Radiation Dose–Volume Effects in the Larynx and Pharynx

doi:10.1016/j.ijrobp.2009.03.079

International Journal of Radiation OncologyBiologyPhysics

Volume 76, Issue 3, Supplement, 1 March 2010, Pages S64-S69

https://doi.org/10.1016/j.ijrobp.2009.03.079 Get rights and content

The dose–volume outcome data for RT-associated laryngeal edema, laryngeal dysfunction, and dysphagia, have only recently been addressed, and are summarized. For late dysphagia, a major issue is accurate definition and uncertainty of the relevant anatomical structures. These and other issues are discussed.

Section snippets

Clinical Significance

Radiotherapy (RT) is the primary modality allowing larynx preservation in patients with tumors in the upper aerodigestive tract. RT-induced laryngeal edema (due to inflammation and lymphatic disruption) is a common and expected side effect. Progressive edema and associated fibrosis can lead to long-term problems with phonation and swallowing (1). Since the primary goal of larynx preservation is speech and swallowing retention, RT-induced laryngeal dysfunction could undermine this therapeutic

Larynx edema

Edema can be assessed using flexible fiberoptic examination. The grade of larynx edema can be scored according to the RTOG scale as follows: 0, no edema; 1, slight edema; 2, moderate edema; 3, severe edema; and 4, necrosis. Some degree of uncertainty is intrinsic to the subjectivity in the interpretation of “slight” and “moderate” in the RTOG scale. Grade 1 edema would correspond to “minimal” thickening of the epiglottis, aryepiglottic folds, arytenoids, and false cords. Grade 2 is a more

Objective evaluation: instrumental assessment

Videofluorography includes modified barium swallow and esophagography to visualize the oral, pharyngeal, and esophageal phases of swallowing (11). Additional instrumental assessors include manometry and functional endoscopic evaluation of swallowing.

Subjective evaluation: observer-assessed

Common Terminology Criteria for Adverse Events (CTCAE) are frequently used to assess acute toxicity, as is the RTOG/European Organization for Research and Treatment of Cancer criteria and the Subjective Objective Management Analytic (SOMA) scale.

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Cited by (185)

