MultiCare Auburn Medical Center

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment.Significance:This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown.

3574 Background: Tissue-based h-CGP is increasingly utilized for treatment selection in patients with advanced solid tumors but has high tumor surface area [TSA] requirements (≥25mm2 for leading commercial tests). P-CGP is recommended when tissue is insufficient for H-CGP. Here we assessed the feasibility and clinical impact on actionable biomarker identification of PCR-CGP. Methods: We performed a post-hoc, non-prespecified analysis on 21,743 consecutive subjects with advanced solid tumors who sent TTS for PCR-CGP from 5/17-12/19 as part of an ongoing observational trial at > 20 U.S. health systems (NCT03061305). PCR-CGP was performed using StrataNGS, a single-site laboratory developed test assessing all CGP biomarker classes (including microsatellite instability (MSI) status and tumor mutation burden [TMB]). We predicted actionable biomarker identification rates for PCR-CGP, H-CGP and P-CGP if applied to all U.S. patients with advanced solid tumors through incorporating population incidence, biomarker frequencies, test TSA and tumor content requirements (or cfDNA detection rates), and performance characteristics. Actionable biomarkers were the 30 in 11 tumor types from the MolDX p-CGP local coverage determination (L38043), pan-tumor NTRK fusions and MSI, and TMB in lung cancer. Results: Among TTS from 21,734 patients with advanced cancer, 20,493 (94.3%) met TSA requirements for PCR-CGP (≥2mm2) vs. 9,281 (42.7%) for H-CGP. PCR-CGP reported results for 98.0% and 95.0% of patients with large (≥25mm2 TSA) and small (2-24mm2) TS, respectively, in a median of 7 business days. Compared to 1,882 orthogonal actionable biomarker results, PCR-CGP accuracy was 96.6% and 96.5% in large and small TTS, respectively. Actionable biomarker frequency was highly correlated in PCR-CGP tested large vs. small TTS (r2= 0.99), as well as in this PCR-CGP cohort vs. a MSKCC institutional pan-cancer H-CGP cohort (r2= 0.92). If applied to all U.S. patients with advanced solid tumors, PCR-CGP has significantly greater predicted actionable biomarker identification rate (88.5%) compared to P-CGP (77.0%, N-1 chi-squared test, p < 0.0001) or H-CGP (54.3%, p < 0.0001). Conclusions: Half of TTS submitted for PCR-CGP did not meet H-CGP tissue requirements. PCR-CGP is feasible for the vast majority of patients and is predicted to expand the actionable biomarker evaluable proportion of patients with advanced solid tumors compared to H-CGP or P-CGP. Clinical trial information: NCT03061305 .

The direction and nature of incisions can impact the healing and appearance of a surgical scar. This can be attributed mainly due to skin tension and direction of force. The aim of this study was to identify differences in healing rates and scar esthetics between transverse and longitudinal portals used for hip arthroscopy. A total of 75 patients underwent bilateral hip arthroscopy for femoroacetabular impingement. All patients received a portal perpendicular to the long axis of the body on the left side (transverse portal) and parallel with the long axis of the body on the right side (longitudinal portal) for the standard anterolateral viewing portal. Postoperatively, patients were reviewed at 2 weeks, 6 weeks, 3 months and 6 months and the portal scars were assessed, photographed and measured. No patients were lost to follow-up. The transverse scars, although slightly longer, were found to be narrower at 6 weeks (3.8 mm versus 2.7 mm, P < 0.01), 3 months (4.3 mm versus 3.4 mm, P = 0.01) and 6 months postoperatively (6.1 mm versus 4.5 mm, P < 0.01). At 3 months (43 mm2 versus 35 mm2, P = 0.029) and 6 months (49 mm2 versus 43 mm2, P = 0.024), transverse incisions were noted to have significantly reduced total area compared with longitudinal incisions. There were no wound complications in either group. This study demonstrates that transverse portal positions for hip arthroscopy have an advantage over longitudinal portal positions in terms of total scar area and thickness up to 6 months postoperatively.

Nutritional status of the dairy cow involves a complex interaction between macronutrients and micronutrients and herd-level management. This chapter discusses several of these interactions and their effects on reproductive performance. The transition period is widely accepted as the 3 weeks immediately before parturition through 3 weeks immediately following parturition. Disorders associated with this period of the reproductive cycle of the dairy cow include, but are not limited to, periparturient paresis, retained fetal membranes (retained placenta), metritis, hepatic lipidosis, ketosis, and displaced abomasum. Milk urea nitrogen (MUN) is closely associated with blood urea nitrogen (BUN). The negative effects of oleic acid, and a combination of oleic, palmitic and stearic fatty acids, have been studied with regard to their direct effect(s) on granulosa cells and cumulus–oocyte complexes and theca cells. In vivo, these negatively correlated effects are secondary to elevated circulating plasma levels of these individual and/or combinations of NEFA.