Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Machine learning based natural language processing of radiology reports in orthopaedic trauma.

OBJECTIVES: To compare different Machine Learning (ML) Natural Language Processing (NLP) methods to classify radiology reports in orthopaedic trauma for the presence of injuries. Assessing NLP performance is a prerequisite for downstream tasks and therefore of importance from a clinical perspective (avoiding missed injuries, quality check, insight in diagnostic yield) as well as from a research perspective (identification of patient cohorts, annotation of radiographs). METHODS: Datasets of Dutch radiology reports of injured extremities (n = 2469, 33% fractures) and chest radiographs (n = 799, 20% pneumothorax) were collected in two different hospitals and labeled by radiologists and trauma surgeons for the presence or absence of injuries. NLP classification was applied and optimized by testing different preprocessing steps and different classifiers (Rule-based, ML, and Bidirectional Encoder Representations from Transformers (BERT)). Performance was assessed by F1-score, AUC, sensitivity, specificity and accuracy. RESULTS: The deep learning based BERT model outperforms all other classification methods which were assessed. The model achieved an F1-score of (95 ± 2)% and accuracy of (96 ± 1)% on a dataset of simple reports (n= 2469), and an F1 of (83 ± 7)% with accuracy (93 ± 2)% on a dataset of complex reports (n= 799). CONCLUSION: BERT NLP outperforms traditional ML and rule-base classifiers when applied to Dutch radiology reports in orthopaedic trauma.

Ossification of abdominal scar tissue: a case series with a translational review on its development.

PURPOSE: Bone formation in abdominal scar tissue is a form of heterotopic ossification. It is a rare and underreported phenomenon following abdominal surgery. Heterotopic ossification (HO) is the formation of bone where normally no bone is present and two theories on its pathogenesis prevail: (1) physical dislocation of small bony fragments from the xyphoid process or os pubis into the wound, (2) differentiation of locally available multipotent mesenchymal stromal cells into osteoblasts resulting in the calcification of extracellular matrix. Multipotent mesenchymal stromal cells can differentiate into different cell types by exposing them to different stimuli. We hypothesize that pro-osteogenic signals derived from e.g., macrophages steers multipotent mesenchymal stromal cells involved in the wound healing towards osteogenesis. METHODS: In a retrospective case study we analyzed ossified tissue, patient demographics, medical history, number of laparotomies, scar location, indication for surgery and time in which HO occurred. RESULTS: Ten (8 male, 2 female) patients had proven HO. The mean age was 62 (46-80) years. The mean time for HO to occur was 99 (24-382) days after the previous laparotomy. The mean number of relaparotomies was 3 (1-9). CONCLUSION: We conclude that ossification of abdominal scar tissue is a rare but innocent finding and provides interesting leads to other fields of research.

Gender differences in mathematics performance: a meta-analysis.

Reviewers have consistently concluded that males perform better on mathematics tests than females do. To make a refined assessment of the magnitude of gender differences in mathematics performance, we performed a meta-analysis of 100 studies. They yielded 254 independent effect sizes, representing the testing of 3,175,188 Ss. Averaged over all effect sizes based on samples of the general population, d was -0.05, indicating that females outperformed males by only a negligible amount. For computation, d was -0.14 (the negative value indicating superior performance by females). For understanding of mathematical concepts, d was -0.03; for complex problem solving, d was 0.08. An examination of age trends indicated that girls showed a slight superiority in computation in elementary school and middle school. There were no gender differences in problem solving in elementary or middle school; differences favoring men emerged in high school (d = 0.29) and in college (d = 0.32). Gender differences were smallest and actually favored females in samples of the general population, grew larger with increasingly selective samples, and were largest for highly selected samples and samples of highly precocious persons. The magnitude of the gender difference has declined over the years; for studies published in 1973 or earlier d was 0.31, whereas it was 0.14 for studies published in 1974 or later. We conclude that gender differences in mathematics performance are small. Nonetheless, the lower performance of women in problem solving that is evident in high school requires attention.