Metabolomic biomarkers associated with trismus and dysphagia, radiation therapy, tumour stage and location in patients with head and neck cancer

Head and neck cancer (HNC) due to its nature and proximity to essential vasculature, along with different treatments, can lead to stroke, significantly contributing to morbidity and mortality. Our aim is to systematically evaluate the association of stroke incidence, mortality, and predictors with HNC treatment. Pubmed, Web of Science, Embase, and ScienceDirect were searched from inception to July 2024 for articles reporting stroke incidences, mortality, or associated risk factors following treatment in HNC patients. A random-effects meta-analysis assessed cumulative incidence and mortality rates with proportional analysis and risk factors using hazard ratios (HRs) associated with HNC treatment. Subgroup analyses of incidence and mortality were conducted for pre- and post-2010 periods, reflecting changes in stroke protocols. Out of 1561 studies, 69 studies with 258 850 HNC patients were included. The global cumulative incidence of stroke in HNC was 4.1% (95% CI: 3.3%-5.0%), with similar rates before and after 2010 (4.4% vs. 4.0%). In patients undergoing chemoradiotherapy (CRT), stroke incidence was 4.9% (95% CI: 3.5%-6.7%) with a median time to first stroke of 45 months (range: 14-51.7 months). Following radiation therapy (RT), stroke incidence was 3.8% (95% CI: 2.7%-5.3%) with a median time to stroke of 36 months (range: 6.8-130 months). The incidence rates of stroke in HNC patients were higher compared to the general population (HR: 1.69, 95% CI: 1.24-2.31, p = 0.001). Stroke mortality decreased from 28.5% (95% CI: 11.6%-54.9%) pre-2010 to 14.5% (95% CI: 11.6%-17.9%) 2010-2024. Stroke mortality was 39.3% (95% CI: 17.8%-66.0%) post-CRT and 21% (95% CI: 7.2%-47.7%) post-RT. Hypertension (HR = 1.75), diabetes (HR = 1.71), and age > 65 (HR = 2.17) increased stroke risk (p < 0.0001 for all). Geographically, South Korea (6.6%) had the highest incidence of stroke. This is the first systematic review to analyze the association between stroke and HNC treatment. Stroke mortality decreased from 28.5% to 14.5% (pre-2010 vs. 2010-2024), with the highest mortality in the CRT group (39.3%). Given that stroke occurs 36-45 months after CRT, a screening protocol within 3-4 years is crucial.

Introduction Dysphagia is a common issue in patients with head and neck cancer (HNC) and is known to negatively impact their quality of life. To evaluate the impact of dysphagia on the quality of life of HNC patients, the M. D. Anderson Dysphagia Inventory (MDADI) questionnaire was developed. Objective The present study aimed to culturally adapt and validate the MDADI for Persian-speaking individuals. The MDADI is a self-administered questionnaire designed to assess the impact of dysphagia on the quality of life of HNC patients. Methods The original MDADI questionnaire was translated into Persian using the forward-backward method, following the guidelines of the World Health Organization (WHO) for cultural adaptation. The content validity of the Persian version, MDADI-P, was assessed by 10 speech-language pathologists using the content validity index (CVI). Seventy-five HNC patients completed the MDADI-P to evaluate its convergent validity, which was determined by comparing the results with the Short-Form 36 (SF-36) questionnaire. Internal consistency and test-retest reliability were assessed using Cronbach α coefficient and intraclass correlation (ICC), respectively. Results The scale content validity index (S-CVI) for the MDADI-P was 0.90, indicating good content validity. The MDADI-P demonstrated satisfactory internal consistency (Cronbach α coefficient = 0.728) and test-retest reliability (ICC = 0.91). The total MDADI-P score exhibited a significant correlation with the physical and mental components of the SF-36 (0.456 and 0.349, respectively, p < 0.05). Conclusion The findings of the present study confirm the suitability of the MDADI-P in terms of content validity, construct validity, internal consistency, and test-retest reliability.

