Endodontic-Restorative Pre-Radiation Therapy of Head and Neck Cancer Patients (EndoRest)

A Clinical Trial Pilot Study Investigating a New Dental Protocol for Pre-Radiation Endodontic-Restorative Therapy of Head and Neck Cancer Patients

Pilot study involving 20 patients undergoing dental treatment prior to radiation therapy. Comparison of outcome parameters to existing data of age and gender matched patients.

Study Overview

• Status: Withdrawn
• Conditions: Head and Neck Cancer; Caries; Pulpitis - Irreversible
• Intervention / Treatment: Procedure: Root canal treatment and crown

Detailed Description

Advanced radiation therapy systems are part of head/neck cancer treatment. 2-3 weeks prior to the initiation of radiation therapy (preRT), patients undergo dental screening, simple restorations and the removal of teeth deemed a osteoradionecrosis risk, often including asymptomatic, vital teeth. Time limitations preRT generally prohibit a traditional multi-visit approach for endodontic treatment, crown preparation, and an externally fabricated restoration. Precision restorative dentistry, with CAD/CAM milled ceramic restorations allow for immediate post-endodontic rehabilitation on the same. The Center for Clinical and Translational Research (CCTR) at PDM conducts the ARMOR trial, a randomized, controlled trial testing the efficacy of two oral care protocols enrolling 120 cancer patients from the Perelman Center for Advanced Medicine (PCAM) over 3.5 years. This pilot study will enroll 20 patients of the ARMOR trial for endodontic treatment and restoration of posterior asymptomatic and vital teeth using microscopic endodontics and digital precision CAD/CAM restoration. These teeth would otherwise be extracted due to time limitations preRT. Patients will be seen for the dental treatment within the time window from diagnosis to initiation of radiation therapy. Patients will be evaluated for (1) feasibility of the suggested protocol (primary objective); quality of life as in the ARMOR trial; 2) tooth survival; 3) endodontic status [PAI index]; 4) periodontal prognosis and status [McGuire-Nunn Criteria, etc]; and 5) restorative status [USPHS Criteria, etc] (secondary objectives) at 1,2,5 months follow-ups of the ARMOR trial. For control, data for tooth survival and QLQ will be compared to 20 other participants of the ARMOR trial (10/10 per study arm) that do not participate in the EndoRest substudy and to 20 other matching participants patients (age, gender) from an existing, comparable dataset of the ORA-RAD studies of the Penn Study arm at PDM Oral Medicine. Periodontal status and restorative status (iff applicable) will be compared to contra-lateral or counter-arch teeth of the individual participant.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • School of Dental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient volunteering to participate in the study.
2. Patients eligible for participation in the ARMOR trial (current head and neck cancer patient trial conducted at Penn Dental Medicine[PDM])
3. Non-contributory medical history (Patient can be seen for dental appointment in PDM).
4. No history of previous endodontic treatment on the tooth/teeth selected for treatment.
5. Asymptomatic and vital teeth with deep decay (Irreversible pulpitis due to decay reaching pulp).

Exclusion Criteria:

Economic status, gender, race or ethnicity are not of concern for the proposed investigation and therefore for study exclusion. Patients will not be eligible to participate in the study if any of the following exclusion criteria applies:

