Jaw Reconstruction With Printed Titanium and Free Tissue Transfer
Conditions: Neoplasm, Oral, Osteoradionecrosis of Jaw, Mandibular Diseases, Jaw Cancer, Jaw Diseases, Surgery
Sponsor: University of South Wales

JaW PrinT Protocol v1.8_22.12.2017 
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The “JaW PrinT” Study:  
 
Jaw reconstruction With Printed or flexed Titanium and 
free tissue transfer. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A collaboration between Abertawe Bro Morgannwg University Health Board, 
University of South Wales and Renishaw PLC. 
 
 
 
 
 
 

JaW PrinT Protocol v1.8_22.12.2017 
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Table of Contents 
Table of Contents ..................................................................................................... 2 
List of Abbreviations ................................................................................................. 3 
1.0 Study Team ...................................................................................................... 3 
1.1 Details of Research Team ............................................................................................................................. 3 
2.0 Literature Review and Study Rationale............................................................ 4 
2.1 
Introduction / context ............................................................................................................................... 4 
2.2 
Computer aided 3D planning and crude customisation of mandibular 
reconstruction osseosynthesis plates ............................................................................................................ 6 
2.3 
3D printing in mandibular reconstruction ...................................................................................... 6 
2.4 
Summary ........................................................................................................................................................... 7 
3.0 Study aims and objectives ............................................................................... 7 
3.1 
Primary outcome .......................................................................................................................................... 7 
3.2 
Secondary outcomes ................................................................................................................................... 7 
4.0 Study design..................................................................................................... 8 
4.1 
Inclusion criteria ........................................................................................................................................ 12 
4.2 
Exclusion criteria ....................................................................................................................................... 12 
4.3 
Recruitment .................................................................................................................................................. 12 
4.4 
Randomization ............................................................................................................................................ 12 
4.5 
Study procedures....................................................................................................................................... 13 
4.5.1 
Baseline Assessment ..........................................................................................................................13 
4.5.2 
Perioperative/inpatient data collection ..................................................................................13 
4.5.3 
6 weeks follow up................................................................................................................................14 
4.5.3 
6 months follow up.............................................................................................................................14 
4.5.4 
1 year follow up ...................................................................................................................................14 
5.0 Risk management .......................................................................................... 15 
6.0 Statistical analysis .......................................................................................... 16 
7.0 Data management and quality control .......................................................... 16 
8.0 Ethical considerations .................................................................................... 16 
9.0 Funding .......................................................................................................... 17 
10.0 Study timeline .............................................................................................. 17 
11.0 References ................................................................................................... 18 
12.0 Appendices .................................................................................................. 20 
Appendix A ................................................................................................................................................................ 20 
Appendix B ................................................................................................................................................................ 23 
 
 

JaW PrinT Protocol v1.8_22.12.2017 
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List of Abbreviations 
 
ABMUHB 
Abertawe Bro Morgannwg Health Board 
CAD-CAM 
Computer aided design – Computer aided manufacture 
CMF 
 
Cranio-maxillo-facial (surgery) 
CBCT  
Cone-beam computer tomography (dental) 
CT 
 
Computer tomography (medical) 
H&N  
Head & Neck (surgery) 
HRQOL 
Health related quality of life 
ORN 
 
Osteoradionecrosis (of the mandible) 
PI 
 
Principal investigator 
PSI 
 
Patient-specific implant 
SLM 
 
Selective laser melting 
3D 
 
Three-dimensional 
 
 
1.0 Study Team 
 
Mr Alexander Goodson 
Postgraduate (PhD) student 
investigator 
 
Professor Mark Williams 
Chief Investigator & PhD Director of 
Studies 
 
Mr Madhav Kittur 
Principal Investigator for ABMU 
Health Board 
 
Mr Peter Evans 
 
 
 
Co-investigator, ABMU Health Board 
 
 
1.1 Details of Research Team 
 
Name:  
Professor Mark Williams 
Role:  
Chief Investigator 
Address: 
Faculty of Life Sciences and Education 
 
 
University of South Wales 
 
 
Cemetery Road 
Glyntaff 
CF37 4BD 
 
 
 
Telephone: 
01443 654578 
Email:  
mark.williams@southwales.ac.uk 
 

JaW PrinT Protocol v1.8_22.12.2017 
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Name:  
Mr Alexander Goodson 
Role:  
PhD Student Investigator 
Address: 
Faculty of Life Sciences and Education 
 
