Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC

The Rhinoplasty Health Care Monitor: Using Validated Questionnaires and a Web-Based Outcome Dashboard to Evaluate Personal Surgical Performance

Background: Self-assessment provides valuable feedback in the life-long process of mastering rhinoplasty. This study presents a method to measure and evaluate data-based performance of a single surgeon using a web-based dashboard. Methods: In this prospective analytic cohort study, all patients referred to the senior author for functional-aesthetic (revision) rhinoplasty between April 2014 and September 2020 are included. Patients completed the Nasal Obstruction Symptom Evaluation (NOSE) scale, Utrecht Questionnaire (UQ), and visual analog scales before and after rhinoplasty. Questionnaire scores were exported to a customized web-based dashboard: the rhinoplasty health care monitor. Supported by real-time graphic output, this monitor automatically analyzes functional and aesthetic outcomes. Results: of 603 referred patients, 363 were eligible for rhinoplasty. Mean NOSE scale scores decreased from 66.6 ± 23.5 to 23.2 ± 24.0 (p < 0.001), and mean UQ scores decreased from 12.2 ± 6.3 to 7.1 ± 3.9 (p < 0.001) 1 year after surgery. The rhinoplasty health care monitor visualizes numerous outcome parameters that help the surgeon to analyze results, identify learning needs, and detect trends in performance development. Conclusions: This automated outcome dashboard transparently measures individual surgeon performance. Gauging performance provides means to enhance surgical development and, consequently, patient satisfaction

Benefits of a short, practical questionnaire to measure subjective perception of nasal appearance after aesthetic rhinoplasty

Background: The authors tested a short, practically designed questionnaire to assess changes in subjective perception of nasal appearance in patients before and after aesthetic rhinoplasty. Methods: A prospective cohort study was conducted in a group of 121 patients who desired aesthetic rhinoplasty and were operated on by one surgeon. The questionnaire contained five questions (E1-E5) based on a five-point Likert scale and a visual analogue scale (range, 0 to 10). Two questions were designed as trick questions to help the surgeon screen for signs of body dysmorphic disorder. Results: All patients rated the appearance of their nose as improved after surgery. The visual analogue scale revealed a Gaussian curve of normal distribution (range, 0.5 to 10) around a significant improvement (mean, 4.36 points, p = 0.018). Also, question E1, question E2, and the sum of questions E1 through E5 showed a statistically significant improvement after surgery (p = 1.74 x 10(-36), p = 4.29 x 10(-33), and p = 9.23 x 10(-31), respectively). The authors found a linear relationship between preoperative score on the trick questions and postoperative increase in visual analogue scale score. Test-retest reliability could be investigated in 74 of 121 patients (61 percent) and showed a positive correlation between postoperative (1 year after surgery) and repostoperative response (2 to 4 years after surgery). Conclusions: The authors concluded that a surgeon performing aesthetic rhinoplasty can benefit from using this questionnaire. It is simple, takes no more than 2 minutes to complete, and provides helpful subjective information regarding patients' preoperative nasal appearance and postoperative surgical outcome

The Portuguese version of “The Utrecht questionnaire for outcome assessment in aesthetic rhinoplasty”: validation and clinical application

