Mandibular Reconstruction Preplanning (ViPMR) (ViPMR)

Virtual Preplanning of Mandibular Reconstruction (ViPMR): a Phase III Randomized Controlled Clinical Trial

Virtual Surgical Planning (VSP), where 3D modeling is used to create 3D-printed surgical guides, has been shown to improve outcomes for patients who undergo mandibular reconstruction surgery, usually due to invasion of cancer from the oral cavity to the jaw. This trial will directly compare the outcomes of patients who receive VSP versus patients who receive the current standard of care, which is Free-Hand Surgery (FHS). They will be randomized into either treatment at a 1:1 ratio and bony union rates will be compared between 12-month postoperative CT scans for each treatment group. Secondary objectives include comparing other short and long-term complication rates, reconstruction accuracy, quality of life, and functional outcomes of VSP and FHS. An economic analysis of VSP will also be performed.

Study Overview

• Status: Recruiting
• Conditions: Oral Cancer; Oral Cavity Cancer
• Intervention / Treatment: Procedure: Free-Hand Surgery; Procedure: Virtual Surgical Planning (VSP)

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Eitan Prisman, MD, FRCSC; Phone Number: 6048754126; Email: eitan.prisman@ubc.ca
• Study Contact Backup: Name: Diane Pan; Phone Number: 22935 6048754111; Email: diane.pan@vch.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
      • Recruiting
      • Vancouver General Hospital
      • Contact: Eitan Prisman, MD MA FRCSC; Phone Number: 6048754126; Email: eitan.prisman@ubc.ca
      • Contact: Diane Pan; Phone Number: 6048754111; Email: diane.pan@vch.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• primary diagnosis requiring mandibulectomy and fibular or scapular free flap reconstructive surgery
• are over the age of 18
• cognitive ability and language skills that allow participation in the trial
• provide informed consent

Exclusion Criteria:

