Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Oral Squamous Cell Carcinoma

PVP is based on CT-scan with millimetric thin slice acquisitions of the facial bone and fibulas. The surgeon defines the exact sites of the intended mandibular osteotomies. A single external subcontracted laboratory (Materialise®) produces the various cutting guides for mandibular resection, flap conformation and the preformed plates for flap osteosynthesis. Flap conformation is entirely performed at the donor site before section of the vascular pedicle (flap still vascularized).

Flap modeling and positioning requires one or multiple cuneiform osteotomies. The bone transplant is shaped to restore the contours of the mandibular defect using preoperative imaging studies and the resection specimen. Flap conformation begins at the donor site and is generally completed at the recipient site after fibular pedicle section and before microvascular anastomosis (during ischemia time). The different bone fragments are fixed together and to the native mandible using either titanium miniplates or reconstruction plate and monocortical screws. Regardless of the material used for fixing the fibular flap to the native mandible, the use of a reconstruction plate adapted to the native mandible (or other similar techniques) prior to tumor resection is recommended to guide flap shaping and positioning, and to insure an accurate MR.

PVP-assisted mandibular reconstruction includes the production of the surgical cutting guides required for mandibular resection and fibula free-flap conformation and of the preformed plates for flap osteosynthesis (for all patients, PVP will be done by the same laboratory).

Mandibular Reconstruction (MR) with Preoperative Virtual Planning (PVP).

Conventional Mandibular Reconstruction (MR without PVP)

Michaël CHEVROT, Ph.D

Laure MONARD

Claire MAJOUFRE, Pr

Julien Drouet, Dr

Sophie EL BEDOUI, Dr

Arnaud DAMECOURT, Dr

Florent ESPITALIER, Pr

Alexandre BOZEC, Pr

Franck JEGOUX, Pr

Agnès DUPRET BORIES, Dr

Maria POISSON, Dr

Nadia BENMOUSSA-REBIBO, Dr

Alexandre BOZEC

This is a national multicenter, randomized, stratified, open label study, aiming to compare mandibular reconstruction (MR) with or without preoperative virtual planning (PVP), in patients with oral/oropharyngeal cancer (OOPC).

PVP-assisted MR includes the production of the surgical cutting guides required for mandibular resection and fibula free-flap conformation and of the preformed plates for flap osteosynthesis (for all patients, PVP will be done by the same laboratory: Materialise laboratory).

PVP-assisted MR includes the production of :

* surgical cutting guides required for mandibular resection and fibula free-flap conformation
* preformed plates for flap osteosynthesis

Patients will be selected after the multidisciplinary decision of oncological surgery including segmental mandibulectomy and immediate MR. Patients will be randomized in 2 groups (ratio 1:1, stratified on center and tumor N status \[0-1 vs 2-3\]).

Study Comparing Fibula Free-flap MR With or Without PVP in Patients With OOPC

A Randomized Prospective Multicenter Study Comparing Fibula Free-flap Mandibular Reconstruction With or Without Preoperative Virtual Planning in Patients With Oral or Oropharyngeal Cancer

Oral health-related quality of life (QoL) measured 1 year after surgery using the GOHAI in the 2 groups of patients (MR with or without PVP).

The GOHAI is an oral-disease-specific QoL measure made by the patient. The GOHAI comprises 12 items grouped into three dimensions: the functional dimension (eating, speaking, swallowing); the pain or discomfort dimension (drugs, gingival sensitivity, discomfort when chewing certain foods); and, the psychosocial dimension (concerns, relational discomfort, appearance). The response format for each item is based on a five-point Likert scale: always = 1; often = 2; sometimes = 3; seldom = 4; never = 5. A summary score (ranging from 0 to 60) is calculated for each patient with a higher score indicating better oral health. GOHAI scores close to 30 have been reported in head and neck cancer patients after oncologic surgery and pedicled or free flap reconstruction.

Mean and median time between randomization and surgery

Mean and median total operative time and mean and median flap ischemia time

Surgical complication rates defined as local complication requiring another intervention in the first postoperative month, including free-flap failure rates

Delayed surgical complication rates defined as local complication occurring after the first postoperative month: non-union (pseudo-arthrosis), osteosynthesis-associated infection...

