A comprehensive approach to defining the cutoff value of oligometastasis in head and neck squamous cell carcinoma.

BACKGROUND: Patients with limited distant metastatic disease, also known as oligometastasis, show better survival rates than polymetastatic patients, and may be amenable for curative-intent treatment. The definition of oligometastasis, however, is unknown, and no quantitative analyses on the cutoff value for oligometastasis have been performed before. This study aims to derive specific threshold values for the number of metastases and affected locations that defines oligometastatic disease in head and neck squamous cell carcinoma. METHODS: A retrospective cohort study was conducted including all patients diagnosed with distant metastases between 2006 and 2021. For each patient, the number of distant metastases and affected locations was recorded on the basis of the available imaging at the time of diagnosis. Cox regression analyses and a machine-learning k-means algorithm were used to determine threshold values. RESULTS: A total of 384 patients untreated for their metastatic foci were analyzed. Most patients (n = 207; 53.9%) had metastasis to one anatomic location, followed by metastases in two anatomic locations (n = 62; 16.1%). The majority of patients had ≥9 metastatic foci (n = 174; 45.3%), followed by one focus (n = 74; 19.3%) and two foci (n = 32; 8.3%). Cox regression and machine-learning k-means models showed that although the number of metastases did not predict survival, the number of affected locations did significantly (p < .001), by identifying a threshold of two locations. CONCLUSIONS: Contrary to the prevalent dogma, the definition of oligometastasis should not be defined by the number of metastases but rather by the number of affected locations, with a maximum number of affected locations set at two.

Proximity ligation-based sequencing for the identification of human papillomavirus genomic integration sites in formalin-fixed paraffin embedded oropharyngeal squamous cell carcinomas.

Human papillomavirus (HPV) infections are an increasing cause of oropharyngeal squamous cell carcinomas (OPSCC). Integration of the viral genome into the host genome is suggested to affect carcinogenesis, however, the correlation with OPSCC patient prognosis is still unclear. Research on HPV integration is hampered by current integration detection technologies and their unsuitability for formalin-fixed paraffin-embedded (FFPE) tissues. This study aims to develop and validate a novel targeted proximity-ligation based sequencing method (targeted locus amplification/capture [TLA/TLC]) for HPV integration detection in cell lines and FFPE OPSCCs. For the identification of HPV integrations, TLA/TLC was applied to 7 cell lines and 27 FFPE OPSCCs. Following preprocessing steps, a polymerase chain reaction (PCR)-based HPV enrichment was performed on the cell lines and a capture-based HPV enrichment was performed on the FFPE tissues before paired-end sequencing. TLA was able to sequence up to hundreds of kb around the target, detecting exact HPV integration loci, structural variants, and chromosomal rearrangements. In all cell lines, one or more integration sites were identified, in accordance with detection of integrated papillomavirus sequences PCR data and the literature. TLC detected integrated HPV in 15/27 FFPE OPSCCs and identified simple and complex integration patterns. In general, TLA/TLC confirmed PCR data and detected additional integration sites. In conclusion TLA/TLC reliably and robustly detects HPV integration in cell lines and FFPE OPSCCs, enabling large, population-based studies on the clinical relevance of HPV integration. Furthermore, this approach might be valuable for clonality assessment of HPV-related tumors in clinical diagnostics.

The Rhinoplasty Health Care Monitor: An Update on the Practical and Clinical Benefits after 10 Years of Prospective Outcome Measurements.

The era of value-based health care is characterized by an increasing interest in patient-reported health outcomes. For this purpose we developed the rhinoplasty health care monitor (RHM), a streamlined outcome measurement protocol, including all rhinoplasty patients since 2014. Statistical analyses of patient-reported outcome data are automated and visually presented on a custom web-based dashboard. We describe the clinical and practical benefits of the RHM and discuss how routine prospective outcome measurements have upgraded our care standards. For this prospective study, 979 consecutive patients referred for functional (revision) rhinoplasty from April 2014 to August 2023 were included. Preoperative and 3- and 12-month postoperative scores on the Nasal Obstruction Symptom Evaluation scale (NOSE), Utrecht Questionnaire (UQ), and visual analog scales (VAS) were obtained. Of 979 referred patients, 599 (61.2%) were eligible for rhinoplasty. One year postoperatively, mean NOSE scale sum score improved from 69.1 ± 22.8 to 23.1 ± 23.5 (p < 0.001). Functional VAS scores improved from 4.1 ± 2.8 (left) and 4.1 ± 2.8 (right) to 7.5 ± 1.9 (left) and 7.3 ± 2.0 (right; p < 0.001). Mean UQ sum score improved from 12.0 ± 6.4 to 6.8 ± 3.3 and aesthetic VAS score improved from 4.5 ± 2.5 to 7.4 ± 1.7 (p < 0.001) 1 year postoperatively. Benefits of the outcome routine were improved patient selection, data-driven expectation management and patient empowerment, and targeted critical appraisals of surgical performance. In conclusion, routine, automated, prospective outcome monitoring provides physicians with a response to the increasing demand for data-driven insights in health outcomes. The limited effort that is needed to gather and monitor outcome data is heavily repaid by valuable insights into aspects of care that can be improved.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Evaluation of the Sensitivity of Metabolic Profiling by Rapid Evaporative Ionization Mass Spectrometry: Toward More Radical Oral Cavity Cancer Resections.