Radiation Dose Sensitivity of Subregions of the Larynx to Patient-Reported Swallowing Outcomes
2024, Advances in Radiation Oncology
To assess any correlation between swallowing dysfunction and radiation dose to 5 subregions of the larynx.
A cohort of 136 patients with head and neck cancer, treated with either photon or proton radiation therapy, was assessed using an endpoint of patient-reported swallowing scores, evaluated with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 survey, within 1 month after treatment. Five subregions of the larynx were contoured, and dosimetric metrics were extracted for each subregion as well as the total larynx. Univariate and multivariate logistic regression statistical analyses were used to determine statistical correlation with the dose metrics and clinical variables. Univariate regression models were statistically compared using a non-nested model test.
Under univariate analysis, unilateral versus bilateral nodal irradiation (P = .004), concurrent chemotherapy (P = .007), and surgery (P = .015) were statistically significant predictors of poor swallowing score. Unilateral versus bilateral irradiation was statistically significant under multivariate analysis (P = .039). The epiglottis was the most predictive subregion of swallowing score, with a majority (21 of 25) of dosimetric variables being identified as statistically significant. The maximum dose to the epiglottis was the most significant dosimetric variable tested for poor swallowing score in both univariate (P = .003) and multivariate (P = .051) analyses. Comparison of univariate models indicated a general preference for epiglottic variables with the mean dose to the epiglottis being preferred at a statistically significant level in many cases.
These results show the relatively increased sensitivity of the epiglottis compared with the rest of the larynx when considering patient-reported decrements in quality-of-life swallowing score and support both the inclusion of the epiglottis in standard larynx contours and the assessment of the epiglottis dose during plan evaluation. Our data suggest that keeping the mean and max doses to the epiglottis <20 to 37 Gy and <53 to 60 Gy, respectively, will reduce swallowing difficulties.
NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT
2023, Physica Medica
This study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6–24 months after radiotherapy for oropharynx cancer.
The treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders.
Xerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58–0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy.
Based on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2–3 the risk for radiation induced xerostomia that is observed at 6–24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6–24 months post-RT by 2.0–2.3 times.
ROE (Radiotherapy Outcomes Estimator): An open-source tool for optimizing radiotherapy prescriptions
2023, Computer Methods and Programs in Biomedicine
Radiotherapy prescriptions currently derive from population-wide guidelines established through large clinical trials. We provide an open-source software tool for patient-specific prescription determination using personalized dose-response curves.
We developed ROE, a plugin to the Computational Environment for Radiotherapy Research to visualize predicted tumor control and normal tissue complication simultaneously, as a function of prescription dose. ROE can be used natively with MATLAB and is additionally made accessible in GNU Octave and Python, eliminating the need for commercial licenses. It provides a curated library of published and validated predictive models and incorporates clinical restrictions on normal tissue outcomes. ROE additionally provides batch-mode tools to evaluate and select among different fractionation schemes and analyze radiotherapy outcomes across patient cohorts.
ROE is an open-source, GPL-copyrighted tool for interactive exploration of the dose-response relationship to aid in radiotherapy planning. We demonstrate its potential clinical relevance in (1) improving patient awareness by quantifying the risks and benefits of a given treatment protocol (2) assessing the potential for dose escalation across patient cohorts and (3) estimating accrual rates of new protocols.
Protocol determination for OSL in vivo measurements of absorbed dose in the oral mucosa in oral cancer patients: A pilot study
2023, Radiation Physics and Chemistry
Radiation-induced oral mucositis (RIOM) is one of the major oral complications caused by radiotherapy (RT), and can lead a negative impact on patients’ quality of life. Considering that there is no specific radiation therapy dose constraint for oral mucosa, the need to study the correlation between absorbed dose and effect in this area is crucial. This pilot study aims to report in vivo OSL dosimetry protocol to investigate the dose distribution in the oral mucosa in patients with oral cancer using Intraoral customised Stent (IOS). For measurements, aluminium oxide nanoDot dosimeters and a microStar ii OSL reader from Landauer Inc. were used. The OSL dosimetry system was calibrated with a 6 MV photon beam using an Elekta Synergy linear accelerator and solid water phantoms following the recommendations of the AAPM TG 191 protocol. The dose distribution in the oral mucosa using seven OSL dosimeters fixed on the intraoral stent was evaluated and compared with the dose distribution available from the RT planning for the patient. Our experimental results showed the expected linearity response of the nanoDot dosimeters from 20 to 200 cGy. The repeatability of readings was better than 1.0% in all commissioning measurements. The uncertainty budget of the commissioning analysis resulted in an overall type An uncertainty of ∼3.4% at the 1-sigma level for dose calculation, compatible with the TG 191 protocol. The dose distribution in the oral mucosa was assessed and dose deviations up to 35% can be found in high dose gradient regions of the treatment planning. This type of deviation may impact on the development and progression of RIOM, as analysed in this protocol. It is feasible to establish this procedure in vivo dosimetry for a patient undergoing RT using a multidisciplinary approach. Additionally, intraoral customised stents can decrease radiation doses in the oral mucosa, and the understanding of the dose distribution in the oral mucosa may help to minimise damages from radiation.
Management of symptoms and treatment-related toxicities of head and neck cancers
2023, Palliative Radiation Oncology
Malignancies of the head and neck can be challenging to manage due to frequent involvement of the mucosal surfaces of the aerodigestive surfaces causing bleeding, airway obstruction, pain, malnutrition, and impaired communication abilities. Toxicity and impairment caused by invasive neoplasms can result in severe morbidity and can significantly affect a patient’s quality and length of life. Radiation therapy is an essential component in the management of head and neck cancer in the definitive, adjuvant, and palliative settings, but likewise can cause severe acute and late morbidity, even after successful treatment. Tumor-related morbidity and treatment-related toxicity are frequent in head and neck cancers due to the many vital organs-at-risk (OARs) within a compact anatomic space—including the serial neural structures (brainstem, spinal cord, brachial plexus), salivary glands (parotid, submandibular), mucosa (oral cavity, oropharynx), pharyngeal constrictors, larynx, major vasculature, endocrine organs (thyroid, pituitary), functional soft tissue, and the mandible. For instance, the rapidly proliferating mucosa of the oral cavity and oropharynx are sensitive to radiation, and together with associated muscles and soft tissues provide crucial functionality for speech, swallowing, and nutritional intake. In the acute term, effects on OARs may be dose-limiting, and result in significant weight loss requiring feeding tube placement or compromised disease control. Late toxicity, including soft tissue fibrosis, chronic feeding tube dependence, and increased stroke and aspiration risk may involve profound quality of life changes and even portend mortality. Due to the potentially serious nature of tumor infiltration, and both acute and late toxicities, efforts must be made to prevent and actively manage these complications. This chapter will summarize the acute and late effects of treatment as well as major principles of management for tumor-related complications.
Head and Neck Radiation Therapy Patterns of Practice Variability Identified as a Challenge to Real-World Big Data: Results From the Learning from Analysis of Multicentre Big Data Aggregation (LAMBDA) Consortium
2023, Advances in Radiation Oncology
Outside of randomized clinical trials, it is difficult to develop clinically relevant evidence-based recommendations for radiation therapy (RT) practice guidelines owing to lack of comprehensive real-world data. To address this knowledge gap, we formed the Learning from Analysis of Multicenter Big Data Aggregation consortium to cooperatively implement RT data standardization, develop software solutions for data analysis, and recommend clinical practice change based on real-world data analyzed. The first phase of this “Big Data” study aimed at characterizing variability in clinical practice patterns of dosimetric data for organs at risk (OARs) that would undermine subsequent use of large-scale, electronically aggregated data to characterize associations with outcomes. Evidence from this study was used as the basis for practical recommendations to improve data quality.
Dosimetric details of patients with head and neck cancer treated with radiation therapy between 2014 and 2019 were analyzed. Institutional patterns of practice were characterized, including structure nomenclature, volumes, and frequency of contouring. Dose volume histogram (DVH) distributions were characterized and compared with institutional constraints and literature values.
Plans for 4664 patients treated to a mean plan dose of 64.4 ± 13.2 Gy in 32 ± 4 fractions were aggregated. Before implementation of TG-263 guidelines in each institution, there was variability in OAR nomenclature across institutions and structures. With evidence from this study, we identified a targeted and practical set of recommendations aimed at improving the quality of real-world data.
Quantifying similarities and differences among institutions for OAR structures and DVH metrics is the launching point for next steps to investigate potential relationships between DVH parameters and patient outcomes.

View all citing articles on Scopus

: Conflict of interest: none.

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QUANTEC: Organ-Specific PaperRadiation Dose–Volume Effects in the Larynx and Pharynx

Section snippets

Clinical Significance

Larynx edema

Objective evaluation: instrumental assessment

Subjective evaluation: observer-assessed

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat 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

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Effects of head and neck radiation therapy on vocal function

J Otolaryngol

Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer

N Engl J Med

QUANTEC: Organ-Specific Paper
Radiation Dose–Volume Effects in the Larynx and Pharynx