Evaluating the Potential of AI Chatbots in Treatment Decision-making for Acquired Bilateral Vocal Fold Paralysis in Adults.

OBJECTIVES: The development of artificial intelligence-powered language models, such as Chatbot Generative Pre-trained Transformer (ChatGPT) or Large Language Model Meta AI (Llama), is emerging in medicine. Patients and practitioners have full access to chatbots that may provide medical information. The aim of this study was to explore the performance and accuracy of ChatGPT and Llama in treatment decision-making for bilateral vocal fold paralysis (BVFP). METHODS: Data of 20 clinical cases, treated between 2018 and 2023, were retrospectively collected from four tertiary laryngology centers in Europe. The cases were defined as the most common or most challenging scenarios regarding BVFP treatment. The treatment proposals were discussed in their local multidisciplinary teams (MDT). Each case was presented to ChatGPT-4.0 and Llama Chat-2.0, and potential treatment strategies were requested. The Artificial Intelligence Performance Instrument (AIPI) treatment subscore was used to compare both Chatbots' performances to MDT treatment proposal. RESULTS: Most common etiology of BVFP was thyroid surgery. A form of partial arytenoidectomy with or without posterior transverse cordotomy was the MDT proposal for most cases. The accuracy of both Chatbots was very low regarding their treatment proposals, with a maximum AIPI treatment score in 5% of the cases. In most cases even harmful assertions were made, including the suggestion of vocal fold medialisation to treat patients with stridor and dyspnea. ChatGPT-4.0 performed significantly better in suggesting the correct treatment as part of the treatment proposal (50%) compared to Llama Chat-2.0 (15%). CONCLUSION: ChatGPT and Llama are judged as inaccurate in proposing correct treatment for BVFP. ChatGPT significantly outperformed Llama. Treatment decision-making for a complex condition such as BVFP is clearly beyond the Chatbot's knowledge expertise. This study highlights the complexity and heterogeneity of BVFP treatment, and the need for further guidelines dedicated to the management of BVFP.

Individualized Dynamic Prediction Model for Patient-Reported Voice Quality in Early-Stage Glottic Cancer.

OBJECTIVE: Early-stage glottic cancer (ESGC) is a malignancy of the head and neck. Besides disease control, preservation and improvement of voice quality are essential. To enable expectation management and well-informed decision-making, patients should be sufficiently counseled with individualized information on expected voice quality. This study aims to develop an individualized dynamic prediction model for patient-reported voice quality. This model should be able to provide individualized predictions at every time point from intake to the end of follow-up. STUDY DESIGN: Longitudinal cohort study. SETTING: Tertiary cancer center. METHODS: Patients treated for ESGC were included in this study (N = 294). The Voice Handicap Index was obtained prospectively. The framework of mixed and joint models was used. The prognostic factors used are treatment, age, gender, comorbidity, performance score, smoking, T-stage, and involvement of the anterior commissure. The overall performance of these models was assessed during an internal cross-validation procedure and presentation of absolute errors using box plots. RESULTS: The mean age in this cohort was 67 years and 81.3% are male. Patients were treated with transoral CO2 laser microsurgery (57.8%), single vocal cord irradiation up to (24.5), or local radiotherapy (17.5%). The mean follow-up was 43.4 months (SD 21.5). Including more measurements during prediction improves predictive performance. Including more clinical and demographic variables did not provide better predictions. Little differences in predictive performance between models were found. CONCLUSION: We developed a dynamic individualized prediction model for patient-reported voice quality. This model has the potential to empower patients and professionals in making well-informed decisions and enables tailor-made counseling.

Longitudinal Patient-Reported Voice Quality in Early-Stage Glottic Cancer.