Objective To describe the characteristics of dysphagia in patients with head and neck cancer during radiotherapy, and analyze the cause of dysphagia and the relationship between dysphagia and weight change. Methods Patients with head and neck cancer treated with radiotherapy in Beijing Cancer Hospital from November 2017 to June 2018 were recruited. The M. D. Anderson Dysphagia Inventory (MDADI) was used to assess the dysphagia of patients before (T1), during (T2) and at the end (T3) of the radiotherapy. Meanwhile, the weight, dietary intake and radiation adverse effects were investigated. Generalized estimating equations were used to analyze the impact factors of dysphagia and the relationship among dysphagia, dietary intake and weight change. Results Ninety-six patients were completely investigated and the incidence of dysphagia were 6.3% (6/96), 80.2% (77/96) and 85.4% (82/96) in T1, T2 and T3. With the progress of radiotherapy, the total score and the scores of 4 dimensions of MDADI dropped and the dietary intake declined. The average weight loss was (5.09±3.31)kg, and 76.1% of the patients had weight loss over 5% at the end of radiotherapy. The occurrence of dysphagia was associated with the radiotherapy-related oral and laryngeal mucositis and the weight loss was closely associated with the site of radiation, dysphagia, and dietary intake decline. Conclusions The dysphagia of patients with head and neck cancer is affected by radiation adverse effects, and is most severe at the end of radiotherapy. Dysphagia might result in dietary intake decline and weight loss. Clinicians should pay close attention to the swallowing function of the patients and take measures earlier accordingly. Key words: Head and neck cancer; Radiotherapy; Dysphagia; Weight loss; Dietary intake

The aim of this study was to validate the Swedish version of the dysphagia-specific quality-of-life questionnaire, the M. D. Anderson Dysphagia Inventory (MDADI). Patients with oropharyngeal dysphagia due to neurologic disease (n=30) and head and neck (H&N) cancer patients with post-treatment subjective dysphagia (n=85) were compared to an age- and gender-matched nondysphagic control group (n=115). A formal forward-backward translation was performed and followed international guidelines. Validity and reliability were tested against the Short-Form 36 (SF-36) and Hospital Anxiety and Depression Scale (HADS). Internal-consistency reliability was calculated by means of Cronbach's α coefficient. Test-retest reliability was assessed by intraclass correlation (ICC). Convergent and discriminant validity were assessed by correlations between MDADI, SF-36, and HADS. Known-group validity was examined and statistically tested. Of 126 eligible patients, 115 agreed to participate (response rate=91.3%). The age of the participants ranged between 37 and 92 years. Most of the MDADI items showed good variability and only minor floor or ceiling effects in solitary items were found. The internal-consistency reliability (Cronbach's α) of the MDADI total score was 0.88 (after correction for systematic errors in the subjects' responses to two reversed questions). All estimates reached over the satisfactory >0.70 reliability standard for group-level comparison. ICC ranged between 0.83 and 0.97 in the test-retest. The mean MDADI total score was 66.9 (SD=14.7) for the H&N cancer patients, 65.0 (16.9) for the neurologic patients, and 97.5 (4.4) for the control group (P<0.001; study patients vs. controls). The MDADI was also sensitive to disease severity as measured by different food textures. The Swedish version of the MDADI showed good psychometric properties and is a valid instrument to assess dysphagia-related quality of life. It was also shown to be a reliable instrument after correction for systematic errors in the subjects' responses to two reversed questions. Its known-group validity enables the differentiation between dysphagic and nondysphagic patients for group-level research.

Head and neck cancer (HNC) represents a heterogeneous group of tumours requiring multimodality approaches. It is debatable whether HNC treatment in geriatric patients should be different to that delivered for younger patients. Furthermore, the risk of death seems to be higher in HNC patients with higher co-morbidity status. Despite the fact that there is no significant difference in outcome in younger versus older patients, older HNC patients are more likely to receive nonstandard, less aggressive therapies than younger patients. Age alone should not be the basis for selecting treatment options in older HNC patients. A thorough pretreatment evaluation of co-morbidities should always be performed, and radical surgical options should not be excluded in older HNC patients treated with curative intent, as postoperative complications occur no more frequently in older patients than in younger patients. Locoregional control and disease-free survival in older patients treated with radiation therapy (either with curative intent or in the palliative setting) are comparable to the results seen in younger HNC patients, with the same acute toxicity profile. In patients receiving systemic therapies, special attention must be given to modification of chemotherapy dosages according to renal and hepatic function. Molecular-targeted therapies appear to be very useful in such patients because of their favourable tolerability. In conclusion, once all physiological and biological risk factors have been addressed, a large proportion of geriatric patients can and should be offered the same HNC treatment as is offered to younger patients.

