The objective of this retrospective analysis was to determine the reliability of transcutaneous oxygen tension measurement (TcPO2) in predicting outcomes of diabetics who underwent hyperbaric oxygen therapy for lower extremity wounds. Six hyperbaric facilities provided TcPO2 data under several possible conditions: breathing air, breathing oxygen at sea level, and breathing oxygen in the chamber. Overall, 75.6% of the patients improved after hyperbaric oxygen therapy. Baseline sea-level air TcPO2 identified the degree of tissue hypoxia but had little statistical relationship with outcome prediction because some patients healed after hyperbaric oxygen therapy despite very low prehyperbaric TcPO2 values. Breathing oxygen at sea level was unreliable for predicting failure, but 68% reliable for predicting success after hyperbaric oxygen therapy. TcPO2 measured in chamber provides the best single discriminator between success and failure of hyperbaric oxygen therapy using a cutoff score of 200 mmHg. The reliability of in-chamber TcPO2 as an isolated measure was 74% with a positive predictive value of 58%. Better results can be obtained by combining information about sea-level air and in-chamber oxygen. A sea-level air TcPO2 < 15 mmHg combined with an in-chamber TcPO2 < 400 mmHg predicts failure of hyperbaric oxygen therapy with a reliability of 75.8% and a positive predictive value of 73.3%.
The objectives of this study were to report outcomes of a large number of patients receiving hyperbaric oxygen therapy (HBO(2)T) for diabetic lower-extremity ulcers, and to identify likely outcome predictors. Five hyperbaric facilities supplied data on 1,006 patients. A sixth clinic served as a validation sample for the regression-based prediction model, and later additional data from Memorial Hermann Hospital were added. The severity of lower-extremity lesions was assessed upon initiation of HBO(2)T using the Modified Wagner scale, and the outcome described as healed, partially healed, not improved, amputated, or died. Overall, 73.8% of patients improved (granulated or healed). Factors significantly related to outcome included renal failure, pack-year smoking history, transcutaneous oximetry, number of HBO(2)T treatments, and interruption of treatment regimen. Number of treatments per week and treatment pressure (2.0 vs. 2.4 atmospheres absolute) were not significant factors in outcome. Concomitant administration of autologous growth factor gel did not improve outcome. A multiple regression model was fitted to the data that can be used to predict the outcome of diabetic patients undergoing HBO(2)T. Given the high cost of amputation and rehabilitation, these data suggest that hyperbaric oxygen treatment should be an important adjunctive therapy to heal lower-extremity lesions, especially those with a Wagner grade of 3 or higher.
Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non–small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups. Patients and Methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity. Results: 152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7–53.0]. Patients aged <75 (n = 84) and ≥75 (n = 68) had ORRs of 48.8% (95% CI: 37.7–60.0) and 39.7% (95% CI: 28.0–52.3), respectively. Treatment-naïve (n = 69) versus previously treated (n = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9–57.4) vs. 44.6% (33.7–55.9); median duration of response (95% CI): 10.8 (6.9–not estimable) vs. 11.1 (9.5–18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies. Conclusions: Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations. See related commentary by Rosner and Spira, p. 1055
The purpose of this project was to evaluate the safety of negative pressure wound therapy using the vacuum-assisted closure (V.A.C.) Therapy System (KCI, San Antonio, TX) in diabetic foot ulcers (DFUs) among wound centre outpatients. We defined events that could represent complications or adverse events (AEs) as a result of treatment with the V.A.C., including symptoms of infection, pain, bleeding and periwound skin breakdown. The frequency of these AEs among V.A.C. patients with DFUs was compared with those among similar non V.A.C. patients. This project prospectively queried data collected during routine clinical care from 16 outpatient wound centres using the Intellicure electronic medical record system. The electronic records were de-identified according to HIPAA requirements and pooled to create a data repository dedicated to research (the Intellicure Research Consortium). Analysis was performed on 1331 DFUs representing 16,438 outpatient visits. A total of 1299 non V.A.C. and 72 V.A.C. DFUs were available for analysis. There was either no statistical difference between the AEs of V.A.C. versus non V.A.C. patients or the V.A.C. exerted a protective effect. We conclude that the V.A.C. is safe in outpatient use.
9121 Background: Tepotinib, a potent, highly selective, oral, MET inhibitor, showed meaningful activity in patients (pts) with NSCLC with high-level METamp by LBx in VISION. Exploratory biomarker analyses are presented herein. Methods: Pts had 0–2 prior therapy lines, high-level METamp by LBx (Guardant360; MET copy number ≥2.5), and no MET exon 14 skipping or EGFR/ ALK alterations. Pts received tepotinib 500 mg once daily (450 mg active moiety). Primary endpoint was objective response by independent review; data cut-off: Aug 20, 2021. Exploratory biomarker analysis included LBx at baseline (BL), on treatment, and end of treatment (EOT). Early molecular response (eMR) was defined as undetectable METamp 6–8 weeks on treatment. Results: 24 pts were enrolled (median age: 63.4 years [yrs]; smokers: 88%; ECOG PS 1: 88%; adenocarcinoma: 67%). Treatment duration was ≥1 yr in five pts and ≥2 yrs in two pts (both ongoing). Overall, objective response rate (ORR) was 41.7% (95% CI: 22.1, 63.4). Treatment-naïve pts (n=7) had an ORR of 71.4% (29.0, 96.3), median (m) DOR was 14.3 months (2.8, not estimable [ne]), and mPFS was 15.6 months (1.4, ne). BL biomarker analyses according to clinical benefit (CR/PR/SD [n=11] vs PD/NE [n=13]) showed association with better outcomes in pts with focal METamp, or without MYCamp or RB1 mutation (Table). MYCamp/ RB1 mutation was detected in 4/7 pts with neuroendocrine/not otherwise specified histology; MYCamp in 2/3 pts with neuroendocrine histology. Low BL ctDNA mutant allele frequency (MAF) was associated with better outcomes. 14 pts had eMRs (ORR 71.4%); persistent METamp (n=4) was associated with lack of clinical response. 2/9 pts with EOT biomarker profiles had emerging resistance mechanisms (MET kinase domain mutations Y1230 and D1228); both had METamp re-emergence. Treatment-related adverse events included edema (composite term; any grade: 46%; Grade 3: 13%) and constipation (any grade: 17%; Grade ≥3: 0%). Conclusions: Tepotinib showed meaningful activity, especially in first line, in the first trial of a MET inhibitor in EGFR WT NSCLC with high-level METamp to enroll based on a convenient LBx assay. BL biomarker analyses indicated focal METamp, MYC/RB1 WT, and low ctDNA MAF were associated with improved outcomes. Serial LBx could monitor molecular response and evaluate resistance. Clinical trial information: NCT02864992. [Table: see text]
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