Oral Care Program for Mouth Side Effects During Head and Neck Radiation Therapy

BACKGROUND

Oral toxicity is among the most burdensome consequences of head and neck radiation therapy. Mucositis, xerostomia, dysgeusia, mucosal pain and impaired oral intake develop during treatment, peak in the later treatment weeks, and can persist for weeks afterwards. Their consequences are not confined to discomfort: reduced oral intake leads to weight loss and dehydration, pain and mucosal injury lead to unplanned clinic and emergency visits, and severe toxicity can interrupt radiation delivery, which is itself associated with poorer disease control.

The OSEM (Oral Side-Effect Management) program combines a baseline structural risk assessment, a weekly patient-reported outcome instrument, a supportive-care product kit, and structured weekly review by a clinical coordinator with a defined escalation pathway to the treating radiation oncologist. No controlled evidence establishes that the program reduces oral symptom severity. That is the question this study asks.

THE INTERVENTION IS A BUNDLE

The test-arm intervention is delivered as a bundle and this study cannot attribute an observed effect to any single component. That limitation is accepted deliberately: the program is delivered as a bundle in practice, and a study of this size cannot support a factorial design. Component attribution is a question for a subsequent trial.

BLINDING

Participants and site staff cannot be blinded, since a kit is either received or not. Three mitigations apply. The primary endpoint is patient-reported and is collected identically in both arms, on the same schedule and in the same mode. Secondary clinical endpoints are adjudicated by a reviewer blinded to allocation, working from records with allocation redacted. The statistician conducting the primary analysis is blinded to arm identity until the analysis is locked.

BASELINE RISK SCORING

An OSEM Stage 1 baseline risk score is computed for every participant in both arms before the first delivered radiation fraction. It is recorded for research only. It is not returned to the participant or to the treating team in either arm, and it does not inform clinical management.

WHAT IS COMMON TO BOTH ARMS AND WHAT IS NOT

The weekly questionnaire is completed by the participant at Premier, ordinarily on the day of the scheduled radiation oncologist visit, and is identical in both arms. Weekly review by the clinical coordinator, the severity band that review acts on, and the escalation pathway are features of the intervention arm only.

Standard of care is unchanged in both arms, including the weekly radiation oncologist assessment and the after-hours on-call service. Nothing is withheld from control participants, and the kit components and equivalent products remain commercially available to anyone.

STATISTICAL APPROACH

This is a pilot study. The primary analysis compares the standardized area under the weekly oral symptom score curve between arms using analysis of covariance, adjusted for the stratification factor and for the baseline oral symptom score, with the treatment effect reported as an adjusted mean difference with a confidence interval. Where the distribution is materially non-normal, a prespecified rank-based alternative is used and the parametric result reported alongside.

No hypothesis test is prespecified for the binary clinical event endpoints, because the study is not powered for them. They are reported as proportions with exact confidence intervals and risk differences. A principal purpose of the study is to estimate the parameters needed to design an adequately powered confirmatory trial.

LIMITATIONS

Premier Cancer Center is a freestanding radiation oncology practice. Capture of acute care received outside Premier is incomplete, and completeness is reported as a limitation by arm rather than assumed.

In a head and neck cohort, concurrent chemoradiation triggers an automatic high-risk condition in the Stage 1 model, so baseline risk variation is limited by design. No claim about Stage 1 discriminative performance can be made from this study.

• ORAL CARE PRODUCT KIT (Other), also known as OC ORAL CARE KIT, PEACE OF MOUTH KIT: A kit of six commercially available consumer oral care products, supplied at enrollment, at approximately week 5, and at the final treatment visit in week 7 - three kits in total, each a one-month supply. Each kit contains: dry mouth candies, 6 packs, xylitol-based, 3 lemon and 3 sour cherry; nausea candies, 1 pack, ginger, xylitol-based; soothing mouth rinse, 30 single-dose stick packs of sodium chloride and sodium bicarbonate, one per day; sensitivity toothpaste with 10% nano-hydroxyapatite and xylitol, 3 oz; a soft bamboo-handled toothbrush; and a lip balm. A reusable bottle for preparing the daily rinse comes with the first kit only. Use is at the participant's discretion, following written instructions in each kit. Participants may stop any component at any time and are told to do so if it causes discomfort. No component is a prescription or over-the-counter drug, and none is FDA-approved to treat or prevent any disease.

Primary outcomes

• Oral symptom burden: area under the weekly oral symptom score curve [From the first delivered radiation fraction (Time 0) through the end-of-treatment assessment, up to 7 weeks and the a 4 week end of trial follow up.]: The weekly oral symptom score is the sum of eight patient-reported oral symptom domains - mouth pain, mouth sores, dry mouth, dry or chapped lips, taste changes, trouble eating or drinking, nausea when eating or drinking, and dizziness or dark urine - each graded on a four-level scored severity collapse. The score ranges from 0 to 42, where a higher score indicates greater symptom burden. Area under the curve is computed by the trapezoidal rule across available weekly assessments and standardized for the number of assessments contributed, so that participants with different course lengths are comparable. A lower area under the curve indicates lower symptom burden across the radiation course.

