Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study.

BACKGROUND: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19-positive patients and infections in the surgical team were determined by univariate analysis. RESULTS: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. CONCLUSIONS: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. LAY SUMMARY: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment.

Risk Factors for Sleep Disturbances in Patients Scheduled for Radiotherapy of Head-and-Neck Cancer.

BACKGROUND/AIM: Many patients with head-and-neck cancer are scheduled for irradiation. This study was performed to determine the frequency of and risk factors for pre-radiotherapy sleep disturbances in these patients. PATIENTS AND METHODS: A total of 103 patients with head-and-neck cancer scheduled for radiotherapy were included in this retrospective study. Eighteen characteristics were evaluated including timing of start of radiotherapy relative to COVID-19 pandemic; age; gender; Karnofsky performance score; Charlson comorbidity index; history of another malignancy; family history of malignancy; distress score; number of emotional, physical or practical problems; request for psychological support; tumor site and stage; upfront surgery; planned chemotherapy; and brachytherapy boost. RESULTS: The frequency of pre-radiotherapy sleep disturbances was 42.7%. This was significantly associated with age ≤63 years (p=0.049), Karnofsky performance score ≤80 (p=0.002), Charlson comorbidity index ≥3 (p=0.005), history of another malignancy (p=0.012), emotional (p=0.001) or physical (p<0.001) problems, and request for psychological support (p=0.002). CONCLUSION: Sleep disturbances were frequent in patients assigned to radiotherapy of head-and-neck cancer. Recognizing risk factors for sleep disturbance helps identify patients requiring psychological support.

Feasibility study of the Vitom 3D exoscope in ENT surgery using an animal model: relevance to coronavirus disease 2019.

OBJECTIVE: The application of a 4K display resolution three-dimensional exoscope system (Vitom 3D) was evaluated to determine the feasibility of adopting the system in ENT surgery in the coronavirus disease 2019 era and beyond. METHODS: Eighteen ENT surgeons performed structured otological tasks on fresh-frozen sheep heads using the Vitom 3D. Structured feedback of the participants' experience was analysed. RESULTS: Seventy-four per cent and 94 per cent of participants reported that the Vitom 3D was ergonomic and comfortable to use respectively. Whilst colour fidelity and image quality were very good, 50 per cent of participants reported image distortion and pixilation at the highest magnification. All participants agreed that there was an increased educational value to exoscope technology. Half the participants preferred the microscope over the Vitom 3D for fine otological work, which may reflect the learning curve. CONCLUSION: The Vitom 3D exoscope is a promising and viable alternative for performing otological surgery when using full personal protective equipment in the coronavirus disease 2019 era.

Novel fusion sarcomas including targetable NTRK and ALK.

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

Mortality risk in post-operative head and neck cancer patients during the SARS-Cov2 pandemic: early experiences.

PURPOSE: The objective of this report is to outline our early experience with head and neck cancer patients in a tertiary referral center, during the SARS-Cov2 pandemic, and to describe the poor outcomes of patients who acquired the infection. METHODS: In this case series from a single-center, national tertiary referral center for head and neck cancer we describe three consecutive head and neck cancer patients who contracted SARS-Cov2 during their inpatient stay. RESULTS: Of the three patients described in our case series that contracted SARS-Cov2, two patients died from SARS-Cov2 related illness. CONCLUSION: We have demonstrated the significant implications that SARS-Cov2 has on head and neck cancer patients, with 3 patients acquiring SARS-Cov2 in hospital, and 2 deaths in our that cohort. We propose a complete separation in the location of where these patients are being managed, and also dedicated non-SARS-Cov2 staff for their peri-operative management. LEVEL OF EVIDENCE: IV.

Evaluation of UV-C Decontamination of Clinical Tissue Sections for Spatially Resolved Analysis by Mass Spectrometry Imaging (MSI).

