A protocol for stakeholder engagement in head and neck cancer pragmatic trials.

Meaningful engagement with stakeholders in research demands intentional approaches. This paper describes the development of a framework to guide stakeholder engagement as research partners in a pragmatic trial proposed to evaluate behavioral interventions for dysphagia in head and neck cancer patients. We highlight the core principles of stakeholder engagement including representation of all perspectives, meaningful participation, respectful partnership with stakeholders, and accountability to stakeholders; and describe how these principles were operationalized to engage relevant stakeholders throughout the course of a large clinical trial.

Mandibular dose-volume predicts time-to-osteoradionecrosis in an actuarial normal-tissue complication probability (NTCP) model: External validation of right-censored clinico-dosimetric and competing risk application across international multi-institutional observational cohorts and online graphical user interface clinical support tool assessment.

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors. Methods: Demographic, clinical and dosimetric data were retrospectively obtained for a clinical observational cohort of 1129 patients with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. ORNJ was diagnosed in 198 patients (18%). A multivariable logistic regression analysis with forward stepwise variable selection identified significant predictors for ORNJ. These predictors were then used to train a Weibull Accelerated Failure Time (AFT) model, which was externally validated using an independent cohort of 265 patients (92 ORNJ cases and 173 controls) treated at Guy's and St. Thomas' Hospitals. Findings: Our model identified that each unit increase in D25% is significantly associated with a 12% shorter time to ORNJ (Adjusted Time Ratio [ATR] 0·88, p<0·005); pre-RT dental extractions was associated to a 27% faster (ATR 0·73, p=0·13) onset of ORNJ; male patients experienced a 38% shorter time to ORNJ (ATR 0·62, p = 0·11). The model demonstrated strong internal calibration (integrated Brier score of 0·133, D-calibration p-value 0.998) and optimal discrimination at 72 months (Harrell's C-index of 0·72). The model also showed good generalization to the independent cohort, despite a slight drop in performance. Interpretation: This study is the first to demonstrate a direct relationship between radiation dose and the time to ORNJ onset, providing a novel characterization of the impact of delivered dose not only on the probability of a late effect (ORNJ), but the conditional risk during survivorship. Funding: This work was supported by various funding sources including NIH, NIDCR, NCI, NAPT, NASA, BCM, Affirmed Pharma, CRUK, KWF Dutch Cancer Society, NWO ZonMw, and the Apache Corporation.

Effects of Statistical Practices for Longitudinal Group Comparison of the Penetration-Aspiration Scale on Power and Effect Size Estimation: A Monte Carlo Simulation Study.

Multiple bolus trials are administered during clinical and research swallowing assessments to comprehensively capture an individual's swallowing function. Despite valuable information obtained from these boluses, it remains common practice to use a single bolus (e.g., the worst score) to describe the degree of dysfunction. Researchers also often collapse continuous or ordinal swallowing measures into categories, potentially exacerbating information loss. These practices may adversely affect statistical power to detect and estimate smaller, yet potentially meaningful, treatment effects. This study sought to examine the impact of aggregating and categorizing penetration-aspiration scale (PAS) scores on statistical power and effect size estimates. We used a Monte Carlo approach to simulate three hypothetical within-subject treatment studies in Parkinson's disease and head and neck cancer across a range of data characteristics (e.g., sample size, number of bolus trials, variability). Different statistical models (aggregated or multilevel) as well as various PAS reduction approaches (i.e., types of categorizations) were performed to examine their impact on power and the accuracy of effect size estimates. Across all scenarios, multilevel models demonstrated higher statistical power to detect group-level longitudinal change and more accurate estimates compared to aggregated (worst score) models. Categorizing PAS scores also reduced power and biased effect size estimates compared to an ordinal approach, though this depended on the type of categorization and baseline PAS distribution. Multilevel models should be considered as a more robust approach for the statistical analysis of multiple boluses administered in standardized swallowing protocols due to its high sensitivity and accuracy to compare group-level changes in swallowing function. Importantly, this finding appears to be consistent across patient populations with distinct pathophysiology (i.e., PD and HNC) and patterns of airway invasion. The decision to categorize a continuous or ordinal outcome should be grounded in the clinical or research question with recognition that scale reduction may negatively affect the quality of statistical inferences in certain scenarios.

Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma.

The incidence of human papilloma virus-mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH+) and CGRP+ sensory-afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43+) and immature cholinergic (ChAT+DCX+) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP+ nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP+ and cholinergic (ChAT+) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP+ and ChAT+ neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.

Clinical Implementation of DIGEST as an Evidence-Based Practice Tool for Videofluoroscopy in Oncology: A Six-Year Single Institution Implementation Evaluation.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

A Hard Truth to Swallow: Critically Evaluating the MD Anderson Dysphagia Inventory (MDADI) as an Endpoint in Human Papillomavirus-associated Oropharyngeal Cancer Trials.

The MD Anderson Dysphagia Inventory (MDADI), a measure of swallowing-related quality of life, has become the preferred patient-reported outcome measure (PROM) in contemporary clinical trials evaluating the experience of human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) survivors. With many potentially practice-changing studies using the MDADI composite score as either a primary or coprimary endpoint, or as a key secondary endpoint, it is important to understand its psychometric properties as judged by contemporary PROM standards, with a particular focus on its application to contemporary HPVOPSCC populations. In this critical review, we evaluate contemporary HPVOPSCC studies reporting MDADI outcomes, followed by a detailed evaluation of the psychometric properties of the MDADI. Although the focus of this review was the MDADI, the issues discussed are not unique to the MDADI and have broader applicability to the evaluation and assessment of other PROMs currently in use. First, it may be possible to improve administration of the instrument, as related to missing items, scoring, and the number of items required. Second, although in many instances, the MDADI has been intended as a direct or surrogate measure of swallowing physiology, the MDADI composite score captures a broader health-related quality of life construct affected by both swallowing and eating, the latter of which may be affected by a range of nonswallowing treatment-related toxicities. Finally, a clinically meaningful change of 10 in the MDADI composite score, widely accepted and applied to the clinical trial setting, represents an undoubtably clinically relevant difference in unselected head and neck cancer survivors. However, the smallest difference that might be clinically important to a highly functional HPVOPSCC cohort remains uncertain. Understanding the purpose and properties of the MDADI instrument and furthering the sophistication with which we apply it in this population would improve its interpretation in clinical trials.

A custom device for managing recurrent tracheoesophageal voice prosthesis dislodgement and aspiration due to treatment refractory, severely enlarged puncture: A video case report.

We report the case of a laryngectomized patient with an enlarged tracheoesophageal puncture (TEP) that is refractory to standard treatments and culminating in life-threatening recurrent dislodgement and aspiration of custom fabricated dual extra-large flange voice prostheses (VP). The fabrication and use of a novel intraluminal prosthetic device to prevent dislodgement, lessen aspiration, and preserve TE voice is described. A custom device insetting a commercial VP into the posterior wall of a LaryTube (coined "inset-VP") was devised with the primary goal of eliminating chronic VP dislodgement and lessening aspiration while maintaining TE voice. Tools required to fabricate the device included a commercial laryngectomy tube, standard-flanged commercial indwelling voice prosthesis, felt-tip marker, 6 mm biopsy punch, and silk suture. After 7 months of using an inset-VP LaryTube device, the patient has experienced zero episodes of VP aspiration. Thin liquid aspiration control is equivalent or better than prior management with custom 24-30 mm dual collar prostheses. TEP voice is fluent and functional with device in place. Novel strategies are needed to manage the rare but devastating effects of a severely enlarged TEP. Solutions to manage symptoms need to be patient-specific, aligning with their anatomy, physiology, psychosocial needs, and goals. The inset-VP device described in this report may offer improved prosthetic retention in select patients with enlarged TE puncture and frequent VP dislodgements.

Clinical and prognostic differences in oropharyngeal squamous cell carcinoma in USA and Denmark, two HPV high-prevalence areas.

BACKGROUND: Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. METHODS: OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). RESULTS: There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). CONCLUSIONS: We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.

