Objectives: To assess whether there are differences in the effects of time to treatment interval (TTI) on patient survival for head and neck cancer (HNC) sites in order to provide evidence that can support decision-making regarding prioritizing treatment. Materials and methods: Patients in the Netherlands with a first primary HNC without distant metastasis between 2010 and 2014 were included for analysis (N =10,486). TTI was defined as the time from pathologic diagnosis to the start of initial treatment. Overall survival (OS), cox regression analyses and cubic spline hazard models were calculated and visualized. Results: Overall, the hazard of dying was higher (HR = 1.003; 95 % CI 1.001-1.005) with each additional day until treatment initiation. The pattern, as visualized in cubic spline graphs, differed by site the hazard increased more steeply with increasing TTI for oral cavity cancer. For oropharyngeal and laryngeal cancer, a slight increase commenced after a longer TTI than for oral cavity cancer, while there was hardly an increase in hazard with increasing TTI for hypopharyngeal cancer. Conclusion: The relationship between longer TTI and decreased survival was confirmed, but slight variations in the pattern of the hazard of dying by TTI by tumour site were observed. These findings could support decisions on prioritizing treatment. However, other aspects such as extent of treatment and quality of life should be investigated further so this can also be included.

Purpose Diagnostic endoscopy with biopsy under general anesthesia (DE-GA) is still considered as the established standard to assess laryngopharyngeal cancer patients. Office-based flexible laryngoscopic biopsy (FLB) offers an alternative, but the effect on oncological outcome remains uncertain. Therefore, the diagnostic process and survival of patients undergoing FLB, compared to those undergoing DE-GA were evaluated. Methods Patients suspected of laryngopharyngeal cancer who underwent FLB were evaluated. Patients with FLB-confirmed squamous cell carcinoma (SCC) were matched with DE-GA patients based on tumor site, T-classification, N-classification, age, and p16 overexpression. Time from first visit to diagnosis (FVD), time to treatment interval (TTI), disease-specific survival (DSS) and overall survival (OS) were analyzed. Results FLB yielded a definitive diagnosis in 155/164 (95 %) patients. No complications were observed. Ninety-eight of the 124 patients in which FLB revealed a SCC received curative treatment and were compared with 98 matched patients who underwent DE-GA. Median FVD interval was 6 days after FLB and 15 days after DE-GA (p < 0.001). Median TTI interval (FLB: 28 days, DE-GA: 28 days) was equal (p = 0.91). Oncological outcomes were comparable (p > 0.05) between FLB (OS: 2-yr: 76 %, 5-yr: 42 %; DSS: 2-yr: 86 %, 5-yr: 85 %) and DE-GA groups (OS: 2-yr: 76 %, 5-yr: 50 %; DSS: 2-yr: 81 %, 5-yr: 79 %). Conclusion FLB in the outpatient setting demonstrates a high diagnostic accuracy, is safe, accelerates the diagnostic process and has no negative effects on clinical outcome compared to DE-GA. Therefore, FLB should be considered as the standard diagnostic procedure in patients suspected of laryngopharyngeal cancer.

Background and purpose: As a result of rapid tumor growth in head and neck squamous cell carcinoma (HNSCC), delay in treatment initiation can result in tumor progression and inferior outcome. Especially older and frail patients are prone to develop adverse events. The aim of this study was to assess the effect of delay on development of adverse events and recurrence in older HNSCC patients. Materials and methods: This cohort study with prospectively collected data included all newly diagnosed, curatively treated HNSCC patients (>60 years) between 2015 and 2017. Time-to-treatment interval and geriatric domains were assessed. Adverse events were defined as postoperative complications (ClavienDindo classification) and acute radiation-induced toxicity (Common Terminology Criteria of Adverse Events). Multivariable regression models were performed, using adverse events and recurrence as outcome variables. Results: A total of 245 patients were included. Median time-to-treatment was 26 days for surgery patients and 40 days for radiotherapy patients (p < 0.001). Delayed treatment initiation was not associated with postoperative complications or acute radiation-induced toxicity. Delay was significantly associated with recurrence risk within two years after treatment initiation in a model adjusted for stage and tumor location in patients treated with initial surgery (HR:4.1, 95%CI:1.2- 14.0, p = 0.024). For patients treated with radiotherapy, delay was not significantly associated with recurrence risk. Conclusion: Delayed treatment initiation was independently associated with increased recurrence risk in patients treated with initial surgery. Delay was not associated with short-term adverse events. These findings highlight the importance of establishing fast-track care pathways to minimize delays and improve especially long-term outcome. (c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 173 (2022) 154-162 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

