Session Item

Abstract

Radiotherapy in the head and neck region is associated with a wide variety of acute and late toxicities. The risk of these toxicities can be estimated using multivariable Normal Tissue Complication Probability (NTCP) models. Recently, we developed a comprehensive toxicity risk profile for head and neck cancer patients planned for definitive radiotherapy, describing the relationship between dose to fourteen different organs at risk and twenty-two toxicities at 10 different time points during and after completion of treatment. These models were developed in 750 head and neck cancer (HNC) patients and externally validated in an independent cohort of 395 HNC patients.

The profile is divided in different domains, including swallowing, salivary, mucosal, speech, pain and general domain and each domain includes both physician-rated toxicity according to the CTCAE as well as patient-rated head and neck cancer and general symptoms as assessed by the EORTC QLQ-C30 and EORTC QLQ-H&N35.

The models were developed based on prospectively collected data and according to a predefined modelling strategy accounting for a number of methodological key challenges in NTCP model development and validation, including missing data, non-linear response dose relationships, multicollinearity between predictors, overfitting, and generalisability

The profile consists of the dose to fourteen organs at risk that were associated with at least one toxicity in which the oral cavity was the most important organ at risk involved in the development of twelve out of twenty-two toxicities. Other important organs included the parotid and submandibular glands, buccal mucosa, and swallowing muscles. In addition, baseline toxicity, treatment modality, and tumour site were common predictors of toxicity.

This comprehensive toxicity risk profile provides an essential tool towards a more individualised approach and gives more insight into how radiation exposure to various organs at risk in the head and neck region translates into multiple aspects of radiation-induced toxicities in the head and neck region and which other covariables influence these dose effect relationships.

Recent analyses showed that many of these toxicities have an impact on the more general dimensions of quality of life. Based on the magnitude of these relationships, a priority map can be given to different toxicities and corresponding organs at risk in the dose optimisation process, aiming at a dose distribution resulting in the best quality of life to HNC patients (model-based optimization). Moreover, these profiles can be used for a more advanced way of selecting patients for proton therapy (model-based selection).

At present, some of these models have been clinically introduced to optimize the dose in HNC patients treated with definitive radiotherapy or chemoradiation in our clinic which resulted in significant reductions of numerous radiation-induced toxicities.

In conclusion, the comprehensive toxicity profile enables a more personalised approach for optimising the dose distribution for HNC patients that eventually resulted in significant reductions of several acute and late toxicities. Moreover, this profile can be used to estimate the potential benefit of more advanced radiation technologies like proton therapy. The oral cavity should be regarded as the most important organ at risk in head and neck radiotherapy.