Revisiting Feeding Tube Utilization in Oropharynx Cancer: 6-Year Prospective Registry Analysis.

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients. STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021. SETTING: Single-institution NCI-Designated Comprehensive Cancer Center. METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI]). RESULTS: Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66]). CONCLUSIONS: In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration.

Comparison of Machine Leaning Models for Prediction of Acute Pain Severity and On-Treatment Opioid Utilization in Oral Cavity and Oropharyngeal Cancer Patients Receiving Radiation Therapy: Exploratory Analysis from a Large-Scale Retrospective Cohort.

Background: Acute pain is a common and debilitating symptom experienced by oral cavity and oropharyngeal cancer (OC/OPC) patients undergoing radiation therapy (RT). Uncontrolled pain can result in opioid overuse and increased risks of long-term opioid dependence. The specific aim of this exploratory analysis was the prediction of severe acute pain and opioid use in the acute on-treatment setting, to develop risk-stratification models for pragmatic clinical trials. Materials and Methods: A retrospective study was conducted on 900 OC/OPC patients treated with RT during 2017 to 2023. Clinical data including demographics, tumor data, pain scores and medication data were extracted from patient records. On-treatment pain intensity scores were assessed using a numeric rating scale (0-none, 10-worst) and total opioid doses were calculated using morphine equivalent daily dose (MEDD) conversion factors. Analgesics efficacy was assessed based on the combined pain intensity and the total required MEDD. ML models, including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting Model (GBM) were developed and validated using ten-fold cross-validation. Performance of models were evaluated using discrimination and calibration metrics. Feature importance was investigated using bootstrap and permutation techniques. Results: For predicting acute pain intensity, the GBM demonstrated superior area under the receiver operating curve (AUC) (0.71), recall (0.39), and F1 score (0.48). For predicting the total MEDD, LR outperformed other models in the AUC (0.67). For predicting the analgesics efficacy, SVM achieved the highest specificity (0.97), and best calibration (ECE of 0.06), while RF and GBM achieved the same highest AUC, 0.68. RF model emerged as the best calibrated model with ECE of 0.02 for pain intensity prediction and 0.05 for MEDD prediction. Baseline pain scores and vital signs demonstrated the most contributed features for the different predictive models. Conclusion: These ML models are promising in predicting end-of-treatment acute pain and opioid requirements and analgesics efficacy in OC/OPC patients undergoing RT. Baseline pain score, vital sign changes were identified as crucial predictors. Implementation of these models in clinical practice could facilitate early risk stratification and personalized pain management. Prospective multicentric studies and external validation are essential for further refinement and generalizability.

Tongue electrical impedance myography correlates with functional, neurophysiologic, and clinical outcome measures in long-term oropharyngeal cancer survivors with and without hypoglossal neuropathy: An exploratory study.

BACKGROUND: This pilot study analyzed correlations between tongue electrical impedance myography (EIM), standard tongue electromyography (EMG), and tongue functional measures in N = 4 long-term oropharyngeal cancer (OPC) survivors. METHODS: Patients were screened for a supportive care trial (NCT04151082). Hypoglossal nerve function was evaluated with genioglossus needle EMG, functional measures with the Iowa oral performance instrument (IOPI), and multi-frequency tissue composition with tongue EIM. RESULTS: Tongue EIM conductivity was higher for patients with EMG-confirmed cranial nerve XII neuropathy than those without (p = 0.005) and in patients with mild versus normal EMG reinnervation ratings (16 kHz EIM: p = 0.051). Tongue EIM correlated with IOPI strength measurements (e.g., anterior maximum isometric lingual strength: r2 = 0.62, p = 0.020). CONCLUSIONS: Tongue EIM measures related to tongue strength and the presence of XII neuropathy. Noninvasive tongue EIM may be a convenient adjunctive biomarker to assess tongue health in OPC survivors.

The Acceptability of Behavioural Swallowing Interventions for Head and Neck Cancer Patients During Radiotherapy: A Qualitative Study Exploring Experiences of Clinical Trial Speech-Language Pathologists.