OBJECTIVE: Patient-reported voice quality is an important outcome during counseling in early-stage glottic cancer. However, there is a paucity of adequate longitudinal studies concerning voice outcomes. This study aimed to investigate longitudinal trajectories for patient-reported voice quality and associated risk factors for treatment modalities such as transoral CO2 laser microsurgery, single vocal cord irradiation, and local radiotherapy. STUDY DESIGN: A longitudinal observational cohort study. SETTING: Tertiary cancer center. METHODS: Patients treated for Tcis-T1b, N0M0 glottic cancer were included in this study (N = 294). The Voice Handicap Index was obtained at baseline and during follow-up (N = 1944). Mixed-effects models were used for investigating the different trajectories for patient-reported voice quality. RESULTS: The mean follow-up duration was 43.4 (SD 21.5) months. Patients received transoral CO2 laser microsurgery (57.8%), single vocal cord irradiation (24.5%), or local radiotherapy (17.5%). A steeper improvement during the first year after treatment for single vocal cord irradiation (-15.7) and local radiotherapy (-12.4) was seen, compared with a more stable trajectory for laser surgery (-6.1). All treatment modalities showed equivalent outcomes during long-term follow-up. Associated risk factors for different longitudinal trajectories were age, tumor stage, and comorbidity. CONCLUSION: Longitudinal patient-reported voice quality after treatment for early-stage glottic cancer is heterogeneous and nonlinear. Most improvement is seen during the first year of follow-up and differs between treatment modalities. No clinically significant differences in long-term trajectories were found. Insight into longitudinal trajectories can enhance individual patient counseling and provide the foundation for an individualized dynamic prediction model.

Decisional Conflict in Patients With Head and Neck Cancer.

Importance: Patients who experience less decisional conflict (DC) are more engaged in treatment and less prone to decisional regret, nervousness, and fretting. Objectives: To assess DC among patients with head and neck squamous cell carcinoma (HNSCC) after the treatment decision consultation and the association between DC and quality of life as well as the degree of control patients experience in the decision-making process using the control preference scale and the association with DC. Design, Setting, and Participants: This prospective cohort study with 2 separate cohorts was conducted at a tertiary cancer center and included patients who were eligible for curative treatment of a primary squamous cell carcinoma between January 2014 and August 2018. The 2 cohorts comprised 102 patients with small laryngeal squamous cell carcinoma (SLSCC) and 161 patients with other HNSCC. Main Outcomes and Measures: Decisional Conflict Scale (DCS) score, which was scored within 2 weeks after the treatment decision consultation. Other measures included patient characteristics, tumor characteristics, and Control Preference Scale , EuroQol-5D, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, Hospital Anxiety and Depression Scale (HADS), Eating Assessment Tool, and Voice Handicap Index (VHI) scores. Results: Of 263 patients, 50 (19%) were women; the mean (SD) age was 66.1 (11.4) years in the SLSCC group and 64.9 (9.8) years in the other HNSCC group. In the SLSCC group, 51 patients (50%) experienced clinically significant DC (total score ≥25) compared with 74 patients (46%) in the other HNSCC group. In the SLSCC group, there was a large difference in the median EuroQol-5D, Global Health status, HADS anxiety, HADS depression, and VHI scores between the patients with a total DCS score of less than 25 and total DCS score of 25 or greater, whereas in the other HNSCC group, this only applied to the VHI. Forty-four patients (43.1%) in the SLSCC group felt their treatment choice was a shared decision, and 39 (38.2%) made the decision themselves. In the other HNSCC group, 62 (38.5%) felt that the physician decided, and 56 (34.8%) felt it was a shared decision. In both groups there was a weak association between control preference scale scores and DC. Conclusions and Relevance: The results of this cohort study found that almost half of patients (48%) experienced clinically significant DC. Several quality-of-life measures associated with clinically significant DC were identified. These results suggest that there is room for improvement in aiming to reduce decision delay and decision-related distress.

Development and Assessment of a Model for Predicting Individualized Outcomes in Patients With Oropharyngeal Cancer.

