Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

Single-arm studies involving patient-reported outcome data in oncology: a literature review on current practice.

Patient-reported outcomes (PROs) are increasingly used in single-arm cancer studies. We reviewed 60 papers published between 2018 and 2021 of single-arm studies of cancer treatment with PRO data for current practice on design, analysis, reporting, and interpretation. We further examined the studies' handling of potential bias and how they informed decision making. Most studies (58; 97%) analysed PROs without stating a predefined research hypothesis. 13 (22%) of the 60 studies used a PRO as a primary or co-primary endpoint. Definitions of PRO objectives, study population, endpoints, and missing data strategies varied widely. 23 studies (38%) compared the PRO data with external information, most often by using a clinically important difference value; one study used a historical control group. Appropriateness of methods to handle missing data and intercurrent events (including death) were seldom discussed. Most studies (51; 85%) concluded that PRO results supported treatment. Conducting and reporting of PROs in cancer single-arm studies need standards and a critical discussion of statistical methods and possible biases. These findings will guide the Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Data in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) in developing recommendations for the use of PRO-measures in single-arm studies.

Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures.

Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

A multicenter international prospective study of the validity and reliability of a COVID-19-specific health-related quality of life questionnaire.

PURPOSE: To develop and validate a health-related quality of life (HRQoL) questionnaire for patients with current or previous coronavirus disease (COVID-19) in an international setting. METHODS: This multicenter international methodology study followed standardized guidelines for a four-phase questionnaire development. Here, we report on the pretesting and validation of our international questionnaire. Adults with current or previous COVID-19, in institutions or at home were eligible. In the pretesting, 54 participants completed the questionnaire followed by interviews to identify administration problems and evaluate content validity. Thereafter, 371 participants completed the revised questionnaire and a debriefing form to allow preliminary psychometric analysis. Validity and reliability were assessed (correlation-based methods, Cronbach's α, and intra-class correlation coefficient). RESULTS: Eleven countries within and outside Europe enrolled patients. From the pretesting, 71 of the 80 original items fulfilled the criteria for item-retention. Most participants (80%) completed the revised 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire included 61 items that fulfilled criteria for item retention or were important to subgroups. Item-scale correlations were > 0.7 for all but nine items. Internal consistency (range 0.68-0.92) and test-retest results (all but one scale > 0.7) were acceptable. The instrument consists of 15 multi-item scales and six single items. CONCLUSION: The Oslo COVID-19 QLQ-W61© is an international, stand-alone, multidimensional HRQoL questionnaire that can assess the symptoms, functioning, and overall quality of life in COVID-19 patients. It is available for use in research and clinical practice. Further psychometric validation in larger patient samples will be performed.

Comparing the use of patient-reported outcomes in clinical studies in Europe in 2008 and 2018: a literature review.

PURPOSE: Several guidelines for the use of patient-reported outcomes (PROs) in clinical studies have been published in the past decade. This review primarily aimed to compare the number and compliance with selected PRO-specific criteria for reporting of clinical studies in Europe using PROs published in 2008 and 2018. Secondarily, to describe the study designs, PRO instruments used, patient groups studied, and countries where the clinical studies were conducted. METHODS: A literature search was conducted in MEDLINE to identify eligible publications. To assess the number of publications, all abstracts were screened for eligibility by pairs of reviewers. Compliance with PRO-specific criteria and other key characteristics was assessed in a random sample of 150 eligible full-text publications from each year. Randomized controlled trials (RCTs) were assessed according to the full CONSORT-PRO checklist. RESULTS: The search identified 1692 publications in 2008 and 4290 in 2018. After screening of abstracts, 1240 from 2008 and 2869 from 2018 were clinical studies using PROs. By full-text review, the proportion of studies discussing PRO-specific limitations and implications was higher in 2018 than in 2008, but there were no differences in the other selected PRO-specific criteria. In 2018, a higher proportion of studies were longitudinal/cohort studies, included ≥ 300 patients, and used electronic administration of PRO than in 2008. The most common patient groups studied were those with cancer or diseases of the musculoskeletal system or connective tissue. CONCLUSION: The number of clinical studies from Europe using PROs was higher in 2018 than in 2008, but there was little difference in compliance with the PRO-specific criteria. The studies varied in terms of study design and PRO instruments used in both publication years.

Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale.

PURPOSE: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. METHODS: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. RESULTS: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. CONCLUSIONS: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.

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.

Health-related quality of life issues, including symptoms, in patients with active COVID-19 or post COVID-19; a systematic literature review.