OBJECTIVE:To assess the impact of delay in treatment initiation on hospitalization, overall survival, and recurrence in older patients with head and neck cancer (HNC). STUDY DESIGN:Retrospective multicenter study. SETTING:Two tertiary referral centers. METHODS:All patients with newly diagnosed HNC (≥60 years) treated between 2015 and 2017 were retrospectively included. Time-to-treatment intervals were assessed (ie, calendar days between first visit and start of treatment). Multiple multivariable models were performed with hospital admission days (>14 days), survival, and recurrence as dependent outcome variables. RESULTS:In total, 525 patients were enrolled. The mean age was 70.7 years and 70.7% were male. Median time to treatment was 34.0 days, and 36.3% started treatment within 30 days (P = .576 between centers). Patients with radiotherapy had longer time to treatment than surgical patients (39.0 vs 29.0 days, P < .001). Current smoking status, stage IV tumors, and definitive radiotherapy were significantly associated with delay in the multivariable analysis. Time-to-treatment interval ≥30 days was a significant predictor of longer hospital admission (>14 days) in the first year after treatment in an adjusted model (odds ratio, 4.66 [95% CI, 2.59-8.37]; P < .001). Delay in treatment initiation was not associated with overall survival or tumor recurrence. CONCLUSION:This study highlights the importance and challenges of ensuring timely treatment initiation in older patients with HNC, as treatment delay was an independent predictor of hospitalization. During oncologic workup, taking time to consider patient-centered outcomes (including minimizing time spent in hospital) while ensuring timely start of treatment requires well-structured, fast-track care pathways.

Abstract Objective Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health‐related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival. Methods Patients with mucosal HNSCC were prospectively included. HRQOL and 2‐year overall survival were analysed using linear mixed‐model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation. Results Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL‐scores (indicating better HRQOL) during 2‐year follow‐up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score—β: 2.62, 95% CI: 0.57–4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65–15.76, p = 0.005) and stage‐IV tumours (HR: 12.37, 95% CI: 2.81–54.39, p = 0.001). Delay was not associated with worse overall survival. Conclusion Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL‐scores or decreased overall survival during 2‐year follow‐up.

