Clinical implication of genetic intratumor heterogeneity for targeted therapy in head and neck cancer.

BACKGROUND: Genomic profiling is increasingly used both in therapeutic decision-making and as inclusion criteria for trials testing targeted therapies. However, the mutational landscape may vary across different areas of a tumor and intratumor heterogeneity will challenge treatments or clinical decisions based on single tumor biopsies. The purpose of this study was to assess the clinical relevance of genetic intratumor heterogeneity in head and neck squamous cell carcinomas (HNSCC) using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). MATERIALS AND METHODS: This prospective study included 33 whole tumor specimens from 28 patients with primary or recurrent HNSCC referred for surgery. Three tumor blocks were selected from central, semi-peripheral, and peripheral positions, mimicking biopsies in three different locations. Genetic analysis of somatic copy number alterations (SCNAs) was performed on the three biopsies using Oncoscan, focusing on 45 preselected HNSCC genes of interest. Clinical relevance was assessed using the ESCAT score to investigate whether and how treatment decisions would change based on the three biopsies from the same tumor. RESULTS: The SCNAs identified among 45 preselected genes within the three tumor biopsies derived from the same tumor revealed distinct variations. The detected discrepancies could potentially influence treatment approaches or clinical decisions in 36% of the patients if only one tumor biopsy was used. Recurrent tumors exhibited significantly higher variation in SCNAs than primary tumors (p = .024). No significant correlation between tumor size and heterogeneity (p = .7) was observed. CONCLUSION: In 36% of patients diagnosed with HNSCC, clinically significant intratumor heterogeneity was observed which may have implications for patient management. This finding substantiates the need for future studies that specifically investigate the clinical implications associated with intratumor heterogeneity.

Diagnostic accuracy of combined optical- and radio-guided SNB for neck staging of oral squamous cell carcinoma lesions in the anterior oral cavity.

PURPOSE: The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity. METHODS: Prospective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up. RESULTS: In all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%. CONCLUSION: Optical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injection.

Second primary cancer following primary oral squamous cell carcinoma: a population-based, retrospective study.

BACKGROUND: Second primary cancer (SPC), defined as a metachronous solid cancer resulting from neither a recurrence of the primary cancer nor a metastasis, is a leading long-term cause of death for survivors of primary oral squamous cell carcinoma (OSCC). This study examined the risk of SPC following treatment of primary OSCC. MATERIALS AND METHODS: This semi-national, population-based, retrospective study included all patients with primary OSCC treated with curative intent in Eastern Denmark in 2000-2014. The presence of SPC was confirmed from medical records and the Danish Pathology Data Bank. The rate of SPC was compared to the occurrence of any cancer in the Eastern Danish population using data from the Danish Cancer Registry. RESULTS: A total of 936 patients with primary OSSC were enrolled. Of these, 219 patients (23%) were diagnosed with SPC during the follow-up (median 8.9 years, IQR: 5.4-12.6 years). The rate of SPC was four times higher than the occurrence of any cancer among the Eastern Danish population i.e., with a standardized incidence ratio (SIR) of 4.13 (95%CI: 3.55-4.80). SPCs were most frequently found in head and neck region (n = 97, SIR = 43.6), lower respiratory organs (n = 38, SIR = 5.6) and gastrointestinal organs (n = 33, SIR = 3.2) with increased SPC rates in all locations. Among patients who developed SPC within the study period the median time from OSCC to the first SPC was 4.4 years (IQR: 2.5-6.2). Significant associations were found between both smoking and excessive alcohol consumption after treatment of OSCC and the risk of SPC. CONCLUSIONS: A noteworthy increased rate of SPC following treatment of primary OSCC was found, especially in the head and neck region and in the lungs. Healthcare professionals should be aware of this increased risk.

The impact of tobacco smoking on survival of patients with oral squamous cell carcinoma: a population-based retrospective study.

