Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy.

Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets. We discovered three conserved cellular communities or ecotypes associated with underlying genomic alterations and distinct clinical outcomes. We show that one ecotype defined by tumor-associated macrophages and epithelial-like malignant cells predicts response to immune-checkpoint inhibition but not chemotherapy and validate our findings in an independent cohort. Our results may enable identification of patients with soft tissue sarcomas who could benefit from immunotherapy and help develop new therapeutic strategies.

Evaluation of the PROMIS Upper Extremity Against Validated Patient-Reported Outcomes in Patients With Early Carpometacarpal Osteoarthritis.

PURPOSE: Internal consistency, construct, and criterion validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity (UE) v1.2 were evaluated in patients with early-stage carpometacarpal (CMC) osteoarthritis (OA). We hypothesized that in patients with early CMC OA, PROMIS UE scores would: (1) be lower than those in asymptomatic controls; (2) correlate with established patient-reported outcomes; (3) correlate with pinch and grip strengths; and (4) not correlate with radiographic disease progression. METHODS: Patients with early CMC OA (modified Eaton stage 0 or 1) and matched asymptomatic control patients completed the PROMIS UE, Australian and Canadian Osteoarthritis Hand Index, and Patient-Rated Wrist-Hand Evaluation at 2 time points. The PROMIS UE's internal consistency was evaluated by Cronbach's alpha, construct validity by Spearman correlation coefficients among the patient-reported outcome measures, and criterion validity using measures of strength. A floor or ceiling effect was indicated if more than 15% of patients achieved the lowest or highest possible score. RESULTS: The PROMIS UE had high internal consistency. Patients with early CMC OA had a lower score than healthy controls (average, 42 vs 54, respectively). We observed moderate to high correlations between the PROMIS UEv1.2, Australian and Canadian Osteoarthritis Hand Index, and Patient-Rated Wrist-Hand Evaluation and good criterion validity when compared to key pinch and grip strengths. The PROMIS UE did not correlate to radiographic disease severity. CONCLUSIONS: The PROMIS UE had a high correlation with Australian and Canadian Osteoarthritis Hand Index and a moderate correlation with Patient-Rated Wrist-Hand Evaluation. The PROMIS UE had high internal consistency and good criterion validity. CLINICAL RELEVANCE: The PROMIS UE is a valid assessment for disability in patients with early CMC OA and can serve as a clinical adjunct to an outcome assessment.

Single Assessment Numeric Evaluation (SANE) in Hand Surgery: Does a One-Question Outcome Instrument Compare Favorably?

PURPOSE: Patient-reported outcome measures are increasingly used to measure patient status, impairments, and disability, but often require lengthy surveys and place a considerable burden on patients. We hypothesized that the Single Assessment Numeric Evaluation (SANE), composed of a single question, would be a valid and responsive instrument to provide a global assessment of hand function. METHODS: The SANE, Patient-Reported Outcomes Measurement Information System-Upper Extremity (PROMIS-UE), and Quick-Disabilities of the Arm, Shoulder, and Hand (QuickDASH) data are routinely collected electronically in our hand and upper-extremity center. To identify our cohort, we used Current Procedural Terminology codes to query our electronic medical record research data repository for the 7 most common hand surgery procedures performed over 2 years from December 2016 to 2018. These procedures included carpal tunnel release, trigger finger release, thumb carpometacarpal arthroplasty, wrist arthroscopy, distal radius fracture fixation, first dorsal compartment release, and cubital tunnel release. Patients undergoing a single isolated procedure with questionnaires obtained in the preoperative and/or postoperative period were included in the analysis. Convergent validity, coverage, and responsiveness for each instrument were assessed. RESULTS: We identified 214 patients for inclusion. The SANE score had a moderate to strong correlation with the QuickDASH and PROMIS-UE. Floor and ceiling effects for the SANE were less than 10% at baseline and follow-up. Overall, the QuickDASH was the most responsive, followed by SANE and PROMIS-UE; all 3 instruments exceeded the acceptable thresholds for responsiveness and demonstrated significant changes before to after surgery. Responsiveness of the SANE varied by procedure and was acceptable for carpal tunnel release, carpometacarpal arthroplasty, wrist arthroscopy, and trigger finger release. CONCLUSIONS: The single-item SANE is a reasonable measure of global function in patients undergoing common hand procedures and demonstrates psychometric properties comparable to those of the PROMIS-UE and QuickDASH outcome scores. CLINICAL RELEVANCE: The SANE score is a reasonable outcome measure of global hand function that may have utility in demonstrating response to treatment in a practice setting and may provide a useful adjunct to multiple-item measures in clinical research studies.

The AUSCAN and PRWHE Demonstrate Comparable Internal Consistency and Validity in Patients With Early Thumb Carpometacarpal Osteoarthritis.

BACKGROUND: The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Patient-Rated Wrist-Hand Evaluation (PRWHE) are 2 patient-related outcome measures to assess pain and disability in patients with osteoarthritis (OA). The purpose of this study was to evaluate the AUSCAN and PRWHE in a large-scale, longitudinal cohort of patients with early thumb carpometacarpal (CMC) OA. METHODS: We obtained baseline data on 135 individuals (92 with early CMC OA participants and 43 asymptomatic controls) and at follow-up (year 1.5) on 83 individuals. We assessed the internal consistency using Cronbach alpha, and construct and criterion validity using other pain scales and objective measures of strength, respectively. We also examined the correlation between the AUSCAN and PRWHE and correlation coefficients at baseline and follow-up, as well as the correlation between changes in these instruments over the follow-up period. RESULTS: Internal consistency was high for both AUSCAN and PRWHE totals and subscales (Cronbach α > 0.70). Both instruments demonstrated construct validity compared with the Verbal Rating Scale ( r = 0.52-0.60, P < .01), an assessment of pain, and moderate criterion validity compared with key pinch and grip strength ( r = -.24 to -.33, P < .05). These instruments were highly correlated with each other at baseline and follow-up time points ( r = 0.76-.94, P < .01), and changes in a patient's total scores over time were also correlated ( r = 0.83, P < .01). CONCLUSIONS: The AUSCAN and PRWHE are both valid assessments for pain and/or disability in patients with early thumb CMC OA.