The PRO-ACTIVE randomized clinical trial offers 3 swallowing therapies to Head and Neck Cancer (HNC) patients during radiotherapy (RT) namely: reactive, proactive low- ("EAT-RT" only) and high-intensity ("EAT-RT + exercises"). Understanding the experiences of the trial Speech-Language Pathologists (SLPs) will be useful to inform clinical implementation. This study assessed SLP opinions of acceptability and clinical feasibility of the 3 trial therapies. 8 SLPs from 3 Canadian PRO-ACTIVE trial sites participated in individual interviews. Using a qualitative approach, data collection and thematic analysis were guided by the Theoretical Framework of Acceptability. Member checking was conducted through a follow-up focus group with willing participants. Seven themes were derived: intervention coherence, burden, barriers/facilitators, self-efficacy, attitude, ethicality, and perceived effectiveness. SLPs felt all 3 therapies had potential benefit yet perceived more advantages of proactive therapies compared to reactive. Compared to exercises, SLPs particularly endorsed the EAT-RT component. A major barrier was keeping patients motivated, which was impacted by acute toxicity and sometimes conflicting instructions from the healthcare team. Strategies utilized by to overcome barriers included: scaling exercises and/or diet up/down according to the changing patient needs and communicating therapy goals with healthcare team. A model was derived describing the perceived acceptability of the swallowing therapies according to SLPs, based on the interconnection of main themes. Proactive therapies were perceived as more acceptable to trial SLPs, for facilitating patient engagement. The perceived acceptability of the swallowing therapies was related to seven interconnected aspects of providers' experience. These findings will inform the implementation and potential uptake of the PRO-ACTIVE swallowing therapies in clinical practice.

Exploring the Acceptability of Behavioral Swallowing Interventions for Head and Neck Cancer Patients During Radiotherapy: A Qualitative Study of Patients' Experience.

The PRO-ACTIVE randomized clinical trial offers 3 swallowing therapies to Head and Neck Cancer (HNC) patients during radiotherapy namely: reactive, proactive low- ("EAT-RT" only), and high-intensity ("EAT-RT + exercises"). Understanding the perceived acceptability of these interventions is important to inform eventual implementation into clinical practice. This study explored patients' perspectives using qualitative methodology. At 2 Canadian PRO-ACTIVE trial sites, 24 trial participants were recruited for individual semi-structured interviews, representing each of the 3 trial arms. Data collection and thematic analysis were guided by the Theoretical Framework of Acceptability (TFA). Member checking was conducted through follow-up focus groups. Seven themes were derived reflecting the TFA constructs. Overall, regardless of trial arm, patients reported a positive experience with therapy. Patients identified benefits of EAT-RT therapy, reporting that it provided meaningful feedback on diet progress and supported goal setting for oral intake. Patients who received proactive therapies valued the opportunity to set expectations early, build mealtime routine iteratively over time, and have an extended engagement with the SLP. Regardless of trial arm, patients agreed proactive therapy aligned with what they think is best and that therapy intensity should accommodate individual needs. This study identified the value to HNC patients of receiving swallowing interventions during RT and setting realistic expectations around swallowing. Compared to reactive care, proactive therapies were perceived helpful in consolidating habits early, establishing realistic expectations around swallowing and building an extended rapport with the SLP. These findings will inform the implementation of proactive versus reactive swallowing therapies in clinical practice.

Multi-organ spatial stratification of 3-D dose distributions improves risk prediction of long-term self-reported severe symptoms in oropharyngeal cancer patients receiving radiotherapy: development of a pre-treatment decision support tool.

