MD Anderson Symptom Inventory-Head Research Articles

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

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. To determine the association between primary surgery or radiotherapy and long-term PROs. 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. Primary radiotherapy and surgery for OPSCC. 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. 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 (β, -0.1; 95% CI, -0.7 to 0.6), NDII (β, -1.7; 95% CI, -6.7 to 3.4), and EAR (β, -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. 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.

Patient-Reported Symptom Severity, Health-Related Quality of Life, and Emotional Distress Trajectories During and After Radiation Therapy for Human Papillomavirus–Associated Oropharyngeal Cancer: A TROG 12.01 Secondary Analysis

This secondary analysis of clinical trial TROG 12.01, involving patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma, aimed to identify patient-reported outcome (PRO) trajectories before, during, and after chemoradiotherapy. Head and neck cancer symptom severity (HNSS) and interference (HNSI), generic health-related quality of life (HRQL), and emotional distress were assessed with the MD Anderson Symptom Inventory-Head and Neck, Functional Assessment of Cancer Therapy-General, and Hospital Anxiety and Depression Scale questionnaires, respectively. Latent class growth mixture modeling (LCGMM) was used to identify distinct underlying trajectories. Baseline and treatment variables were compared between trajectory groups. The LCGMM identified latent trajectories for all PROs: HNSS, HNSI, HRQL, anxiety, and depression. Four HNSS trajectories (HNSS1-4) were identified, distinguished by differences in HNSS at baseline, during the peak of treatment symptoms, and during early and intermediate recovery. All trajectories were stable beyond 12 months. The reference trajectory (HNSS4, n=74) score was 0.1 (95% confidence interval [CI], 0.1-0.2) at baseline, peaking at 4.6 (95% CI, 4.2-5.0), with rapid early recovery (1.1; 95% CI, 0.8-2.2) and gradual improvement to 12 months (0.6; 95% CI, 0.5-0.8). Patients in HNSS2 (high baseline, n=30) reported higher baseline scores (1.4; 95% CI, 0.8-2.0) but were otherwise similar to HNSS4. Patients in HNSS3 (low acute, n=53) reported reduced acute symptoms (2.5; 95% CI, 2.2-2.9) with stable scores beyond 9 weeks after chemoradiotherapy (1.1; 95% CI, 0.9-1.4). Patients in HNSS1 (slow recovery, n=25) had slower recovery from an acute peak of 4.9 (95% CI, 4.3-5.6) to 0.9 (95% CI, 0.6-1.3) at 12 months. Age, performance status, education, receipt of cetuximab, and baseline anxiety varied between trajectories. The other PRO models demonstrated clinically relevant trajectories, with distinct associations with baseline factors. LCGMM identified distinct PRO trajectories during and after chemoradiotherapy. These and their associations with variations in the characteristics and treatment factors of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma provide clinically relevant insights into identifying patients who may require increased support before, during, or after chemoradiotherapy.

Distinct Dysphagia Profiles in Patients With Oral Cancer After Surgery.

To determine distinct profiles based on symptom severity in patients undergoing surgery for oral cancer and examine whether these profiles differ by participant characteristics. 300 patients who underwent surgery for oral cancer at two outpatient clinics between June and December 2021. Symptoms were assessed using the MD Anderson Symptom Inventory-Head and Neck Cancer Module. Sociodemographic and clinical characteristics were collected. Latent profile analysis was performed. Five distinct dysphagia profiles were identified, which qualitatively differed regarding co-occurrence patterns of dysphagia, mucus-related symptoms, speech disturbances, and psychoneurologic symptoms. Significant differences were reported in interference to function, number of co-occurring symptoms, time since diagnosis and treatment completion, use of symptom management medications, oral cancer stage and site, and treatment completed. Identifying distinct dysphagia profiles can improve patient outcomes and help in planning specific nursing interventions to influence nutritional and functional status in oral cancer survivors. Dysphagia and dry mouth can persist beyond one year post-treatment, so follow-up dysphagia assessments are needed.