Radical resection for patients with oral cavity cancer remains challenging. Rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical vapors has been reported for real-time classification of normal and tumor tissues for numerous surgical applications. However, the infiltrative pattern of invasion of oral squamous cell carcinomas (OSCC) challenges the ability of REIMS to detect low amounts of tumor cells. We evaluate REIMS sensitivity to determine the minimal amount of detected tumors cells during oral cavity cancer surgery. A total of 11 OSCC patients were included in this study. The tissue classification based on 185 REIMS ex vivo metabolic profiles from five patients was compared to histopathology classification using multivariate analysis and leave-one-patient-out cross-validation. Vapors were analyzed in vivo by REIMS during four glossectomies. Complementary desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was employed to map tissue heterogeneity on six oral cavity sections to support REIMS findings. REIMS sensitivity was assessed with a new cell-based assay consisting of mixtures of cell lines (tumor, myoblasts, keratinocytes). Our results depict REIMS classified tumor and soft tissues with 96.8% accuracy. In vivo REIMS generated intense mass spectrometric signals. REIMS detected 10% of tumor cells mixed with 90% myoblasts with 83% sensitivity and 82% specificity. DESI-MSI underlined distinct metabolic profiles of nerve features and a metabolic shift phosphatidylethanolamine PE(O-16:1/18:2))/cholesterol sulfate common to both mucosal maturation and OSCC differentiation. In conclusion, the assessment of tissue heterogeneity with DESI-MSI and REIMS sensitivity with cell mixtures characterized sensitive metabolic profiles toward in vivo tissue recognition during oral cavity cancer surgeries.

Public awareness of the association between human papillomavirus and oropharyngeal cancer.

BACKGROUND: Early diagnosis of human papillomavirus (HPV) associated oropharyngeal cancer (OPC) is associated with improved survival. To achieve early diagnosis, it might be beneficial to increase awareness of the link between HPV and OPC. This increase of awareness could also be an important way to increase vaccination rates. The aim of our study was to explore the current public knowledge in the Netherlands regarding the association of HPV with OPC. METHODS: An online cross-sectional survey was used and sent by the company Flycatcher Internet Research to 1539 of their panel members. Data were analyzed statistically by gender, age, educational level and the participants' use of alcohol and tobacco. RESULTS: The response rate was 68% (1044 participants). Our data revealed that 30.6% of the participants had heard of HPV. There was a knowledge gap regarding HPV in males (P < 0.001), people older than 65 years (P < 0.001), people with low education level (P < 0.001) and current smokers (P < 0.001). Of the respondents who had heard of HPV, only 29.2% knew of the association between HPV and OPC. We also found that only 49.7% of the population knew of the existence of an HPV vaccine. CONCLUSIONS: The results of this survey indicate that the public awareness of HPV and the association of HPV with OPC is lacking. Interventions to increase awareness of HPV and its association with non-cervical cancer should be considered. This might help to increase the HPV vaccine uptake both for girls and boys and earlier diagnosis of this disease leading to improved survival.

The Effect of Cranial Nerve Stimulation on Swallowing: A Systematic Review.

