Clinical investigation
Head and neck
Dosimetric Predictors of Laryngeal Edema

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Purpose: To investigate dosimetric predictors of laryngeal edema after radiotherapy (RT).

Methods and Materials: A total of 66 patients were selected who had squamous cell carcinoma of the head and neck with grossly uninvolved larynx at the time of RT, no prior major surgical operation except for neck dissection and tonsillectomy, treatment planning data available for analysis, and at least one fiberoptic examination of the larynx within 2 years from RT performed by a single observer. Both the biologically equivalent mean dose at 2 Gy per fraction and the cumulative biologic dose–volume histogram of the larynx were extracted for each patient. Laryngeal edema was prospectively scored after treatment. Time to endpoint, moderate or worse laryngeal edema (Radiation Therapy Oncology Group Grade 2+), was calculated with log rank test from the date of treatment end.

Results: At a median follow-up of 17.1 months (range, 0.4– 50.0 months), the risk of Grade 2+ edema was 58.9% ± 7%. Mean dose to the larynx, V30, V40, V50, V60, and V70 were significantly correlated with Grade 2+ edema at univariate analysis. At multivariate analysis, mean laryngeal dose (continuum, hazard ratio, 1.11; 95% confidence interval, 1.06–1.15; p < 0.001), and positive neck stage at RT (N0-x vs. N +, hazard ratio, 3.66; 95% confidence interval, 1.40–9.58; p = 0.008) were the only independent predictors. Further stratification showed that, to minimize the risk of Grade 2+ edema, the mean dose to the larynx has to be kept ≤43.5 Gy at 2 Gy per fraction.

Conclusion: Laryngeal edema is strictly correlated with various dosimetric parameters; mean dose to the larynx should be kept ≤43.5 Gy.

Introduction

Intensity-modulated radiotherapy (IMRT) is being increasingly used for the treatment of head and neck squamous cell carcinomas (1, 2, 3).

In this particular setting, IMRT has several potential advantages over conformal radiotherapy (1): (1) to “paint” the high dose region around the target volume and thus spare at least part of the surrounding normal structures such as the parotids (4, 5), the upper aerodigestive mucosa (6), the submandibular glands (7); (2) to avoid field matching within the gross tumor volume and/or region at high risk of failure; and (3) to avoid multiple sequential treatment phases.

The IMRT technique should be planned with an accurate a priori knowledge of which organs at risk (OAR) surround the target(s) and their tolerances to radiation. Ideally, the latter should be tailored to the individual patient and take into account other patient-related factors such as pre-existing conditions and comorbidity, and treatment-related factors such as medications.

For tissues and/or organs with a serial architecture (i.e., the spinal cord), tolerance depends on the maximum dose. Tolerance doses for most serial tissues and organs in the head-and-neck region are available from the literature and are corroborated by decades of experience with standard two-dimensional radiotherapy (8).

However, for OARs that show a significant volume effect, the situation is complicated by the fact that a prerequisite for optimal IMRT planning would be the knowledge of the amount of the OAR that can receive a given dose of radiation. With the notable exception of the parotid glands (4), the available clinical data do not allow an accurate definition of dose–volume objectives for most other OARs in the head-and-neck region. Possible reasons include the lack of individual three-dimensional dosimetry along with the prospective and systematic application of a validated scoring system.

Regarding larynx edema, additional complicating factors include its accessibility (improved with the introduction of flexible fibroscopes) and the fact that up to 50% of patients with laryngeal edema experience recurrent disease (9, 10, 11).

Within these limitations, Emami et al. suggested a 5% and 50% risk of larynx edema at 5 years with doses of 45 Gy and 80 Gy, respectively (8). Moreover, it was believed that irradiation of less than 50% of the larynx would not have changed these estimates. More recently, Radiation Therapy Oncology Group (RTOG) protocols 0025 and 0022 on IMRT for head-and-neck squamous cell carcinoma recommended that a mean laryngeal dose of less than 45 Gy be administered and that less than two thirds of the glottic larynx receive 50 Gy, respectively, although no references or specific endpoints were provided for these estimates (12, 13).

Since 2002, every patient seen for a follow-up examination in the department of Radiation Oncology at University of Texas Medical Branch (UTMB) underwent direct fiberoptic vision of the larynx with prospective scoring of laryngeal edema. In the present paper we correlated laryngeal toxicity with 3D dosimetry data.

Section snippets

Patients

Patients with biopsy-proven squamous cell carcinoma of the head and neck region and treated at UTMB with primary radiotherapy from January 2002 to February 2006 were considered for the present retrospective study, that was approved by the Institution Review Board at the UTMB.

In addition, patients had to satisfy each of the following four criteria. (1) The larynx had to be uninvolved by cancer at both initial flexible fiberoptic examination and pretreatment computed tomography. (2) No major

Results

As a result of the selection criteria, patients with primary laryngeal and/or hypopharyngeal tumors and those who were treated with upfront surgery were excluded from the present study. Three patients with oropharyngeal primaries and contiguous laryngeal involvement were excluded as well. For 2 patients we were unable to restore the original treatment plan. Finally, 9 patients did not satisfy Criterion 4. This left 66 patients eligible for the present analysis. Main patient and tumor

Discussion

The present study shows that the risk of laryngeal edema is strictly correlated with several dosimetric variables. Among them, mean dose and V50 are the best predictors, with mean dose being slightly more correlated with the endpoint and V50 being more useful from a practical standpoint of IMRT plan optimization. To minimize the risk of edema, the mean laryngeal dose should be kept as low as possible, with the lowest rate observed among patients with values ≤43.5 Gy. If V50 is used instead, the

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Conflict of interest: none.

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