Patient-Reported Financial Toxicity in a Population-Based Cohort of Oropharynx Cancer Survivors

Patients with oropharyngeal squamous cell carcinoma (OPSCC) are at high risk for financial toxicity (FT), but the nature, extent, and predictors of FT experienced after primary radiation therapy (RT) or surgery are poorly understood. We used a population-based sample of patients from the Texas Cancer Registry with stage I to III OPSCC diagnosed from 2006 to 2016 and treated with primary RT or surgery. Of 1,668 eligible patients, 1,600 were sampled, 400 responded, and 396 confirmed OPSCC. Measures included the MD Anderson Symptom Inventory Head and Neck, Neck Dissection Impairment Index, and a financial toxicity instrument adapted from the Individualized Cancer Care (iCanCare) study. Multivariable logistic regression evaluated associations of exposures with outcomes. Of 396 analyzable respondents, 269 (68%) received primary RT and 127 (32%) surgery. The median time from diagnosis to survey was 7 years. Due to OPSCC, 54% of patients experienced material sacrifice (including 28% who reduced food spending and 6% who lost their housing), 45% worried about financial problems, and 29% experienced long-term FT. Independent factors associated with more long-term FT included female sex (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.23-2.40), Black non-Hispanic race (OR, 2.98; 95% CI, 1.26-7.09), unmarried status (OR, 1.50; 95% CI, 1.11-2.03), feeding tube use (OR, 3.98; 95% CI, 2.29-6.90), and worst versus best quartile on the MD Anderson Symptom Inventory Head and Neck (OR, 1.89; 95% CI, 1.23-2.90) and Neck Dissection Impairment Index (OR, 5.62; 95% CI, 3.79-8.34). Factors associated with less long-term FT included age >57 years (OR, 0.54; 95% CI, 0.41-0.71; P < .001) and household income ≥$80,000 (OR, 0.60; 95% CI, 0.44-0.82; P=.001). Primary RT versus surgery was not associated with long-term FT (OR, 0.92; 95% CI, 0.68-1.24). Oropharynx cancer survivors experience high rates of material sacrifice and long-term FT, and we identified important risk factors. Chronic symptom burden was associated with significantly worse long-term financial status, supporting the hypothesis that toxicity mitigation strategies may reduce long-term FT.

Patient-Reported Financial Toxicity in a Population-Based Cohort of Oropharynx Cancer Survivors after Primary Radiotherapy or Surgery

<h3>Purpose/Objective(s)</h3> Patients with oropharynx cancer are at risk for financial toxicity due to the intensive treatment and impact on critical normal functions such as eating and speaking. The nature, extent, and predictors of financial toxicity experienced after primary radiotherapy (RT) or surgery are not well-described in this population. Since the treatment strategy for oropharynx cancer is likely sensitive to patient preferences, the effects on financial toxicity may inform decision-making and facilitate interventions. <h3>Materials/Methods</h3> We identified a population-based sample of oropharynx cancer patients from the Texas Cancer Registry aged ≥18, diagnosed 2006-2016, stage I-III, and treated with primary RT or primary surgery +/- post-operative RT (PORT). Out of 1,668 eligible patients, 1,600 were mailed an invitation, survey, and $10 gift card in 2020-21. The survey included demographic and treatment questions, the MD Anderson Symptom Inventory Head and Neck (MDASI-HN), Neck Dissection Impairment Index (NDII), Effectiveness of Auditory Rehabilitation (EAR) scale, and an 8-question financial toxicity instrument adapted from the iCanCare study. Multivariable (MVA) logistic regression identified predictors of self-reported long-term financial decline attributable to cancer and treatment with p<0.05 considered significant. <h3>Results</h3> In total, 400 patients responded (25% response rate), of whom 271 (68%) received primary RT and 129 (32%) primary surgery. Of primary surgery patients, 105 (83%) received PORT while 22 (17%) did not. Median time from diagnosis to survey was 7 years. Overall, due to oropharynx cancer, 45% used personal savings, 19% could not make bill payments, 28% cut down on food spending, 2% had utilities turned off, 6% could no longer afford their housing, and 54% experienced some form of financial toxicity. Patients who received primary surgery without PORT used less personal savings (p=0.04) with less short-term financial toxicity overall (p=0.04). At the time of survey, 45% of patients worried about financial problems because of their cancer and treatment. On MVA, factors associated with worse long-term financial status included younger age (≤57 years), primary RT (only in >57 years), female sex, Black non-Hispanic race, unmarried status, lower income, tonsil subsite, more recent diagnosis, and worse scores on the MDASI-HN, NDII, and EAR. <h3>Conclusion</h3> In this population-based cohort, oropharynx cancer survivors reported high rates of short- and long-term financial toxicity, with nearly half worrying about financial problems due to their cancer at a median 7 years after diagnosis. Higher chronic symptom burden was associated with worse long-term financial status while the effect of primary RT vs surgery was significantly modified by age. The subset of primary surgery without PORT reported less short-term financial toxicity. Identifying patients with risk factors for financial toxicity presented here may allow for appropriate intervention and counseling.