BACKGROUND: This article aims to evaluate the impact of smoking status, accumulated tobacco exposure (ATE), and smoking cessation on overall- and disease-free survival (OS and DFS) of patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Patients with primary OSCC treated with curative intent between 2000 and 2019 in Copenhagen were included (n = 1808). Kaplan-Meier curves and multivariable Cox regression analyses were performed to compare the survival of patients with different smoking history. Interactions between ATE and (A) tumor subsite and (B) excessive alcohol consumption (EAC) on the survival were evaluated using multivariable Cox regression analyses with interaction terms. RESULTS: We included 1717 patients with known smoking status (62.8% males, median age: 64 years (IQR: 57-71 years)), who had a 5-year OS of 53.7% (95%CI: 49.8%-57.9%). Based on fully adjusted multivariable Cox regression analyses, significantly elevated hazard ratios (HRs) for OS and DFS were identified for current, but not former smokers, compared to never-smokers. An approximately linear relationship between continuous ATE and survival estimates was identified. ATE analyzed as a categorical variable showed significantly elevated HRs for OS of patients with all categories (060 PYs), however only for DFS of patients with >60 PYs, compared to 0 PYs. Furthermore, an unfavorable long-term prognosis was evident after >3.5 (OS) and >2.5 (DFS) years from diagnosis for patients who continued smoking compared to patients with smoking cessation at diagnosis. The survival estimates of patients with different tumor subsite and alcohol consumption differed with increasing ATE. CONCLUSION: Tobacco smoking (assessed as smoking status and ATE) was associated with inferior survival (OS and DFS) among patients with OSCC. Unfavorable long-term prognosis was significant for patients who continued smoking compared to patients with smoking cessation at diagnosis. The impact of ATE on survival of patients with OSCC may depend on the tumor subsite and/or alcohol consumption.

Days alive and out of hospital following primary surgery for oral cavity squamous cell carcinoma.

BACKGROUND: Days Alive and Out of Hospital (DAOH) is a recently introduced, readily obtainable postoperative outcome measure method that expresses procedure and disease-associated morbidity and mortality. In this study, we evaluated DAOH with 30- and 365-days follow-up periods after primary surgery (DAOH30 and DAOH365, respectively) for patients with oral cavity squamous cell carcinoma (OSCC). The aim of this study is to identify patient-, procedure- and disease-associated risk factors for patients treated with primary surgery for primary OSCC. MATERIAL AND METHODS: This retrospective cohort study from a prospective collected database represents patients from Eastern Denmark surgically treated for primary OSCC in the period 2000-2014. DAOH30 and DAOH365 were calculated and associations with patient characteristics including comorbidity, tumor characteristics, clinical outcomes such as length of stay, readmission, and mortality were evaluated. Tests for difference and significance between groups were assessed with Mann-Whitney U test and quantile linear regression. RESULTS: We included 867 patients (63% males, median age: 63 years (IQR 56-70 years)). Median DAOH30 and DAOH365 after OSCC surgery were 25 days (IQR 21-27 days) and 356 days (IQR 336-360 days), respectively. Alcohol consumption had a significant association with a lower DAOH365, p < 0.01, but not with DAOH30. Advanced T-stage, adjuvant radiotherapy (RT) and increased Charlson Comorbidity Index (CCI) score was significantly associated with a lower DAOH30 and DAOH365. CONCLUSION: In this population-based study in OSCC patients treated with primary surgery, we found that DAOH after 30 days was 25 days (83%), while DAOH after 365 days was 356 days (98%). Advanced T-stage acts as a predictor for significant DAOH30 and DAOH365 reduction while excessive alcohol consumption predicts a significant DAOH365 reduction. Readmission within 30 days following surgery was associated with further readmission within one year.

Needs assessment in patients surgically treated for head and neck cancer-a randomized controlled trial.

PURPOSE: To investigate the effect and feasibility of a head and neck cancer-specific needs assessment tool integrated into nursing rehabilitation consultations early in the post-surgical period on quality of life, symptom burden, and referrals for multidisciplinary follow-up. METHODS: Ninety-two surgically treated patients with head and neck cancer were enrolled in a two-arm randomized controlled trial. All participants received nursing rehabilitation consultations prior to discharge, and two weeks and two months post-operative. The intervention group had their needs assessed using Patient Concerns Inventory, while standard care used a systematic questioning approach. Primary outcome was quality of life. Secondary outcomes were symptom burden and referrals for multidisciplinary rehabilitation follow-up. RESULTS: No significant differences were found in quality of life or symptom burden between groups. However, 35% more patients in the intervention group were referred for rehabilitation. The attrition rate was similar in both groups, with a dropout rate of six in each group. No patients declined using the Patient Concerns Inventory. CONCLUSION: The intervention showed no improvement in QoL or symptom burden compared to standard care. However, the results suggest that important needs were identified and addressed. Especially emotional and existential needs, which were accommodated through referrals and professional advice. Nursing rehabilitation consultations using the Patient Concerns Inventory are feasible and may ensure that patient preferences and priorities are incorporated in their care. TRIAL REGISTRATION: ClinicalTrials.com (NCT03443258). Date of registration: May 31st, 2018.