Clinical tissue specimens are often unscreened, and preparation of tissue sections for analysis by mass spectrometry imaging (MSI) can cause aerosolization of particles potentially carrying an infectious load. We here present a decontamination approach based on ultraviolet-C (UV-C) light to inactivate clinically relevant pathogens such as herpesviridae, papovaviridae human immunodeficiency virus, or SARS-CoV-2, which may be present in human tissue samples while preserving the biodistributions of analytes within the tissue. High doses of UV-C required for high-level disinfection were found to cause oxidation and photodegradation of endogenous species. Lower UV-C doses maintaining inactivation of clinically relevant pathogens to a level of increased operator safety were found to be less destructive to the tissue metabolome and xenobiotics. These doses caused less alterations of the tissue metabolome and allowed elucidation of the biodistribution of the endogenous metabolites. Additionally, we were able to determine the spatially integrated abundances of the ATR inhibitor ceralasertib from decontaminated human biopsies using desorption electrospray ionization-MSI (DESI-MSI).

Social isolation stress facilitates chemically induced oral carcinogenesis.

Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.

Impact of treatment delay due to the pandemic of COVID-19 on the efficacy of immunotherapy in head and neck cancer patients.

Immunotherapy has been a new standard for recurrent/metastatic head and neck cancers (R/M HNC). One of the prominent characteristics of cancer immunotherapy is the induction of immune memory followed by endured treatment response. However, whether and how a treatment delay would impact on the efficacy of immunotherapy has not been well determined. During the outbreak of COVID-19, a number of cancer patients in Wuhan, the epicenter of the pandemic in China, had experienced long-lasting city lockdown and delay of immunotherapies. Here, we retrospectively analyzed 24 HNC patients treated with immune checkpoint inhibitors in our cancer institute prior to the outbreak of COVID-19 who were re-evaluated after the restoration of regular medical care. Of these 24 patients, 10 patients had achieved complete response (CR) or partial response (PR), 12 patients had achieved stable disease (SD), and 2 patients had received just one cycle treatment without efficacy evaluation before treatment delay. The median delay was 3.75 months (range 1.73-8.17 months). Re-evaluation after treatment delay revealed that ten patients (10/10) who achieved CR or PR, two patients (2/2) who received just one cycle treatment without efficacy evaluation and seven patients (7/12) who achieved SD before outbreak of COVID-19 maintained tumor response after treatment delay. Among the rest five patients who had achieved SD, four patients were re-evaluated as progressive disease (PD) due to treatment delay and one patient died after treatment interruption without re-evaluation. Our results from a small cohort of R/M HNC patients showed that treatment delay of three to four months might have mild, if any, impact on the efficacy of immunotherapy for patients with controlled disease.

TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients.

BACKGROUND: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. METHODS: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC. RESULTS: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation. CONCLUSIONS: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.

Will a tumor pandemic come after the COVID-19 pandemic? Head and Neck cancer perspective.

The COVID-19 pandemic demands a reassessment of head and neck oncology treatment paradigms by posing several challenges for oncology services, with unprecedented pressure on the regional health care system. Since February 2020 this has severely disrupted health-care services, leading to accumulating clinic caseload and substantial delays for operations. The head and neck cancer services have been faced with the difficult task of managing the balance between infection risk to health-care providers and the risk of disease progression from prolonged waiting times. Herein, we share our experience in Firenze (Italy) and propose our action plan on the management of head and neck cancer services via multi-institution collaboration.

Outcomes of elective head and neck confirmed or suspected cancer surgery during the COVID-19 pandemic.

PURPOSE: To analyse the complication outcomes of COVID-19 negative patients undergoing elective head and neck surgery during the COVID-19 pandemic. METHODS: This was a retrospective case review of all patients undergoing elective head and neck surgery for confirmed or suspected head and neck cancer. RESULTS: There were no mortalities recorded in the cohort of patients analysed. At 30 days, pulmonary complications had occurred in 4 patients (9%). None of these were related to COVID infection. CONCLUSION: With careful pre-operative screening of patients for COVID-19 and post-operative care in a COVID-19 clean ward, head and neck surgery can proceed safely during the epidemic. This data could help to minimise delay in treatment by allowing a greater number of elective head and neck cancer operations to proceed.