This systematic review summarizes published studies on the effect of cranial nerve stimulation (CNS) on swallowing and determines the level of evidence of the included studies to guide the development of future research on new treatment strategies for oropharyngeal dysphagia (OD) using CNS. Studies published between January 1990 and October 2019 were found via a systematic comprehensive electronic database search using PubMed, Embase, and the Cochrane Library. Two independent reviewers screened all articles based on the title and abstract using strict inclusion criteria. They independently screened the full text of this initial set of articles. The level of evidence of the included studies was assessed independently by the two reviewers using the A-B-C rating scale. In total, 3267 articles were found in the databases. In the majority of these studies, CNS was used for treatment-resistant depression or intractable epilepsy. Finally, twenty-eight studies were included; seven studies on treatment of depression, thirteen on epilepsy, and eight on heterogeneous indications. Of these, eight studies reported the effects of CNS on swallowing and in 20 studies the swallowing outcome was described as an adverse reaction. A meta-analysis could not be carried out due to the poor methodological quality and heterogeneity of study designs of the included studies. These preliminary data suggest that specific well-indicated CNS might be effective in reducing OD symptoms in selective patient groups. But it is much too early for conclusive statements on this topic. In conclusion, the results of these studies are encouraging for future research on CNS for OD. However, randomized, double-blind, sham-controlled clinical trials with sufficiently large sample sizes are necessary.

Evaluating the safety of oral methylene blue during swallowing assessment: a systematic review.

OBJECTIVE: Methylene blue (MB) is frequently administered during fiberoptic endoscopic evaluation of swallowing (FEES) to enhance visualization of pharyngeal bolus transit. However, the safety of MB is being questioned since serious adverse events (AEs) such as hemodynamic instability, hemolysis, and serotonin syndrome were reported. The aim of this study is a systematic analysis of the literature to obtain an evidence-based overview of AEs due to oral administration of MB and to determine its safety as a food dye during swallowing assessment. METHODS: A systematic literature search was carried out in PubMed, Embase, and Cochrane Library. Two reviewers independently selected articles describing oral administration of MB as a main diagnostic/therapeutic intervention, dosage, and AEs. Expert opinions, conference papers, sample size < 10, and animal studies were excluded. Level of evidence of the included studies was determined. RESULTS: A total of 2264 unduplicated articles were obtained. Seventeen studies met the inclusion criteria with 100% agreement between the two reviewers. Among these, twelve studies were randomized controlled trials. In a pooled population of 1902 patients receiving oral MB, three serious AEs were reported related to MB. Non-serious AEs showed a dose-related trend and were usually mild and self-limiting. A meta-analysis could not be performed as studies were methodologically too heterogeneous. CONCLUSION: Serious AEs due to oral administration of MB are rare (n = 3, 0.16%). MB-related non-serious AEs are mild, self-limiting, and show a dose-related trend. These findings indicate that it is safe to use small amounts of MB as a food dye during swallowing examinations.

Patients with Head-and-Neck Cancer: Dysphagia and Affective Symptoms.

OBJECTIVE: Affective symptoms are common in patients with head-and-neck cancer. This study determined the association between the presence of aspiration and symptoms of anxiety and depression, as well as patient characteristics in patients with head-and-neck cancer and dysphagia. METHODS: Eighty-four patients with head-and-neck cancer and dysphagia completed the Hospital Anxiety and Depression Scale and underwent a standardized fiberoptic endoscopic evaluation of swallowing. Linear regression analysis was performed to explore the associations. RESULTS: Fifty-two (61.9%) patients presented clinically relevant symptoms of anxiety or depression. Forty-eight (57.1%) patients presented with aspiration during fiberoptic endoscopic evaluation of swallowing. A significant negative association was found between the presence of aspiration and affective (anxiety and depression) symptoms (p = 0.04). Male patients presented significantly lower symptom scores of anxiety compared to females (p = 0.04). CONCLUSIONS: Clinically relevant affective symptoms were present in more than half of all patients with head-and-neck cancer and dysphagia. Surprisingly, a significant negative association was found between the presence of aspiration and these affective symptoms. Gender was also significantly associated with affective symptoms. These results suggest that there is a need for further investigation into the impact of psychological distress on patients with head-and-neck cancer and dysphagia.

Association Between Pharyngeal Pooling and Aspiration Using Fiberoptic Endoscopic Evaluation of Swallowing in Head and Neck Cancer Patients with Dysphagia.