We appreciate the ideas shared with us by Dr. Rujittika Mungmunpuntipantip from Thailand and Prof. Dr. Viroj Wiwanitkit from India [[1]Mungmunpuntipantip R. Wiwanitkit V. Head and neck cancer diagnoses and faster treatment initiation during COVID-19: correspondence.Radiother Oncol. 2022; Google Scholar]. By using the word 'incidence', we may have given the impression that we think of a decline in incidence in the sense that less head and neck cancers have developed during the first COVID-19 wave rather than a decrease in the number of diagnosed cases. Although from a societal point of view the 'incidence' does appear lower in terms of less diagnoses and/or necessary treatments in hospitals, we do not think that less persons were affected by head and neck cancer. We agree that the decline in the number of diagnoses during the first wave is likely related to reluctance of patients to visit their general practitioner with tumour-related symptoms and the limited access of care. However, if this could solely be explained by reluctance and limited access, an increase in head and neck cancer diagnoses after the first wave would be expected, a phenomenon we did not observe during the subsequent second half of 2020 as can be observed in Figure 1A of our original article [[2]Schoonbeek R.C. de Jel D.V.C. van Dijk B.A.C. Willems S.M. Bloemena E. Hoebers F.J.P. et al.Fewer head and neck cancer diagnoses and faster treatment initiation during COVID-19 in 2020: a nationwide population-based analysis.Radiother Oncol. 2022; 167: 42-48https://doi.org/10.1016/j.radonc.2021.12.005Google Scholar]. We think this might partly be explained by excess deaths due to other causes [[2]Schoonbeek R.C. de Jel D.V.C. van Dijk B.A.C. Willems S.M. Bloemena E. Hoebers F.J.P. et al.Fewer head and neck cancer diagnoses and faster treatment initiation during COVID-19 in 2020: a nationwide population-based analysis.Radiother Oncol. 2022; 167: 42-48https://doi.org/10.1016/j.radonc.2021.12.005Google Scholar]. To support our finding that the number of diagnosed cases was significantly lower than expected, we compared the crude rate (number of cases per 1,000,000 population) in the year 2020 with the crude rates for 2018 and 2019 using the incidence rate ratio. The corresponding p-values can be found in the Supplementary Table 1 of our original article [[2]Schoonbeek R.C. de Jel D.V.C. van Dijk B.A.C. Willems S.M. Bloemena E. Hoebers F.J.P. et al.Fewer head and neck cancer diagnoses and faster treatment initiation during COVID-19 in 2020: a nationwide population-based analysis.Radiother Oncol. 2022; 167: 42-48https://doi.org/10.1016/j.radonc.2021.12.005Google Scholar]. Part of this table is reproduced in Table 1.Table 1Part of Table 1 of the Supplementary information [2]Schoonbeek R.C. de Jel D.V.C. van Dijk B.A.C. Willems S.M. Bloemena E. Hoebers F.J.P. et al.Fewer head and neck cancer diagnoses and faster treatment initiation during COVID-19 in 2020: a nationwide population-based analysis.Radiother Oncol. 2022; 167: 42-48https://doi.org/10.1016/j.radonc.2021.12.005Google Scholar – Detailed information on the overall incidence and p-values for the incidence rate ratios.Overall incidence (crude rate)per 1,000,000 inhabitantsOverall incidence (absolute numbers (n))2020 (COVID)20192018p-value 2018 vs. 2020p-value 2019 vs. 20202020 (COVID)20192018January14.6514.0615.070.7450.648255243259February12.4613.4812.570.9290.407217233216March11.4812.2012.850.2460.539200211221April9.1312.7111.750.0170.001159220202May11.9415.4215.410.0060.006208267265June14.7513.4515.280.6870.308257233263July15.7814.8315.220.6760.475275257262August12.8513.9013.180.7860.397224241227September14.2212.7913.570.6130.252248222234October13.8013.6316.110.0790.895241237278November11.7912.2415.98<0.0010.701206213276December14.1313.3312.670.2400.521247232219 Open table in a new tab The recently published paper by Stevens et al., mentioned by Mungmunpuntipantip and Wiwanitkit, showed a decline in primary head and neck malignancies, but not in the number of patients presenting with a mucosal squamous cell carcinoma during the first half of 2020 compared to corresponding period in 2019 [[3]Stevens M.N. Patro A. Rahman B. Gao Y. Liu D. Cmelak A. et al.Impact of COVID-19 on presentation, staging, and treatment of head and neck mucosal squamous cell carcinoma.Am J Otolaryngol - Head Neck Med Surg. 2022; 43Google Scholar]. This stability in mucosal squamous cell carcinomas could be due to the fact that Stevens et al included data of a single tertiary centre. This centre was never closed during the pandemic while many outside clinics temporarily closed during the first months of this period. This may have resulted in a higher number of patients with suspected head and neck malignancies directly seeking help in the tertiary centre. Furthermore, it was suggested that there were more possibilities for patients to be seen faster [[3]Stevens M.N. Patro A. Rahman B. Gao Y. Liu D. Cmelak A. et al.Impact of COVID-19 on presentation, staging, and treatment of head and neck mucosal squamous cell carcinoma.Am J Otolaryngol - Head Neck Med Surg. 2022; 43Google Scholar]. The patients diagnosed in this tertiary centre in 2020 may therefore have been patients that would have been diagnosed elsewhere or later in time. Information on the origin of patients and on future periods, as suggested by the authors, may indeed be very helpful. Our findings are based on the entire population of the Netherlands: a clearly defined area without expected changes in the proportion of inhabitants diagnosed with head and neck cancer in another country. None. Head and neck cancer diagnoses and faster treatment initiation during COVID-19: CorrespondenceRadiotherapy and OncologyVol. 169PreviewWe would like to share ideas on the publication "Fewer head and neck cancer (HNC) diagnoses and faster treatment initiation during COVID-19 in 2020: a nationwide population-based analysis [1]." Schoonbeek et al. noted that "the incidence of HNC during the Netherlands' first COVID-19 wave was significantly lower than … healthcare system, the standard treatment for HNC patients could be delivered within a shorter time interval [1]." We concur that there might be a change due to COVID-19. The change of incidence might be due to difficulty of healthcare facilities assessment during COVID-19 lockdown. Full-Text PDF