Swallowing Exercise During Head and Neck Cancer Treatment: Results of a Randomized Trial.

The diagnosis and treatment of head and neck cancer (HNC) can have substantial impact on swallowing function, nutritional balance, physical function and quality of life (QoL). Early initiated swallowing exercises are hypothesized to improve swallowing function in HNC patients. The aim was to investigate the effects of swallowing exercises and progressive resistance training (PRT) during radiotherapy on swallowing function, physical function and QoL in patients with pharynx-, larynx-, oral cavity cancer or unknown primary compared to usual care. In a multi-centre RCT participants were assigned to (a) twice-weekly PRT and daily swallowing exercises throughout treatment or (b) usual care. Outcomes were measured at end of treatment and 2, 6 and 12 months after. Primary outcome was penetration aspiration score (PAS). Data were analysed on an "intention-to-treat" basis by GEE logistic regression model, linear mixed effects model and cox regression. Of 371 invited HNC patients, 240 (65%) enrolled. Five participants were excluded. At 12 months follow-up, 59 (25%) participants were lost. Analyses showed significant effect on mouth opening, QoL, depression and anxiety at 12 months when comparing intervention to non-active controls. The trial found no effect on swallowing safety in HNC undergoing radiotherapy, but several positive effects were found on secondary outcomes when comparing to non-active controls. The intervention period may have been too short, and the real difference between groups is too small. Nevertheless, the need to identify long-lasting intervention to slow down or avoid functional deteriorations is ever more crucial as the surviving HNC population is growing.

Impact of delay in diagnosis and treatment-initiation on disease stage and survival in oral cavity cancer: a systematic review.

AIM/OBJECTIVES: This study aimed to systematically review the literature on the impact of delay in diagnosis and treatment of oral cavity cancer. METHODS: PubMed and Embase were systematically searched for articles reporting impact of delay in diagnosis and treatment on cancer-stage and survival of oral cavity cancer. Studies comprising at least ten patients, and published since the year 2000, were included. RESULTS: Sixteen studies (n = 45,001, range: 62-18,677 per study, 83% men), from Australia, Asia, Europe, North America and South America, met the inclusion criteria. Eleven studies (n = 1,460) examined delay in diagnosis, while five studies (n = 43,541) reported delay in treatment. Eight of the eleven studies, examining delay in diagnosis (n = 1,220), analyzed the correlation between delay in diagnosis and tumor stage at diagnosis. Three studies found a significant correlation between patient delay and advanced stage at diagnosis (p < 0.05), whereas three other studies did not. The studies reporting a significant correlation were from Asian countries, whereas the three studies that did not find a correlation were from other continents. Studies reporting on professional delay and total diagnostic delay, generally, did not find a significant correlation with advanced cancer at diagnosis. Time to treatment (TTI), defined as time from diagnosis to treatment, was found significantly correlated with survival in three studies (p < 0.01, p < 0.001, p < 0.05), and nonsignificant in two studies. CONCLUSION: A significant correlation between patient delay and advanced stage cancer was reported in Asian studies only, while professional delay and total diagnostic delay were generally found to be non-correlated with advanced stage cancer at diagnosis. TTI was in some studies reported to be correlated with poorer outcome, while other studies did not report a correlation. One study presented that there was no clear advantage in overall survival (OS) for patients treated within 30 days, compared to patients treated between 30 and 44 days.

Impact of time to treatment initiation for patients with oral cavity squamous cell carcinoma: a population-based, retrospective study.

