Most head and neck (H&N) cancer patients receive high-dose radiation therapy (RT), often combined with surgery or chemotherapy. Unfortunately, high-dose RT has significant adverse effects on oral and maxillofacial tissues. Salivary gland damage frequently causes hyposalivation, increasing risk of dental caries and tooth loss. Furthermore, radiation impairs ability of bone to heal, leading to a life-long risk of osteoradionecrosis (ORN), which presents as exposed intraoral bone and is often precipitated by dental extractions. Therefore, these patients are caught in a vicious circle, being at higher risk of needing dental extractions, but with extractions to be avoided post-RT due to the risk for ORN. To attempt to reduce such complications, pre-RT dental assessment is considered a best practice. However, pre-RT dental management practices vary widely and are largely based on expert opinion, due to lack of adequate evidence. Available data are mostly from studies using older RT modalities without concurrent chemotherapy. Current use of Intensity-Modulated Radiation Therapy (IMRT) has potential to reduce severity/incidence of oral complications. Conversely, concurrent use of chemotherapy with RT may aggravate toxicities. However, definitive data do not exist on the extent or severity of oral complications due to current therapeutic regimens, or on risk factors for adverse outcomes. Also, some oral complications, such as periodontal changes, are particularly understudied in this population. This constitutes an important gap in knowledge because it hampers the pre- and post-RT dental management of these patients. The objective of this research is to collect data on dental outcomes in H&N cancer patients receiving modern RT modalities and identify risk factors for adverse outcomes. We will accomplish these objectives by pursuing the following specific aims: 1) Measure 2-year changes in dental caries and periodontal disease, and 2-year rates of tooth loss, after modern RT regimens, and assess risk factors for caries increment, progression of periodontal disease, and tooth loss. 2) Measure 6-month and 18- month changes in stimulated whole salivary flow after modern RT regimens, and assess risk factors for decreased salivary flow. 3) Measure the incidence of exposed intraoral bone after modern RT regimens, and assess risk factors for exposed intraoral bone. We will accomplish these aims by completing our ongoing NIH- funded multi-center prospective cohort study, which has already enrolled 568 of the necessary 575 subjects. Dental and other oral outcomes, and data on risk factors, are recorded in H&N cancer patients before start of RT and every 6 months for 2 years after RT. The proposed research is innovative because this is the first multi-center study with a large enough sample size to identify risk factors associated with adverse dental outcomes in H&N cancer patients after modern RT. Our strong preliminary data clearly demonstrate the feasibility of achieving these aims. This study is highly significant because it will directly provide data to facilitate evidence-based dental management of patients receiving current modalities of H&N RT.

Public Health Relevance

The proposed research is relevant to public health because it will directly provide data to facilitate evidence- based dental management of head and neck cancer patients receiving current modalities of radiation therapy, which is expected to lead to improved clinical outcomes. The proposed research is directly responsive to PAR- 17-154 (which specifically mentions cohort studies prospectively assessing risk factors for disease development). It will also help to achieve Objective 1-3 of the NIDCR Strategic Plan: ?To conduct translational and clinical investigations to improve dental, oral, and craniofacial health?.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DE022939-08
Application #
9966724
Study Section
Special Emphasis Panel (ZDE1)
Program Officer
Fischer, Dena
Project Start
2012-09-26
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
8
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Carolinas Medical Center
Department
Type
DUNS #
074524513
City
Charlotte
State
NC
Country
United States
Zip Code
28203
Brennan, Michael T; Treister, Nathaniel S; Sollecito, Thomas P et al. (2017) Dental disease before radiotherapy in patients with head and neck cancer: Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients. J Am Dent Assoc 148:868-877
Lalla, R V; Treister, N; Sollecito, T et al. (2017) Oral complications at 6 months after radiation therapy for head and neck cancer. Oral Dis 23:1134-1143
Lalla, Rajesh V; Long-Simpson, Leslie; Hodges, James S et al. (2017) Clinical registry of dental outcomes in head and neck cancer patients (OraRad): rationale, methods, and recruitment considerations. BMC Oral Health 17:59