Postswallow pharyngeal pooling may be a risk factor for tracheal aspiration. However, limited literature shows the potential association between pharyngeal pooling and aspiration in head and neck cancer (HNC) patients. This study investigates the relationship between postswallow pharyngeal pooling and aspiration in HNC patients with oropharyngeal dysphagia. Furthermore, the effects of tumor stage, tumor location, and cancer treatment on aspiration were examined. Ninety dysphagic HNC patients underwent a standardized fiberoptic endoscopic evaluation of swallowing (FEES) using thin and thick liquid boluses. For each swallow, three visuoperceptual ordinal variables were scored: postswallow vallecular pooling, postswallow pyriform sinus pooling, and aspiration. Logistic regression analyses with correction for the location of pooling, tumor stage, tumor location, and cancer treatment were performed to explore the association between pooling and aspiration. No significant association was found between postswallow vallecular pooling and aspiration for thin liquid. However, severe versus mild-to-moderate postswallow vallecular pooling of thick liquid was significantly associated to aspiration. Similar results were seen after correction for the presence of pyriform sinus pooling, tumor stage, tumor location, or type of cancer treatment. This study showed a significant association between severe postswallow pyriform sinus pooling of thick liquid and aspiration, independent of the presence of vallecular pooling, tumor stage, tumor location, or cancer treatment. Concluding, location (valleculae versus pyriform sinuses), liquid bolus consistency (thin versus thick liquid), and amount of postswallow pharyngeal pooling (no pooling, mild/moderate pooling, severe pooling) have an influence on the probability of aspiration in dysphagic HNC patients, and they should be carefully considered during FEES, even in the absence of aspiration during the examination.

Swallow-related quality of life and oropharyngeal dysphagia in myotonic dystrophy.

PURPOSE: This study describes swallow-related quality of life (SWAL-QOL) in patients with myotonic dystrophy type 1 (DM1) and investigates its association with swallowing function and disease severity. METHODS: A SWAL-QOL questionnaire was completed by 75 DM1 patients and 25 healthy control subjects. The severity of the disease was evaluated using the muscular impairment rating scale (MIRS). Twenty-eight DM1 patients underwent a videofluroscopic swallowing examination (VFS). Spearman's correlation coefficient was used to measure the direction and strength of associations. RESULTS: The SWAL-QOL median scores were significantly lower for the DM1 group than for the healthy control group. The scores for the majority of the SWAL-QOL domains were lower in patients with proximal muscular weakness (MIRS 4 and 5). Postswallow vallecular pooling and piecemeal deglutition were the most impaired VFS outcome variables. CONCLUSION: Our results suggest that a multidimensional swallowing assessment is recommended for DM1 patients as SWAL-QOL and VFS measure different aspects of the swallowing function, thus providing complementary information.

Tumor control of cervical lymph node metastases of unknown primary origin: the impact of the radiotherapy target volume.

PURPOSE: Debate on the extent of treatment of neck metastasis of cancer of unknown primary tumors (CUPs) is still ongoing. In two Dutch tertiary referral centers, the post-surgical radiation target volume changed from the bilateral neck including the pharyngeal axis to the unilateral neck only, in the course of the last decade. This study aims to investigate the outcome of patients with CUP before and after de-escalation of post-surgical radiotherapy. METHODS: Data of two Dutch tertiary referral centers were merged. Disease-free survival (DFS), overall survival (OS), and regional control rate (RCR) of 80 patients diagnosed with CUP (squamous cell and undifferentiated carcinomas) between 1990 and 2009 were retrospectively analyzed. RESULTS: Thirty patients received bilateral neck and pharyngeal axis radiotherapy and 42 patients ipsilateral radiotherapy only. In another eight patients, the postsurgical radiation target volume was expanded to the contralateral neck or to the pharyngeal axis, due to suspicious lesions on imaging. The 5-year DFS, OS and RCR were 60%, 51.2%, and 80%, respectively, in the total patient population. RCR did not differ in patients treated with ipsilateral as compared to bilateral radiotherapy nor did 5-year OS and DFS. No tumors occurred in the pharyngeal axis. CONCLUSION: In this study, omitting elective treatment of the contralateral neck and pharyngeal axis did not lead to a decrease in locoregional control or survival rates when treating patients with CUP.

Upregulation of AKR1C1 and AKR1C3 expression in OPSCC with integrated HPV16 and HPV-negative tumors is an indicator of poor prognosis.