Diet and nutrition are critical in health and disease and are highly impacted by the presence and treatment for head and neck cancer (HNC). The purpose of this paper is to present oral examination findings and taste and smell test results in patients during and following HNC. Patients with HNC were evaluated during and following radiation therapy with/without chemotherapy. Oral examination findings including mucositis, saliva, oral hygiene (plaque levels, gingivitis), and taste and smell testing was completed on all subjects. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0, and the Scale of Subjective Total Taste Acuity (STTA) were used to provide patient report of symptoms. Mucositis and pain affected oral diet during therapy and improved in follow-up. Weight loss of 5% during and 12% following treatment was identified. Tobacco use was associated with increased severity of mucositis and increased weight loss. The subjects maintained excellent oral hygiene as reflected in plaque levels and gingivitis. Spicy/pungent perception was the most strongly disliked of testing stimuli. Umami and fat taste perception were reported of highest intensity during HNC treatment and rated as moderate in intensity after treatment. These results suggest improvement in these taste functions over time following treatment. Salt taste was of high intensity and associated with strong dislike in follow-up. In HNC patients, oral status and taste change occurs throughout the cancer trajectory and represent potential concerns in cancer survivorship. Taste change (as evaluated by taste testing) occurred in all HNC patients, whereas olfactory changes occurred in 30% of cases. Management of oral changes and symptoms should be considered in all HNC patients in addition to dietary and nutritional guidance in patient care to promote oral intake. Continuing study of taste changes may further define this problem and support dietary and nutritional guidance and product development.

Background: The aim of the study was to investigate the prevalence of facial pain in patients with Head and Neck Cancer (HNC) and trismus three years after cancer treatment. Furthermore, the study aimed to assess the effect of a structured jaw exercise program on pain. Methods: One hundred patients with HNC and trismus (i.e. Maximum Interincisal Opening (MIO) ≤35 mm) post-radiotherapy were prospectively followed up to three years with regard to prevalence of facial pain. Fifty of the patients participated in a structured 10-week intervention program with jaw exercise post-cancer treatment and 50 of the patients comprised a matched control group. Facial pain during last month was reported by the patient on a 7-point Likert scale. Results: Facial pain was common in HNC patients with trismus before undergoing cancer treatment (n=59, 59%) and more than half of the patients (n=46, 51%) reported facial pain at the three-year follow-up. Patients with facial pain at the three-year follow-up had lower MIO (34.8 vs. 39.6 mm, p=0.0005) compared to pain free patients. Fewer patients in the exercise intervention group (n=13, 28%) reported facial pain compared to the control group (n=33, 77%) (p<0.0001). The odds ratio for being pain free three years post-cancer treatment was 8.63 times higher (p<0.0001) if the patients had undergone structured jaw exercise. Conclusion: There is a high prevalence of facial pain in HNC and trismus. Structured jaw exercise seems to be effective for improving facial pain in trismus patients up to three years after HNC treatment.

Dysphagia is often caused by radiotherapy (RT) in patients with head and neck cancer (HNC), and reduced tongue pressure (TP) is often associated with swallowing dysfunction in the oral stage. However, the evaluation of dysphagia by measuring TP has not yet been established in HNC patients. Herein, we conducted a clinical trial to evaluate the usefulness of TP measurement using a TP-measuring device as an objective indicator of dysphagia induced by RT in HNC patients. This ELEVATE trial is a prospective, single-center, single-arm, non-blind, non-randomized trial to evaluate the usefulness of a TP measurement device for dysphagia associated with the treatment of HNC. Eligible participants include patients with oropharyngeal or hypopharyngeal cancer (HPC) undergoing RT or chemoradiotherapy (CRT). The TP measurements are conducted before, during, and after RT. The primary endpoint is the change in the maximum TP values from before RT to 3 months after RT. Moreover, as secondary endpoints, the correlation between the maximum TP value and the findings of video-endoscopic and video-fluoroscopic examinations of swallowing will be analyzed at each evaluation point, as well as changes in the maximum TP value from before RT to during RT and at 0, 1, and 6 months after RT. This trial aimed to investigate the usefulness of evaluation by measuring TP for dysphagia associated with HNC treatment. We expect that an easier evaluation for dysphagia will improve rehabilitation programs for dysphagia. Overall, we expect this trial to contribute to the improvement of patients' quality of life (QOL).

