Dysphagia-Optimised Intensity-Modulated Radiotherapy: A Breakthrough in Mitigating Swallowing Dysfunction After Head and Neck Cancer Treatment

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Cancers of the pharynx pose a significant health challenge, impacting approximately 3000 patients annually in the UK (Reference 1). While radiotherapy and chemoradiotherapy are effective treatments, they often come with adverse effects on patients’ quality of life. The most common long-term complications include dry mouth, dysphagia, and soft tissue fibrosis, affecting the majority of patients (Reference 2).

Understanding the Causes:

The multifactorial nature of swallowing dysfunction post-radiotherapy is primarily attributed to the radiation’s impact on the pharyngeal musculature crucial for swallowing initiation and completion. The pharynx comprises an interior longitudinal muscle layer and an external circular layer, including the superior, middle, and inferior constrictor muscles. Additionally, the glottis, supraglottic larynx, and anterior oral cavity are identified as organs at risk in the swallowing mechanism (Reference 4).

Clinical Consequences:

Swallowing dysfunction can manifest in varying degrees, from mild restrictions in diet to severe complications, potentially necessitating a permanent gastrostomy tube and long-term supportive care. Patient-reported outcome measures following radiotherapy for head and neck cancer reveal a clinically relevant and statistically significant decline in swallowing function, with persistent issues even a year post-treatment (Reference 8).

Aspiration, the inhalation of food into the lungs, poses a significant risk, leading to increased morbidity and mortality. Studies have reported aspiration rates ranging from 30% to 62% in patients with head and neck cancer who underwent chemoradiotherapy, emphasizing the gravity of the issue (Reference 10). Notably, aspiration contributes to 19% of non-cancer deaths, underlining the broader impact on overall health (Reference 11).

Current Radiotherapy Techniques:

Intensity-modulated radiotherapy (IMRT) stands as the predominant radiotherapy technique for head and neck cancer in the UK. Studies have supported its efficacy in treating cancer while minimizing toxicity to organs at risk, such as the salivary glands (Reference 3). However, despite these advantages, long-term swallowing issues persist.

A Novel Approach – Dysphagia-Optimised IMRT:

Dysphagia-optimised IMRT (DO-IMRT) emerges as a promising solution. This innovative radiotherapy technique specifically targets the dysphagia and aspiration risk structures within the pharyngeal muscles, aiming to reduce radiation doses to these critical areas (Reference 12).

Research Hypothesis:

The study aims to test the hypothesis that DO-IMRT will yield superior outcomes in reducing long-term swallowing problems compared to standard IMRT. The research seeks to bridge the existing gap in improving patient quality of life after head and neck cancer treatment.

Discussion: Dysphagia-Optimised IMRT and Swallowing Outcomes in Head and Neck Cancer Patients

To date, the Dysphagia-Optimised Intensity-Modulated Radiotherapy (DO-IMRT) trial (DARS) stands as a pioneering randomized study, uniquely assessing the impact of DO-IMRT on patient-reported swallowing outcomes. This groundbreaking trial focuses on sparing the pharyngeal constrictor muscles, demonstrating a significant improvement in the MDADI score one year post-treatment and beyond.

Choice of Primary Outcome Measure:

The selection of the MDADI composite score as the primary outcome measure is well-founded. This widely used and validated patient-reported scoring system is acknowledged for its effectiveness in assessing swallowing following head and neck cancer treatment. The trial’s findings, revealing a 7.2-point difference in the MDADI composite score at one year, may fall slightly below the predefined clinically meaningful score of 10 points. However, the study suggests that smaller differences in MDADI scores, such as the 9.8-point difference adjusted for tumor site, tumor stage, and chemotherapy use, can be clinically significant, aligning with insights from Carlsson and colleagues.

Secondary Endpoints and Additional Benefits:

The trial further explores secondary endpoints, showcasing the superiority of DO-IMRT over standard IMRT. Although statistical significance is not uniformly reached, more participants receiving DO-IMRT report improved normalcy of diet and public eating scores. Notably, understandability of speech remains unaffected by pharyngeal muscle function, consistent with expectations. The UW-QOL swallowing domain, a significant secondary endpoint, consistently demonstrates improvement with DO-IMRT across multiple time points.

Physiological Changes and Prior Studies:

Understanding the significant physiological changes post-radiotherapy, the trial builds upon prior studies indicating the feasibility of reducing radiation doses to the pharyngeal muscles using DO-IMRT. Feng and colleagues’ pioneering work revealed positive outcomes without an increase in local tumor recurrence in the spared pharyngeal muscle region. This study, in conjunction with others, contributes to a robust foundation supporting the benefits of DO-IMRT in preserving swallow function.

Comparative Analysis with Previous Research:

A critical aspect of the discussion involves comparing the DARS trial with existing literature. The systematic review incorporating 16 papers and 1012 participants highlights the scarcity of studies consistently reporting both objectively measured and patient-reported swallowing outcomes. Notably, the DARS trial contributes to this multidimensional assessment, providing valuable insights into the efficacy of DO-IMRT.

Study Limitations and Strengths:

Acknowledging limitations, the trial reports swallowing outcomes up to two years post-treatment, with Vainshtein and colleagues suggesting the maintenance of swallow function up to six years post-DO-IMRT. The patient cohort primarily comprises HPV-positive oropharyngeal cancers, limiting generalizability to other patient groups. Despite these limitations, the multicenter nature of the trial and rigorous masking procedures strengthen the study’s credibility.

Implications for Future Research:

The results prompt considerations for future research, suggesting that understanding which parts of the pharyngeal constrictor muscle are crucial for swallowing preservation could refine the DO-IMRT technique further. Different dose distributions, including IMRT, proton beam, or adaptive radiotherapy techniques, warrant exploration. Modeling dose distributions against outcomes may provide insights into tailoring DO-IMRT to specific patient profiles, optimizing the preservation of swallow function.

In conclusion, the DARS trial substantiates the potential of DO-IMRT in ameliorating long-term swallowing issues post-head and neck cancer treatment. As we delve into an era of personalized medicine, further research holds the key to unlocking the full spectrum of benefits this innovative technique can offer to patients, enhancing their quality of life beyond the immediate treatment period.


reference link : https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00265-6/fulltext#seccestitle160

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