Different studies have shown that HPV16-positive OPSCC can be subdivided based on integration status (integrated, episomal and mixed forms). Because we showed that integration neither affects the levels of viral genes, nor those of virally disrupted human genes, a genome-wide screen was performed to identify human genes which expression is influenced by viral integration and have clinical relevance. Thirty-three fresh-frozen HPV-16 positive OPSCC samples with known integration status were analyzed by mRNA expression profiling. Among the genes of interest, Aldo-keto-reductases 1C1 and 1C3 (AKR1C1, AKR1C3) were upregulated in tumors with viral integration. Additionally, 141 OPSCC, including 48 HPV-positive cases, were used to validate protein expression by immunohistochemistry. Results were correlated with clinical and histopathological data. Non-hierarchical clustering resulted in two main groups differing in mRNA expression patterns, which interestingly corresponded with viral integration status. In OPSCC with integrated viral DNA, often metabolic pathways were deregulated with frequent upregulation of AKR1C1 and AKR1C3 transcripts. Survival analysis of 141 additionally immunostained OPSCC showed unfavorable survival rates for tumors with upregulation of AKR1C1 or AKR1C3 (both p <0.0001), both in HPV-positive (p ≤0.001) and -negative (p ≤0.017) tumors. OPSCC with integrated HPV16 show upregulation of AKR1C1 and AKR1C3 expression, which strongly correlates with poor survival rates. Also in HPV-negative tumors, upregulation of these proteins correlates with unfavorable outcome. Deregulated AKR1C expression has also been observed in other tumors, making these genes promising candidates to indicate prognosis. In addition, the availability of inhibitors of these gene products may be utilized for drug treatment.

Medically Unexplained Oropharyngeal Dysphagia at the University Hospital ENT Outpatient Clinic for Dysphagia: A Cross-Sectional Cohort Study.

Medically unexplained oropharyngeal dysphagia (MUNOD) is a rare condition. It presents without demonstrable abnormalities in the anatomy of the upper aero-digestive tract and/or swallowing physiology. This study investigates whether MUNOD is related to affective or other psychiatric conditions. The study included patients with dysphagic complaints who had no detectible structural or physiological abnormalities upon swallowing examination. Patients with any underlying disease or disorder that could explain the oropharyngeal dysphagia were excluded. All patients underwent a standardized examination protocol, with FEES examination, the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Severity Scale (DSS). Two blinded judges scored five different FEES variables. None of the 14 patients included in this study showed any structural or physiological abnormalities during FEES examination. However, the majority did show abnormal piecemeal deglutition, which could be a symptom of MUNOD. Six patients (42.8%) had clinically relevant symptoms of anxiety and/or depression. The DSS scores did not differ significantly between patients with and without affective symptoms. Affective symptoms are common in patients with MUNOD, and their psychiatric conditions could possibly be related to their swallowing problems.

Methadone versus Fentanyl in Patients with Radiation-Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial.

BACKGROUND: Pain is still a burden for many patients with cancer. A recent trial showed the superiority of methadone over fentanyl in neuropathic pain, and we expect that this finding could influence the number of patients treated with methadone. METHODS: We performed a randomized controlled noninferiority trial in patients with nociceptive pain. Eighty-two strong-opioid-naïve patients with head and neck cancer with substantial pain (pain numeric rating scale [NRS] score ≥ 4) due to radiation therapy were included. Forty-two patients were treated with methadone, and 40 with fentanyl. Patients were evaluated at 1, 3, and 5 weeks. The primary outcomes were reduction in average pain and clinical success (50% pain decrease). We set the predefined noninferiority margin at 1 on the NRS and 10% clinical success. Secondary outcomes were pain interference, global perceived effect (GPE), side effects, and opioid escalation index. RESULTS: Noninferiority was shown for decrease in NRS for maximum and mean pain scores at 1 and 3 weeks. Noninferiority was shown for clinical success at 1 week only. The opioid escalation index was lower in the methadone group at 3 and 5 weeks as compared to fentanyl (1.44 vs. 1.99, P = 0.004; and 1.50 vs. 2.32, P = 0.013). The pain interference in the methadone group was significantly decreased at 3 weeks only. GPE and side effects were not different. CONCLUSION: This is the first study to show noninferiority of methadone compared to fentanyl at 1 and 3 weeks in the treatment of radiation-induced nociceptive pain in patients with head and neck cancer.

Intake of meat and fish and risk of head-neck cancer subtypes in the Netherlands Cohort Study.