• severe comorbidities including metastatic disease
• do not have a recent (within 30 days) CT scan and are unable/unwilling to receive a head CT scan at the latest 6 days prior to surgery
• prior history of head or neck cancer within last 5 years
• prior history of head or neck radiation treatment at any time
• pregnant of lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Free-Hand Surgery (FHS); In FHS, the site surgeon will proceed with the surgery as per their routine practice.	Procedure: Free-Hand Surgery; The SS will adopt their standard procedure for the mandibular resection and reconstruction. This typically involves bending a titanium fixation plate, harvesting of the bony flap, and shaping of the segments all intraoperatively based on the SS's judgement.
Experimental: Virtual Surgical Planning (VSP); The trial research engineer (RE), located at Vancouver General Hospital (VGH), will segment the CT data to create a 3D model for surgical planning. During the teleconference between site surgeon (SS) and RE, the RE will load the CT data and the segmented 3D model into the virtual planning environment. With the RE navigating the software, which was created in-house at VGH and used in a previous case series, the SS will determine the extent of disease and define the resection planes. After the cutting planes are created, the RE will use the software to create the reconstruction plan with either the patient-specific fibula or scapula. Once the surgeon is satisfied with the plan, the teleconference will end and the RE will create and 3D print the surgical guides for the mandible, for the fibula or scapula, as well as the 3D computed reconstruction.	Procedure: Virtual Surgical Planning (VSP); The 3D reconstruction model, not requiring sterilization, will be sent directly to the SS. Prior to surgery, the SS will prebend a titanium fixation plate to the reconstruction model. Both the surgical cutting guides and titanium plate will be sterilized prior to use in surgery. If the planned resection cannot proceed (possibly due to tumour growth), the surgical team will note the reason for abandonment and conduct a standard FHS. Intraoperatively, the SS will apply the mandibular cutting guide to make the resection, remove the resected component and apply the pre-bent plate. Next, either the fibular or scapular cutting guide is applied to harvest the transplant which is then secured to the plate. The flap is re-vascularized by joining it to blood vessels in the neck.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bony Union	The primary outcome is nonunion as assessed by two independent radiologists at Vancouver General Hospital, blinded to the intervention, based on the 12-month postoperative CT scan. Each apposition (between native bone-flap or between flap segments) will be assessed as nonunion, partial union, and complete union. Cases where there is disagreement between reviewers will undergo consensus review, any persisting disagreements will be reviewed by a third radiologist and classification will be based on the majority vote.	Assessed on CT scans 12 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Intracondylar Distance	Comparison to assess structural reconstruction accuracy of postoperative versus preoperative cephalometrics. This will be calculated as the absolute value of postoperative intracondylar distance minus preoperative intercondylar distance (millimeters).	Assessed between preoperative CT (at least 6 days prior to surgery) and postoperative CT (5 days after date of surgery) scans
Difference in Mandibular Angles	Comparison to assess structural reconstruction accuracy of postoperative versus preoperative cephalometrics. This will calculated as the absolute value of postoperative mandibular angle minus preoperative mandibular angle (degrees).	Assessed between preoperative CT (at least 6 days prior to surgery) and postoperative CT (5 days after date of surgery) scans
University of Washington Quality of Life (UWQoL)	A questionnaire that measures quality of life which records responses on the 5-point Likert scale; minimum of 1 (strongly disagree) and maximum of 5 (strongly agree).	Measure documented at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
EQ-5D-5L Survey	Another questionnaire which measures quality of life. Responses recorded as checkboxes that are ticked if applicable to the participant. Participant health is measured on a scale of 0 (worst health imaginable) to 100 (best health imaginable).	Measure documented at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
Dysphagia	Measured through responses to the M.D. Anderson Dysphagia Inventory (MDADI) for assessment of dysphagia. MDADI records responses on the 5-point Likert scale; minimum of 1 (strongly disagree) and maximum of 5 (strongly agree).	Measure documented at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
Oral Health	Measured through responses to the General Oral Health Assessment Index (GOHAI). Responses recorded one of 5 choices with a point value assigned to each (1 = always, 2 = often, 3 = sometimes, 4 = seldom, and 5 = never).	Measure documented at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
Fibula harvest site complications	Measured through responses to the Lower-Limb Tasks Questionnaire (LLTQ) if patient had fibula harvested for reconstruction. or the Disabilities of the Arm, Shoulder, Hand (DASH) questionnaire if patients had scapula harvested for reconstruction. Intends to measure donor site morbidity by assessing ease of task completion (4 = no difficulty, 3 = mild difficulty, 2 = moderate difficulty, 1 = severe difficulty, 0 = unable), as well as importance of task (4 = very important, 3 = moderately important, 2 = mildly important, 1 = not important).	Measure documented at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
Scapula harvest site complications	Measured through responses to the Disabilities of the Arm, Shoulder, Hand (DASH) questionnaire if patients had scapula harvested for reconstruction. Intends to measure donor site morbidity by assessing difficulty during tasks (1 = no difficulty, 2 = mild difficulty, 3 = moderate difficulty, 4 = severe difficulty, 5 = unable).	Measure documented at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
Economic analysis	Measured through responses to Health Utilization Questionnaire (HUQ) survey to measure impact to patients economic state as a result of their surgery. Records whether participant has experienced certain situations as no or yes (and asks frequency of these situations). Also asks for associated costs that may	Measure documented at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
Occlusal force (bite force)	Measured through Dental PreScale System (DPS-Fujifilm Global) as an assessment of patient bite force.	Measure documented at time of baseline clinic visit and at 1, 6, and 12 months post-surgery (4 visits total)
Dental Implantability	Oral surgeon on the trial will assess the feasibility of the creation of dental implants for the patient postoperatively; responses will recorded as either feasible (1) or infeasible (0).	Up to 100 days after the post-operative CT scan.
Operative Time	Time from first incision to the end of surgical closure as documented on the nursing record.	Initial Surgery
Ischaemic Time	Time from cutting off blood supply to operative region to restoring blood supply and flow as documented on the nursing record.	Initial Surgery
Length of Stay	Time from admission into hospital preoperatively to discharge from hospital postoperatively as documented on patient's medical chart or date of death, whichever came first.	From date of patient's preoperative hospital admission until the date of hospital discharge postoperatively or date of death from any cause, whichever came first, assessed up to 100 days
Rate of Plate Extrusion	Complication with plate where may partially or fully be exposed to external environment.	Patients will be monitored for 1 year post-operatively
Rate of Flap Failure	Complication with flap where donor bone no longer viable as reconstruction piece and replacement required. May be due to ischemic necrosis, infection, osteoradionecrosis, fracturing, etc.	Patients will be monitored for 1 year post-operatively
Rate of Cancer Reoccurrence	Complication where cancer that was confirmed to be removed (negative resection margins, subsequent chemoradiotherapy results, etc.) reoccurs in the mandibular region. It does not have to be the same type or continuation of previous cancer; any cancer found within mandibular region postoperatively qualifies.	Patients will be monitored for 1 year post-operatively
Adverse Events	Any additional complication or adverse event not covered by other secondary outcomes will be recorded from patient chart review and through a structured interview with the patients.	Charts and interviews reviewed at time of baseline clinic visit and at 1, 3, 6, 9 and 12 months post-surgery (6 visits total)
Occlusion	Extent of oral occlusion measured during in-person clinic assessments; can be recorded as normal occlusion, malocclusion Class I, malocclusion Class II, or malocclusion Class III.	Measure documented at time of baseline clinic visit and at 1, 6, and 12 months post-surgery (4 visits total)
Jaw Mobility	Assessment of jaw freedom of movement will be taken during in-person clinic assessments; recorded as measurement of maximal mouth opening (millimeters) from top lip to bottom lip.	Measure documented at time of baseline clinic visit and at 1, 6, and 12 months post-surgery (4 visits total)

Collaborators and Investigators

• Sponsor: University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2022
• Primary Completion (Estimated): October 15, 2025
• Study Completion (Estimated): October 15, 2026

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Oral Cavity Cancer; Oral Cancer; Mandibular Reconstruction
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms
• Other Study ID Numbers: H20-03314

Drug and device information, study documents

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