The PRO-ACTIVE trial protocol: a randomized study comparing the effectiveness of PROphylACTic swallow InterVEntion for patients receiving radiotherapy for head and neck cancer

Abstract

Background Swallowing therapy is commonly provided as a treatment to lessen the risk or severity of dysphagia secondary to radiotherapy (RT) for head and neck cancer (HNC); however, best practice is not yet established. This trial will compare the effectiveness of prophylactic (high and low intensity) versus reactive interventions for swallowing in patients with HNC undergoing RT. Methods This multi-site, international randomized clinical trial (RCT) will include 952 adult patients receiving radiotherapy for HNC and who are at high risk for post-RT dysphagia. Participants will be randomized to receive one of three interventions for swallowing during RT: RE-ACTIVE, started promptly if/when dysphagia is identified; PRO-ACTIVE EAT, low intensity prophylactic intervention started before RT commences; or, PRO-ACTIVE EAT+EXERCISE, high intensity prophylactic intervention also started before RT commences. We hypothesize that the PRO-ACTIVE therapies are more effective than late RE-ACTIVE therapy; and, that the more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to the low intensive PRO-ACTIVE (EAT). The primary endpoint of effectiveness is duration of feeding tube dependency one year post radiation therapy, selected as a pragmatic outcome valued equally by diverse stakeholders (e.g., patients, caregivers and clinicians). Secondary outcomes will include objective measures of swallow physiology and function, pneumonia and weight loss, along with various patient-reported swallowing-related outcomes, such as quality of life, symptom burden, and self-efficacy. Discussion Dysphagia is a common and potentially life-threatening chronic toxicity of radiotherapy, and a priority issue for HNC survivors. Yet, the optimal timing and intensity of swallowing therapy provided by a speech-language pathologist is not known. With no clearly preferred strategy, current practice is fraught with substantial variation. The pragmatic PRO-ACTIVE trial aims to specifically address the decisional dilemma of when swallowing therapy should begin (i.e., before or after a swallowing problem develops). The critical impact of this dilemma is heightened by the growing number of young HNC patients in healthcare systems that need to allocate resources most effectively. The results of the PRO-ACTIVE trial will address the global uncertainty regarding best practice for dysphagia management in HNC patients receiving radiotherapy. Trial registration The protocol is registered with the US Patient Centered Outcomes Research Institute, and the PRO-ACTIVE trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT03455608; First posted: Mar 6, 2018; Last verified: Jun 17, 2021. Protocol Version: 1.3 (January 27, 2020).

Exploring patient experiences with a telehealth approach for the PRO-ACTIVE trial intervention in head and neck cancer patients

“…MDACC is located in Houston, Texas, USA, and is a world leading center devoted exclusively to cancer care, research and education. Full details on the eligibility criteria for the PRO-ACTIVE parent trial are provided elsewhere [8,9]; however in brief, these were adult patients with head and neck cancer who were planned to receive bilateral radiation therapy at or above 60 gy and who had a functional swallow before starting their radiotherapy. Given that PRO-ACTIVE is a pragmatic trial, we did not exclude patients based on tumour stage or type, or any additional cancer treatment.…”

“…Supportive services including dysphagia management for head and neck cancer patients were largely affected [3][4][5] since both swallowing evaluation and treatment sessions involve close physical proximity between patients and their clinicians, including several aerosol-generating procedures [4,6]. Accordingly, the conduct of ongoing clinical trials was also severely impacted [7], including the PRO-ACTIVE trial (Prophylactic Swallow Intervention for Patients Receiving Radiotherapy for Head and Neck Cancer) [8,9].…”

“…PRO-ACTIVE is a large multi-site, 3-arm, pragmatic randomized controlled trial, evaluating the effectiveness of prophylactic swallowing therapy for head and neck cancer patients undergoing radiation therapy [9]. In the PRO-ACTIVE trial, patients are randomized to receive one of three behavioural swallowing interventions: a low intensity face-to-face swallowing therapy with an SLP that starts before radiation therapy, continues bi-weekly during radiotherapy and includes a clinical swallowing assessment, education on symptom management, and a structured program (EAT-RT) to facilitate safe but challenging oral intake [10]; a high intensity swallowing therapy that is similar to the EAT-RT program but with the addition of swallowing exercises conducted in between meals; and, a control group who is offered the high intensity therapy late during radiotherapy but only to patients who develop swallowing issues while receiving radiation therapy.…”

Exercise-based dysphagia rehabilitation for adults with oesophageal cancer: a systematic review

“…Recent advances in dysphagia research include the development of validated rating scales, improved understanding of optimum intervention dosages, the development of new interventions guided by underlying swallow pathophysiology and better awareness of adherence promotion and goal-oriented treatment. As a result of this and improved research quality, the evidence base for dysphagia rehabilitation is emerging across clinical populations including head and neck cancer [ 38 – 45 ] where a need for further high quality research appears to be under way in a proposed randomised control trial by Martino et al [ 81 ]. There is a strong rationale for exercise-based dysphagia rehabilitation in oesophageal cancer to optimise clinical and quality of life outcomes.…”

The role of the speech and language therapist in the rehabilitation of speech, swallowing, voice and trismus in people diagnosed with head and neck cancer

“…30 The PRO-ACTIVE trial is now underway to evaluate the benefit of prophylactic swallowing exercise protocols. 31 Radiation treatment effects can result in hypofunction of the salivary glands due to direct damage within the radiation field, 6 causing people to experience xerostomia and this has a negative impact on appetite, caries prevention and the continuation of oral intake. SLTs work with people to find ways to add moisture to foods and textures, as well as encouraging lubrication of the oral cavity and tissues of the hypopharynx through steam inhalation and continued hydration.…”