BACKGROUND: The increasing incidence of oral cavity squamous cell carcinoma (OSCC) is challenging the capacity to treat patients efficiently. The aim of this study was to evaluate the impact of time to treatment initiation (TTI) on overall survival (OS) and recurrence free survival (RFS) for patients with primary OSCC. MATERIAL AND METHODS: All patients with primary OSCC treated with curative intent at Rigshospitalet in the period 2000-2014 with known date of diagnosis and treatment initiation were included. Correlation analyses between TTI and Charlson comorbidity index (CCI), UICC stage, and year of diagnosis were performed in addition to uni- and multivariate Cox proportional hazard regression analyses. Further, interaction analysis of TTI and UICC stage were conducted. RESULTS: Eight hundred and sixty-two patients (64% men) with a median age at diagnosis of 62 years (range: 28-95 years) were included. The median TTI was 31 days (range: 2-137 days). Correlation analyses showed correlations between TTI and CCI, TTI and UICC stage, and TTI and year of diagnosis (rho = -0.10, p-value = <.01; rho = 0.16, p-value = <.001; rho = -0.47 p-value = <.001). Univariate analyses showed a statistically significant increase in hazard ratio for both OS and RFS with a five-day increase in TTI (HR = 1.05, 95%CI: 1.02-1.07 and HR = 1.04, 95%CI: 1.02-1.07). However, when adjusting for age, sex, smoking, UICC stage, tumor sublocation, CCI, and year of diagnosis in a multivariate analysis, the increase in HR with TTI was not statistically significant. There was no statistically significant interaction between TTI and UICC stage. CONCLUSION: Survival of OSCC patients decreased with increasing TTI, yet not statistically significant in multivariate analysis. There was no difference in the effect of TTI between patients diagnosed in low or advanced stages.

The impact of comorbidities on survival in oral cancer patients: a population-based, case-control study.

BACKGROUND: Comorbidities have shown to highly influence the outcome and risk of death of head and neck cancer patients. The purpose of this study was to examine the comorbidities among oral cavity squamous cell carcinoma (OSCC) patients, and to investigate the impact of comorbidities on overall survival (OS) and recurrence free survival (RFS). METHODS: Patients diagnosed with OSCC in Eastern Denmark in the period 2000-2014 and treated with curative intend were included. Patients data were linked to the Danish National Patients Register to identify comorbidities based on the Charlson Comorbidity Index (CCI) at the time of diagnosis and five years after diagnosis. Each patient was age-and sex-matched in a 1:10 ratio with an age and sex matched reference group. RESULTS: A total of 1,183 patients and 11,830 controls were included. Overall this study found comorbidities to be more common among OSCC compared to the reference group both at the time of diagnosis and five years after. The 5-year OS among patients with a CCI score of zero, one, two, and three or above was 60%, 44%, 41%, and 40%, respectively. Similarly, the multivariate cox-regression analysis showed that patients with increasing CCI score also had an increasing risk of death compared to patients with no comorbidities. CONCLUSION: OSCC patients had significantly higher comorbidity burden at diagnosis and risk of developing additional comorbidities after diagnosis compared to the reference population. Survival outcomes decreased significantly with higher CCI.

Sinonasal cancer in Denmark 2008-2015: a population-based phase-4 cohort study from DAHANCA.

BACKGROUND: Sinonasal cancer is considered a rare disease with poor survival. Its treatment has changed profoundly in recent years, primarily following the introduction of intensity-modulated radiation therapy (IMRT) and minimally invasive endoscopic surgery. Danish national guidelines on treatment of patients diagnosed with sinonasal carcinoma were introduced in 2007. The aim of this phase-4 study was to assess the effect of the implementation of guidelines by describing treatment outcomes in a consecutive nationwide cohort. METHODS: All patients diagnosed with sinonasal carcinoma in Denmark from 2008 to 2015 were identified in the nationwide clinical database, DAHANCA, and were followed until May 2020. Overall survival (OS) was analysed using Kaplan-Meier estimator. Cumulative incidence of locoregional failure (LRF) and disease-specific mortality (DSM) were analysed using the Aalen-Johansen estimator. Competing risks were death from other causes (DSM) and distant failure and death (LRF). Analysis of prognostic factors was performed using Cox proportional hazard analysis. Start of follow-up was time of diagnosis. The results are presented as estimates with 95% confidence intervals (95% CIs). RESULTS: A total of 331 patients were identified. Curatively intended treatment was performed in 264 patients (80%). Non-compliance with treatment guidelines was registered in 24 patients (9%). Non-compliance was associated with LRF (hazard ratio [HR], 2.0 [95% CI: 1.1-3.5]). Among patients qualified for curative treatment, failure occurred in 109 patients (41%), primarily at the primary tumour site (81%). Anatomical tumour site and disease stage were independent prognostic factors. The 5-year OS was 56% in patients treated with curative intent, and a combined treatment strategy showed reduced LRF (HR, 0.53 [95% CI: 0.30-0.92]) in a multivariate analysis. CONCLUSIONS: Guideline compliance and a combined treatment approach reduced the incidence of LRF and thereby increased OS. Our results confirm those of international studies. Treatment of sinonasal carcinoma remains a challenge that requires multidisciplinary team coordination.