1. Symptoms or necrotic tooth with presence of periapical radioluceny.
2. History of previous endodontic treatment on the teeth to be treated.
3. Teeth affected by fractures.
4. Compromised periodontal status with pockets exceeding 4 mm, exceeding mobility I or gingival edema).
5. At the discretion of the PI, patient is unlikely or unwilling to follow study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Root canal treatment and crown restoration	Procedure: Root canal treatment and crown; Pre-radiation one day root canal treatment and CAD/CAM chair side fabricated crowns for head and neck cancer patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with successful completion of endodontic and restorative treatment of teeth (Feasibility)	Evaluation of whether the proposed one-day root canal treatment plus crown restoration protocol can be utilized and executed prior to radiation treatment of head and neck cancer patients. The evaluation will be on a per patient, not per tooth, basis. Failure is defined as the inability to complete endodontic treatment and definitive restoration of a qualifying tooth in a study participant, resulting in the need for pre-radiation extraction of the tooth.	1-5 days
Delay in RT initiation, calculated on a scale of 0-100 for the study, as described below (Feasibility)	Evaluation of whether the onset of radiation therapy was delayed due to participation in the EndoRest study. The evaluation will be on a per patient, not per tooth, basis. Delay in RT start will be scored on the following scale: 5 points: RT started as planned; no delays 4 points: RT delayed by 1 day due to participation in the EndoRest study 3 points: RT delayed by 2 days due to participation in the EndoRest study 2 points: RT delayed by 3 days due to participation in the EndoRest study 0 points: RT delated by 4 or more days due to participation in the EndoRest study The total points for all participants in the study will be summed. A score of >=90 indicated that the protocol is feasible. A total score <90 indicates that the protocol is not feasible.	2-10 days
Number of participants who need post-radiation extraction of a qualifying tooth.	Evaluation of whether a qualifying tooth for which endodontic and restorative treatment was successfully completed was extracted in the time interval post-radiation therapy up to 5 months after the initial visit.	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of quality of life (QOL) based on the EORTC-QLQ-C30	Quality of life and function will be assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) with the Head and Neck specific questionnaire add-on (HN43). This questionnaire assesses general quality of life as well as issues specific to head and neck cancer patients (e.g. difficulty swallowing, pain, dry mouth). All questions on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire EORTC-QLQ are assigned a score of 0-100. A higher score indicates a higher response level (for function questions, a high score indicates a high level of function, indicating a better outcome. For symptom questions, a high score indicates a high level of symptomology, indicating a worse outcome).	5 months
Evaluation of tooth survival	Tooth survival after completion of endodontic-restorative treatment will be assessed in all participants using standard survival analysis techniques.	5 months
Evaluation of endodontic status using the PAI	Endodontic status will be assessed using the periapical index (PAI). PAI uses a scale of 0-5, with 0 meaning "healthy" and 5 meaning "severe periodontitis with exacerbated features."	5 months
Evaluation of periodontal status	Periodontal status will be assessed through probing depths of periodontal pockets of the treated tooth.	5 months
Evaluation of restorative status using the USPHS criteria	Restoration status will be assessed using United States Public Health System (USPHS) criteria. The USPHS criteria assesses anatomical form, marginal adaptation, color match, marginal discoloration, surface roughness, and caries, in a single assessment tool. Higher scores indicate less favorable outcomes.	5 months

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Collaborators: School of Dental Medicine
• Investigators: Principal Investigator: Frank Setzer, DMD, PhD, MS, University of Pennsylvania

Publications and helpful links

General Publications

• Kataoka SH, Setzer FC, Fregnani ER, Pessoa OF, Gondim E Jr, Caldeira CL. Effects of 3-dimensional conformal or intensity-modulated radiotherapy on dental pulp sensitivity during and after the treatment of oral or oropharyngeal malignancies. J Endod. 2012 Feb;38(2):148-52. doi: 10.1016/j.joen.2011.09.022. Epub 2011 Nov 14.
• Kataoka SH, Setzer FC, Gondim-Junior E, Fregnani ER, Moraes CJ, Pessoa OF, Gavini G, Caldeira CL. Late Effects of Head and Neck Radiotherapy on Pulp Vitality Assessed by Pulse Oximetry. J Endod. 2016 Jun;42(6):886-9. doi: 10.1016/j.joen.2016.02.016. Epub 2016 Apr 9.
• Wahl MJ. Osteoradionecrosis prevention myths. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):661-9. doi: 10.1016/j.ijrobp.2005.10.021.
• Nabil S, Samman N. Incidence and prevention of osteoradionecrosis after dental extraction in irradiated patients: a systematic review. Int J Oral Maxillofac Surg. 2011 Mar;40(3):229-43. doi: 10.1016/j.ijom.2010.10.005. Epub 2010 Nov 5.
• Chang DT, Sandow PR, Morris CG, Hollander R, Scarborough L, Amdur RJ, Mendenhall WM. Do pre-irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible? Head Neck. 2007 Jun;29(6):528-36. doi: 10.1002/hed.20538.
• Ben-David MA, Diamante M, Radawski JD, Vineberg KA, Stroup C, Murdoch-Kinch CA, Zwetchkenbaum SR, Eisbruch A. Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions. Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):396-402. doi: 10.1016/j.ijrobp.2006.11.059. Epub 2007 Feb 22.
• Clayman L. Clinical controversies in oral and maxillofacial surgery: Part two. Management of dental extractions in irradiated jaws: a protocol without hyperbaric oxygen therapy. J Oral Maxillofac Surg. 1997 Mar;55(3):275-81. doi: 10.1016/s0278-2391(97)90542-5. No abstract available.
• Hentz C, Diaz AZ, Borrowdale RW, Emami B, Kase M, Choi M. Establishing a targeted plan for prophylactic dental extractions in patients with laryngeal cancer receiving adjuvant radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016 Jul;122(1):43-9. doi: 10.1016/j.oooo.2016.01.021. Epub 2016 Feb 13.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2022
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Restoration; Tooth Retention
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Stomatognathic Diseases; Tooth Diseases; Dental Pulp Diseases; Head and Neck Neoplasms; Pulpitis
• Other Study ID Numbers: UPCC 06321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be made available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No