The PSS-HN is a 3-item scale designed to evaluate functional performance of H\&N cancer patients, specifically Normalcy of Diet, Eating in Public, and Understandability of Speech. Each subscale is rated based on semi-structured interview with a score of 0 to 100, with higher scores indicating better performance. The subscale scores are reported separately, and the Normalcy of Diet subscale will be the primary score of interest for this trial.

The PSS-HN can be rated by health professionals including speech \& language therapists and research nurses. The person collecting this data will remain consistent, as far as is feasible, throughout the course of the study. Scores are determined following an unstructured interview.

Functional outcomes assessed by mouth opening range/capacity at baseline and at 1 year.

It will be performed by using a caliper square to measure in millimeters the inter-incisor gap, assessed by the investigator.

The MDADI is a self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the QoL of patients with head and neck cancer. It surveys QoL issues relevant to swallowing via several subscales: Emotional, Functional, and Physical. A fourth measurement, the Global subscale, is a single question designed to establish quickly an overall assessment that pertains to swallowing. A score ranging from 0 to 100 is calculated for each subscale, with higher scores indicating higher levels of dysphagia.

The SHI is a well-validated and widely used self-questionnaire for assessing speech problems in OOPC patients. It comprises 3 items and provides insight into the nature and severity of patients' complaints. Response categories for all but 1 item range on a 5-point scale (''never,'' ''almost never,'' ''sometimes,'' ''almost always,'' and ''always''). The questionnaire also includes an overall speech quality item, with 4 response categories (''good,'' ''reasonable,'' ''poor,'' and ''severe''). A total SHI score is calculated by summing all items (score range, 0-120), with higher scores indicating higher levels of speech related problems.

Functional dental status (\>6; 4-6, \<4 functional dental units; type of dental rehabilitation) of the patients

Subjective assessment of the aesthetic outcome in the head and neck area using a visual analog scale (VAS) by the patient and the surgeon (assessed separately).

The AESTHETIC VAS is a validated, subjective measure for esthetical perception. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "very poor looking"(0) and "very nice looking" (10).

Morphological results measured by the differences between the preoperative and postoperative measurements on 3D-CT-scan. The mandibular angle (in degrees) measured the amplitude of the angle existing between the ramus and body of the mandible.

Morphological results measured by the differences between the preoperative and postoperative measurements on 3D-CT-scan. The bi-gonial diameter (in millimeter), a measure of the contracture/reduction of the arch, is intended to measure the preservation of the native mandibular arch anatomy.

Morphological results measured by the differences between the preoperative and postoperative measurements on 3D-CT-scan. The lateral deviation (in millimeter) of gnathion in relation to the midsagittal plane will determined the degree of mandibular asymmetry.

Evolution of patient QoL GOHAI score at 6 months (this score will be compared to the score measured at baseline and at 1 year).

The GOHAI is an oral-disease-specific QoL measure made by the patient. The GOHAI comprises 12 items grouped into three dimensions: the functional dimension (eating, speaking, swallowing); the pain or discomfort dimension (drugs, gingival sensitivity, discomfort when chewing certain foods); and, the psychosocial dimension (concerns, relational discomfort, appearance). The response format for each item is based on a five-point Likert scale: always = 1; often = 2; sometimes = 3; seldom = 4; never = 5. A summary score (ranging from 0 to 60) is calculated for each patient with a higher score indicating better oral health. GOHAI scores close to 30 have been reported in head and neck cancer patients after oncologic surgery and pedicled or free flap reconstruction.

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

The EORTC QLQ-C30 is a general self-report questionnaire designed to assess QoL in cancer patients. It consists of five functioning scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea, and vomiting), a global QoL scale, and six single questions assessing additional symptoms commonly reported by cancer patients.

As recommended by the EORTC, the scales and single-item variables of the QLQ-C30 will be linearly transformed into a score from 0 to 100. A high score for a functioning scale and for the global QOL scale represents a better level of functioning, whereas a high score for a symptom scale or a single item scale denotes a high level of symptoms or problems.

The EORTC QLQ-H\&N35 is a tumor specific self-report questionnaire for head and neck cancer patients including seven symptoms scales (pain, swallowing, senses, speech, social eating, social contacts, and sexuality) and six single items (teeth problems, mouth opening, dry mouth, sticky saliva, coughing, and feeling ill).

As recommended by the EORTC, the scales and single-item variables of the H\&N35 questionnaire will be linearly transformed into a score from 0 to 100. A high score for a functioning scale and for the global QOL scale represents a better level of functioning, whereas a high score for a symptom scale or a single item scale denotes a high level of symptoms or problems.