ObjectiveTo investigate if severe dysphagia following radiotherapy for head and neck cancer (HNC) could be predicted by patient and tumor characteristics, feeding tube use, weight factors, jaw opening function, and saliva secretion.MethodsData was collected from 94 HNC patients 6 to 36 months post radiotherapy. Swallowing function was assessed by videofluroscopy (VFS). Severe dysphagia was defined by Penetration Aspiration Scale (PAS) as PAS≥5 or a total score ≤60 on the M. D. Anderson Dysphagia Inventory (MDADI).ResultsThirty‐three patients (35%) had PAS ≥5 and 19 (20%) a MDADI ≤60, that is, presented with severe dysphagia. Univariable logistic regression analysis (UVA) gave that tumor of the tonsil, overweight at time of VFS and each unit increase in Body Mass Index (BMI) predicted less risk of PAS ≥5. Dependency of feeding tube at time of VFS and each month's continued use and weight loss ≥7.5% since treatment to time of VFS predicted increased risk of PAS ≥5. Predictive variables from the UVA of PAS ≥5 (tumor of the tonsil, overweight, and total duration of feeding tube), were analyzed by multivariate logistic regression analysis. All retained power as independent predictors. UVA for MDADI showed that use of feeding tube at time of VFS predicted MDADI ≤60 with the risk increasing each month. Each increasing unit of BMI decreased risk of MDADI ≤60.ConclusionLong time users of feeding tube and higher weight‐loss are at risk of severe dysphagia. This makes collaboration between professionals working with dysphagia an important step in detecting severe dysphagia.Level of Evidence: 3.

The Presence of Second Primary Esophageal Tumor (Spet) is Still an Independent Negative Prognostic Factor for Head and Neck Cancer (Hnc) Patients: a Retrospective Study

e18016 Background: Chronotherapy in cancer is optimizing the administration time of anti-cancer treatment according to circadian rhythm and cellular phase to improve the efficacy against tumor cells while decreasing side effects on normal cells. Several randomized controlled trials (RCT) evaluated chronotherapy of chemotherapy (chrono-chemotherapy: time-specific infusions) and/or radiotherapy (chrono-radiotherapy: morning radiotherapy) in various cancers and reported improved treatment efficacy and reduced toxicity. However, the effect of chronotherapy in HNC treatment is unclear as there are no prior systematic reviews reported. Therefore, this systematic review summarizes available clinical evidence on the effect of chrono-chemotherapy (CCT) and chrono-radiotherapy (CRT) on treatment response and adverse events in HNC adult patients. Methods: We conducted a systematic search using Medical Subject Headings (MeSH) in four online databases (OVID, Embase, CINAHL and Scopus), and 6078 articles identified were published in English between the databases' inception date and June 30, 2022. We included original peer-reviewed retrospective and prospective human studies investigating CCT and/or CRT versus conventional treatments in HNC patients. We excluded articles that contained no abstract, were unrelated to HNC, were pre-clinical and case reports, or did not include time-specific interventions in their methods. Results: 16 studies were finally included. Overall, studies were heterogenous in demographics, study design, intervention, and outcome measures, thus meta-analysis could not be performed. Nine studies (RCT = 3, Non-RCT = 2 &amp; Retro = 4) investigated CRT. Squamous cell carcinoma (SCC) was mainly reported as the primary tumor (stage I-II). 7/9 studies reported a significant reduction in the incidence of oral mucositis (Grade ≥3) in the CRT group as opposed to conventional radiotherapy (RT) groups (p &lt; 0.05). In contrast, treatment response was investigated in 4/9 studies and was insignificant (p &gt; 0.05). Seven studies (RCT = 5 &amp; Retro = 2) investigated CCT in patients diagnosed with SSC (stage II-IV). All included studies had concurrent RT. Different chemotherapeutic agents were used in combinations or as a single agent, namely Cisplatin, 5- Fu, Paclitaxel and Docetaxel. CCT groups in all studies achieved a significant reduction in Nausea &amp; Vomiting (Grade ≥3), while a significant reduction in Leukopenia &amp; Thrombocytopenia (Grade ≥3) was reported in 2 studies only (p &lt; 0.05). Treatment response (OS and PFS) was not significantly different (p &gt; 0.05) between both groups except 2 studies reported significantly higher ORR in chronotherapy groups (p &lt; 0.05). Conclusions: CCT and CRT in HNC treatment in most studies provided evidence of toxicity reduction while treatment response was maintained. However, large multicentric randomized controlled studies with standardized protocols and optimized designs are still needed.