PURPOSE: To date, the role of meat and fish intake in head-neck cancer (HNC) etiology is not well understood and prospective evidence is limited. This prompted us to study the association between meat, fish, and HNC subtypes, i.e., oral cavity cancer (OCC), oro- and hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), within the Netherlands Cohort Study (NLCS). METHODS: In 1986, 120,852 participants (aged 55-69 years) completed a baseline 150-item food frequency questionnaire (FFQ), from which daily meat and fish intake were calculated. After 20.3 years of follow-up, 430 HNC overall (134 OCC, 90 OHPC and 203 LC) cases and 4,111 subcohort members were found to be eligible for case-cohort analysis. Multivariate hazard ratios were calculated using Cox's proportional hazards model within quartiles of energy-adjusted meat and fish intake. RESULTS: Processed meat intake, but not red meat intake, was positively associated with HNC overall [HR(Q4 vs. Q1) = 1.46, 95% CI 1.06-2.00; ptrend = 0.03]. Among HNC subtypes, processed meat was positively associated with OCC, while no associations were found with OHPC and LC. Fish intake was not associated with HNC risk. Tests for interaction did not reveal statistically significant interaction between meat, fish, and alcohol or smoking on HNC overall risk. CONCLUSIONS: In this large cohort study, processed meat intake was positively associated with HNC overall and HNC subtype OCC, but not with OHPC and LC.

Experiences and preferences of patients visiting a head and neck oncology outpatient clinic: a qualitative study.

The objective of this study is to report on an in-depth evaluation of patient experiences and preferences at a Head and Neck Oncology outpatient clinic. A qualitative research design was used to determine the experiences and preferences of Head and Neck Cancer patients in an Oncology Outpatient Clinic, Maastricht University Medical Center, The Netherlands. Head and Neck Cancer Patients, treated for at least 6 months at the Oncology Clinic, were included. A qualitative research design with patient interviews was used. All interviews were recorded and transcribed verbatim to increase validity. Analysis was done with use of the template approach and qualitative data analysis software. Three of the six dimensions predominated in the interview: (1) respect for patients' values, preferences and expressed need, (2) information, communication and education and (3) involvement of family and friends. The dimensions physical comfort; emotional support; coordination and integration of care were considered to be of less significance. The findings from this study resulted in a deeper understanding of patients' experiences and preferences and can be useful in the transition towards a more patient-centered approach of health care.

Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study.

BACKGROUND: Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer. METHODS: The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification. FINDINGS: Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages. INTERPRETATION: Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification. FUNDING: None.

Experiences and preferences of patients visiting an otorhinolaryngology outpatient clinic: a qualitative study.

BACKGROUND: Patient-centred care has received considerable attention in the last few decades, but the patients' perspective remains underexposed. This study reports on an in-depth evaluation of patients' experiences and preferences at an otorhinolaryngology outpatient department. METHODS: Qualitative research was conducted on patients' experiences and preferences at an otorhinolaryngology outpatient department in an academic hospital. The study comprised two phases. First, semi-structured interviews were held with 22 patients. Second, results from the interviews were verified and deepened in a focus group (N = 7). RESULTS: Overall, experience with patient-centred care was positive at the outpatient department. Three of the six dimensions of patient-centred care predominated in the interviews and the focus group: information, communication and education; coordination and integration of care; and respect for patients' values, preferences and expressed needs. The negative experiences were mostly in these dimensions. The dimensions physical comfort and involvement of family and friends were of lesser significance. Opinion on emotional support--relieving fear and anxiety differed as to whether this was the responsibility of the doctor or the patient. CONCLUSION: Qualitative research provided a deeper understanding of patients' experiences and preferences at an otorhinolaryngology outpatient department. Such an in-depth evaluation can be useful in the transition towards patient-centred care.

The impact of redesigning care processes on quality of care: a systematic review.

BACKGROUND: This literature review evaluates the current state of knowledge about the impact of process redesign on the quality of healthcare. METHODS: Pubmed, CINAHL, Web of Science and Business Premier Source were searched for relevant studies published in the last ten years [2004-2014]. To be included, studies had to be original research, published in English with a before-and-after study design, and be focused on changes in healthcare processes and quality of care. Studies that met the inclusion criteria were independently assessed for excellence in reporting by three reviewers using the SQUIRE checklist. Data was extracted using a framework developed for this review. RESULTS: Reporting adequacy varied across the studies. Process redesign interventions were diverse, and none of the studies described their effects on all dimensions of quality defined by the Institute of Medicine. CONCLUSIONS: The results of this systematic literature review suggests that process redesign interventions have positive effects on certain aspects of quality. However, the full impact cannot be determined on the basis of the literature. A wide range of outcome measures were used, and research methods were limited. This review demonstrates the need for further investigation of the impact of redesign interventions on the quality of healthcare.