UNICANCER

Mouth and Tooth Diseases

Mouth Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Cancer

Lip and Oral Cavity Cancer

In FHS, the site surgeon will proceed with the surgery as per their routine practice.

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.

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.

Virtual Surgical Planning (VSP)

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.

Free-Hand Surgery

Eitan Prisman, MD, FRCSC

Diane Pan

Eitan Prisman, MD MA FRCSC

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.

Both patient groups will receive the standard presurgical work-up including CT imaging, quality of life questionnaires, and a functional evaluation of bite force and jaw mobility.

Experimental arm - VSP: The trial research engineer (RE) will coordinate with the site surgeon (SS) to create and 3D-print surgical cutting guides for the mandible, for the fibula or scapula, and a 3D computed reconstruction. This reconstruction model will be used to pre-bend a titanium fixation plate. This plate and the surgical cutting guides will be sterilized prior to use. 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 will be applied to harvest the transplant which is then secured to the plate. The flap is re-vascularized using blood vessels in the neck.

Control arm - FHS: In FHS, the SS will proceed with surgery as per their routine practice.

Mandibular Reconstruction Preplanning (ViPMR)

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

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.

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).

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).

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).

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).

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).

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).

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).

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).

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

Measured through Dental PreScale System (DPS-Fujifilm Global) as an assessment of patient bite force.

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).

Time from first incision to the end of surgical closure as documented on the nursing record.

Time from cutting off blood supply to operative region to restoring blood supply and flow as documented on the nursing record.

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.

Complication with plate where may partially or fully be exposed to external environment.

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.

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.

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.

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.

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.

University of British Columbia

Clinical Associate Professor

Diseases and Abnormalities at or Before Birth

Musculoskeletal Diseases

Congenital Abnormalities

Mandibular Neoplasms

Dentofacial Deformities

Maxillary Neoplasms

Maxillofacial Abnormalities

Craniofacial Abnormalities

Musculoskeletal Abnormalities

Stomatognathic System Abnormalities

Jaw Neoplasms

Skull Neoplasms

Bone Neoplasms

Bone Diseases

Jaw Diseases

Maxillary Diseases

Mandibular Diseases

3D-printed patient-specific plate will be used for reconstruction in this patient group

conventional commercial plates will be used for reconstruction in this patient group

We adopt an in-house approach for designing by surgeons. All patient-specific devices are designed in 3-matic 13.0 (Materialise). Both cutting and transferring guides are then additively manufactured by Fused Deposition Manufacturing (FDM) using ULTEM 1010, or by Stereolithography using MED610 resin (Stratasys Ltd, Eden Prairie, MN, USA). Both ULTEM 1010 and MED610 are FDA cleared biocompatible materials applicable to high-temperature autoclaving.

Patient-specific surgical plates are designed by delineating a plate path on bone surface, then followed by the placement of screw holes. Surgical plates are generated by the built-in command in 3-matic. After that, surgical plates are fabricated by SLM using grade 2 titanium powder.

3D-printed patient-specific plate

Bone segments will be stabilized using commercial titanium surgical plates (DePuy Synthes, United States), which are bent manually before fastening the screws.\[

Conventional commercial reconstruction plate

Yuxiong Su, Dr.

Objectives: The aim of this randomised controlled clinical trial is to evaluate surgical accuracy and efficiency of computer-assisted jaw reconstruction using 3D-printed patient-specific titanium surgical plates versus conventional plates.

Hypothesis to be tested: The investigators hypothesize that compared to conventional surgical plates, 3D-printed patient-specific surgical plates improve surgical accuracy and efficiency of computer assisted jaw reconstruction.

Design and subjects: This is an open-label, prospective, double-arm, and single-centre randomised controlled clinical trial. Patients with maxillary or mandibular neoplastic, inflammatory and congenital diseases who require immediate or secondary reconstructive surgery will be invited to participate in the study.

Study instruments: 3D-printed patient-specific titanium surgical plates and conventional plates.

Main Outcome Measures: The primary endpoint is the accuracy of reconstruction. The secondary endpoints include the accuracy of osteotomy, reconstruction time, total operative time, intraoperative blood loss, length of post-operative hospital stay, and postoperative adverse events.

Data analysis: The accuracy parameters, reconstruction time, total operative time, intraoperative blood loss, length of post-operative hospital stay will be presented as mean values with standard deviations. The post-operative adverse events will be calculated and presented as frequency with standard deviation.