Background: Inevitably, the emergence of COVID-19 has impacted non-COVID care. Because timely diagnosis and treatment are essential, especially for patients with head and neck cancer (HNC) with fast-growing tumours in a functionally and aesthetically important area, we wished to quantify the impact of the COVID-19 pandemic on HNC care in the Netherlands. Material and Methods: This population-based study covered all, in total 8468, newly diagnosed primary HNC cases in the Netherlands in 2018, 2019 and 2020. We compared incidence, patient and tumour characteristics, primary treatment characteristics, and time-to-treatment in the first COVID-19 year 2020 with corresponding periods in 2018 and 2019 (i.e. pre-COVID). Results: The incidence of HNC was nearly 25% less during the first wave (n = 433) than in 2019 (n = 595) and 2018 (n = 598). In April and May 2020, the incidence of oral cavity and laryngeal carcinomas was significantly lower than in pre-COVID years. There were no shifts in tumour stage or alterations in initial treatment modalities. Regardless of the first treatment modality and specific period, the median number of days between first visit to a HNC centre and start of treatment was significantly shorter during the COVID-19 year (26-28 days) than pre-COVID (31-32 days, p < 0.001). Conclusion: The incidence of HNC during the Netherlands' first COVID-19 wave was significantly lower than expected. The expected increase in incidence during the remainder of 2020 was not observed. Despite the overloaded healthcare system, the standard treatment for HNC patients could be delivered within a shorter time interval. (C) 2021 The Author(s). Published by Elsevier B.V.

OBJECTIVE:Head and neck squamous cell carcinomas (HNSCC) are relatively fast-growing tumours, and delay of treatment is associated with tumour progression and adverse outcomes. The aim of this study is to identify determinants of delay in a head and neck oncology centre.METHODS:This cohort study with prospectively collected data investigated associations between patient (including geriatric assessment at first consultation), tumour and treatment characteristics and treatment delay. Two quality indicator intervals assessing value-based healthcare were studied: care pathway interval (CPI, interval between first visit in an HNOC and treatment initiation) and time-to-treatment initiation (TTI, interval between histopathological confirmation of HNSCC and treatment initiation), using regression analyses.RESULTS:Stage-IV tumours and initial radiotherapy were independent predictors of delay in CPI. Initial radiotherapy was associated with delay in TTI. Overall, 37% of the patients started treatment within 30 days after first consultation (67% in case of initial surgical treatment and 11.5% if treated with (chemo)radiation, p < 0.001). Geriatric assessment outcomes were not associated with delay. Indicators for delay in initial surgery patients were stage-IV tumours (CPI).CONCLUSION:The majority of HNSCC patients encounter delay in treatment initiation, specifically in patients with advanced-stage tumours or when radiotherapy is indicated.

Objectives: As a result of the increasing number of diagnostic scans, incidental findings (IFs) are more frequently encountered during oncological work-up in patients with head and neck squamous cell carcinomas (HNSCC). IFs are unintentional discoveries found on diagnostic imaging. Relevant IFs implicate clinical consequences, resulting in delay in oncologic treatment initiation, which is associated with unfavorable outcomes. This study is the first to investigate the incidence and nature of IFs over the years and establish the effect of relevant IFs on delay. Material and methods: This retrospective study compared two time periods (2010-2011 and 2016-2017), described associations between relevant IFs and delay in carepathway interval (days between first visit and treatment initiation) and assessed the effect of relevant IFs on overall two-year survival. Results: In total, 592 patients were included. At least one IF was found in 61.5% of the patients, most frequently on chest-CT. In 128 patients (21.6%) a relevant IF was identified, resulting for the majority in radiologist recommendations (e.g. additional scanning). Presence of a relevant IF was an independent significant factor associated with delay in treatment initiation. The risk of dying was higher for patients with a relevant IF, although not significant in the multivariable model (HR: 1.46, p = 0.079). Conclusion: In diagnostic work-up for HNSCC patients, relevant IFs are frequently encountered. As the frequency of additional imaging rises over the years, the number of IFs increased simultaneously. These relevant IFs yield clinical implications and this study described that relevant IFs result in significant delay in treatment initiation.