PURPOSE: This systematic review was performed to identify all relevant health-related quality of life (HRQoL) issues associated with COVID-19. METHODS: A systematic literature search was undertaken in April 2020. In four teams of three reviewers each, all abstracts were independently reviewed for inclusion by two reviewers. Using a pre-defined checklist of 93 criteria for each publication, data extraction was performed independently by two reviewers and subsequently compared and discussed. If necessary, a third reviewer resolved any discrepancies. The search was updated in February 2021 to retrieve new publications on HRQoL issues including issues related to the long-term consequences of COVID-19. RESULTS: The search in April 2020 identified 3342 potentially relevant publications, and 339 publications were selected for full-text review and data extraction. We identified 75 distinct symptoms and other HRQoL issues categorized into 12 thematic areas; from general symptoms such as fever, myalgia, and fatigue, to neurological and psychological issues. The updated search revealed three extra issues experienced during active disease and long-term problems with fatigue, psychological issues and impaired cognitive function. CONCLUSION: This first comprehensive systematic review provides a detailed overview of the wide range of HRQoL issues experienced by patients with COVID-19 throughout the course of the disease. It demonstrates the devastating impact of the disease and provides critically important information for clinicians, to enable them to better recognize the disease and to provide knowledge important for treatment and follow-up. The results provided the foundation for the international development of a COVID-19 specific patient-reported HRQoL questionnaire.

Long-term outcome in patients operated with hybrid esophagectomy for esophageal cancer - a cohort study.

Background: Over the past two decades, hybrid and total minimally invasive esophagectomy for esophageal cancer (EC) has increasingly been implemented with the aim to improve morbidity, functional result and ultimately the prognosis in these patients. However, more results are warranted and in this single-center study we report long-time outcome in a cohort of cancer patients treated with hybrid esophagectomy (HE).Material and methods: Hundred and nine patients with EC operated with HE from November 2007 to June 2013 were included. Clinical, pathological and survival data were retrieved from the patient administration system and the Norwegian Cause of Death Registry. Patients alive were asked to fill out the Ogilvie dysphagia score, EORTC QLQ-C30 and EORTC QLQ-OG25. Survival was analyzed by Kaplan-Meier's method and prognostic factors by uni- and multivariable Cox regression analyses.Results: Median overall follow-up time was 55 months (range 2-135) after R0-2 resection (n = 109) and 76 months (5-135) for R0 resection (n = 100). Five-year overall survival rate was 49% and 53%, respectively. Anastomotic leakage rate and 90-days mortality were 5% and 2%, respectively. Six patients (6%) had later surgery for metastases to mediastinum, hepatoduodenal ligament, brain, lung, liver or bladder median 26 months (4-51) after HE. Forty-one out of 51 patients alive (80%) filled out questionnaires after median 65.5 months (63-123) follow-up. All patients could eat normal food without (n = 37) or with (n = 4) problems. Nearly, half of the patients reported problems with reflux, one-third experienced fatigue and anxiety while one out of four had weight loss and episodes of dyspnea.Conclusions: In this patient series, HE offered low postoperative mortality and good overall long-term survival. Most survivors maintained good quality of life more than five years post treatment. There was a low rate of serious postoperative complications.

Dose painting for re-irradiation of head and neck cancer.

BACKGROUND: For patients with recurrent or second primary disease, re-irradiation can be challenging due to overlap with previously irradiated volumes. Dose painting may be attractive for these patients, as the focus is on delivering maximal dose to areas of high tumor activity. Here, we compare dose painting by contours (DPBC) treatment plans based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with conventional plans. MATERIAL AND METHODS: We included 10 patients with recurrent or second primary head and neck cancer (HNC) eligible for re-irradiation. Our conventional re-irradiation regimen is hyperfractionated radiotherapy 1.5 Gy twice daily over 4 weeks, giving a total dose of 60 Gy. For DPBC, we defined two prescription volumes, PV33 and PV66, corresponding to 33 and 66% of the highest FDG uptake in the tumor. The clinical target volume (CTV) prescription dose was 60 Gy, PV33; 65-67 Gy and PV66; 70-73 Gy. The DPBC plan is to be given the first 20 fractions and the conventional plan the last 20 fractions. Dose to organs at risk (OARs) were compared for DPBC and conventional treatment. By summation of the initial curative plan and the re-irradiation plan, we also evaluated differences in dose to the 2 ccm hot spot (D2cc). RESULTS: We achieved DPBC plans with adequate target coverage for all 10 patients. There were no significant differences in OAR doses between the standard plans and the DPBC plans (p=.7). Summation of the initial curative plan and the re-irradiation plan showed that the median D2cc increased from 130 Gy (range 113-132 Gy; conventional) to 140 Gy (range 115-145 Gy; DPBC). CONCLUSIONS: Our proposed DPBC could be straightforwardly implemented and all plans met the objectives. Re-irradiation of HNC with DPBC may increase tumor control without more side effects compared to conventional radiotherapy.