 
University of South Wales 
 
 
Glyntaf Campus 
 
 
Pontypridd, CF37 1DL 
 
Telephone: 
01443 654578 
Email:  
alex.goodson@southwales.ac.uk 
 
Name:  
Mr Madhav Kittur 
Role: 
Principal Investigator for ABMU Health Board 
Address: 
Morriston Hospital 
 
 
Heol Maes Eglwys 
Morriston 
Swansea 
SA6 6NL 
Telephone: 
01792 703162 
Email:  
madhav.kittur@wales.nhs.uk 
 
Name:  
Mr Peter Evans 
Role:  
Co-investigator 
Address: 
Morriston Hospital 
 
 
Heol Maes Eglwys 
Morriston 
Swansea 
SA6 6NL 
Telephone: 
01792 703162 
Email:  
peterllewelyn.evans@wales.nhs.uk 
 
2.0 Literature Review and Study Rationale 
 
2.1 
Introduction / context 
 
Head and neck (H&N) cancer includes cancers originating from various (and 
often overlapping) sub-sites in the head and neck region (including the oral 
cavity, pharynx, larynx, nose and paranasal sinuses).  H&N cancer is the eighth 
most common cancer in the UK (2014).  In the UK (mainland) it is four times 
commoner in men than women, and geographically European age-standardised 
(AS) incidence rates are higher in males in Wales than England (with rates 
highest in Scotland overall for both sexes).    H&N cancer incidence has increased 
in both sexes since the 1990s with a greater percentage increase amongst 
females, closing the gender difference in incidence over 
time.(Cancer_Research_UK)   
For head and neck cancer in general, late stage disease is a commoner 
presentation than early stage disease (62% are stage III/IV at presentation 

JaW PrinT Protocol v1.8_22.12.2017 
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versus 38% at stage I/II).(NICR, 2016)  Consequently, major resective surgery, 
aiming for cure (with immediate reconstruction for optimal functional outcome) 
is commonplace.  In the case of oral cancer specifically, advanced tumours 
frequently involve the mandible (lower jaw bone), requiring resection/removal 
of part of the mandible to a variable extent, depending on the nature of the 
tumour (with/without postoperative radiotherapy, depending upon patient and 
tumour-specific factors).   
Radiotherapy is commonly used in head and neck cancer in isolation (as an 
alterative to surgery), most commonly for laryngeal and tongue base tumours as 
it helps to preserve natural speech and swallowing.  However for advanced 
squamous cell carcinomas (SCCs), combined treatment modalities (surgery and 
radiotherapy / chemotherapy and radiotherapy) offer the highest chance of 
cure.(Nutting, 2016)  For patients in whom radiotherapy is used, there is an 
additional lifelong risk of developing osteoradionecrosis (ORN) of the mandible 
as a side-effect.  Osteoradionecrosis is in effect, “hypovascularity and necrosis of 
bone followed by trauma-induced or spontaneous mucosal breakdown, leading 
to a non-healing wound.”(Butterworth et al., 2016)  In the latter stages of the 
disease process, ORN can result in pathological fracture of the mandible and/or 
an orocutaneous fistula, requiring free tissue transfer to repair the defect.(Lyons 
and Brennan, 2014)  Consequently, in the context of managing head and neck 
cancer, mandibular reconstruction with titanium plates and free tissue transfer 
is commonly performed; not only for immediate reconstruction after surgical 
resection of advanced tumours, but also for treatment of late-stage ORN.  
Furthermore, similar techniques can be used for extensive and progressive (but 
histologically benign) jaw tumours.  
Choice of reconstructive technique for mandibular defects depends on the 
amount of bone to be resected.(Brown et al., 2016)  However, in larger defects, it 
is felt by many surgeons that the gold standard for mandibular reconstruction is 
a fibula free flap (autologous vascularized bone and soft tissue, transplanted 
from the leg and anastomosed to an arteriovenous supply in the neck) supported 
within an osseosynthesis plate to facilitate primary bony union/healing.(Kokosis 
et al., 2016)  Other choices of bony free-flaps can be used such as the deep 
circumflex iliac artery (DCIA) flap, favoured over the fibula free flap by some 
authors.(Chen et al., 2014)  Most osseosynthesis plates used for this purpose are 
composed of titanium, because of its intrinsic biocompatibility and high 
strength-to-weight ratio.(Parthasarathy, 2014).  Traditionally, titanium was 
flexed or moulded intraoperatively by eye (during surgery) to reconstruct 
mandibular defects, without the modern benefits of preoperative 3D computer-
aided planning.  The process of flexing a rigid osseosynthesis plate for 
mandibular reconstruction inherently contributes to the overall duration of the 
surgery, is dependent upon the experience and skill of the surgeon and carries 
the risk of human error in dimensional accuracy of the reconstruction, simply 
because it is done ‘by hand and by eye’. Furthermore, manually deforming 
titanium implants in this manner creates intrinsic stresses within the implanted 
material, potentially weakening the overall reconstruction in the long term 
whilst subjected to cyclical loading forces from mastication/chewing for 
example.(Park et al., 2016)   

JaW PrinT Protocol v1.8_22.12.2017 
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2.2 
Computer aided 3D planning and customisation of mandibular 
reconstruction osseosynthesis plates 
 
Three dimensional (3D) planning and virtual surgery has evolved in recent years 
and it is postulated that it improves efficiency, accuracy, creativity and 
reproducibility in CMF surgery in particular.(Steinbacher, 2015)  Rapid 
prototyping is a process by which a stereolithigraphic resin model can be 
produced following collection of data from 3D imaging such as computer 
tomography (CT) scanning.  The process of virtual surgery (following analysis of 
3D imaging data) provides the means to rapid-prototype a stereolithigraphic 
resin model/mould upon which a titanium implant can be flexed, pressed or 
moulded preoperatively (and most importantly, checked against the 
stereolithigraphic model) for subsequent intraoperative use. This technique has 
become commonplace in UK maxillofacial centres.  When compared to 
traditional intraoperative shaping techniques, it improves accuracy and 
efficiency in mandibular reconstruction (notably eliminating the time taken 
during surgery to bend the plate by eye that would otherwise be required using 
the traditional approach, yet allowing as much time as needed by the technician 
preoperatively to achieve the best ‘handmade’ result possible).(Gil et al., 2015)  
Nevertheless, this type of ‘customisation’ still remains open to considerable 
inaccuracies/human errors of the technician in flexing the plate by hand.  
Furthermore the risk of introducing mechanical weaknesses by flexing the plate 
remains.  
 
Besides producing patient-specific implants (PSIs), 3D planning and virtual 
surgery facilitates the production of intraoperative surgical cutting and drilling 
guides/’stents’, which improve accuracy of bone cuts (osteotomies) in 
mandibular reconstruction with fibula free flaps and aids precise placement of 
osseointegrated dental implants (Wang et al., 2016, Allum, 2008).   
 
2.3 
3D printing in mandibular reconstruction 
 
It is clear that to date, 3D CAD-CAM has improved the accuracy of mandibular 
reconstructions in head & neck oncology surgery.  With the advent of “3D 
printing” (more specifically selective laser melting; SLM), it has been proposed 
by one author group that laser sintered mandibular reconstruction plates reduce 
the duration of surgery and frequency of complications, as well as producing a 
more accurate reconstruction due to the elimination of human error in the final 
stages of fabrication (in contrast to the “pre-flexing to a rapid-prototyped 
stereolithigraphic model” approach).  The authors suggest that further 
randomized studies would be useful to determine whether CAD-CAM 
mandibular reconstruction is economically sustainable in maxillofacial oncology 
surgery (Tarsitano et al., 2016).  Currently a team in Hong Kong are 
prospectively evaluating clinical outcomes and complications of laser sintered 
mandibular reconstruction plates in a proposed series of 48 patients (Su, 2017).  
However, to date there are no randomized trials comparing clinical and 

JaW PrinT Protocol v1.8_22.12.2017 
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economic outcomes in 3D-printed mandibular reconstruction plates and cutting 
guides versus manually pre-flexed plate techniques.    
 
2.4 
Summary 
 
In summary, 3D printing (SLM) of titanium provides an opportunity to negate 
the impact of human error in customisation of mandibular reconstruction 
osseosynthesis plates and alignment of osteotomies, potentially improving upon 
the predictability and precision of mandibular reconstruction in head & neck 
cancer patients.  However, with a lack of high-level evidence to date, there is no 
clear consensus on whether the SLM approach provides a better treatment 
solution when compared to other more established, but potentially more crude 
techniques of plate customization (pre-flexing to a rapid prototyped model).  
Consequently a situation of clinical equipoise exists and in this context, warrants 
a well-designed observational study to evaluate any differences between the two 
treatment approaches.  
 
3.0 Study aims and objectives 
 
3.1 
Primary outcome 
 
Primarily, the study aims to evaluate: 
 
1. Predictability and resultant dimensional accuracy of mandibular 
reconstructions performed using: 
 
o Fibular free-flap reconstruction of the mandible with a customized 
pre-flexed mandibular reconstruction plate and cutting guides 
(Treatment pathway A) 
 
OR 
 
o Fibular free-flap reconstruction of the mandible with a customized 
SLM mandibular reconstruction plate and cutting guides 
(Treatment pathway B) 
 
3.2 
Secondary outcomes 
 
Secondarily, the study aims to compare treatment pathways A and B for: 
 
2. The duration of surgery (in particular individual components of the 
surgery such as flap warm ischaemia time, duration of osteotomies and 
plate fixation procedures.  

JaW PrinT Protocol v1.8_22.12.2017 
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3. The operators’ perceptions of the overall intraoperative usability, 
confidence with the technique and immediate satisfaction of the surgical 
result. 
4. The need to make minor adjustments to either the plate, osteotomy or 
screw holes in order to fit the plate during surgery.  
5. Incidence of postoperative complications (as recorded during inpatient 
stay as well as at 6 weeks, 6 months and 1 year outpatient follow up 
visits), for example: 
a. Localised infection 
b. Plate extrusion/exposure 
c. Length of hospital stay (including duration of intensive care / high-
dependency / ward requirements) 
d. Mal / non / delayed-union of the bony components of the 
mandibular reconstruction (from objective analysis of clinically 
routine postoperative CT scan imaging) 
e. Plate fractures/failures 
6. Medium-term (up to 1 year) functional outcomes, for example: 
a. Feasibility of dental implant rehabilitation (specifically in the 
technical context of clinical and/or radiological perspective of 
bone quality and anatomy as well as in the holistic context of the 
patient’s suitability overall, in order to determine the importance 
of reconstructed bony anatomy in the decision processes and 
planning of dental rehabilitation) 
b. Objective evaluation of changes in dental occlusion (with the aid of 
dental model analysis).  
c. Objective assessment of changes in facial aesthetics (facial 
symmetry based upon baseline and postoperative 3D photography 
(stereophotogrammetry). 
7. Patient-perceived quality of life: 
a. using a validated quality of life assessment tools: 
i. University of Washington Quality of Life Questionnaire v4 
ii. Short-form Derriford appearance scale (DAS24) 
iii. Liverpool oral rehabilitation questionnaire 
b. by time to return to work / social status at 1 year (where 
applicable) 
8. Economic implications (with economic analysis taking the above clinical 
and social outcomes into account). 
 
4.0 Study design 
 
JaW PrinT is a ‘real-world’ prospective observational pilot study, evaluating the 
clinical effectiveness, usability and economics of two approaches to mandibular 
reconstruction surgery (figure 1).  Patient participants will be recruited 
prospectively over a minimum period of 18 months (with observation of at least 
10 participants in each treatment pathway).  The figures are based upon the 
historical clinical practice of the research site, with both techniques in equal use; 

JaW PrinT Protocol v1.8_22.12.2017 
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choice depending on resources, surgical training requirements and surgeon’s 
clinical preference.  
 
As a purely observational study, treatment choice will be made in the normal 
clinical manner and will in no way be influenced by the study itself.  
 
Participants will be followed up at their routine outpatient clinics (6 weeks, 6 
months and 1 year postoperatively) with prospective outcomes data collection 
(figure 1). 
  
 
 
 
 

JaW PrinT Protocol v1.8_22.12.2017 
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PI to prospectively identify potential study participants from weekly maxillofacial and 
H&N surgery clinics 
 
•
Participants to be recruited over a minimum period of 18 months; minimum of 10 patients in each 
treatment pathway. 
•
On clinic, potential participants will be asked by the PI if they are interested in taking part in the study.  
•
The  PI, after meeting the potential participant, will confirm their eligibility.  
•
Eligible participants meeting inclusion and exclusion criteria will be sent an invitation letter with a  
participant information sheet and a consent form (emphasizing the option to either decline or accept the 
offer of study participation).  
 
Preoperative baseline data collection (CRF01 form). 
•
Medical history and screening of comorbidities (including comorbidity score & performance status), smoking and alcohol status. 
•
Evaluate for history of any previous radiotherapy treatment (date started and completed, regime details). 
•
Physical assessment (BMI, oral hygeine status). 
•
Detailed social history 
•
University of Washington QoL Questionnaire v4. 
•
Short-form Derriford appearance scale (DAS24). 
•
Liverpool oral rehabilitation questionnaire. 
•
3D Photograph (Stereophotogrammetry) of the head and neck 
•
Baseline clinical blood tests (FBC, U&E, Clotting screen) 
Do not enter 
study 
Treatment allocated in normal clinical manner by surgeon to either 
pathway A (surgery with pre-flexed plate) or pathway B (surgery 
with SLM plate). 
 
Participant blinded to treatment allocation at this stage 
Pathway A 
(Customized pre-
flexed plate) n ≥10 
Pathway B 
(Customized SLM 
plate) n ≥10 
Perioperative / inpatient data collection (CRF02 form). 
•
Prior to commencing surgery, bite registration to be obtained (using viscoelastic silicone impression putty) 
•
At surgery, record of: 
o
Times at which mandibular osteotomies are first started (cutting guides first placed onto mandible) and completed 
o
Time of knife-to-skin for flap harvest 
o
Time of flap detachment 
o
Time of completing fixation of the plate (with flap) in its final resting position  (i.e. when completion of fixation to the residual mandible)  
o
Time of completing arterial anastomosis 
•
Record of need for any intraoperative adjustment to the plate, osteotomies and/or planned drill hole positions.  
•
Surgeon rating of usability, confidence of use, satisfaction with reconstructive procedure. 
•
Scrub nurse rating of usability, confidence of use, satisfaction with reconstructive procedure. 
•
Record of days-stayed on ITU / HDU and/or Ward, date of discharge. 
•
Record of all complications as inpatient (peri & post operative). 
Consent 
•
At the next routine clinical appointment, the potential patient participant’s decision will be noted.  
•
Should the patient wish to participate, the PI will obtain their written informed consent accordingly. 

JaW PrinT Protocol v1.8_22.12.2017 
11 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 weeks follow up (CRF03 form). 
•
Physical assessment (BMI, oral hygeine status). 
•
University of Washington QoL questionnaire. 
•
Short-form Derriford appearance scale (DAS24). 
•
Liverpool oral rehabilitation questionnaire. 
•
Report on complications. 
•
3D Photograph (Stereophotogrammetry) of the head and neck. 
•
Detailed social history (e.g. current occupation / employment) 
6 months follow up (CRF04 form). 
•
Data recorded as per CRF03 form. 
•
Postoperative CT mandible scan (evaluation of actual vs. planned dimensions, quantitative evaluation of bony cortical union at osteotomy sites) 
1 year follow up (CRF05 form). 
•
Data recorded as per CRF03 form. 
•
Dental assessment (including routine cone beam CT scan) and restorative dentist rating of technical and practical feasibility of prosthetic rehabilitation 
options 
End of study 
Patients informed of treatment type received. 
Figure 1.  The JaW PrinT study design 

JaW PrinT Protocol v1.8_22.12.2017 
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4.1 
Inclusion criteria 
 
• Age over 18 years 
• Able to provide informed consent 
• A planned fibular free-flap reconstruction of the mandible 
• Planned post operative surveillance CT scan 6 months following surgery 
4.2 
Exclusion criteria 
 
• Clinically unfit or inappropriate (based upon prognosis/life expectancy) 
for reconstruction using free tissue transfer techniques 
• Patients with planned surgical defects involving reconstruction of the 
condyle: i.e. Brown class Ic, IIc or IVc.  (Clinical use of printed plates for 
condylar reconstructions would in effect be ‘off-licence’ and non-standard 
treatment which is beyond the remit of an observational research study).  
• Flap failure within the study follow-up period, as this would require early 
removal of the flap and therefore preclude collection of follow-up 
outcome data.  However, any flap failures (and associated clinical 
complications/events) will be recorded and reported.  
4.3 
Recruitment 
 