Head and neck cancers (HNC) are relatively fast-growing tumours, and delay in treatment initiation is associated with tumour progression and adverse outcome. An overview of factors contributing to delay can provide critical insights on necessary adjustments to optimize care pathways. This systematic review aims to identify factors associated with delay and summarize the effect of delay on oncological outcome measures.A search strategy was conducted according to PRISMA guidelines to search electronic databases for studies assessing the carepathway interval (days between first visit in head and neck oncology center and treatment initiation) and/or time-to-treatment-initiation interval (days between histological diagnosis and treatment initiation) and 1) determinants of delay and/or 2) effect of delay on outcome within these timeframes. Due to heterogeneity between included studies, a meta-analysis was not possible.Fifty-two studies were eligible for quantitative analysis. Non-Caucasian race, academic setting, Medicaid/no insurance and radiotherapy as primary treatment were associated with delay. Advanced tumour stage was related to increased time-to-treatment initiation in the four common sites combined (oral cavity, oropharynx, hypopharynx, larynx). Separate determinants for delay in different tumour locations were identified. In laryngeal, oral cavity cancer and the four common HNC sites combined, delay in start of treatment is associated with decreased overall survival, although no cut-off time point could be determined.Race, facility type, type of insurance and radiotherapy as primary treatment were associated with delay and subsequent inferior survival in the four common sites combined.

Introduction: Head and neck cancers (HNC) are relatively fast-growing tumours, and delay in treatment initiation is associated with tumour progression and adverse outcome. An overview of factors contributing to delay can provide critical insights on necessary adjustments to optimize care pathways. This systematic review aims to identify factors associated with delay and summarize the effect of delay on oncological outcome measures. Methods: A search strategy was conducted according to PRISMA guidelines to search electronic data-bases for studies assessing the carepathway interval (days between first visit in head and neck oncology center and treatment initiation) and/or time-to-treatment-initiation interval (days between histological diagnosis and treatment initiation) and 1) determinants of delay and/or 2) effect of delay on outcome within these timeframes. Due to heterogeneity between included studies, a meta-analysis was not possible. Results: Fifty-two studies were eligible for quantitative analysis. Non-Caucasian race, academic setting, Medicaid/no insurance and radiotherapy as primary treatment were associated with delay. Advanced tumour stage was related to increased time-to-treatment initiation in the four common sites combined (oral cavity, oropharynx, hypopharynx, larynx). Separate determinants for delay in different tumour locations were identified. In laryngeal, oral cavity cancer and the four common HNC sites combined, delay in start of treatment is associated with decreased overall survival, although no cut-off time point could be determined. Conclusion: Race, facility type, type of insurance and radiotherapy as primary treatment were associated with delay and subsequent inferior survival in the four common sites combined. (C) 2021 The Authors. Published by Elsevier Ltd.

CASE PRESENTATION: A 37-year-old woman presented with a 2-month history of recurrent hemoptysis and coughing. Her symptoms started 2 months after the delivery of her third child. In total, she endured four episodes of hemoptysis. All pregnancies were induced by intracytoplasmic sperm injections. She lacked a pulmonary or smoking history and had no history of foreign body aspiration or intubation. There was no dyspnea, dysphagia, fever, or chest pain, and the patient did not complain of purulent sputum. She currently did not use medication and was generally in good health.

N-terminal B‑type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a prosthetic valve and investigate its relationship with cardiac function and exercise capacity.

Background— Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency. Methods and Results— Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%; P =0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3–93.1 mL/m 2 ; P =0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m 2 at 8 months, P =0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation. Conclusions— hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies.