Evaluation of oral mucositis, candidiasis, and quality of life in patients with head and neck cancer treated with a hypofractionated or conventional radiotherapy protocol: a longitudinal, prospective, observational study.

BACKGROUND: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, recently, Radiotherapy (RT) protocols requiring fewer sessions (hypofractionated) have been used to shorten RT treatment and minimize patient exposure to medical centers, and decrease the risk of SARS-CoV-2 infection. METHODS: This longitudinal, prospective, observational study aimed to compare the quality of life (QoL) and the incidence of oral mucositis and candidiasis in 66 patients with head and neck cancer (HNC) who undergo a hypofractionated RT protocol (GHipo), total of 55 Gy for 4 weeks, or a conventional RT protocol (GConv), total of 66 - 70 Gy for 6 - 7 weeks. PURPOSE: To assess the incidence and severity of oral mucositis, the incidence of candidiasis, and QoL were evaluated using the World Health Organization scale, clinical evaluation, and the QLC-30 and H&N-35 questionnaires, respectively, at the beginning and the end of RT. RESULTS: The incidence of candidiasis did not show differences between the two groups. However, at the end of RT, mucositis had a higher incidence (p < 0.01) and severity (p < 0.05) in GHipo. QoL was not markedly different between the two groups. Although mucositis worsened in patients treated with hypofractionated RT, QoL did not worsen for patients on this regimen. CONCLUSIONS: Our results open perspectives for the potential use of RT protocols for HNC with fewer sessions in conditions that require faster, cheaper, and more practical treatments.

Head and neck cancer recurrence with limited mouth opening, radiation fibrosis and confirmed COVID-19 infection: Approach to airway management.

We present a case that describes the airway management of a patient with recurrent head and neck cancer and confirmed COVID-19 infection. Securing airway of these patients with anticipated difficulty and at the same time limiting virus exposure to providers can be challenging. The risk of aerosolization during awake tracheal intubation is extreme as it carries a high risk of transmitting respiratory infections. A multidisciplinary team discussion before the procedure highlighted aspects of both airway management and the urgency of surgical procedure where particular care and modifications are required. Successful flexible bronchoscopy and intubation was done under inhalational anaesthetics with spontaneous breathing. Although fiberoptic intubation during sleep,in anticipated difficult airways, have led to enhanced intubation time, this technique was opted to minimize the risk of aerosol generation associated with topicalisation, coughing and hence reduced incidence of cross infection to health care workers.

What Did the Pandemic Teach Us About Palliative Radiation in Head and Neck Cancer?

Objective: To assess the feasibility and efficacy of palliative radiotherapy dose regimens for patients with locally advanced head and neck cancer. Methods: Fifty patients of previously untreated, inoperable, stage IVA and IVB squamous cell carcinoma of the head and neck, deemed unfit for radical treatment, were included in the study from May 2020 to June 2020. Two palliative radiotherapy regimens were used. First was a single fraction radiation with 8 Gy for patients with limited life expectancy and poor performance status, which was repeated after 4 weeks in case of good symptom relief. The second regimen was used for patients with good performance status and consisted of fractionated radiation with 30 Gy in 10 fractions over 2 weeks, which was followed by supplementary radiation with 25 Gy in 10 fractions over 2 weeks in patients with good symptomatic response at 2 weeks. Symptoms were assessed at baseline and at the end of 4 weeks after treatment completion using the numerical rating score. Patients were followed up for a median of 4.5 months and assessed for symptom control and overall survival. Results: Forty-eight patients completed treatment and were included for analysis. Of the 24 patients who received single fraction radiation, 13 (54.2%) were given the second dose. Improvement in pain and dysphagia were reported in 57.9% and 60% patients, respectively. A total of 55.5% noted decrease in size of the neck node. Twenty-four patients received fractionated radiation and 15 (62.5%) were given the second course after 2 weeks. Relief in pain and dysphagia was reported in 68.2% and 63.6% patients, respectively. There were no grade 3/4 toxicities. Symptom control lasted for at least 3 months in 30% of the patients who received single fraction radiation and 54.2% of the patients who received fractionated radiation. The estimated 6-month overall survival of the entire cohort was 51.4%. Conclusion: Judicious use of palliative radiation in advanced incurable head and neck cancers provides effective and durable symptom relief and should be used after careful consideration of patient prognosis, logistics of treatment, and goals of care.

Radiobiological approach to treatment gaps in locally advanced head and neck cancers radical radiotherapy arising from the COVID-19 pandemic.

Gaps of radiotherapy treatment are one of the factors recognized as unfavorable in terms of tumor control and disease prognosis. All strategies for compensating the negative effect of radiotherapy treatment gaps are based on radiobiological models. Using the modified square linear formalism (Dale`s equation) it is possible to calculate the additional dose in order to compensate the accelerated tumor repopulation effect. SARS-CoV-2 infection is an important factor that can lead to an interruption of irradiation for medium and long- term intervals. We aim to present the radiobiological data underlying the recalculation of radiotherapy treatment and exemplification for different clinical scenarios in the case of head and neck cancers (Ref. 17). Keywords: adiobiology, treatment gaps, locally advanced head and neck cancers, radical radiotherapy, COVID-19 pandemic.

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren's Syndrome Patients.

Patients with head and neck cancer (HNC) and patients with primary Sjögren's syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers.

Manual Therapy for Patients With Radiation-Associated Trismus After Head and Neck Cancer.

Importance: Trismus is highly prevalent in head and neck cancer (HNC) survivorship. Current standards for trismus treatment include various stretch-based exercise protocols as a primary and single treatment modality with limited evidence regarding the role of manual therapy (MT) for this indication. Objective: To assess the effect size and associations of response to MT to increase oral opening in the setting of radiation-associated trismus. Design, Setting, and Participants: This retrospective case series was conducted at the University of Texas MD Anderson Cancer Center between 2016 and March 2020 (before COVID-19 interruption) and included 49 disease-free survivors of HNC who were referred for treatment of radiation-associated trismus. Intervention: Intraoral MT (including or excluding external head and neck) targeting the muscles of mastication. Main Outcomes and Measures: Maximum interincisal opening (MIO) before and after the initial MT session compared with serial MT sessions. Covariates were examined to determine the association with response to MT for trismus. Results: A total of 49 survivors of HNC (13 women [27%]; 24 [49%] 64 years or younger; 25 [51%] 65 years or older; mean [range] of 6.6 [0-33] years postradiotherapy were included, 9 [18.4%] of whom underwent a single MT session; 40 [81.6%] who underwent multiple sessions [mean, 6; median (range), 3 (2-48)]). The MIO improved after a single session by a mean (SD) of 4.1 (1.9) mm (0.45 effect size) and after serial MT sessions by a mean (SD) of 6.4 (4.8) mm with an effect size of 0.7. No covariates were found to be clinically meaningfully associated with MIO improvement following MT. Conclusions and Relevance: The findings of this case series study suggest that MT improved MIO with a medium to large effect size in survivors of HNC with radiation-associated trismus. The results suggest that the largest increase in oral opening was achieved after the initial treatment and although gains were more modest, oral opening continued to improve with serial treatment. Covariates were not associated with MT response, suggesting that patients with clinical features often considered treatment refractory (eg, advanced disease, multiple lines of oncology treatment, ≥5 years posttreatment) may benefit from treatment with MT. Manual therapy may be a beneficial frontline or adjuvant treatment when combined with traditional stretching therapy. A clinically meaningful increase in oral opening has the potential to improve swallow function, speech, pain, and quality of life.

Impact of COVID-19 Pandemic on Patterns of Care and Outcome of Head and Neck Cancer: Real-World Experience From a Tertiary Care Cancer Center in India.

PURPOSE: The COVID-19 pandemic has caused unprecedented health, social, and economic unrest globally, particularly affecting resource-limited low-middle-income countries. The resultant curfew had made the access to and delivery of cancer care services an arduous task. We have reported the patterns of care and 1-year outcome of head and neck squamous cell carcinoma (HNSCC) treatment before and during COVID-19 lockdown at our institution. MATERIALS AND METHODS: Patients who underwent radiation therapy (RT) for nonmetastatic HNSCC between March 1, 2020, and July 31, 2020, were included in the COVID-RT group, and those who were treated between October 1, 2019, and February 29, 2020, were included in the preCOVID-RT group. RESULTS: A total of 25 patients were in the COVID-RT group, and 51 patients were in the preCOVID-RT group. An increase in the incidence of locally advanced cancers across all subsites was observed in the COVID-RT group. There was a steep increase in the median overall RT treatment duration (52 v 44) and median break days during RT (10 v 2) in the COVID-RT group. The median follow-up period of all patients was 18 months. The progression-free survival at 1 year in the COVID-RT group and preCOVID-RT group was 84% and 90%, respectively (P = .08), and overall survival at 1 year was 86% and 96%, respectively (P = .06). CONCLUSION: Our study elucidates the adverse impact of the COVID-19 curfew on cancer care and has demonstrated safe delivery of RT for HNSCC without major acute adverse effects. Despite a significant increase in treatment breaks, early outcome data also suggest that 1-year progression-free survival and overall survival are comparable with that of the pre-COVID-19 times; however, longer follow-up is warranted.

Patient-reported outcomes and complications during head and neck cancer radiotherapy before versus during the COVID-19 pandemic.

PURPOSE: This study compares patient-reported outcomes and treatment-related complications during radiotherapy before (August 2019-January 2020) versus during (March-Sept 2020) the COVID-19 pandemic. MATERIALS AND METHODS: The MD Anderson Symptom Inventory-head and neck module was used to assess curative intent in H&N cancer patients' symptoms during radiotherapy. RESULTS: There were 158 patients in the pre-pandemic cohort and 137 patients in the pandemic cohort. There was no significant difference in enteral feeding requirements between the cohorts (21% versus 30%, p = 0.07). Weight loss was higher during the pandemic (mean - 5.6% versus 6.8%, p = 0.03). On multivariate analysis, treatment during the pandemic was associated with higher symptom scores for coughing/choking while eating (2.7 versus 2.1, p = 0.013). CONCLUSIONS: Complication rates during H&N radiotherapy during the COVID-19 pandemic were similar at our institution relative to the pre-pandemic era, although weight loss was greater and patients reported more severe choking/coughing while eating.

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.

Effect of Surgical Mask on Setup Error in Head and Neck Radiotherapy.

PURPOSE: With the widespread prevalence of Corona Virus Disease 2019 (COVID-19), cancer patients are suggested to wear a surgical mask during radiation treatment. In this study, cone beam CT (CBCT) was used to investigate the effect of surgical mask on setup errors in head and neck radiotherapy. METHODS: A total of 91 patients with head and neck tumors were selected. CBCT was performed to localize target volume after patient set up. The images obtained by CBCT before treatment were automatically registered with CT images and manually fine-tuned. The setup errors of patients in 6 directions of Vrt, Lng, Lat, Pitch, Roll and Rotation were recorded. The patients were divided into groups according to whether they wore the surgical mask, the type of immobilization mask used and the location of the isocenter. The setup errors of patients were calculated. A t-test was performed to detect whether it was statistically significant. RESULTS: In the 4 groups, the standard deviation in the directions of Lng and Pitch of the with surgical mask group were all higher than that in the without surgical mask group. In the head-neck-shoulder mask group, the mean in the Lng direction of the with surgical mask group was larger than that of the without surgical mask group. In the lateral isocenter group, the mean in the Lng and Pitch directions of the with surgical mask group were larger than that of the without surgical mask group. The t-test results showed that there was significant difference in the setup error between the 2 groups (p = 0.043 and p = 0.013, respectively) only in the Lng and Pitch directions of the head-neck-shoulder mask group. In addition, the setup error of 6 patients with immobilization open masks exhibited no distinguished difference from that of the patients with regular immobilization masks. CONCLUSION: In the head and neck radiotherapy patients, the setup error was affected by wearing surgical mask. It is recommended that the immobilization open mask should be used when the patient cannot finish the whole treatment with a surgical mask.