Two-Year Patient-Reported Outcomes after Ipsilateral IMRT for T1-2 N2b Squamous Cell Carcinoma of the Tonsils

<h3>Purpose/Objective(s)</h3> Although unilateral neck irradiation is frequently implemented in patients with well-lateralized stage T1-2 HPV+ tonsillar squamous cell carcinoma (SCC) to minimize toxicity, its role in patients with N2b (AJCC-7 staging) nodal disease remains controversial. We have separately reported on contralateral nodal recurrence risk in patients with N2b disease receiving unilateral neck radiation. The quality-of-life patient reported outcomes (PRO) in these patients have not been previously reported. Our hypothesis was that patients with AJCC 7^th edition T1-2 N2b tonsillar squamous cell carcinoma treated with unilateral neck radiation had mild quality-of-life PROs. <h3>Materials/Methods</h3> The PROs of 44 AJCC-7 T1-2 N2b tonsillar squamous cell carcinoma (SCC) patients from two academic institutions treated with definitive, ipsilateral intensity modulation radiation therapy (IMRT) with or without systemic therapy were reviewed retrospectively. PROs were completed using either the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN) at the first institution, or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35 (EORTC QLQ-H&N35) at the second institution. The primary endpoint was the head and neck-related PROs at 2 years after completion of radiation. <h3>Results</h3> Twenty-eight of 30 and 4 of 14 patients from the first and second institutions, respectively, met the primary endpoint and were further analyzed. Of these, 34.4% received radiation alone without systemic therapy and 93.7% received ipsilateral-only neck IMRT. The most common head and neck-related PRO was dry mouth at the first and second institutions (64.2% and 100%, respectively); the least common was difficulty with voice or speech at both institutions (14% and 0%, respectively). There were also no reports of mouth pain or soreness, trouble with teeth, opening mouth, or swallowing liquid/pureed food at the second institution. The overall symptom severity for all PRO categories in both modules were in the mild range, with the highest mean score reported for dry mouth: 2.54 out of 10 on MDASI-HN for the first institution and 2.5 out of 4 on EORTC QLQ-H&N35 for the second institution. The rest of the mean scores for the first institution were < 1.5, while the remainder for the second institution were ≤ 2. The locoregional control and overall survival after a median follow-up of 4.5 years were each 100%. <h3>Conclusion</h3> We assessed the 2-year quality-of-life PROs for ipsilaterally radiated tonsillar SCC from 2 institutions using either MDASI-HN or EORTC QLQ-H&N35, and most patients reported mild symptom burden. These findings suggest that ipsilateral-only IMRT is well tolerated in patients with AJCC-7 N2b disease and can be safely employed as a de-escalation strategy.

Optimized decision support for selection of transoral robotic surgery or (chemo)radiation therapy based on posttreatment swallowing toxicity.

A primary goal in transoral robotic surgery (TORS) for oropharyngeal squamous cell cancer (OPSCC) survivors is to optimize swallowing function. However, the uncertainty in the outcomes of TORS including postoperative residual positive margin (PM) and extranodal extension (ENE), may necessitate adjuvant therapy, which may cause significant swallowing toxicity to survivors. A secondary analysis was performed on a prospective registry data with low- to intermediate-risk human papillomavirus-related OPSCC possibly resectable by TORS. Decision trees were developed to model the uncertainties in TORS compared with definitive radiation therapy (RT) and chemoradiation therapy (CRT). Swallowing toxicities were measured by Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), MD Anderson Dysphagia Inventory (MDADI), and the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) instruments. The likelihoods of PM/ENE were varied to determine the thresholds within which each therapy remains optimal. Compared with RT, TORS resulted in inferior swallowing function for moderate likelihoods of PM/ENE (>60% in short term for all instruments, >75% in long term for DIGEST and MDASI) leaving RT as the optimal treatment. Compared with CRT, TORS remained the optimal therapy based on MDADI and MDASI but showed inferior swallowing outcomes based on DIGEST for moderate-to-high likelihoods of PM/ENE (>75% for short-term and >40% for long-term outcomes). In the absence of reliable estimation of postoperative PM/ENE concurrent with significant postoperative PM, the overall toxicity level in OPSCC patients undergoing TORS with adjuvant therapy may become more severe compared with patients receiving nonsurgical treatments thus advocating definitive (C)RT protocols.