Importance: Recent insights into the biologic characteristics and treatment of oropharyngeal cancer may help inform improvements in prognostic modeling. A bayesian multistate model incorporates sophisticated statistical techniques to provide individualized predictions of survival and recurrence outcomes for patients with newly diagnosed oropharyngeal cancer. Objective: To develop a model for individualized survival, locoregional recurrence, and distant metastasis prognostication for patients with newly diagnosed oropharyngeal cancer, incorporating clinical, oncologic, and imaging data. Design, Setting, and Participants: In this prognostic study, a data set was used comprising 840 patients with newly diagnosed oropharyngeal cancer treated at a National Cancer Institute-designated center between January 2003 and August 2016; analysis was performed between January 2019 and June 2020. Using these data, a bayesian multistate model was developed that can be used to obtain individualized predictions. The prognostic performance of the model was validated using data from 447 patients treated for oropharyngeal cancer at Erasmus Medical Center in the Netherlands. Exposures: Clinical/oncologic factors and imaging biomarkers collected at or before initiation of first-line therapy. Main Outcomes and Measures: Overall survival, locoregional recurrence, and distant metastasis after first-line cancer treatment. Results: Of the 840 patients included in the National Cancer Institute-designated center, 715 (85.1%) were men and 268 (31.9%) were current smokers. The Erasmus Medical Center cohort comprised 300 (67.1%) men, with 350 (78.3%) current smokers. Model predictions for 5-year overall survival demonstrated good discrimination, with area under the curve values of 0.81 for the model with and 0.78 for the model without imaging variables. Application of the model without imaging data in the independent Dutch validation cohort resulted in an area under the curve of 0.75. This model possesses good calibration and stratifies patients well in terms of likely outcomes among many competing events. Conclusions and Relevance: In this prognostic study, a multistate model of oropharyngeal cancer incorporating imaging biomarkers appeared to estimate and discriminate locoregional recurrence from distant metastases. Providing personalized predictions of multiple outcomes increases the information available for patients and clinicians. The web-based application designed in this study may serve as a useful tool for generating predictions and visualizing likely outcomes for a specific patient.

Predicting survival in head and neck cancer: External validation and update of the prognostic model OncologIQ in 2189 patients.

BACKGROUND: Disclosing prognostic information is necessary to enable patients to make well-informed treatment decisions. OncologIQ is a prognostic model that predicts the overall survival (OS) probability in patients with head and neck squamous cell carcinoma (HNSCC). We aimed to externally validate and update the model with new prognostic factors and translate it to a clinically useful tool. METHODS: A consecutive retrospective sample of 2189 patients eligible for curative treatment of a primary HNSCC were selected. Discriminative performance was determined using the C-statistic. RESULTS: External validation showed systematic underestimation of OS in the new population, and reasonable discrimination (C-statistic 0.67). Adding smoking, pack years, BMI, weight loss, WHO performance, socioeconomic status, and p16 positivity to the recalibrated multivariable model, improved the internally validated C-statistic to 0.71. The model showed minor optimism and was translated in an online tool (www.oncologiq.nl). CONCLUSIONS: The updated model enables personalized patient counseling during treatment decision consultations.

Dissemination patterns and chronology of distant metastasis affect survival of patients with head and neck squamous cell carcinoma.

OBJECTIVES: To define metastatic categories based on their prognostic significance. We hypothesized that oligometastasis in patients with head and neck squamous cell carcinoma (HNSCC) is associated with better post-distant metastasis disease specific survival (post-DM DSS) compared to patients with polymetastasis. Furthermore, the impact on survival of synchronous versus metachronous distant metastasis (DM) occurrence was assessed. MATERIALS AND METHODS: Retrospective cohort study in which patients with DM were stratified into three groups: oligometastasis (maximum of 3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site) and explosive-disseminating metastasis (spread to ≥3 anatomic sites or >3 metastatic foci in 2 anatomic sites). In addition, patients were divided into synchronous versus metachronous DM. RESULTS: Between January 1, 2006 and December 31, 2013, a total of 2687 patients with HNSCC were identified, of which 324 patients developed DM. In this group, 115 (35.5%) patients had oligometastasis, 64 (19.8%) patients had explosive metastasis and 145 (44.8%) patients had explosive-disseminating metastasis. Their median post-DM DSS were 4.7 months, 4.1 months and 1.7 months respectively (p < .001). Synchronous DM was associated with more favorable survival rates in univariable and multivariable analyses than metachronous DM with recurrence of the index tumor (6-month post-DM DSS probability of 0.51 vs 0.17, p < .001). CONCLUSION: Oligometastasis in HNSCC signifies a better prognosis than a polymetastatic pattern. Metachronous DM occurrence with recurrence of the primary index tumor is associated with an unfavorable prognosis.

