts (17%), TMB-H/FS-P 39pts (18%). FS-P was associated with higher RR 23.81 vs. 12.8 % (p = 0.02). Regardless of TMB, the median PFS for FS-P vs. FS-A was 7.9 and 4.0 mo, respectively (p < 0.01). TMB-L/FS-P had superior PFS (5.1 mo) compared to TMB-L/FS-A (3.6 mo) group (p < 0.01). The 15-month PFS probability was 12% for TMB-L/FS-A vs. 38% for TMB-L/FS-P. No statistically significant difference was detected in OS between the groups. From the pan-cancer cohort, histologies with more than 40% of samples in the TBM-L/FS-P (MSS) group were: CRC, RCC, PDAC, biliary, breast, esophageal, and endometrial cancers. Additional genomic data will be presented. Conclusions: FSM are frequently found on commercial NGS testing in tumors that are MSS and TMB-L. The presence of FSM may complement TMB in predicting benefit from immunotherapy. If validated in additional cohorts, FSM presence could be utilized to identify pts that may benefit from ICI, particularly for tumors with low TMB.