European white paper: oropharyngeal dysphagia in head and neck cancer.

PURPOSE: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. METHODS: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. RESULTS: Twenty-four sections on HNC-specific OD topics. CONCLUSION: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Does multiparametric imaging with 18F-FDG-PET/MRI capture spatial variation in immunohistochemical cancer biomarkers in head and neck squamous cell carcinoma?

BACKGROUND: The purpose of this study is to test if functional multiparametric imaging with 18F-FDG-PET/MRI correlates spatially with immunohistochemical biomarker status within a lesion of head and neck squamous cell carcinoma (HNSCC), and also whether a biopsy with the highest FDG uptake was more likely to have the highest PD-L1 expression or the highest percentage of vital tumour cells (VTC) compared with a random biopsy. METHODS: Thirty-one patients with HNSCC were scanned on an integrated PET/MRI scanner with FDG prior to surgery in this prospective study. Imaging was quantified with SUV, ADC and Ktrans. A 3D-morphometric MRI scan of the specimen was used to co-register the patient and the specimen scans. All specimens were sectioned in consecutive slices, and slices from six different locations were selected randomly from each tumour. Core biopsies were performed to construct TMA blocks for IHC staining with the ten predefined biomarkers. The spatial correlation was assessed with a partial correlation analysis. RESULTS: Twenty-eight patients with a total of 33 lesions were eligible for further analysis. There were significant correlations between the three imaging biomarkers and some of the IHC biomarkers. Moreover, a biopsy taken from the most FDG-avid part of the tumour did not have a statistically significantly higher probability of higher PD-L1 expression or VTC, compared with a random biopsy. CONCLUSION: We found statistically significant correlations between functional imaging parameters and key molecular cancer markers.

Rationale and design of a randomised controlled trial investigating the effect of multidisciplinary nutritional rehabilitation for patients treated for head and neck cancer (the NUTRI-HAB trial).

BACKGROUND: Eating problems frequently affect quality of life and physical, psychological and social function in patients treated for head and neck cancer (HNC). Residential rehabilitation programmes may ameliorate these adverse effects but are not indicated for all individuals. Systematic assessment of rehabilitation needs may optimise the use of resources while ensuring referral to rehabilitation for those in need. Yet, evidence lacks on which nutrition screening and assessment tools to use. The trial objectives are: 1) To test the effect of a multidisciplinary residential nutritional rehabilitation programme compared to standard care on the primary outcome body weight and secondary outcomes health-related quality of life, physical function and symptoms of anxiety and depression in patients curatively treated for HNC and 2) To test for correlations between participants' development in outcome scores during their participation in the programme and their baseline scores in Nutritional Risk Screening 2002 (NRS 2002), the Scored Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF), and M. D. Anderson Dysphagia Inventory (MDADI) and to assess sensitivity, specificity and predictive values of the three tools in relation to a clinically relevant improvement in outcome scores. METHODS: In a randomised controlled trial, 72 patients treated for HNC recruited through a nationwide survey will be randomised to a multidisciplinary residential nutritional rehabilitation programme or to a wait-list control group. Data are collected at baseline, three and six months. Primary outcome is change in body weight, and secondary outcomes include changes in quality of life, physical function and symptoms of anxiety and depression. Potential correlations between intervention effect and baseline scores in NRS 2002, PG-SGA-SF and MDADI will be tested, and sensitivity, specificity and predictive values of the three tools in relation to a clinically relevant improvement in outcome scores will be assessed. DISCUSSION: This is the first randomised controlled trial to test the effect of a multidisciplinary residential nutritional rehabilitation programme in patients treated for HNC. Recruitment through a nationwide survey gives a unique possibility to describe the trial population and to identify potential selection bias. As the trial will explore the potential of different nutrition screening and assessment tools in the assessment of rehabilitation needs in patients treated for HNC, the trial will create knowledge about how selection and prioritisation of nutritional rehabilitation aimed at patients treated for HNC should be offered. The results may contribute to a better organisation and use of existing resources in benefit of patients treated for HNC. TRIAL REGISTRATION: The trial is registered by The Danish Data Protection Agency (registration 2012-58-0018, approval number 18/14847) and the Regional Committees on Health Research Ethics for Southern Denmark (journal number 20182000-165). ClinicalTrials.gov Identifier: NCT03909256. Registered April 9, 2019.

Patients' and health professionals' experience of the Danish fast track treatment pathway for head and neck cancer patients receiving oral rehabilitation.