87: Patient Reported Outcomes During Head and Neck Cancer Radiotherapy Using the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN)

87: Patient Reported Outcomes During Head and Neck Cancer Radiotherapy Using the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN)

Feasibility and Acceptability of Implementing Site-Specific Patient-Reported Outcome Measure in Head and Neck Cancer Clinics: A Prospective Institutional Study

PurposeTo assess the feasibility and acceptability of implementing the MD Anderson Symptom Inventory–Head and Neck (MDASI-HN) module in cancer clinics and its effect on patient-reported experience. MethodsWe conducted a prospective, longitudinal study at a tertiary cancer institution between September 2020 and August 2021. Patients with newly diagnosed head and neck (HN) cancer who were evaluated to receive radiation therapy with or without chemotherapy and could communicate in English were approached to participate. The primary outcome was feasibility and acceptability of the MDASI-HN implementation in the radiation oncology department assessed by patient and provider exit surveys. Secondary outcomes were patient-reported experience as recorded by a shortened Your Voice Matters survey (YVM) in 2 cohorts pre- and post-MDASI-HN implementation and symptom scores. Descriptive statistics were used for exit surveys and symptom scores. Mann-Whitney tests were used to assess differences in positive responses between pre- and postimplementation for each YVM question. Cochrane-Armitage tests were used to examine changes in patient-reported experience over time. ResultsFifty-one patients were enrolled in the postimplementation cohort and 29 (60%) responded to the exit survey. Eighty-nine percent of patients reported that MDASI-HN made it easier to remember symptoms, and 86% recommend its use in routine care. Four of the 5 radiation oncology HN providers (80%) responded to exit surveys; 75% felt the MDASI-HN provided clinically relevant information, improved communication with patients, and did not increase clinic time. The overall patient-reported experience was not affected by the implementation (P = .82). The probability of positive responses over time was significant (P = .025) in the clinic coordination domain for the postimplementation cohort. ConclusionsImplementation of MDASI-HN was feasible and acceptable by patients and providers. Although the overall patient-reported experience was not affected by implementation, some aspects improved as treatment progressed.

Symptom profile of head and neck patients initiating care in a survivorship clinic.

e24047 Background: After treatment, and at a time point of low risk of relapse, cancer patients at our institution transition to Survivorship Clinics (SC) that focus on wellness, late effects management, and psychosocial functioning in additional to cancer screening. We describe the self-reported symptoms of Head and Neck (HNC) survivors at the time of transition to SC, and the level to which these symptoms interfered with their function. Methods: Survivors reporting to their first in person SC appointment were assessed using the MD Anderson Symptom Inventory Head and Neck (MDASI–HN). This validated patient-reported outcome (PRO) instrument consists of 28 questions grouped into three subscales (core symptoms, disease specific symptoms, and interference items). Symptom severity is measured using a 0 to 10 scale (0 = not present, 10 = as bad as can be imagined). Descriptive statistics were used to characterize the sample. Percent of patients reporting moderate to severe symptoms (&gt; = 4) are also noted. Results: This sub-analysis consisted of 377 patients seen for their initial transition visit to the survivorship clinic. Patients were mostly male (83%) and Caucasian (89%), with an average age of 63.8 years, and on average 41.5 months from diagnosis. Most common cancers were oropharynx (49%), oral cavity (33.7%), and larynx/hypopharynx (12.5%), nasopharynx (4.5%). Average symptom reports are presented in table. In rank order of prevalence (4% to 31% of patients), the top reported moderate to severe symptoms included dry mouth, swallowing/chewing, mucus, remembering, distress, and shortness of breath associated with moderated to severe interference in general activity in 8% of patients. Conclusions: HNC survivors report multiple persistent symptoms of moderate to high severity in a significant number, most commonly mouth dryness and swallowing and chewing difficulty. PROs can identify patients with high symptom burden, and lead in interventions to support the patients at their SC visit.[Table: see text]

Factors associated with adherence to remote patient monitoring for early detection of dehydration risk during radiation treatment for head and neck cancer.

