Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Tumor-Stroma Ratio and Programmed Cell Death Ligand 1 Expression in Preoperative Biopsy and Matched Laryngeal Carcinoma Surgical Specimen

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical-pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical-pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS = 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols

Effectiveness of Dupilumab in the Treatment of Patients with Uncontrolled Severe CRSwNP: A “Real-Life” Observational Study in Naïve and Post-Surgical Patients

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents 25–30% of all CRS cases, and in the most severe forms it is associated with a poor quality of life and a high rate of nasal polyps’ recurrence after surgery. Dupilumab has been suggested as a treatment option for severe CRSwNP. Methods: Patients with severe CRSwNP receiving dupilumab from January 2021 were followed up at 1, 3, 6, 9 and 12 months from the first administration and were considered for this study. At baseline and at each follow-up, patients underwent nasal endoscopy and completed the Sinonasal Outcome Test (SNOT)-22, a Visual Analogue Scale (VAS) for smell/nasal obstruction, the Nasal Congestion Score and the Asthma Control Test. Peak nasal inspiratory flow (PNIF), a smell test, nasal cytology and blood eosinophilia were also evaluated. Results: Forty-seven patients were included in the study. Of these, 33 patients had a history of previous surgery (ESS) and had recurrent nasal polyps, while 14 patients were naïve to nasal surgery. Both subjective and objective parameters improved after biological treatment and were correlated with each other (p < 0.05), except for the SNOT-22 and the nasal polyp’s score. No correlations were found between nasal and blood eosinophilia. No differences were observed when comparing the post-surgical and the naïve groups. Conclusions: Dupilumab improves nasal obstruction and the sense of smell and reduces the level of local inflammation in severe CRSwNP patients in a similar way in both naïve and post-surgical patients

Tumor-stroma ratio, neoangiogenesis and prognosis in laryngeal carcinoma. A pilot study on preoperative biopsies and matched surgical specimens.

Objectives The interaction between tumor cells and stroma is critical in tumorigenesis, tumor neo angiogenesis and cancer progression. The aims of this study were to: (i) evaluate the concordance between tumor-stroma ratio (TSR) and microvascular density (MVD) on paired biopsy and surgical specimens of laryngeal carcinoma (LSCC); (ii) investigate the association of TSR with angiogenesis (CD105- and CD31-assessed MVD); (iii) assess the prognostic role of TSR and MVD evaluated on preoperative biopsies and paired surgical specimens. Methods TSR, CD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 43 consecutive cases. Results TSR showed good agreement between biopsies and surgical specimens (AC1 statistic: 0.7957). In biopsies, TSR low/stroma-rich cases showed higher CD105-assessed MVD (p=0.0380). In surgical specimens both median CD105- and CD31-assessed MVD were significantly higher in TSR low/stroma-rich than in TSR high/stroma-poor patients (p=0.0089 and p=0.0391). In the univariate Cox’s model, TSR predicted disease-free survival (DFS) in both biopsies and surgical specimens (p=0.0003 and p=0.0002). DFS was associated with CD105- and CD31-assessed MVD in biopsies (p<0.0001 for both) and surgical specimens (p<0.0001 for both). Considering biopsies, the multivariate analysis found both TSR (p=0.0032; HR=6.112, 95%CI: 1.833-20.378) and CD105-assessed MVD (p=0.0002; HR=1.201, 95%CI: 1.090-1.322) as DFS predictor. In paired surgical specimens, both TSR (p=0.0074; HR=6.137, 95%CI: 1.626-23.172) and CD105-assessed MVD (p=0.0005; HR=1.172 95%CI 1.071-1.282) retained their significance in multivariate analysis. Conclusions If confirmed by large prospective studies, TSR and MVD could be proposed as prognostic biomarkers of LSCC for a possible treatment intensification or targeted therapy

Artificial intelligence for automatic detection and segmentation of nasal polyposis: a pilot study

PurposeAccurate diagnosis and quantification of polyps and symptoms are pivotal for planning the therapeutic strategy of Chronic rhinosinusitis with nasal polyposis (CRSwNP). This pilot study aimed to develop an artificial intelligence (AI)-based image analysis system capable of segmenting nasal polyps from nasal endoscopy videos.MethodsRecorded nasal videoendoscopies from 52 patients diagnosed with CRSwNP between 2019 and 2022 were retrospectively analyzed. Images extracted were manually segmented on the web application Roboflow. A dataset of 342 images was generated and divided into training (80%), validation (10%), and testing (10%) sets. The Ultralytics YOLOv8.0.28 model was employed for automated segmentation.ResultsThe YOLOv8s-seg model consisted of 195 layers and required 42.4 GFLOPs for operation. When tested against the validation set, the algorithm achieved a precision of 0.91, recall of 0.839, and mean average precision at 50% IoU (mAP50) of 0.949. For the segmentation task, similar metrics were observed, including a mAP ranging from 0.675 to 0.679 for IoUs between 50% and 95%.ConclusionsThe study shows that a carefully trained AI algorithm can effectively identify and delineate nasal polyps in patients with CRSwNP. Despite certain limitations like the focus on CRSwNP-specific samples, the algorithm presents a promising complementary tool to existing diagnostic methods

Measuring Nasal Patency and the Sense of Smell in CRSwNP Patients Treated with Dupilumab

: Chronic rhinosinusitis with nasal polyps (CRSwNP) in the most severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with dupilumab in different rhinological units were followed up at 1, 3, 6 and 12 months from the first administration and were considered for this study. At baseline (T0) and at each follow-up, patients underwent nasal endoscopy and completed the sinonasal outcome test (SNOT)-22, a visual analogue scale (VAS) for smell/nasal obstruction, peak nasal inspiratory flow (PNIF) and the Sniffin' Sticks identification test (SSIT). The aim of the present study was to evaluate the effects of dupilumab in patients with severe uncontrolled CRSwNP on recovering nasal obstruction and smell impairment. Moreover, the method between PNIF and SSIT with the highest correlation with patients' response to dupilumab was evaluated. One hundred forty-seven patients were included. All parameters improved during treatment (p < 0.001). At T0, no correlations were found between PNIF and nasal symptoms. Nevertheless, during the following evaluations significant correlations between PNIF changes and both nasal symptoms and NPS were observed (p < 0.05). At T0, SSIT did not correlate with SNOT-22. Similarly to PNIF, during the follow-up SSIT changes significantly correlated with nasal symptom and NPS (p < 0.05). Comparing PNIF and SSIT correlations with SNOT-22 and NPS, PNIF showed a higher correlation with both. Dupilumab improves nasal obstruction and the sense of smell. PNIF and SSIT are effective tools in monitoring patients' response to dupilumab