Analysis of quality of life (QOL) has revealed that preservation of swallowing, speech, and breathing functions has a direct impact on QOL and that these functions are important patient-reported outcomes. The purposes of this study were to adapt and culturally validate the M.D. Anderson Dysphagia Inventory (MDADI) to the Brazilian Portuguese language and to evaluate QOL related to dysphagia in patients treated for head and neck cancer. This was a cross-sectional study that included 72 adult patients with a mean age of 63 years who were treated for head and neck cancer. Construct validity and reliability analyses were performed through the comparison of the MDADI with three other health-related QOL questionnaires administered at the time of enrollment and MDADI application 2 weeks thereafter, respectively. Reliability was established by assuring both internal consistency (Cronbach's α) and test-retest reliability (intraclass correlation coefficient, ICC). Test-retest reliability for the total score in the MDADI had an ICC greater than 0.795 (p < 0.001). The MDADI had significant statistical correlations with the other questionnaires. Patients treated for head and neck cancer had a mean total score of 83 on the MDADI, which is indicative of minimal limitation in overall QOL. In conclusion, the present study validates the adaptation of the MDADI to the Brazilian Portuguese language and provides another tool to evaluate the impact of dysphagia on the QOL of head and neck cancer patients.

131 Background: Financial toxicity (FT) describes objective and subjective burden of costs associated with medical care. Patients with head and neck cancer (HNC) and lung carcinoma are acutely impacted by FT, as these cancers disproportionately occur in populations that are poor, unemployed, and/or of minority backgrounds compared to patients with other cancers. Our group recently published results showing delay in time to treatment initiation (TTI) was associated with poorer survival in HNC patients. Another study reported that FT was associated with worse progression-free survival in non-small cell lung cancer patients. In this study, we sought to investigate the association between FT, TTI and clinical outcomes among HNC and lung carcinoma patients, as well as predictors of FT. Methods: A retrospective analysis of 140 patients diagnosed with either HNC or lung carcinoma between January 2007 and March 2018 with quality-of-life data collected prospectively at the time of radiation oncology treatment was conducted. Participants responded to a question about their experience on ‘financial difficulties’ with a 4-point Likert Scale within the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) quality of life assessment. FT was low when patients indicated ‘1’ (not at all) or ‘2’ (a little), and high if patients indicated ‘3’ (quite a bit), and ‘4’ (very much). Chi-square test and Student’s t-test were used to compare characteristics of patients with and without FT. The association between FT and TTI and survival outcomes were analyzed using the Kaplan-Meier methods and Cox proportional-hazards regression models. Results: The study sample included 70 patients with HNC (mean [SD] age, 64.3 [12.0]; 62.7% male) and 70 patients with lung carcinoma (mean [SD] age, 69.1 [10.2]; 38.0% male). Over half (N = 80, 55.2%) reported experiencing financial toxicity (64% HNC vs. 45.7% lung carcinoma). Younger age (&lt; 60 years), having Medicaid, and having small-cell lung carcinoma were associated with greater FT (p = 0.049, p = 0.042, p = 0.034, respectively). Patients who reported having poorer health and quality of life also experienced greater FT (p = 0.030, p = 0.016, respectively). HNC patients who experienced greater FT were less likely to experience treatment delay (p = 0.035). After adjusting for age, sex, ethnicity, tumor site, and tumor stage, FT was associated with worse survival outcomes in all patients (HR = 1.52, 95% CI 1.06-2.19). Conclusions: Greater FT was associated with younger age, having Medicaid, and having small-cell lung carcinoma. HNC patients who experienced greater FT were less likely to experience treatment delay, which suggests that delay may not be a causative factor for the worsened survival seen with patients who report FT.

Prospective Dysphagia Quality of Life Scores and Treatment Outcomes in Oropharyngeal Cancer Patients: Is it Time to Reconsider the Prophylactic Percutaneous Endoscopic Gastrostomy?

Patient-reported outcomes following parotid-sparing intensity-modulated radiotherapy for head and neck cancer. How important is dysphagia?