Expected results: This randomised control trial will prove improved accuracy and efficiency of reconstruction using 3D printed patient-specific titanium surgical plates. This study is expected to provide high-level evidence to push forward the popularity of using 3D medical printing technology in surgical field.

This randomised controlled clinical trial was based on our previous clinical trial "Three-Dimensional Printing of Patient-Specific Titanium Plates in Jaw Surgery: A Pilot Study" (HKU/HA HKW IRB, No. UW 16-315; registered in ClinicalTrials.gov with a No. of NCT03057223; supported by HMRF Project no.: 05161626).

Over the past few decades, autologous vascularized bone flaps have become the preferred choice for head and neck reconstruction. The anastomosed blood supply endows vascularized bone flaps with improved survival rate and inherent anti-infection performance. Along with the development of microvascular surgery, surgeons are seeking more accurate reconstruction to enhance better aesthetic and functional outcomes. However, a main disadvantage of autologous bone flaps is the mismatch in the shape of donor bone, which need to be cut and trimmed to fit the defects and better restore the natural appearance. Much efforts have been devoted to facilitate bone manipulations, and then the computer-assisted surgery (CAS) emerged in the 21st century as a viable option. In CAS, surgeons do virtual plans in computer, which then guide the precise harvest and arrangement of bone segments for repairing defects in the operating theatre. Bone segments can be fine-navigated to best restore the original skeleton. In previous researches, various devices have been developed to navigate bone segments according to virtual plans, including cutting templates, skull models, and surgical navigation system.

However, the missing link between bone navigation and accurate reconstruction is the plate fixation procedure. In a conventional manner, bone segments are fixed using commercial off-the-shelf titanium plates, which should be manually bent and twisted to fit bone anatomy. The manual contouring process is often tedious and technique-demanding, and adversely affect the precise location of bone segments. What's worse, repeated bending can even lead to poor fatigue performance. The disadvantages of conventional surgical plates make it necessary to develop patient-specific surgical plates. Compared to conventional plates, patient-specific surgical plates are designed and manufactured in 3D structures aligned with individual bone contours. Instead of contouring plates based on anatomical structure of bones in conventional plates, patient-specific surgical plates navigate the folding and precise location of bone segments, and hopefully improve the accuracy of reconstruction. Meanwhile, since no plate bending is required, patient-specific surgical plates can be used to optimize bone reconstruction in a more efficient and standardized manner.

In recent years, with the rapid development of additive manufacturing (3D printing), it is now feasible to manufacture patient-specific metal implants with topologically optimized structures. Many efforts have been made to develop porous bone scaffolds for regenerative medicine, which are endowed with customized porosity to achieve optimal biomechanical properties. However, although additively manufactured bone scaffolds demonstrate excellent performance in some complicated cases, they still cannot replace the dominant role of autologous vascularized bone flaps in head and neck reconstruction. Therefore, it is of crucial importance to explore the application of additive manufactured (3D printed) patient-specific surgical plates, albeit not much research has been done in this direction.

In our previous study (HKU/HA HKW IRB, No. UW 16-315) supported by Health and Medical Research Fund (Project no.: 05161626), the investigators have successfully manufactured patient-specific titanium plates with high precision through selective laser melting (SLM) technology, which is a high-tech 3D printing technology that fully melts titanium powders into complete entities in the layer by layer manner. SLM enables the fabrication of patient-specific titanium surgical plates with tailored structures and outstanding biomechanical properties. Our results showed promising clinical outcomes in the application of 3D printed patient-specific titanium plates in head and neck reconstruction. Furthermore, the investigators did a retrospective study comparing the patients who had undergone jaw reconstructive surgery using 3D printed patient-specific surgical plates versus conventional titanium plates and the result showed superior accuracy of reconstruction outcomes in the study group with the use of 3D printed patient-specific surgical plates. However, there were significant limitations in our study. First, as a retrospective study, the innate flaw of study design was unavoidable, such as selection bias. Second, there was significantly difference in follow-up periods between the study group and control group. The imaging data used for accuracy analysis were obtained during different post-operative periods, which compromised the final outcomes. Finally, surgical efficiency endpoints, such as operation time, blood loss, and post-operative hospital stay, which could be significantly affected by multiple confounding factors, are difficult to control by retrospective study design. Hence, there is still lack of high-level evidence concerning the advantages of 3D printed patient-specific surgical plates in head and neck reconstruction. Whether 3D printed patient-specific surgical plates improve surgical accuracy and efficiency compared to conventional plates in computer assisted jaw reconstruction should be further investigated before large-scale clinical application.

Therefore, the investigators aim to evaluate surgical accuracy and efficiency of computer-assisted jaw reconstruction using 3D-printed patient-specific titanium surgical plates versus conventional plates in a prospective randomised controlled clinical trial. Our study is expected to provide high-level evidence to push forward the popularity of using 3D medical printing new technology in the surgical field.

Methods

The methodology has already been set up and has been proved feasible in our earlier studies. The PI has been working on computer aided surgical simulation, virtual planning, and 3D printed surgical templates in the maxillofacial surgery for several years and has published a series of articles.

1. Computer-assisted Surgery

   The CAS techniques used in head and neck reconstruction are well established in our unit and have been described previously. Briefly, CAS is composed of three main phases: the pre-operative phase of the virtual surgery and 3D printing of patient-specific devices, intra-operative phase involving precision-enhanced surgery to install the patient-specific devices, and post-operative phase involving the accuracy analysis. The patient-specific devices can include cutting guides, positioning guides, and the patient-specific titanium plates. In our trial, the study group will use cutting guides and patient-specific titanium plates, whereas the control group will use cutting guides, positioning guides, and conventional plates.

   In the pre-operative phase, the virtual surgery will be performed by surgeons using the ProPlan CMF 2.0 software (Materialise, Leuven, Belgium). The patient's CT data is initially segmented to rebuild 3D virtual models of the maxilla or mandible using ProPlan's interactive interface. Next, bone resection is performed in the 3D models for en bloc removal of any tumours. Meanwhile, bone grafts are harvested from fibula or iliac crest to repair defects and restore the normal appearance. Finally, the virtually reconstructed maxilla or mandible is used to design patient-specific devices to navigate the bone segments.
2. Additive Manufacturing of Patient-specific Devices

   Compared to the conventional approach of designing patient-specific devices using engineering companies, we have adopt an in-house approach that allow the surgeons to design and manufacture the devices. All patient-specific devices are designed in 3-matic 13.0 (Materialise). Cutting guides, which guide and adapt to bone surface for accurate bone resection, are generated by wrapping to the bone surface.

   For the study group, patient-specific surgical plates are designed by delineating the plate path on the bone surface, followed by the placement of screw holes. Surgical plates are generated by a built-in command in 3-matic. Next, the surgical plates are fabricated by SLM using grade 2 titanium powder. For the control group, positioning guides will be designed for the bone segment alignment and inset.

   Both cutting and positioning guides will be additively manufactured by Fused Deposition Manufacturing (FDM) using ULTEM 1010, or by Stereolithography using MED610 resin (Stratasys Ltd, Eden Prairie, MN, USA). Both ULTEM 1010 and MED610 are FDA cleared biocompatible materials usable in high-temperature autoclaving.
3. Surgical Procedures

   In the present study, all patients in both groups will undergo CAS carried out by the same chief surgeon (PI). During the surgery, patient-specific cutting guides will enable precise jawbone resection and bone flap osteotomy.

   In the control group, the arrangement of bone segments will be manipulated according to the positioning guide. Bone segments will be stabilized using commercial titanium surgical plates (DePuy Synthes, United States), which are bent manually before fastening with screws. In the study group, patient-specific surgical plates will be designed and fabricated to custom-fit the bone contours of reconstructed maxilla or mandible. The screw holes embedded in cutting guides correspond to the 3D-printed patient-specific surgical plates, which will guide the position of surgical plates and bone segments, thereby facilitating folding, positioning, and fixation of bone segments in the real surgery. Standard peri-operative management will be similar in both groups. Post-operative follow-up will be conducted in a routine manner.
4. Data collection procedures

CT scan will be obtained at baseline (before surgery) and post-operatively (within 1 month after the surgery). The accuracy of reconstruction will be independently assessed by two assessors. Training will be provided using previous cases, and calibration between the two assessors will be done with the aim of achieving over 90% inter-assessor agreement in three consecutive training cases before starting the measurement of subject cases in this study. Other information such as reconstruction time, total operative time, intra-operative blood loss, length of post-operative hospital stay, and post-operative adverse events will be recorded.