Treatment of head and neck carcinoma of unknown primary: Cracking a nut with a sledgehammer?

OBJECTIVES: To compare the impact on survival and late radiation toxicity of patients with squamous cell carcinoma of unknown primary who were treated with ipsilateral neck dissection and ipsilateral postoperative radiotherapy (PORT) and patients treated with ipsilateral neck dissection and PORT to both sides of the neck plus the pharyngeal axis. METHODS: Retrospective cohort study performed at the Erasmus University Medical Center in which 78 patients with squamous cell carcinoma of unknown primary were identified. Thirty-nine patients received PORT to both sides of the neck plus the pharyngeal axis (BILAX) and another 39 patients were irradiated on the ipsilateral neck (IPSI) only. The endpoints of the present study were 3-year overall survival (OS), 3-year disease-free survival (DFS), and overall late radiation toxicity. RESULTS: The 3-year OS rate of the entire group of 78 patients was 74.2% and the 3-year DFS rate was 72.7%. The 3-year OS rates for the IPSI and the BILAX groups were 74.4% and 74.1%, respectively (P = .654). The most common late radiation toxicity experienced was xerostomia (64.8%), which was significantly more often seen in the BILAX group than in the IPSI group (83.8% and 44.1%, respectively, P = .001). Overall late radiation toxicity was significantly higher in the BILAX group (P = .003). CONCLUSION: There was no significant difference in OS and DFS rates between the IPSI and the BILAX group. Late radiation toxicity was significantly higher in the BILAX group. LEVEL OF EVIDENCE: Level 2b: Individual retrospective cohort study.

A cause-specific Cox model for second primary tumors in patients with head and neck cancer: A RONCDOC study.

BACKGROUND: The aim of this study was to identify risk factors for the development of second primary tumors (SPTs) in the head and neck region, lungs, and esophagus in patients with head and neck cancer. METHODS: We collected data from 1581 patients. A cause-specific Cox model for the development of an SPT was fitted, accounting for the competing risks residual/recurrent tumor and mortality. RESULTS: Of all patients, 246 (15.6%) developed SPTs. Analysis showed that tobacco and alcohol use, comorbidity, and the oral cavity subsite were risk factors for SPTs. The C-index, the discriminative accuracy, of the model for SPT was 0.65 (95% confidence interval, 0.61-0.68). CONCLUSIONS: Our results show that there is potential to identify patients who have an increased risk to develop an SPT. This might increase their survival chances and quality of life. More research is needed to provide head and neck clinicians with definitive recommendations.

Keys to successful implementation of routine symptom monitoring in head and neck oncology with "Healthcare Monitor" and patients' perspectives of quality of care.

BACKGROUND: Value-based health care is increasingly used to facilitate a systematic approach during follow-up of patients. We developed Healthcare Monitor (HM): a structure of electronic patient-reported outcome measures (ePROs) for the longitudinal follow-up of head and neck cancer (HNC) patients. This study shares key lessons from implementation and seeks to provide insight into how patients experience HM. METHODS: We conducted a mixed-methods study using quantitative data from a nonrandomized retrospective survey of patients who received HM (n = 45) vs standard care (n = 46) and qualitative data from structured interviews (n = 15). RESULTS: Implementation of HM included significant challenges. Finding common ground among clinicians, administrators, and IT staff was most important. Qualitative findings suggest that patients experienced better doctor-patient communication and increased efficiency of the consultation using HM. Patients felt better prepared and experienced more focus on critical issues. Quantitative analysis did not show significant differences. CONCLUSIONS: Integration of HM into routine care for HNC patients may have increased patient-centered care and facilitated screening of symptoms. However, future research is needed to analyze the potential benefits more extensively.

Head and neck cancer patients' preferences for individualized prognostic information: a focus group study.