6076 Background: Remote patient monitoring (RPM) may improve the early detection and mitigation of cancer treatment-related complications, health-related outcomes and quality of life. RPM’s success may depend, in part, on patients’ adherence to remote monitoring protocols. However, factors that influence adherence to RPM are largely unknown. Daily blood pressure/pulse (BP/P), weight, and electronic patient-reported outcomes (ePROs) were monitored remotely in head and neck cancer (HNC) patients undergoing radiation treatment (RT) to identify dehydration risk. We evaluated potential factors associated with RPM adherence. Methods: During RT (average 6 to 7 weeks), participants were asked to take daily (Monday-Friday) measures of BP/P and weight using Bluetooth-enabled devices and to complete daily ePROs using a mobile tablet application (app). Data were provided to their physicians for daily review. The MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) was completed at baseline and end of RT, and 6-8 weeks post-RT completion. The Patient Activation Measure (PAM) was completed at baseline and 6-8 weeks post-RT completion. A device usability survey measuring perceived usefulness of RPM was completed at the end of RT. Adherence to daily monitoring was recorded objectively. Longitudinal analyses compared the relationship between demographic, clinical, and PRO data and monitoring adherence. Results: Participants (n = 169) were 80% male, 87% White, and 91% married. Overall adherence to monitoring BP/P, weight, and ePROs was 83%, 82% and 74%, respectively. Greater HN-specific symptom severity and interference was associated with decreased adherence to daily monitoring of BP/P, weight, and ePROs (P&lt; 0.021). Higher PAM scores were associated with higher adherence to daily monitoring of BP/P only (p = 0.006). Participants reported modest levels of perceived usefulness of RPM across four categories: symptom management, early problem detection, illness monitoring by healthcare provider, and feeling of security during RT. Only a single item indicating perceived feeling of security was associated with greater adherence to daily monitoring of blood pressure/pulse (p = 0.032) and weight (p = 0.007). Conclusions: A benefit of frequent RPM may be early detection and mitigation of symptoms during RT for HNC, however, increasing symptom burden experienced during treatment may interfere with adherence to daily monitoring. Better adherence may be attributed to patients perceiving a sense of security from daily monitoring and may suggest a potentially important value that patients gain from RPM. Understanding factors that impact patient adherence to RPM may help improve acceptability and clinical utility of RPM in oncology. Clinical trial information: NCT02253238.

The influence of radiation dose on taste impairment in a prospective observational study cohort of oropharyngeal cancer patients

Background To analyze the influence of radiation dose on late radiation-associated taste impairment in oropharyngeal cancer (OPC) patients treated with intensity-modulated radiotherapy (IMRT) using the taste bud bearing tongue mucosa as organ at risk. Material and methods This study is part of an ongoing, prospective observational study. Cancer-free OPC survivors with at least 24 months from IMRT were included in this analysis. Scores for taste impairment and dry mouth were extracted from the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN) with scores of ≥5 considered as moderate-to-severe symptoms. The mean dose, minimum and maximum dose to the taste bud bearing tongue mucosa, the ipsi- and contralateral parotid and submandibular glands were extracted and analyzed for correlation with moderate-to-severe taste impairment. Results One hundred sixteen T1–4 OPC patients were included (81% males, median age: 55). The primary tumor was in the tonsil in 92 cases (79%) and in the base of tongue in 21 cases (18%). Patients were treated with 64.2–72.0 Gy; 37 patients (32%) received concurrent chemotherapy and 22 (19%) concurrent targeted therapy. After a median of 58 months from RT (IQR: 43–68) 38 patients (33%) suffered from moderate-to-severe long-term radiation-associated taste impairment. No dose volume parameter of the taste bud bearing tongue mucosa and the salivary glands was significantly associated with moderate-to-severe taste impairment for the whole patient cohort. For patients without concurrent chemotherapy, the minimum and mean dose to the ipsilateral parotid gland, and the maximum dose to the submandibular gland was significantly associated with late taste impairment (all p < 0.05). A significant correlation was found between taste impairment and dry mouth (p < 0.001). Conclusion The dose to the ipsilateral parotid gland seems to play an important role in the development of late taste impairment. The influence of dose to the taste bud bearing tongue mucosa remains unclear and needs further investigation.

Patient-reported outcomes and complications during head and neck cancer radiotherapy before versus during the COVID-19 pandemic.

PurposeThis study compares patient-reported outcomes and treatment-related complications during radiotherapy before (August 2019–January 2020) versus during (March–Sept 2020) the COVID-19 pandemic.Materials and methodsThe MD Anderson Symptom Inventory-head and neck module was used to assess curative intent in H&N cancer patients’ symptoms during radiotherapy.ResultsThere were 158 patients in the pre-pandemic cohort and 137 patients in the pandemic cohort. There was no significant difference in enteral feeding requirements between the cohorts (21% versus 30%, p = 0.07). Weight loss was higher during the pandemic (mean − 5.6% versus 6.8%, p = 0.03). On multivariate analysis, treatment during the pandemic was associated with higher symptom scores for coughing/choking while eating (2.7 versus 2.1, p = 0.013).ConclusionsComplication rates during H&N radiotherapy during the COVID-19 pandemic were similar at our institution relative to the pre-pandemic era, although weight loss was greater and patients reported more severe choking/coughing while eating.

Risk Factors of Patient-Reported Xerostomia Among Oropharyngeal Cancer Survivors Treated with Definitive Radiotherapy

<h3>Purpose/Objective(s)</h3> Xerostomia is a common sequela of radiation therapy (RT) and chemoradiotherapy (CRT). Head and neck cancer treatment can contribute to salivary glands injury with diminished salivary production and changes in consistency, volume, and pH of saliva. Previous studies examining xerostomia have investigated RT regimens, dosimetric predictors, and quality of life (QoL) associations but few have identified clinicodemographic risk factors for xerostomia and quantified their associations among oropharyngeal carcinoma (OPC) survivors. The objective of this study was to identify risk factors for xerostomia among long-term OPC survivors. <h3>Materials/Methods</h3> This was a cross-sectional study conducted at a comprehensive cancer center. Study participants included disease-free, adult OPC survivors who completed curative definitive radiotherapy treatment between January 2000 and December 2013, and responded to a survey administered from September 2015 to July 2016. This study included 881 OPC survivors with a median survival duration at time of survey of 7 years (range, 1-16 years) of which self-reported xerostomia scores were available for 853 participants. The primary outcome variable was patient-reported xerostomia measured using the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified using multivariable logistic regression. <h3>Results</h3> Of 853 OPC survivors who responded to the xerostomia question, 337 (39.5%) reported moderate to severe xerostomia. Multivariable logistic regression identified current smoking at time of survey (OR:2.57, 95% CI: 1.20-5.53, <b>P</b> = 0.016) as a risk factor for moderate to severe xerostomia and concurrent cetuximab chemotherapy (OR:0.63; 95% CI: 0.41-0.97, <b>P</b> = 0.038) as a protective factor. Additionally, female sex (OR:1.81, 95% CI: 1.21-2.71, <b>P</b> = 0.004) and less than high school education (OR:1.68, 95% CI: 1.15-2.45, <b>P</b> = 0.008) were risk factors for moderate to severe xerostomia and bilateral intensity modulated radiotherapy (IMRT) combined with proton therapy (OR:0.34, 95% CI: 1.16-0.73, <b>P</b> = 0.005) and ipsilateral IMRT (OR:0.18, 95% CI: 0.07-0.46, <b>P</b> < 0.001) were protective. <h3>Conclusion</h3> In this large xerostomia study, about 4 out of 10 OPC survivors reported moderate to severe xerostomia over long-term follow-up. Continued smoking after cancer diagnosis, sex, and education were identified as important risk factors of moderate to severe xerostomia and concurrent cetuximab therapy and more modern RT regimens had a protective association. Sustained smoking post-diagnosis is a modifiable risk factor which can be addressed with continued smoking cessation efforts. Lastly, these results can inform future research and targeted patient-centered interventions to monitor and manage RT-associated xerostomia and preserve QoL among OPC patients.

Sub-Acute Post-Treatment Dysphagia and Shortness of Breath Symptoms Associate With Worse Survival in Oropharyngeal Cancer

Post-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness of breath may empirically guide earlier detection of disease recurrence, their association with patient outcomes is less well studied, especially for HPV-positive disease. This study aimed to investigate the association between patient reported dysphagia and shortness of breath at 3-to-6 months following radiotherapy (RT) and overall survival (OS).Data were collected from oropharyngeal cancer patients that received RT with curative intent from 2015-2019. Included patients had self-reported scores for shortness of breath, choking/coughing ("choke"), and difficulty swallowing/chewing ("swallow"), which were surveyed via the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) questionnaire at 3-to-6 months after RT. Symptom severity was scored from 0-10. Significant predictors of OS were analyzed via Cox regression. Symptom scores were also discretized for Kaplan-Meier (KM) analysis, with more severe symptoms being 6+ for "swallow" and "choke" and 2+ for shortness of breath.Symptom scores were collected at 3-to-6 months from 470 patients. The majority (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9-42.1). Univariable Cox regression (Table 1) showed significant associations between OS and MDASI scores for shortness of breath, "choke," and "swallow." Furthermore, a composite variable integrating scores of all three symptoms had the best predictive value for OS (c-index = 0.748). Symptom severity stratified patients based on OS for all three symptoms, with more severe symptoms predicting worse OS on KM analysis (P < 0.001 for all symptoms). On subset analysis more severe symptoms remained significantly associated with worse OS among HPV-positive patients (P < 0.01 for all symptoms).Quantitative early patient-reported measures of dysphagia and shortness of breath are significant predictors of OS in head and neck cancer, in particular for HPV-positive disease. Integrating quantitative symptom surveys into post-treatment surveillance may be beneficial for individualizing follow-up strategies.

Determinants of patient-reported xerostomia among long-term oropharyngeal cancer survivors.

This study was conducted to identify clinicodemographic risk factors for xerostomia among long-term oropharyngeal cancer (OPC) survivors. This cross-sectional study included 906 disease-free, adult OPC survivors with a median survival duration at the time of survey of 6 years (range, 1-16 years); self-reported xerostomia scores were available for 877 participants. Study participants had completed curative treatment between January 2000 and December 2013 and responded to a survey administered from September 2015 to July 2016. The primary outcome variable was cancer patient-reported xerostomia measured with the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified via multivariable logistic regression. Moderate to severe xerostomia was reported by 343 of the respondents (39.1%). Female sex (odds ratio [OR], 1.82; 95% CI, 1.22-2.71; P = .003; Bayesian false-discovery probability [BFDP] = 0.568), high school or lower education (OR, 1.73; 95% CI, 1.19-2.52; P = .004; BFDP = 0.636), and current cigarette smoking at the time of survey (OR, 2.56; 95% CI, 1.19-5.47; P = .016; BFDP = 0.800) were risk factors for moderate to severe xerostomia, and bilateral intensity-modulated radiotherapy (IMRT) combined with proton therapy and ipsilateral IMRT were protective. In this large xerostomia study, modern radiotherapy was a protective factor, and continued cigarette smoking at the time of survey, female sex, and high school or lower education were identified as other contributing risk factors associated with moderate to severe xerostomia. Importantly, these findings need to be confirmed in prospective studies. These results can inform future research and targeted patient-centered interventions to monitor and manage radiation therapy-associated xerostomia and preserve quality of life among patients with OPC.

Fear of Cancer Recurrence in Survivors of Human Papillomavirus–Associated Oropharyngeal Carcinoma

To estimate the prevalence of and characteristics associated with fear of cancer recurrence (FCR) among human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) survivors. We conducted a cross-sectional study in HPV-OPC survivors ≥12 months from completion of definitive (chemo)radiation therapy (RT/CRT). Eligible patients completed the Fear of Cancer Recurrence Inventory short-form (FCRI-SF), the European Organisation for research and Treatment of Cancer QLQ-C30, MD Anderson Symptom Inventory-Head and Neck, and PROMIS Anxiety and Depression short forms. Associations between FCRI-SF scores and other variables were investigated using linear regression models. A total of 136 HPV-OPC survivors were enrolled; the median age was 61 years (range, 42-87 years), 84% were male, 72% were currently partnered, 83% were current nonsmokers, 67% were regular alcohol consumers, and the median time since treatment was 2.8 years (range, 1.0-5.5 years). Clinical levels of FCR (≥13) were observed in 72 of 135 patients (53%; 95% confidence interval [CI], 45%-62%). Characteristics significantly associated with increasing FCR scores were younger age (-0.9/5 years; 95% CI, -1.7 to -0.01; P = .031), lower global quality of life (-0.8/10 unit increase; 95% CI, -1.4 to -0.2; P=.012), higher symptom interference (0.8/unit increase; 95% CI, 0.1-1.5; P=.017), and a higher burden of anxiety (0.4/unit; 95% CI, 0.3-0.5; P <.001) and depression (0.3/unit; 95% CI, 0.1-0.4; P <.001). Other sociodemographic tumor- and treatment-related characteristics were not statistically significant. Compared with patients reporting nonclinical levels of FCR, significantly more patients reporting clinical levels of FCR than expected believed professional psychological assistance would have been beneficial (60% vs 33%; P = .002). Clinical levels of FCR were observed in approximately half of the HPV-OPC survivors. Survivors reporting higher FCR were younger with worse self-reported global quality of life and higher symptom interference and emotional distress. No other patient, tumor, or treatment factors were associated with higher FCR.

Randomized Trial of Radiation Therapy With Weekly Cisplatin or Cetuximab in Low-Risk HPV-Associated Oropharyngeal Cancer (TROG 12.01) – A Trans-Tasman Radiation Oncology Group Study

The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin. TROG12.01, a randomized, multicenter trial involving 15 sites in Australia and New Zealand enrolled patients with HPV-associated oropharyngeal squamous cell carcinoma, American Joint Committee on Cancer 7th edition stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomized (1:1) to receive radiation therapy (70 Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40 mg/m2, or cetuximab, loading dose of 400 mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks postcompletion of radiation therapy using the area under the curve. Trial was registered on ClinicalTrials.gov: NCT01855451. Between June 17, 2013, and June 7, 2018, 189 patients were enrolled, with 92 in cisplatin arm and 90 in cetuximab included in the main analysis. There was no difference in the primary endpoint of symptom severity; difference in area under the curve cetuximab-cisplatin was 0.05 (95% confidence interval [CI], -0.19, 0.30), P=.66. The T-score (mean number of ≥grade 3 acute adverse events) was 4.35 (standard deviation 2.48) in the cisplatin arm and 3.82 (standard deviation 1.8) in the cetuximab arm, P=.108. The 3-year failure-free survival rates were 93% (95% CI, 86%-97%) in the cisplatin arm and 80% (95% CI, 70%-87%) in the cetuximab arm (hazard ratio=3.0 [95% CI, 1.2-7.7]); P=.015. For patients with low-risk HPV-associated oropharyngeal cancer, radiation therapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared with radiation therapy and weekly cisplatin. Radiation therapy and cisplatin remain the standard of care.