Patients fulfilling the eligibility criteria and willing to participate will be randomised after baseline assessment (1:1 allocation ratio). A priori, an independent statistician will prepare a computer-generated randomisation schedule in a random-sized permuted blocks of four or six patients stratified by location of reconstruction (maxilla/mandible) and gender (F/M) to ensure that the numbers of participants receiving the two interventions are closely balanced within each stratum. The allocation numbers will be concealed in opaque sealed envelopes prepared by a central study coordinator, only opening them after informed consent and baseline measures have been obtained.

3D-Printed Patient-Specific Surgical Plates Versus Conventional Surgical Plates in Jaw Reconstruction

Computer-Assisted Jaw Reconstruction Using 3D-Printed Patient-Specific Surgical Plates Versus Conventional Surgical Plates: A Randomised Controlled Clinical Trial

The primary endpoint is accuracy of reconstruction, which is defined as the distance or angulation deviations of anatomical landmarks between the virtual plan and actual surgical outcome.

Deviation of actual osteotomy from the digital planning

time from the start of flap ischemia to the finish of anastomosis and internal fixation

The University of Hong Kong

Clinical Professor

The patients who underwent primary ablative tumor resection with segmental mandibulectomy and immediate VFF reconstruction were retrieved from the database

tumor resection and mandible reconstruction

This study aims to assess the survival rate of oral squamous cell carcinoma (OSCC) patients following immediate mandibular reconstruction with vascularized fibula flap (VFF) and to identify risk factors influencing the overall survival rate and postoperative outcomes.

Survival Analysis of Oral Cancer Patients

Survival Analysis of Segmental Mandibulectomy With Immediate Vascularized Fibula Flap Reconstruction in Stage IV Oral Squamous Cell Carcinoma Patients

The overall cumulative survival was recorded at the fifth-year.

KU Leuven

Doctor

Symptoms and General Pathology

Wounds and Injuries

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Nervous System Diseases

Nutritional and Metabolic Diseases

Eye Diseases

Skin and Connective Tissue Diseases

Syndrome

Fractures, Bone

Facies

Fetal Growth Retardation

Mandibular Fractures

Fibrous Dysplasia of Bone

Neuroma

Oculocerebrorenal Syndrome

Osteoma

Mandibulofacial Dysostosis

Goldenhar Syndrome

Dysostoses

Disease Attributes

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Osteochondrodysplasias

Mucopolysaccharidosis IV

Bone Diseases, Developmental

Jaw Fractures

Maxillofacial Injuries

Facial Injuries

Craniocerebral Trauma

Trauma, Nervous System

Skull Fractures

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Craniofacial Dysostosis

Coloboma

Eye Diseases, Hereditary

Fibrous Dysplasia

Miller Syndrome

Hemifacial Microsomia

Treacher Collins Syndrome

Craniofacial Microsomia

Goldenhar Disease

Oculo-auriculo-vertebral Spectrum

Mucopolysaccharidosis Type IV

Crouzon Syndrome

Pharmaceutical Solutions

All Drugs and Chemicals

Gastrointestinal Agents

Cimetidine

Patients undergoing surgical procedures for facial reconstruction for whom Biomet Microfixation titanium plates (or Ti mini plates) were utilized for the repair.

Patients undergoing surgical procedures for mandibular reconstruction, including TMJ, for whom Biomet Microfixation titanium plates (or Ti mini plates) were utilized for the repair.

Patients undergoing surgical procedures for midface reconstruction using custom-made prostheses manufactured on PEEK material.

The Facial Plating System provides a comprehensive titanium fixation solution for maxillofacial surgery procedures. More than twenty-five different plating options in two systems, the 1.5 mm and 2.0 mm with a variety of instruments, and high torque screws, including meshes, are part of this system. Plates and screws are made of commercially pure titanium per ASTM F-67, Titanium 6Al 4V Alloy per ASTM F-136.

Titanium Facial Plates

The Mandibular Plating System provides a comprehensive titanium fixation solution for mandibular surgical procedures. Several plating options, a variety of instruments, and high torque screws with various plate shapes are part of this system.

Plates in the Mandibular Plating System have profiles of various thicknesses. Screws are available in self-tapping, locking and non-locking varieties, and in various sizes between 2.0 mm and 2.3 mm in diameter, and 5 mm to 18 mm in length.