Purpose: Identify Oropharyngeal cancer (OPC) patients at high-risk of developing long-term severe radiation-associated symptoms using dose volume histograms for organs-at-risk, via unsupervised clustering. Material and methods: All patients were treated using radiation therapy for OPC. Dose-volume histograms of organs-at-risk were extracted from patients' treatment plans. Symptom ratings were collected via the MD Anderson Symptom Inventory (MDASI) given weekly during, and 6 months post-treatment. Drymouth, trouble swallowing, mucus, and vocal dysfunction were selected for analysis in this study. Patient stratifications were obtained by applying Bayesian Mixture Models with three components to patient's dose histograms for relevant organs. The clusters with the highest total mean doses were translated into dose thresholds using rule mining. Patient stratifications were compared against Tumor staging information using multivariate likelihood ratio tests. Model performance for prediction of moderate/severe symptoms at 6 months was compared against normal tissue complication probability (NTCP) models using cross-validation. Results: A total of 349 patients were included for long-term symptom prediction. High-risk clusters were significantly correlated with outcomes for severe late drymouth (p <.0001, OR = 2.94), swallow (p = .002, OR = 5.13), mucus (p = .001, OR = 3.18), and voice (p = .009, OR = 8.99). Simplified clusters were also correlated with late severe symptoms for drymouth (p <.001, OR = 2.77), swallow (p = .01, OR = 3.63), mucus (p = .01, OR = 2.37), and voice (p <.001, OR = 19.75). Proposed cluster stratifications show better performance than NTCP models for severe drymouth (AUC.598 vs.559, MCC.143 vs.062), swallow (AUC.631 vs.561, MCC.20 vs -.030), mucus (AUC.596 vs.492, MCC.164 vs -.041), and voice (AUC.681 vs.555, MCC.181 vs -.019). Simplified dose thresholds also show better performance than baseline models for predicting late severe ratings for all symptoms. Conclusion: Our results show that leveraging the 3-D dose histograms from radiation therapy plan improves stratification of patients according to their risk of experiencing long-term severe radiation associated symptoms, beyond existing NTPC models. Our rule-based method can approximate our stratifications with minimal loss of accuracy and can proactively identify risk factors for radiation-associated toxicity.

Long-term Patient-Reported Outcomes in a Population-Based Cohort Following Radiotherapy vs Surgery for Oropharyngeal Cancer.

Importance: Oncologic outcomes are similar for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery or radiotherapy. However, comparative differences in long-term patient-reported outcomes (PROs) between modalities are less well established. Objective: To determine the association between primary surgery or radiotherapy and long-term PROs. Design, Setting, and Participants: This cross-sectional study used the Texas Cancer Registry to identify survivors of OPSCC treated definitively with primary radiotherapy or surgery between January 1, 2006, and December 31, 2016. Patients were surveyed in October 2020 and April 2021. Exposures: Primary radiotherapy and surgery for OPSCC. Main Outcomes and Measures: Patients completed a questionnaire that included demographic and treatment information, the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) module, the Neck Dissection Impairment Index (NDII), and the Effectiveness of Auditory Rehabilitation (EAR) scale. Multivariable linear regression models were performed to evaluate the association of treatment (surgery vs radiotherapy) with PROs while controlling for additional variables. Results: Questionnaires were mailed to 1600 survivors of OPSCC identified from the Texas Cancer Registry, with 400 responding (25% response rate), of whom 183 (46.2%) were 8 to 15 years from their initial diagnosis. The final analysis included 396 patients (aged ≤57 years, 190 [48.0%]; aged >57 years, 206 [52.0%]; female, 72 [18.2%]; male, 324 [81.8%]). After multivariable adjustment, no significant differences were found between surgery and radiotherapy outcomes as measured by the MDASI-HN (ß, -0.1; 95% CI, -0.7 to 0.6), NDII (ß, -1.7; 95% CI, -6.7 to 3.4), and EAR (ß, -0.9; 95% CI -7.7 to 5.8). In contrast, less education, lower household income, and feeding tube use were associated with significantly worse MDASI-HN, NDII, and EAR scores, while concurrent chemotherapy with radiotherapy was associated with worse MDASI-HN and EAR scores. Conclusions and Relevance: This population-based cohort study found no associations between long-term PROs and primary radiotherapy or surgery for OPSCC. Lower socioeconomic status, feeding tube use, and concurrent chemotherapy were associated with worse long-term PROs. Further efforts should focus on the mechanism, prevention, and rehabilitation of these long-term treatment toxicities. The long-term outcomes of concurrent chemotherapy should be validated and may inform treatment decision making.