Improved treatment decisions in patients with esophageal cancer.

BACKGROUND: Patients with esophageal cancer seldom achieve long-term survival. This prospective cohort study investigated the selection of patients likely to benefit from curative treatment and whether information on patients' health-related quality of life (HRQL) would assist treatment decisions in the multidisciplinary team. METHODS: Consecutive patients completed HRQL assessments and clinical data were collected before start of treatment. Logistic regression analyses identified clinical factors associated with treatment intent in patients with stage-III disease. Kaplan-Meier method was used for survival analyses and Cox proportional hazards models were used to assess the impact of clinical factors and HRQL on survival in patients planned for curative treatment. RESULTS: Patients with curative treatment intent (n = 90) were younger, had better WHO performance status and less fatigue than patients with palliative treatment intent (n = 89). Median survival for the total cohort (n = 179) and patients with palliative or curative treatment intent was nine, five and 19 months, respectively. In multivariate Cox regression analyses, performance status (0-1 favorable) and comorbidity (ASA I favorable) were factors of importance for survival, whereas measures of HRQL were not. CONCLUSIONS: Patients performance status and comorbidity must be considered in addition to stage of disease to avoid extensive curative treatment in patients with short life expectancy. This study did not provide evidence to support that information on patients HRQL adds value to the multidisciplinary team's treatment decision process.

Radiation-induced long-term dysphagia in survivors of head and neck cancer and association with dose-volume parameters.

BACKGROUND: Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models. METHODS: This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models. RESULTS: Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03-1.10), female sex (OR 2.75, 95% CI 1.45-5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03-1.09). NTCP models overall underestimated the risk of long-term dysphagia. CONCLUSIONS: Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect.

Chronic fatigue in long-term survivors of head and neck cancer treated with radiotherapy.

BACKGROUND: There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL). MATERIAL AND METHODS: In this cross-sectional study we included HNC survivors treated in 2007-2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen's effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire. RESULTS: The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years post-RT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82-6.31), comorbidity (OR 2.17, 95 % CI 1.20-3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16-3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL. CONCLUSIONS: CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up.

Patient-reported outcomes evaluating palliative radiotherapy and chemotherapy in patients with oesophageal cancer: a systematic review.

BACKGROUND: Patient-reported outcomes (PROs) and assessments of treatment-related toxicity provide important information on the effect of palliative chemotherapy and/or radiotherapy. The aim of this study was to review the effect of palliative radiotherapy and/or chemotherapy on symptoms and quality of life assessed by PROs and measurement of toxicity for patients with oesophageal cancer. METHODS: The Central, Medline and Embase databases (1990 to November 2011) were systematically searched for prospective studies of palliative chemotherapy and/or radiotherapy in patients with advanced oesophageal cancer with PRO- and/or toxicity outcomes. The risks of bias were assessed. RESULTS: Of 2677 records identified, only 32 included PROs, of which eight were randomised controlled trials. In studies with sufficient standard of PRO (n = 18), either Health Related Quality of Life (HRQL) (n = 14) or patient-reported dysphagia (n = 4), were assessed. Docetaxel added to cisplatin + fluorouracil (CF) improved HRQL compared to CF only, even though toxicity increased. Epirubicin added to CF resulted in longer preserved HRQL than its comparator in two trials, and non-inferiority in one. All phase II chemotherapy studies reported maintained HRQL or improved dysphagia combined with low level of toxicity. Brachytherapy resulted in better HRQL compared to stent placement in two trials, and external radiotherapy relieved dysphagia. The quality of the HRQL methodology and the interpretation and presentation of the PRO results varied, and clinical significance was seldom discussed. CONCLUSION: PRO endpoints are seldom used and further studies of homogenous patient groups with valid measures and methodology of PROs should be encouraged in the evaluation of palliative treatment. Brachytherapy, external radiotherapy and combination chemotherapy improved HRQL and dysphagia in the few identified studies with sufficient PRO methodology.

Body image concerns in long-term head and neck cancer survivors: prevalence and role of clinical factors and patient-reported late effects.