BACKGROUND: Head and Neck cancer (HNC) is characterized by significant mortality and morbidity. Treatment is often invasive and interferes with vital functions, resulting in a delicate balance between survival benefit and deterioration in quality of life (QoL). Therefore, including prognostic information during patient counseling can be of great importance. The first aim of this study was to explore HNC patients' preferences for receiving prognostic information: both qualitative (general terms like "curable cancer"), and quantitative information (numbers, percentages). The second aim of this study was to explore patients' views on "OncologIQ", a prognostic model developed to estimate overall survival in newly diagnosed HNC patients. METHODS: We conducted a single center qualitative study by organizing five focus groups with HNC patients (n = 21) and their caregivers (n = 19), categorized in: 1) small laryngeal carcinomas treated with radiotherapy or laser, 2) extensive oral cavity procedures, 3) total laryngectomy, 4) chemoradiation, 5) other treatments. The patients' perspective was the main focus. The interview guide consisted of two main topics: life-expectancy and the prognostic model OncologIQ. All focus groups were recorded, transcribed and coded. Themes were derived using content analysis. RESULTS: While all patients considered it somewhat to very important to receive information about their life-expectancy, only some of them wanted to receive quantitative information. Disclosing qualitative prognostic information like "the cancer is curable" would give enough reassurance for most patients. Overall, patients thought life-expectancy should not be discussed shortly after cancer diagnosis disclosure, as a certain time is needed to process the first shock. They had a stronger preference for receiving prognostic information in case of a poor prognosis. Prognostic information should also include information on the expected QoL. The pie chart was the most preferred chart for discussing survival rates. CONCLUSIONS: The participants found it important to receive information on their life-expectancy. While most patients were enough reassured by qualitative prognostic information, some wanted to receive quantitative information like OncologIQs' estimates. A tailor-made approach is necessary to provide customized prognostic information. A clinical practice guideline was developed to support professionals in sharing prognostic information, aiming to improve shared decision making and patient-centered care.

Survival of patients with head and neck cancer with metachronous multiple primary tumors is surprisingly favorable.

BACKGROUND: The objectives of this study are to determine the incidence and survival rate of patients with head and neck squamous cell carcinoma (HNSCC) with multiple primary tumors (MPT) in the HN-region, lung, or esophagus. METHODS: Patient and tumor specific data of 1372 patients with HNSCC were collected from both the national cancer registry and patient records to ensure high-quality double-checked data. RESULTS: The total incidence of MPTs in the HN-region, lung, and esophagus in patients with HNSCC was 11% (149/1372). Patients with lung MPTs and esophageal MPTs had a significant worse 5-year survival than patients with HN-MPTs (29%, 14%, and 67%, respectively, P < 0.001). The 5-year survival rate for synchronous HN MPTs was only 25%, whereas it was surprisingly high for patients with metachronous HN MPT (85%, P < 0.001). CONCLUSIONS: One of 10 patients with HNSCC develop MPTs in the HN-region, lung, or esophagus. The 5-year survival of patients with metachronous HN MPTs was surprisingly favorable.

Integrated prediction and decision models are valuable in informing personalized decision making.

OBJECTIVES: To show how prediction models can be incorporated into decision models, to allow for personalized decisions, and to assess the value of this approach using the management of the neck in early-stage oral cavity squamous cell carcinoma as an example. STUDY DESIGN AND SETTING: In a decision model, three approaches were compared: a "population-based" approach in which patients undergo the strategy that is optimal for the population; a "perfectly predicted" approach, in which each patient receives the optimal strategy for that specific patient; and a "prediction model" approach in which each patient receives the strategy that is optimal based on prediction models. The average differences in costs and quality-adjusted life years (QALYs) for the population between these approaches were studied. RESULTS: The population-based approach resulted on average in 4.9158 QALYs with €8,675 in costs, per patient. The perfectly predicted approach yielded 0.21 more QALYs and saved €1,024 per patient. The prediction model approach yielded 0.0014 more QALYs and saved €152 per patient compared with the population-based approach. CONCLUSION: The perfectly predicted approach shows that personalized care is worthwhile. However, current prediction models in the field of oral cavity squamous cell carcinoma have limited value. Incorporating prediction models into decision models appears to be a valuable method to assess the value of personalized decision making.

Communication of prognosis in head and neck cancer patients; a descriptive qualitative analysis.