A snapshot on radiotherapy for head and neck cancer patients during the COVID-19 pandemic: a survey of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group.

OBJECTIVES: The objective of the paper was to assess real-life experience in the management of head and neck cancer (HNC) patients during the COVID-19 pandemic in radiotherapy departments and to evaluate the variability in terms of adherence to American Society of Radiation Oncology (ASTRO) and European Society for Radiotherapy and Oncology (ESTRO) recommendations. MATERIALS AND METHODS: In May 2020, an anonymous 30-question online survey, comparing acute phase of outbreak and pre-COVID-19 period, was conducted. Two sections exploited changes in general management of HNC patients and different HNC primary tumors, addressing specific statements from ASTRO ESTRO consensus statement as well. RESULTS: Eighty-eight questionnaires were included in the demographic/clinical workflow analysis, and 64 were analyzed for treatment management. Forty-eight percent of radiotherapy departments became part of oncologic hubs. First consultations reduced, and patients were addressed to other centers in 33.8 and 18.3% of cases, respectively. Telematic consultations were used in 50% of follow-up visits and 73.9% of multidisciplinary tumor board discussions. There were no practical changes in the management of patients affected by different primitive HNCs. Hypofractionation was not favored over conventional schedules. CONCLUSIONS: Compared to pre-COVID era, the clinical workflow was highly re-organized, whereas there were no consistent changes in RT indications and schedules.

Head and neck radiotherapy amid the COVID-19 pandemic: practice recommendations of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Management of patients with head and neck cancers (HNCs) is challenging for the Radiation Oncologist, especially in the COVID-19 era. The Italian Society of Radiotherapy and Clinical Oncology (AIRO) identified the need of practice recommendations on logistic issues, treatment delivery and healthcare personnel's protection in a time of limited resources. A panel of 15 national experts on HNCs completed a modified Delphi process. A five-point Likert scale was used; the chosen cut-offs for strong agreement and agreement were 75% and 66%, respectively. Items were organized into two sections: (1) general recommendations (10 items) and (2) special recommendations (45 items), detailing a set of procedures to be applied to all specific phases of the Radiation Oncology workflow. The distribution of facilities across the country was as follows: 47% Northern, 33% Central and 20% Southern regions. There was agreement or strong agreement across the majority (93%) of proposed items including treatment strategies, use of personal protection devices, set-up modifications and follow-up re-scheduling. Guaranteeing treatment delivery for HNC patients is well-recognized in Radiation Oncology. Our recommendations provide a flexible tool for management both in the pandemic and post-pandemic phase of the COVID-19 outbreak.

The 3 Bs of cancer care amid the COVID-19 pandemic crisis: "Be safe, be smart, be kind"-A multidisciplinary approach increasing the use of radiation and embracing telemedicine for head and neck cancer.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID-19) pandemic, government-mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in-person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard-of-care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high-volume cancer center at the domestic epicenter of the COVID-19 crisis.

Head and neck cancer radiotherapy amid COVID-19 pandemic: Report from Milan, Italy.

BACKGROUND: Management of head and neck cancers (HNC) in radiation oncology in the coronavirus disease 2019 (COVID-19) era is challenging. Aim of our work is to report organization strategies at a radiation therapy (RT) department in the first European area experiencing the COVID-19 pandemic. METHODS: We focused on (a) dedicated procedures for HNC, (b) RT scheduling, and (c) health care professionals' protection applied during the COVID-19 breakdown (from March 1, 2020 to April 30, 2020). RESULTS: Applied procedures are reported and discussed. Forty-three patients were treated. Image-guided, intensity modulated RT was performed in all cases. Median overall treatment time was 50 (interquartile range: 47-54.25) days. RT was interrupted/delayed in seven patients (16%) for suspected COVID-19 infection. Two health professionals managing HNC patients were proven as COVID-19 positive. CONCLUSION: Adequate and well-timed organization allowed for the optimization of HNC patients balancing at the best of our possibilities patients' care and personnel's safety.

Hypofractionated radiotherapy alone with 2.4 Gy per fraction for head and neck cancer during the COVID-19 pandemic: The Princess Margaret experience and proposal.

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.