Introduction: The evaluation of surgical outcomes measured by patient satisfaction or quality of life is very important, especially in plastic surgery. There is increasing interest in self-reporting outcomes evaluation in plastic surgery. Objective: The aim of this study was to perform the translation, cross-cultural adaptation and validation of “The Utrecht questionnaire for outcome assessment in aesthetic rhinoplasty” from English to Portuguese. Methods: Retrospective study involving 50 patients undergoing to rhinoplasty comparing the preoperative period with the current postoperative situation (minimum 6 months and maximum 24 months postoperatively). Statistical analysis was performed to assess internal consistency, test–retest reliability, validity and responsiveness. Results: No patients received a negative score on the visual analogue scale comparing preoperative and postoperative appearance. The postoperative improvement on the visual analogue scale revealed a Gaussian curve of normal distribution with a mean improvement of 4.44 points. The test–retest reliability showed a positive correlation between the postoperative response and the same questionnaire repeated ninety-six hours later. The internal consistency was high (Cronbach's alpha value: Preoperative = 0.88; Postoperative = 0.86). The authors observed a significant improvement in response for all individual questions in the postoperative phase as compared with preoperative situation (t-student test – p < 0.05). Conclusion: The Portuguese version of “The Utrecht questionnaire for outcome assessment in aesthetic rhinoplasty” is a valid instrument to assess patients’ outcomes following rhinoplasty surgery. Resumo: Introdução: A avaliação do resultado cirúrgico medido pela satisfação do paciente ou qualidade de vida é muito importante, especialmente na cirurgia plástica, uma especialidade na qual há um crescente interesse na avaliação de resultados por auto-relato. Objetivo: O objetivo deste estudo foi realizar a tradução, a adaptação transcultural e a validação do questionário “The Utrecht questionnaire for outcome assessment in aesthetic rhinoplasty”, do inglês para português. Método: Estudo retrospectivo envolvendo 50 pacientes submetidos a rinoplastia comparando o período pré-operatório com a situação atual (mínimo de 6 meses e máximo de 24 meses de pós-operatório). A análise estatística foi realizada para avaliar a consistência interna, confiabilidade teste-reteste, validade e capacidade de resposta. Resultados: Nenhum paciente recebeu pontuação negativa na escala visual analógica ao comparar a aparência pré- e pós-operatória. A melhora pós-operatória na escala visual analógica revelou uma curva gaussiana de distribuição normal, com melhora média de 4,44 pontos. A confiabilidade teste-reteste mostrou uma correlação positiva entre a resposta pós-operatória e o mesmo questionário repetido noventa e seis horas depois. A consistência interna foi alta (valor do alfa de Cronbach: pré-operatório = 0,88; pós-operatório = 0,86). Os autores observaram uma melhora significante nas respostas para todas as questões individuais na fase pós-operatória em comparação com a situação pré-operatória (teste t de Student – p < 0,05). Conclusão: A versão em português do “The Utrecht questionnaire for outcome assessment in aesthetic rhinoplasty é um instrumento válido para avaliar os resultados do paciente após a cirurgia de rinoplastia. Keywords: Surveys and questionnaires, Rhinoplasty, Quality of life, Plastic surgery, Patient satisfaction, Palavras-chave: Pesquisas e questionários, Rinoplastia, Qualidade de vida, Cirurgia plástica, Satisfação do pacient

The value of averageness in aesthetic rhinoplasty : humans like average noses

Background The aesthetic ideal of the nose eludes clear definition. Averageness may be an important determinant of ideal nasal shape: research has shown that averageness plays an important role in the human perception of facial attractiveness. Objectives To test whether an averaged nasal shape is attractive, and whether deviation away from average is associated with decreased attractiveness. Methods Photographical series of the face were obtained from 80 Caucasian female volunteers aged 25-40 years. A mathematically averaged composite image was created using the first 40 volunteers. Forty-one panel members were recruited to judge the attractiveness of the nose of each original image and the composite, using a 5-point Likert scale ranging from 1 (very ugly) to 5 (very pretty). Deviation of nasal shape from average was calculated using a principal components analysis of standardized nasal landmarks. Results Twenty-one respondents were male (51%). Mean (SD) age of the respondents was 35.3 years (±15.6). The rating of the composite was significantly higher than the distribution of ratings for the 80 original nose images (4.2 vs 2.8, t=31.24, P<.001). The rating of the original nose images correlated negatively with deviation from average shape (r = -.40, n = 80, P<.001). Conclusions In Caucasian females, a mathematically averaged nose is an attractive nose. Furthermore, the more an individual nose shape resembles average shape, the more attractive it is rated. Calculating deviation from average before and after rhinoplasty may aid in objectively measuring aesthetic rhinoplasty outcome.PostprintPeer reviewe

Clinical Benefits of the Utrecht Questionnaire for Aesthetic Outcome Assessment in Rhinoplasty: an update

Presently, there is no consensus on which patient reported outcome measurement (PROM) instrument is best suited to assess the aesthetic outcomes of rhinoplasty. In this regard, at least seven different validated PROMs are available from the literature, each one with advantages and disadvantages. In this article, we review the development, validation, international translation, and clinical application of the Utrecht Questionnaire (UQ). The UQ was developed in 2009 with the idea to be a short and practical tool for the rhinoplasty surgeon to assess the aesthetic outcomes of rhinoplasty. The questionnaire was then validated in 2013. Body image in relation to nasal appearance is quantified with five simple questions on a 5-point Likert scale and a Visual Analogue Scale score. We discuss how the UQ can easily be incorporated and become an important asset in a rhinoplasty practice. Practical benefits, such as its role in the shared-decision making process, patient expectations management, identification of unsuitable patients, avoiding revision surgery, and the evaluation of the surgeon's personal performance curve are exemplified. Currently, the UQ has been translated and validated in four languages, providing scientific opportunities to generate and compare international data for advances in rhinoplasty. We describe some of the significant scientific contributions of leaders in the field of rhinoplasty that used the UQ