Proton Beam Therapy for Head and Neck Carcinoma of Unknown Primary: Toxicity and Quality of Life.

PurposeProton radiation therapy (PRT) may offer dosimetric and clinical benefit in the treatment of head and neck carcinoma of unknown primary (HNCUP). We sought to describe toxicity and quality of life (QOL) in patients with HNCUP treated with PRT.Patients and MethodsToxicity and QOL were prospectively tracked in patients with HNCUP from 2011 to 2019 after institutional review board approval. Patients received PRT to the mucosa of the nasopharynx, oropharynx, and bilateral cervical lymph nodes with sparing of the larynx and hypopharynx. Patient-reported outcomes were tracked with the MD Anderson Symptom Inventory–Head and Neck Module, the Functional Assessment of Cancer Therapy–Head and Neck, the MD Anderson Dysphagia Inventory, and the Xerostomia-Related QOL Scale. Primary study endpoints were the incidence of grade ≥ 3 (G3) toxicity and QOL patterns.ResultsFourteen patients (median follow-up, 2 years) were evaluated. Most patients presented with human papillomavirus–positive disease (n = 12, 86%). Rates of G3 oral mucositis, xerostomia, and dermatitis were 7% (n = 1), 21% (n = 3), and 36% (n = 5), respectively. None required a gastrostomy. During PRT, QOL was reduced relative to baseline and recovered shortly after PRT. At 2 years after PRT, the local regional control, disease-free survival, and overall survival were 100% (among 7 patients at risk), 79% (among 6 patients at risk), and 90% (among 7 patients at risk), respectively.ConclusionTherefore, PRT for HNCUP was associated with highly favorable dosimetric and clinical outcomes, including minimal oral mucositis, xerostomia, and dysphagia. Toxicity and QOL may be superior with PRT compared with conventional radiation therapy and PRT maintains equivalent oncologic control. Further prospective studies are needed to evaluate late effects and cost-effectiveness.

Randomized trial of radiotherapy with weekly cisplatin or cetuximab in low risk HPV associated oropharyngeal cancer (TROG 12.01): A Trans-Tasman Radiation Oncology Group study.

6012 Background: The excellent prognosis of patients with low risk HPV associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiotherapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an EGFR targeting antibody, when combined with radiotherapy would result in a decrease in symptom burden and toxicity with similar efficacy when compared to weekly cisplatin. Methods: TROG 12.01, a randomised, multicentre trial involving 15 sites in Australia and New Zealand enrolled patients with HPV associated oropharyngeal squamous cell carcinoma, AJCC 7th edition Stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history &gt;10 pack years and/or distant metastases). Patients were randomised (1:1) to receive radiotherapy (70Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40mg/m2 or cetuximab, loading dose of 400mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks post completion of radiotherapy using the area under the time-severity curve (AUC). Sample size was 170 evaluable patients to provide at least 90% power to detect an effect size of 0.5, using a 2-sided test at 0.05 level of significance. Trial was registered on ClinicalTrials.gov: NCT01855451. Results: Between 17th June 2013 and 7th June 2018, 189 patients were enrolled and 182 were evaluable, with 92 on cisplatin arm and 90 on cetuximab included in the main analysis. The median follow-up was 4.1 years (0.4 - 5.3). Analyses were performed in all eligible randomised patients that commenced treatment (modified intention-to-treat population). There was no difference in the primary endpoint of symptom severity; difference in AUC cetuximab – cisplatin was 0.05 (95%CI: -0.19, 0.30), p= 0.66. The T-score (mean number of &gt; grade 3 acute adverse events) was 4.35 (SD 2.48) in the cisplatin arm and 3.82 (SD 1.8) in the cetuximab arm, p= 0.108. The 3 -year failure-free survival rates were 93% (95% CI: 86-97%) in the cisplatin arm and 80% (95% CI: 70-87%) in the cetuximab arm (hazard ratio = 3.0 (95% CI: 1.2-7.7); p=0.015. The increase in failures in the cetuximab arm was evenly split between distant and locoregional failures. Conclusions: For patients with low risk HPV associated oropharyngeal cancer, radiotherapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared to radiotherapy and weekly cisplatin. Radiotherapy and cisplatin remains the standard of care. Clinical trial information: NCT01855451.