Titanium Mandibular Plates

The Add-On Condyle is intended to be implanted in the human jaw to replace the mandibular condyle to functionally reconstruct the temporomandibular joint on a temporary basis for patients undergoing ablative tumor surgery requiring the removal of the native mandibular condyle. This device is not for permanent implantation, traumatic injuries, or for treatment of temporomandibular joint disease.

Add-on Condyle

The HTR-PEKK implants are fabricated from polyether-ketone-ketone (PEKK) via selective laser sintering (SLS), a 3D manufacturing technique. The laser sintering machine builds the implant in layers as dictated from a stereolithographic (STL) file of the approved implant. The HTR-PEKK implants are designed individually for each patient to replace bony voids in the facial anatomy using a patient's own CT imaging data. The implant is made to fill an existing or planned void (where appropriate) using computer-aided design technology for anatomy enhancement, correction of trauma injuries, and/or to correct congenital defects in the craniofacial bone.

HTR-PEKK

Mark Sun, PhD

This study will address medical devices manufactured by Biomet Microfixation (d.b.a. Zimmer Biomet) designed for fixation and stabilization of the facial and mandibular skeleton.

The subject devices are:

* plates, screws, and primary instruments from the Biomet Microfixation Facial Plating System, including plates to be specifically used in orthognathic procedures
* plates, screws and primary instruments for the Mandibular Plating System, including and a device intended to temporarily restore the functionality of the temporomandibular joint for patients whose natural condyle has to be resected, subsequent to a tumor ablation ("Add-On Condyle") Additionally, a third device intended for the replacement of bony voids in the facial skeleton will be evaluated in this trial (HTR-PEKK- facial application).

A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.

Clinical Evaluation of Biomet Microfixation Devices Used in Facial & Mandibular Surgical Procedures. Facial Plating System, HTR PEKK (Midface) and Mandibular Plates: A Post Market Clinical Follow-up Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Comparing Fibula Free-flap MR With or Without PVP in Patients With OOPC	NCT04725396	Oropharynx Squa... Oral Cavity Squ...	Mandibular Reco... Conventional Ma...	18 Years -	UNICANCER
Study Comparing Fibula Free-flap MR With or Without PVP in Patients With OOPC	NCT04725396	Oropharynx Squa... Oral Cavity Squ...	Mandibular Reco... Conventional Ma...	18 Years -	UNICANCER
Mandibular Reconstruction Preplanning (ViPMR)	NCT05429099	Oral Cavity Can... Oral Cancer	Virtual Surgica... Free-Hand Surge...	18 Years -	University of British Columbia
3D-Printed Patient-Specific Surgical Plates Versus Conventional Surgical Plates in Jaw Reconstruction	NCT04635865	Mandibular Neop... Maxillary Neopl... Dentofacial Def...	3D-printed pati... Conventional co...	18 Years -	The University of Hong Kong
Survival Analysis of Oral Cancer Patients	NCT04967638	Head and Neck C...	tumor resection...	18 Years - 90 Years	KU Leuven
A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.	NCT04931056	Tumor Facial Fracture Mandibular Frac... Fibrous Dysplas... Osteoma of Mand... Neuroma Cleft Face Hemifacial Micr... Treacher Collin... Miller Syndrome Nager Syndrome	Titanium Facial... Titanium Mandib... Add-on Condyle HTR-PEKK	18 Years - 100 Years	Zimmer Biomet
Survival Analysis of Oral Cancer Patients	NCT04967638	Head and Neck C...	tumor resection...	18 Years - 90 Years	KU Leuven
Validation of the O-bridge Protocol: a Prospective, Multicenter Trial	NCT04007783	Benign or Malig... Stage III-IV Os... Mandibular Reco... Fixed Dental Re... Quality of Life		18 Years -	AZ Sint-Jan AV
Survival Analysis of Oral Cancer Patients	NCT04967638	Head and Neck C...	tumor resection...	18 Years - 90 Years	KU Leuven
Three-Dimensional Printing of Patient-Specific Titanium Plates in Jaw Surgery: A Pilot Study	NCT03057223	Mandibular Neop... Maxillary Neopl... Dentofacial Def... Maxillofacial I...	3D-printed pati...	18 Years -	The University of Hong Kong
Mandibular Reconstruction Preplanning (ViPMR)	NCT05429099	Oral Cavity Can... Oral Cancer	Virtual Surgica... Free-Hand Surge...	18 Years -	University of British Columbia

Spots Global Cancer Trial Database for mandibular reconstruction