Secondary outcomes

• Peak oral symptom severity [From Time 0 through the end-of-treatment assessment, up to 7 weeks and then a final follow up 4 weeks later]: The highest weekly oral symptom score recorded during the radiation course, on the same 0 to 42 scale as the primary outcome measure, where a higher score indicates greater symptom burden.
• Time to first moderate or worse oral symptom [From Time 0 through the end-of-treatment assessment, up to 7 weeks and then a final follow up 4 weeks later]: Time from the first delivered radiation fraction to the first weekly assessment at which any of the eight scored oral symptom domains is recorded at moderate severity or worse.
• Proportion of participants reaching severe or very severe oral symptom severity [From Time 0 through the end-of-treatment assessment, up to 7 weeks and then a final follow up 4 weeks later]: The proportion of participants in whom any of the eight scored oral symptom domains is recorded at severe or very severe at any weekly assessment.
• Unplanned acute-care use attributable to oral toxicity [From Time 0 through the follow-up assessment 4 weeks after the final radiation fraction, up to 11 weeks]: Number of participants with at least one emergency department or urgent care evaluation, or hospitalization, attributable to oral toxicity, impaired oral intake or associated dehydration. Events are ascertained from the Premier medical record and adjudicated by a reviewer blinded to arm allocation. Capture of care received outside Premier is incomplete, and completeness is reported by arm.
• Unplanned radiation treatment interruption attributable to oral toxicity [From Time 0 through the final radiation fraction, up to 7 weeks]: Number of participants with at least one unplanned interruption of radiation delivery attributable to oral toxicity. Occurrence is confirmed from the radiation delivery record and cause from the treating clinician's documentation, adjudicated by a reviewer blinded to arm allocation.
• Enteral or parenteral nutrition escalation attributable to oral toxicity [From Time 0 through the follow-up assessment 4 weeks after the final radiation fraction, up to 11 weeks]: Number of participants with new or escalated enteral or parenteral nutrition support attributable to oral toxicity, adjudicated by a reviewer blinded to arm allocation.
• Change in body weight [Baseline, end of treatment (up to 7 weeks), and follow-up 4 weeks after the final radiation fraction (up to 11 weeks)]: Change in measured body weight from the enrollment baseline to the end-of-treatment assessment, and from the enrollment baseline to the follow-up assessment. Reported in kilograms and as a percentage of baseline weight.
• Oral symptom burden at the follow-up assessment [Follow-up assessment 4 weeks after the final radiation fraction, up to 11 weeks]: The weekly oral symptom score recorded at the follow-up assessment, on the same 0 to 42 scale as the primary outcome measure, where a higher score indicates greater symptom burden.

Other outcomes

• ePRO completion rate [From Time 0 through the follow-up assessment, up to 11 weeks]: The proportion of scheduled ePRO assessments that were submitted, out of the number expected. An assessment is expected at enrollment, in each week a participant is on treatment, and once at the follow-up visit. No item may be skipped, so a submitted assessment is complete by construction: this measure counts whole assessments submitted, not items answered. A missed assessment is recorded with the reason where known. Reported as a percentage, overall and by week, for each arm. A higher percentage indicates more complete data capture. This measure applies to both arms. The instrument, the schedule and the mode of administration are identical in each.
• Clinical coordinator weekly review completion rate [From Time 0 through the final radiation fraction, up to 7 weeks]: The proportion of scheduled weekly clinical coordinator reviews that were completed and documented, out of the number expected. A review is expected in each week a participant is on treatment. A review counts as completed when the six safety-flag questions have been asked, the band and red-flag status reviewed, kit use assessed, and the review recorded. Reviews not completed are recorded as missed, together with the reason. Reported overall and by week, as a percentage. A higher percentage indicates that the weekly review ran as specified. This measure applies to the OSEM Program arm only. The Standard of Care arm receives no clinical coordinator review.
• Time from Stage 2 band review to escalation contact [From Time 0 through the final radiation fraction, up to 7 weeks]: Time elapsed from the clinical coordinator's completion of the weekly Stage 2 band and red-flag review to the first documented contact with the on-call Premier radiation oncologist, measured in hours. Both time points are recorded in the study escalation log at the time they occur. The measure is evaluated only for reviews at which the band or a confirmed red-flag criterion indicated escalation. This measure applies to the OSEM Program arm only. No band review and no escalation pathway operate in the Standard of Care arm, so no value exists for that arm and none is reported. A shorter time indicates faster escalation. The measure is reported descriptively, as a feasibility measure of whether the escalation pathway operates as specified. It is not a comparison between arms.
• Participant-reported kit use [From Time 0 through the final radiation fraction, up to 7 weeks]: Participant self-report of how often each kit component was used in the preceding 7 days, collected on the weekly ePRO. Each of the six components - soothing mouth rinse, sensitivity toothpaste, dry mouth candies, nausea candies, soft toothbrush and lip balm - is answered on a four-level scale: Not at all, A few times, Most days, Every day. The item is not scored and does not contribute to the oral symptom score or the severity band. This measure applies to the OSEM Program arm only, since the Standard of Care arm receives no kit. Reported descriptively as the distribution of responses by component and by week. A higher proportion answering Most days or Every day indicates greater adherence.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Adults aged 18 years or older Histologically confirmed malignancy of a head and neck site Planned definitive or post-operative external beam radiation therapy to a head and neck site, delivered at Premier Cancer Center Planned course of at least 20 fractions over approximately 4 to 7 weeks With or without concurrent systemic therapy Able to provide written informed consent Able to complete an electronic questionnaire in English, with or without assistance

Exclusion Criteria:

Palliative short-course radiation, or a planned course of fewer than 20 fractions Re-irradiation of a previously irradiated head and neck field Radiation delivered at an institution other than Premier Known allergy or sensitivity to any component of the Peace of Mouth Kit Any condition that, in the judgment of the treating radiation oncologist or the Premier Physician of Record, makes participation unsafe or impracticable Inability to complete study assessments

• ABIDA TAHER, Principal investigator, UNCANCER LLC