OBJECTIVES: In shared decision making it is important to adequately, timely and actively involve patients in treatment decisions. Sharing prognostic information can be of key importance. This study describes whether and how prognostic information on life expectancy is included during communication on diagnosis and treatment plans between physicians and head and neck (H&N) oncologic patients in different phases of disease. METHODS: A descriptive, qualitative study was performed of n = 23 audiotaped physician-patient conversations in which both palliative and curative treatment options were discussed and questions on prognosis were expected. Verbatim transcribed consultations were systematically analyzed. A distinction was made between prognostic information that was provided (a) quantitatively: by giving numerical probability estimates, such as percentages or years or (b) qualitatively: through the use of words such as 'most likely' or 'highly improbable'. RESULTS: In all consultations, H&N surgeons provided some prognostic information. In 5.9% of the provided prognostic information, a quantitative method was used. In 94.1% prognostic information was provided qualitatively, using six identified approaches. H&N surgeons possibly affect patients' perception of prognostic content with two identified communication styles: directive (more physician-centered) and affective (more patient-centered). CONCLUSION: This study is first in providing examples of how H&N surgeons communicate with their patients regarding prognosis in all stages of disease. They often exclude specific prognostic information. The study outcomes can be used as a first step in developing a guideline for sharing prognostic information in H&N oncologic patients, in order enable the process of shared decision making.

Nodal response after 46 Gy of intensity-modulated radiotherapy is associated with human papillomavirus-related oropharyngeal carcinoma.

OBJECTIVES/HYPOTHESIS: This study aimed to analyze the effect of human papillomavirus (HPV)-associated T1-2 node-positive oropharyngeal squamous cell carcinoma (OPSCC) on nodal response, recurrent disease, and survival in patients treated according to the Rotterdam protocol. STUDY DESIGN: Retrospective cohort study. METHODS: In total, 77 patients with T1-2 OPSCC with nodal disease, treated between 2000 and 2012, were included in this study. Patients were treated according to the Rotterdam protocol: 46 Gy of IMRT followed by a local boost using cyberknife or brachytherapy (22 Gy) and neck dissection. The presence of HPV was determined by p16INK4A immunostaining. Outcomes were overall survival, disease-free survival, and the extent of nodal response. Nodal stage was determined following the 7th and 8th American Joint Cancer Committee/Union for International Cancer Control classification. RESULTS: Overall, 68.4% of patients had p16-positive disease, and 35.4% of all patients achieved complete nodal response (pN0) after 46 Gy of intensity-modulated radiotherapy (IMRT). Based on the 7th TNM classification, nodal response (partial or complete) was significantly associated with HPV status (P = .002). Patients with p16-positive OPSCC had an odds ratio (OR) of 4.6 to achieve complete nodal response. However, smoking interacted with this effect. Applying the 8th TNM classification, complete or partial response was associated with HPV status but was not significant (OR: 1.7, P = .138). Complete nodal response led to 100% overall survival in p16-positive OPSCC patients. CONCLUSIONS: HPV-related OPSCCs are associated with complete nodal response after 46 Gy of IMRT. Patients with full regional control (pN0) after IMRT and subsequent neck dissection show a significantly better overall survival, but smoking negatively interacts with this effect. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2333-2340, 2018.

Feedback preferences of patients, professionals and health insurers in integrated head and neck cancer care.

BACKGROUND: Audit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers. OBJECTIVE: Investigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example. METHODS: A total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi-structured interviews. Questions focussed on: "Why," "On what aspects" and "How" do you prefer to receive feedback on professional practice and health care outcomes? RESULTS: All stakeholders mentioned that feedback can improve health care by creating awareness, enabling self-reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional practice that matches the health care received, whereas medical specialists and health insurers are interested mainly in health care outcomes. All stakeholders largely prefer a bar graph. Patients prefer a pie chart for patient-reported outcomes and experiences, while Kaplan-Meier survival curves are preferred by medical specialists. Feedback should be simple with firstly an overview, and 1-4 times a year sent by e-mail. Finally, patients and health professionals are cautious with regard to transparency of audit data. CONCLUSIONS: This exploratory study shows how feedback preferences differ between stakeholders. Therefore, tailored reports are recommended. Using this information, effects of audit and feedback can be improved by adapting the feedback format and contents to the preferences of stakeholders.

A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency.

Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and IL-17(+) non-T cells (mainly granulocytes) in matched HPV-positive and HPV-negative OPSCC cases (n = 162). Furthermore, the production of IFN-γ and IL-17 by tumor-infiltrating T cells was analyzed. The number of tumor-infiltrating T cells and Tregs was higher in HPV-positive than HPV-negative OPSCC (p < 0.0001). In contrast, HPV-negative OPSCC contained significantly higher numbers of IL-17(+) non-T cells (p < 0.0001). Although a high number of intra-tumoral T cells showed a trend toward improved survival of all OPSCC patients, their prognostic effect in patients with a low number of intra-tumoral IL-17(+) non-T cells was significant with regard to disease-specific (p = 0.033) and disease-free survival (p = 0.012). This suggests that a high frequency of IL-17(+) non-T cells was related to a poor immune response, which was further supported by the observation that a high number of T cells was correlated with improved disease-free survival in the HPV-positive OPSCC (p = 0.008). In addition, we detected a minor Th17 cell population. However, T cells obtained from HPV-positive OPSCC produced significantly more IL-17 than those from HPV-negative tumors (p = 0.006). The improved prognosis of HPV-positive OPSCC is thus correlated with higher numbers of tumor-infiltrating T cells, more active Th17 cells and lower numbers of IL-17(+) non-T cells.

Resection margins in oral cancer surgery: Room for improvement.

The purpose of this review was to identify publications on resection margins in oral cancer surgery and compare these with the results from 2 Dutch academic medical centers. Eight publications were considered relevant for this study, reporting 30% to 65% inadequate resection margins (ie, positive and close margins), compared to 85% in Dutch centers. However, clinical outcome in terms of overall survival and recurrence seemed comparable. The misleading difference is caused by lack of unanimous margin definition and differences in surgicopathological approaches. This prevents comparison between the centers. Data from Dutch centers showed that inadequate resection margins have a significantly negative effect on local recurrence, regional recurrence, distant metastasis, and overall survival. These results confirm the need for improvement in oral cancer surgery. We underline the need for consistent protocols and optimization of frozen section procedures. We comment on development of optical techniques for intraoperative assessment of resection margins. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2197-E2203, 2016.

Noncompliance to guidelines in head and neck cancer treatment; associated factors for both patient and physician.

BACKGROUND: Decisions on head and neck squamous cell carcinoma (HNSCC) treatment are widely recognized as being difficult, due to high morbidity, often involving vital functions. Some patients may therefore decline standard, curative treatment. In addition doctors may propose alternative, nonstandard treatments. Little attention is devoted, both in literature and in daily practice, to understanding why and when HNSCC patients or their physicians decline standard, curative treatment modalities. Our objective is to determine factors associated with noncompliance in head and neck cancer treatment for both patients and physicians and to assess the influence of patient compliance on prognosis. METHODS: We did a retrospective study based on the medical records of 829 patients with primary HNSCC, who were eligible for curative treatment and referred to our hospital between 2010 and 2012. We analyzed treatment choice and reasons for nonstandard treatment decisions, survival, age, gender, social network, tumor site, cTNM classification, and comorbidity (ACE27). Multivariate analysis using logistic regression methods was performed to determine predictive factors associated with non-standard treatment following physician or patient decision. To gain insight in survival of the different groups of patients, we applied a Cox regression analysis. After checking the proportional hazards assumption for each variable, we adjusted the survival analysis for gender, age, tumor site, tumor stage, comorbidity and a history of having a prior tumor. RESULTS: 17 % of all patients with a primary HNSCC did not receive standard curative treatment, either due to nonstandard treatment advice (10 %) or due to the patient choosing an alternative (7 %). A further 3 % of all patients refused any type of therapy, even though they were considered eligible for curative treatment. Elderliness, single marital status, female gender, high tumor stage and severe comorbidity are predictive factors. Patients declining standard treatment have a lower overall 3-year survival (34 % vs. 70 %). CONCLUSIONS: Predictive factors for nonstandard treatment decisions in head and neck cancer treatment differed between the treating physician and the patient. Patients who received nonstandard treatment had a lower overall 3-year survival. These findings should be taken into account when counselling patients in whom nonstandard treatment is considered.