Development and Standardization of an Osteoradionecrosis Classification System in Head and Neck Cancer: Implementation Based on Risk Model

In recent years, the side effects brought by the treatment of head and neck cancer (HNC), especially radiotherapy, have become a focal point of academic attention. Osteoradionecrosis (ORN) is one of the most severe complications. ORN is widely defined as non-healing mucosal breakdown and bone damage occurring within the irradiated area of the head and neck in the absence of recurrent tumor. It can appear spontaneously or following trauma. This not only severely affects the quality of life of patients but also increases the usage of medical resources. Therefore, there is an urgent need for a standardized, objective ORN classification system to better diagnose and manage this complication.

Research Background and Objectives

The incidence of ORN during traditional treatments can be as high as 40%. With the development of modern radiotherapy techniques and the implementation of strict preventive dental care policies, this proportion has significantly dropped to 4%-8%. However, multiple existing ORN classification systems have issues accurately identifying the severity of ORN, including over-classification, neglecting maxillary ORN, or relying on subjective diagnosis. These issues hinder comparative studies and the design of clinical trials. To address these challenges, Erin E. Watson and colleagues conducted this research, aiming to identify risk factors for ORN and propose a new classification system based on objective clinical and imaging data.

Research Origin and Author Information

This research paper was completed by a team of multidisciplinary experts, with principal authors including Erin E. Watson, Katrina Hueniken, Junhyung Lee, among others. Team members come from several renowned institutions such as Princess Margaret Cancer Centre, University of Toronto, MD Anderson Cancer Centre, etc. The paper was published on May 1, 2024, in the “Journal of Clinical Oncology.”

Research Methods

Study Population and Data Collection

The study subjects included all consecutive head and neck cancer patients who received CURATIVE-INTENT INTENSITY-MODULATED RADIATION THERAPY (IMRT, ≥45 Gy) at Princess Margaret Cancer Centre between 2011 and 2017. These patients all underwent dental evaluation before radiotherapy. Exclusion criteria included a history of head and neck radiotherapy, early-stage glottic cancer, and completely edentulous patients. All relevant clinical, dental, and imaging data were obtained from the institutional database and cross-verified.

ORN Severity Assessment and Classification

This study retrospectively classified ORN using 15 existing classification systems and proposed a new classification system called Clinrad. Clinrad classifies ORN into four stages based on the vertical extent of bone necrosis and the presence of exposed bone/fistula, while also identifying the presence of minor bone spicules. The system was compared with existing systems to assess its effectiveness in identifying and predicting major ORN events (such as mandibular fractures or the need for mandibular resection).

Statistical Analysis and Risk Factor Identification

The study employed multivariable logistic regression models to identify risk factors for ORN, including primary cancer in the oral cavity or oropharynx, receiving IMRT dose ≥60 Gy, current/former smokers, and having III to IV stage periodontal status. Based on these factors, patients were categorized into high-risk and low-risk groups. Their model’s predictive performance was evaluated using AUC values calculated through 10-fold cross-validation.

Research Results

Out of 2732 consecutive head and neck cancer patients, 219 patients (8%) developed ORN. High-risk factors included primary cancer in the oral cavity or oropharynx, receiving IMRT dose ≥60 Gy, current/former smokers, and III to IV stage periodontal disease. The ORN occurrence rate in high-risk patients was 12.7%, compared to 3.1% in low-risk patients, with an AUC value of 0.71. In addition, existing ORN classification systems had a common issue of over-classifying severe ORN events and failing to identify maxillary ORN. In contrast, the Clinrad system performed exceptionally in terms of objectivity and prediction, successfully identifying 5.7% of severe ORN events and outperforming existing systems in various analyses.

Scientific and Practical Value of the Study

This research identifies the primary risk factors for ORN and proposes a new classification system, providing significant references for clinical practice and future clinical trials. The Clinrad system not only enhances the diagnostic accuracy of ORN but also shows greater objectivity and reproducibility compared to existing systems, while also meeting the standardization needs for clinical trials. This innovative classification system is expected to play an important role in clinical care and promote further research and optimization in this field. Moreover, the design approach of this system offers valuable insights for the development of classification systems for other complex conditions.

Research Highlights

1. Identification of High-Risk Factors: The study clearly identifies the major risk factors for ORN, aiding in early screening and intervention.
2. Proposal and Validation of the Clinrad System: This new system, based on objective clinical and imaging data, shows superior classification and predictive performance compared to existing systems.
3. Dual Value in Clinical and Research Applications: The system can improve the accuracy of diagnosis and treatment decisions in daily clinical practice and provides a standardized classification tool for clinical trials.

Conclusion

Through comprehensive risk assessment and classification of head and neck cancer patients, this research proposes a new scientifically and practically valuable osteoradionecrosis classification system. The Clinrad system not only addresses the shortcomings of existing classification systems but also provides new tools and methods for clinical practice and academic research, promoting further optimization of head and neck cancer treatment and improving patient prognosis. This study makes an important contribution to the ongoing development in this field.