PURPOSE: Head and neck cancer (HNC) patients are at risk of long-term body image distress (BID). We aimed to investigate the severity of BID in long-term HNC survivors and to explore the associations between sociodemographic and clinical factors, patient-reported late effects, and cancer-related body image (BI) concerns. METHODS: This cross-sectional study included quality of life and BI assessment in an 8-year (SD = 1.58) follow-up after treatment among 258 HNC survivors. Multinomial logistic regression analysis was used to investigate the relationship between three groups of BI concerns (no concerns, mild to moderate concerns, and BID) and patient-reported late effects. Sociodemographic and clinical variables were included in the model as covariates. RESULTS: A total of 51.2% of participants had mild to moderate BI concerns, and 9.5% reported BID. Compared to those with no BI concerns, participants with BID were more likely to live without a partner, to have had radiotherapy and surgery, and to report worse emotional functioning and higher oral and throat pain. Compared to participants with no BI concerns, those with mild to moderate concerns reported higher oral and throat pain and speech problems. CONCLUSIONS: Some level of cancer-related BI concerns persisted in the majority of HNC survivors many years after treatment, while a small proportion of survivors experienced BID. BI concerns were associated with treatment modality and patients' daily functioning and symptoms. IMPLICATIONS FOR CANCER SURVIVORS: Insight into factors associated with BI problems may help to identify survivors at risk and may facilitate closer follow-up of survivors in need.

Impact of hyperfractionated re-irradiation on quality of life in patients with recurrent or second primary head and neck cancer, a prospective single institutional study.

Purpose: Describe the clinical outcome of hyperfractionated re-irradiation (HFRT) in patients with recurrent or second primary (SP) head and neck cancer (HNC). Methods: This prospective observational study included HNC patients eligible for HFRT. Inclusion criteria: age ≥18 years, recurrent or SP HNC, planned re-irradiation and ability to respond to questionnaires. Patients received 1.5 Gy twice daily, five days a week for three (palliative) or four (curative/local control) weeks, total dose 45/60 Gy. Toxicity was scored with CTCAE v3 at baseline, end of treatment, at three, six, 12 and 36 months follow-up. Health-related quality of life (HRQoL) was measured with EORTC QLQ-C30 and EORTC QLQ-H&N35, pre-treatment and eight times until 36 months. In the main outcome (Global quality of life and H&N Pain), a change score of ≥10 was considered clinically significant, and p-values < 0.05 (two-sided) statistically significant. The Kaplan-Meier method was used for survival analyses. Results: Over four years from 2015, 58 patients were enrolled (37 recurrent and 21 SP). All, but two patients completed treatment as planned. Toxicity (≥grade 3) increased from pre-treatment to end of treatment with improvement in the follow-up period. The mean Global quality of life (QoL) and H&N Pain scores were stable from pre-treatment to three months. Maintained/ improved Global QoL was reported by 60% of patients at three months and 56% of patients at 12 months. For patients with curative, local control and palliative intent, the median survival (range) was 23 (2-53), 10 (1-66) and 14 (3-41) months respectively. Of those alive, the proportion of disease-free patients at 12 and 36 months, were 58% and 48%, respectively. Conclusion: Most HNC patients reported maintained HRQoL at three and 12 months after HFRT despite serious toxicity observed in many patients. Long-term survival can be achieved in a limited proportion of the patients.

Serious Long-Term Effects of Head and Neck Cancer from the Survivors' Point of View.

The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were 'dry mouth' (DM) (n = 476; 46%), 'difficulty swallowing/eating' (DSE) (n = 408; 40%), 'hoarseness/difficulty speaking' (HDS) (n = 169; 16%), and 'pain in the head and neck' (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5-9.0; OR: 2.1, CI: 1.1-3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1-0.6; OR: 0.2, CI: 0.1-0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2-3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3-0.6) but increased odds of HDS (OR: 7.2, CI: 4.3-12.3). This study provides evidence of the serious long-term problems among HNCS.

Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure.

BACKGROUND: We aimed to create a questionnaire to assess the health-related quality of life including functioning, symptoms, and general health status of adult patients with current or previous COVID-19. Here, we report on Phase I and II of the development. METHODS: Internationally recognized methodology for questionnaire development was followed. In Phase I, a comprehensive literature review was performed to identify relevant COVID-19 issues. Decisions for inclusion, exclusion, and data extraction were completed independently in teams of two and then compared. The resulting issues were discussed with health care professionals (HCPs) and current and former COVID-19 patients. The input of HCPs and patients was carefully considered, and the list of issues updated. In Phase II, this updated list was operationalized into items/questions. RESULTS: The literature review yielded 3342 publications, 339 of which were selected for full-text review, and 75 issues were identified. Discussions with 44 HCPs from seven countries and 52 patients from six countries showed that psychological symptoms, worries, and reduced functioning lasted the longest for patients, and there were considerable discrepancies between HCPs and patients concerning the importance of some of the symptoms. The final list included 73 issues, which were operationalized into an 80-item questionnaire. CONCLUSION: The resulting COVID-19 questionnaire covers health-related quality of life issues relevant to COVID-19 patients and is available in several languages. The next steps include testing of the applicability and patients' acceptability of the questionnaire (Phase IIIA) and preliminary psychometric testing (Phase IIIB).