Objective: This study aims to investigate the responsiveness of the Danish treatment pathway for head-and-neck-cancer (HNC) patients receiving oral rehabilitation.Material and Methods: Eighteen HNC-patients who had received oral rehabilitation as well as five medical and four oral health care professionals involved in the treatment of HNC-patients filled in a questionnaire on responsiveness. The responsiveness was further described in individual interviews in the HNC-patients and focus group interviews in the health care professionals. All interviews were semi-structured and analysed using the grounded theory.Results: Patients and health care professionals overall reported good responsiveness of the pathway. Prompt attention was in both groups considered the most important aspect, although the patients found it difficult to cope mentally with the fast-track and the health care professionals reported insufficiencies giving prompt attention. The patients in general described a good relationship with their health care professionals, but along with the health care professionals also reported some problems regarding communication. Further, the health care professionals reported a gap between medical treatment and oral rehabilitation.Conclusions: The Danish treatment pathway for HNC-patients was, in general, evaluated positively. Communication and relationship between patient and health care professional can affect the responsiveness of the pathway.

Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma.

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

Adherence to preventive swallowing exercises for head and neck cancer patients undergoing (chemo)radiotherapy treatment.

Background: In recent years, preventive swallowing exercises have been investigated as a means to limit dysphagia in head and neck cancer patients. However, adherence to exercise regimes has been poorly documented limiting the conclusions drawn on the effects of the interventions. We investigated adherence to a preventive swallowing exercise program and identified possible associations between adherence and four selected baseline factors: HPV status, partner status, concomitant chemotherapy and tumor site and between adherence to swallowing exercises and attendance to supervised training sessions. Material and methods: Forming part of an ongoing RCT (clinicaltrials.gov NCT02385929) adherence to intervention was based on participant provided training-logs. The exercise program consisted of 3 weekly supervised sessions of 30 min each and a home-based exercise program to be performed three times daily. Adherence was calculated as percentage of prescribed exercises completed and dichotomously as high (≥80%∼median) and low (<80%∼median) adherence. Associations between adherence and clinical/demographic factors (HPV, partner status, chemotherapy, tumor site or attendance level) were explored by logistic regression analyses. Results: Full adherence data were available from 45 (76%) participants. The total cohort median adherence to exercises was 78%. No association was found between any of the tested factors and adherence. Discussion: The study found a high adherence to preventive swallowing exercises in HNC patients undergoing (chemo)radiotherapy, both in home-based exercises and in supervised sessions, when compared to other studies, although median adherence to home-based exercises was below the defined 80% threshold. We acknowledge, that adherence in an RCT may be higher than in the everyday clinical situation due to surveillance bias. However, we find it reassuring that HNC patients comply with a preventive swallowing program, which requires some time investment from the patients.

Oral health-related quality of life, oral aesthetics and oral function in head and neck cancer patients after oral rehabilitation.

Head and neck cancer (HNC) is diagnosed in more than 500 000 patients every year worldwide with increasing prevalence. Oral rehabilitation is often needed after HNC treatment to regain oral function, aesthetics and oral health-related quality of life (OHRQoL). The objectives were to evaluate OHRQoL, oral aesthetics and oral function after oral rehabilitation in HNC patients and compare it to that of non-HNC patients. Eighteen patients treated for HNC who subsequently had oral rehabilitation (2014-2017), and a control group of eighteen age- and gender-matched non-HNC patients treated with removable prostheses (2014-2018) were included in a cross-sectional study. The OHRQoL was assessed by the Oral Health Impact Profile 49 questionnaire (OHIP-49), the oral aesthetics by the Prosthetic Esthetic Index (PEI) and the Orofacial Esthetic Scale (OES), and the oral function by the Nordic Orofacial Test-Screening (NOT-S). The HNC patients had worse oral function and OHRQoL than the control patients (mean NOT-S score 4.56 vs 0.56, P < 0.01 and mean OHIP-49 score 42.50 vs 20.94, P = 0.050). When including number of replaced teeth and type of prosthesis in the tests, no significant difference in OHRQoL was found between the groups. No difference was found in the overall aesthetic outcomes (mean PEI total score 32.28 vs 30.67, P = 0.367 and mean OES total score 48.78 vs 53.56, P = 0.321). Multiple regression analyses showed that being HNC patient compared to control patient impaired the oral function. Oral function is significantly impaired in HNC patients compared to non-HNC patients after oral rehabilitation.

Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles.

Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.