Intensity-Modulated Radiotherapy of Head and Neck Cancer Aiming to Reduce Dysphagia: Early Dose–Effect Relationships for the Swallowing Structures

doi:10.1016/j.ijrobp.2007.02.049

International Journal of Radiation OncologyBiologyPhysics

Volume 68, Issue 5, 1 August 2007, Pages 1289-1298

Presented at the 48th Annual Meeting of the American Society of Therapeutic Radiology and Oncology, November 5–9, 2006, Philadelphia, PA.

https://doi.org/10.1016/j.ijrobp.2007.02.049 Get rights and content

Purpose: To present initial results of a clinical trial of intensity-modulated radiotherapy (IMRT) aiming to spare the swallowing structures whose dysfunction after chemoradiation is a likely cause of dysphagia and aspiration, without compromising target doses.

Methods and Materials: This was a prospective, longitudinal study of 36 patients with Stage III–IV oropharyngeal (31) or nasopharyngeal (5) cancer. Definitive chemo-IMRT spared salivary glands and swallowing structures: pharyngeal constrictors (PC), glottic and supraglottic larynx (GSL), and esophagus. Lateral but not medial retropharyngeal nodes were considered at risk. Dysphagia endpoints included objective swallowing dysfunction (videofluoroscopy), and both patient-reported and observer-rated scores. Correlations between doses and changes in these endpoints from pre-therapy to 3 months after therapy were assessed.

Results: Significant correlations were observed between videofluoroscopy-based aspirations and the mean doses to the PC and GSL, as well as the partial volumes of these structures receiving 50–65 Gy; the highest correlations were associated with doses to the superior PC (p = 0.005). All patients with aspirations received mean PC doses >60 Gy or PC V₆₅ >50%, and GSL V₅₀ >50%. Reduced laryngeal elevation and epiglottic inversion were correlated with mean PC and GSL doses (p < 0.01). All 3 patients with strictures had PC V₇₀ >50%. Worsening patient-reported liquid swallowing was correlated with mean PC (p = 0.05) and esophageal (p = 0.02) doses. Only mean PC doses were correlated with worsening patient-reported solid swallowing (p = 0.04) and observer-rated swallowing scores (p = 0.04).

Conclusions: These dose–volume-effect relationships provide initial IMRT optimization goals and motivate further efforts to reduce swallowing structures doses to reduce dysphagia and aspiration.

Introduction

Intensification of the therapy for head and neck cancer, by altered fractionated radiotherapy (RT) or the addition of concurrent chemotherapy, has resulted in improved tumor control rates. The main late sequela following treatment intensification has been increasing rates and severity of long-term dysphagia (1). For example, Radiation Therapy Oncology Group (RTOG) study 91-11 randomized patients between RT alone or RT concurrent with cisplatin and demonstrated improved tumor control rates in the chemo-RT arm. However, 1 year after therapy 23% of the patients in the chemo-RT arm could eat only soft/liquid food, compared with 9% in the RT-alone arm (2). Studies in which the chemo-RT regimens were intensified even further in an effort to improve tumor control rates reported 1-year rates of feeding-tube dependence of 20% in the experimental regimens (1). Evidence has recently emerged that aspiration pneumonia is associated with dysphagia after chemo-RT, constituting an underreported sequela of therapy (3, 4).

Improvements in target dose conformity may reduce the rate and severity of dysphagia following intensive therapy, if these improvements can sufficiently reduce the doses delivered to the anatomic structures whose malfunction after intensive chemo-RT causes dysphagia and aspiration. We have recently initiated studies to investigate this issue. The first step in these studies was the identification of the most important swallowing-related structures. The pharyngeal constrictors (PC) and the glottic and supraglottic larynx (GSL) were found to change anatomically after intensive chemo-RT, and their malfunction explained the posttherapy abnormalities observed in objective assessments of swallowing (5). Certain intensity-modulated radiotherapy (IMRT) strategies (dysphagia/aspiration-specific IMRT) achieved improved sparing of these swallowing structures, without compromising target irradiation, compared with “standard” IMRT (5). We have subsequently initiated a prospective trial aiming to assess the clinical benefits gained by these strategies. Initial results of this trial are presented here, focusing on the relationships between the doses delivered to the swallowing structures that we aimed to spare (PC, GSL, and esophagus) and the changes in the objective and subjective measures of swallowing dysfunction and aspiration from before to 3 months after therapy.

Section snippets

Methods and Materials

This is a prospective, longitudinal study of chemo-IMRT for head-and-neck cancer approved by the Institutional Review Board of the University of Michigan; all patients signed a study-specific informed consent form. Eligible patients were those with Stage III/IV squamous cell carcinoma of the head and neck who had not received prior therapy, had a Karnofsky performance status ≥60, and who were recommended to receive primary therapy with chemo-RT. The main study objective was assessing

Patient characteristics and dysphagia assessments

The study included 36 subjects with oropharyngeal (31) or nasopharyngeal (5) cancer. Patient and tumor characteristics are detailed in Table 1.

The mean doses and the partial volumes receiving specified doses (V_Ds) to the swallowing structures are detailed in Table 2. For each swallowing structure, highly significant correlations were noted between the mean dose (calculated for the whole structure) and the percentage of the volume of the structure that lies inside the PTVs, with Spearman

Discussion

In this clinical study of IMRT aiming at reducing dysphagia, we have found statistically significant, and potentially clinically important, dose–volume effect relationships for dysphagia and aspiration, which can serve as initial dosimetric goals for IMRT. These relationships support the hypothesis that reducing the doses to the swallowing structures may reduce the prevalence and severity of dysphagia; however, they do not yet prove this hypothesis because they do not establish a cause–effect

Acknowledgment

The authors thank Karen Vineberg and Steven Kronenberg for assistance in producing the figures; and Dr. Randall Ten Haken for advice.

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Supported by National Institutes of Health Grant No. CA59827.

Conflict of interest: none.

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Clinical investigationHead and neckIntensity-Modulated Radiotherapy of Head and Neck Cancer Aiming to Reduce Dysphagia: Early Dose–Effect Relationships for the Swallowing Structures

Introduction

Section snippets

Methods and Materials

Patient characteristics and dysphagia assessments

Discussion

Acknowledgment

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Semin Radiat Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Eur J Radiol

Int J Radiat Onc Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Rad Oncol Biol Phys

Int J Rad Onc Biol Phys

Int J Rad Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clinical investigation
Head and neck
Intensity-Modulated Radiotherapy of Head and Neck Cancer Aiming to Reduce Dysphagia: Early Dose–Effect Relationships for the Swallowing Structures