North East London coronavirus disease 2019 protocol for diagnostics in two-week wait head and neck cancer patients.

BACKGROUND: The coronavirus disease 2019 pandemic requires urgent modification to existing head and neck cancer diagnosis and management practices. A protocol was established that utilises risk stratification, early investigation prior to clinical review and a reduction in aerosol generating procedures to lessen the risk of coronavirus disease 2019 spread. METHODS: Two-week wait referrals were stratified into low, intermediate and high risk. Low risk patients were referred back to primary care with advice; intermediate and high risk patients underwent investigation. Clinical encounters and aerosol generating procedures were minimised. A combined diagnostic and therapeutic surgical approach was undertaken where possible. RESULTS: Forty-one patients were used to assess feasibility. Thirty-one per cent were low risk, 35 per cent were intermediate and 33 per cent were high risk. Thirty-three per cent were discharged with no imaging. CONCLUSION: Implementing this protocol reduces the future burden on tertiary services, by empowering primary care physicians to re-refer low risk patients. The protocol is applicable across the UK and avoids diagnostic delay.

Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

[Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model]. / Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: modelo basado en un crecimiento exponencial.

BACKGROUND AND OBJECTIVES: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. MATERIAL AND METHODS: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. RESULTS: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter >4cm or thickness >6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (>6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. CONCLUSIONS: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays.

Changing practice patterns in head and neck oncologic surgery in the early COVID-19 era.

BACKGROUND: The novel coronavirus 2019 (COVID-19) pandemic has changed health care, challenged by resource constraints and fears of transmission. We report the surgical practice pattern changes in a Head and Neck Surgery department of a tertiary cancer care center and discuss the issues surrounding multidisciplinary care during the pandemic. METHODS: We report data regarding outpatient visits, multidisciplinary treatment planning conference, surgical caseload, and modifications of oncologic therapy during this pandemic and compared this data to the same interval last year. RESULTS: We found a 46.7% decrease in outpatient visits and a 46.8% decrease in surgical caseload, compared to 2019. We discuss the factors involved in the decision-making process and perioperative considerations. CONCLUSIONS: Surgical practice patterns in head and neck oncologic surgery will continue to change with the evolving pandemic. Despite constraints, we strive to prioritize and balance the oncologic and safety needs of patients with head and neck cancer in the face of COVID-19.

Changes in head and neck oncologic practice during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has raised controversies regarding safe and effective care of patients with head and neck cancer. It is unknown how much the pandemic has changed surgeon practice. METHODS: A questionnaire was distributed to head and neck surgeons assessing opinions related to treatment and concerns for the safety of patients, self, family, and staff. RESULTS: A total of 88 head and neck surgeons responded during the study period. Surgeons continued to recommend primary surgical treatment for oral cavity cancers. Respondents were more likely to consider nonsurgical therapy for patients with early glottic cancers and HPV-mediated oropharynx cancer. Surgeons were least likely to be concerned for their own health and safety and had the greatest concern for their resident trainees. CONCLUSIONS: This study highlights differences in the willingness of head and neck surgeons to delay surgery or alter plans during times when hospital resources are scarce and risk is high.

Managing head and neck cancer patients with tracheostomy or laryngectomy during the COVID-19 pandemic.

Head and neck cancer patients with tracheostomies and laryngectomies, as well as their healthcare providers, face unique challenges in the context of the current COVID-19 pandemic. This document consolidates best available evidence to date and presents recommendations to minimize the risks of aerosolization and SARS-CoV-2 exposures in both the inpatient and outpatient settings. The cornerstones of these recommendations include the use of closed-circuit ventilation whenever possible, cuffed tracheostomy tubes, judicious use of heat moisture exchange units, appropriate personal protective equipment for providers and patients, meticulous hand hygiene, and minimal manipulation of tracheostomy tubes.