Measuring symptom burden in patients with cancer during a pandemic: the MD Anderson symptom inventory for COVID-19 (MDASI-COVID).

BACKGROUND: Symptom expression in SARS-CoV-2 infection (COVID-19) may affect patients already symptomatic with cancer. Patient-reported outcomes (PROs) can describe symptom burden during the acute and postacute stages of COVID-19 and support risk stratification for levels of care. At the start of the COVID-19 pandemic, our purpose was to rapidly develop, launch through an electronic patient portal, and provide initial validation for a PRO measure of COVID-19 symptom burden in patients with cancer. METHODS: We conducted a CDC/WHO web-based scan for COVID-19 symptoms and a relevance review of symptoms by an expert panel of clinicians treating cancer patients with COVID-19 to create a provisional MD Anderson Symptom Inventory for COVID-19 (MDASI-COVID). English-speaking adults with cancer who tested positive for COVID-19 participated in the psychometric testing phase. Patients completed longitudinal assessments of the MDASI-COVID and the EuroQOL 5 Dimensions 5 Levels (EQ-5D-5L) utility index and visual analog scale, which were presented through an electronic health record patient portal. To test the validity of the MDASI-COVID to distinguish between known groups of patients, we hypothesized that patients hospitalized, including having a hospitalization extended, for COVID-19 versus those not hospitalized would experience higher symptom burden. Correlation of mean symptom severity and interference scores with relevant EQ-5D-5L scores tested concurrent validity. The reliability of the MDASI-COVID was evaluated by calculating Cronbach alpha coefficients and test-retest reliability was evaluated by calculating Pearson correlation coefficients between the initial assessment and a second assessment no more than 14 days later. RESULTS: The web-based scan found 31 COVID-19-related symptoms; rankings of a 14-clinician expert panel reduced this list to 11 COVID-specific items to be added to the core MDASI. Time from literature scan start in March 2020 to instrument launch in May 2020 was 2 months. Psychometric analysis established the MDASI-COVID's reliability, known-group validity, and concurrent validity. CONCLUSIONS: We were able to rapidly develop and electronically launch a PRO measure of COVID-19 symptom burden in patients with cancer. Additional research is needed to confirm the content domain and predictive validity of the MDASI-COVID and define the symptom burden trajectory of COVID-19.

Tissue augmentation treatment for periprosthetic leakage in patients who have undergone a total laryngectomy: A systematic review.

OBJECTIVES: Tracheoesophageal puncture (TEP) is considered the gold standard for voice rehabilitation after total laryngectomy. One of the main causes of treatment failure, and a potentially serious complication, is the TEP enlargement and/or leakage around the voice prosthesis. The injection of biocompatible material to increase the volume of the puncture surrounding tissue has been studied as a popular option for conservative treatment of enlarged tracheoesophageal fistula. The aim of this paper was to perform a systematic review of the efficacy and safety of such treatment. DESINGN: Search conducted in PubMed/MEDLINE, the Cochrane Library, Google Scholar, Scielo and Web of Science and through the meta-searcher Trip Database based on Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) statement. SETTINGS: Human experiments published in peer-reviewed journals, where investigators assessed the use of peri-fistular tissue augmentation for periprosthetic leakage were evaluated. PARTICIPANTS: Laryngectomized patients with voice prosthesis, presenting periprosthetik leak due to enlarged fistula. MAIN OUTCOMES MEASURES: mean-duration without new leak. RESULTS: A total of 196 peri-fistular tissue augmentation procedures in 97 patients were found in the 15 selected articles. The 58.8% of patients had a time without periprosthetic leak after treatment of >6 months. The 88.7% of tissue augmentation treatments resulted in periprosthetic leakage cessation. The general level of evidence of the studies included in this review was low. CONCLUSIONS: Tissue augmentation treatment is a minimally invasive, biocompatible and safe solution that temporarily resolves periprosthetic leaks in many cases. There is no standard technique or material, and treatment needs to be individualised according to the experience of the practitioner and the characteristics of the patient. Future randomised studies are needed to confirm these results.