Participants will be recruited prospectively as they present as new patient cases 
to the ABMU Maxillofacial and Head & Neck cancer multidisciplinary team (MDT) 
clinics.  Once a potential patient participant has been given his/her diagnosis and 
it is confirmed by the principal investigator (PI) that he/she meets the inclusion 
criteria, clinic staff will provide the potential participant with an invitation letter 
introducing the study as well as a patient information sheet and consent form 
(explaining the available options of participating or refraining from the study). 
Patients will be allowed up to 24 hours to decide whether or not to participate as 
to avoid any impact/delay on the scheduling of their clinical treatment.  The PI 
will obtain written informed consent from willing participants. 
 
4.4 
Treatment pathway allocation 
 
Upon recruitment, provision of informed consent and collection of baseline data, 
as per standard clinical practice, the patient participant’s CT scan data is used to 
produce a virtual surgical plan for the mandibular resection and fibular free-flap 
reconstruction.  Once the clinically optimal reconstructive surgical plan is 
established by the surgeon and technician, the choice of surgical approach will 
be made in the routine clinical manner by the surgeon: Pathway A (pre-flexed 
customized mandibular reconstruction plate and cutting guides) or to pathway B 
(SLM customized mandibular reconstruction plate and cutting guides).  Both 

JaW PrinT Protocol v1.8_22.12.2017 
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treatment pathways are already part of routine/standard clinical practice at 
ABMUHB.  
  
The expected/planned patient numbers for this study are based upon the 
historical workload of the Oral and Maxillofacial Surgery department at 
Abertawe Bro Morgannwg University Health Board (ABMUHB) of 10-20 cases 
annually.  A recruitment period of 18 months with follow-up for 1 year fits 
within the time constraints of the postgraduate student investigator’s PhD 
timeline. 
4.5 
Study procedures 
4.5.1 Baseline Assessment 
 
This will be performed using a “baseline case report form” (CRF01), which will 
include past medical history (with attention to any history of previous 
radiotherapy to the head and neck region); a ‘systems review’ to screen for 
undisclosed comorbidities as well as smoking and alcohol status.  The patient 
participant’s comorbidity and performance status scores will also be recorded.  
The qualitative/subjective assessment of oral hygiene status (good/fair/poor) 
by a consultant oral and maxillofacial surgeon will also be recorded.  Collected 
from routine clinical preoperative tests, BMI and serum albumin concentration 
will be recorded as an indicator of nutritional status, along with a full blood 
count, urea and electrolytes and clotting screen. Baseline quality of life 
assessment will be performed using the University of Washington QoL 
Questionnaire v4 (Rogers et al., 2002)(Appendix A).  A baseline assessment of 
the participant’s perceived appearance and oral function will be evaluated using 
the short-form Derriford appearance scale (DAS24) (Carr et al., 2005) which is 
suited as a research of appearance in H&N cancers (Djan and Penington, 2013), 
and the Liverpool oral rehabilitation questionnaire(Pace-Balzan et al., 2006) 
(Appendix B) respectively.  Presurgical facial aesthetics will also be evaluated by 
means of assessing facial symmetry with stereophotogrammetry (clinical 3D 
photography in the medical illustration department) of the head and neck region.  
 
4.5.2 Perioperative/inpatient data collection 
 
During the inpatient phase of the participant’s medical treatment, all data will be 
recorded on the “inpatient case report form” (CRF02).   
 
To evaluate the presurgical dental occlusion (if occluding teeth present), a bite 
registration will be taken whilst the patient participant is anaesthetised.  These 
will be obtained using a viscoelastic silicone impression material. 
 
At surgery, overall time from knife to skin, to transferring the patient participant 
off the operating table will be recorded.  Furthermore the timings of specific 
landmarks of reconstructive components of surgery will be recorded:  
• Times at which mandibular osteotomies are first started (when 
mandibular cutting guides first touches mandible) and completed (when 
mandibular cutting guides removed) 

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14 
• Time of knife-to-skin for flap harvest 
• Time of flap detachment 
• Time of completing fixation of the plate in its final resting position (i.e. 
when completion of fixation to the residual mandible) 
• Time of completing arterial anastomosis 
 
To evaluate the impact of cutting guides on the fit of the bony flap, the surgeon 
will be asked to record the number of subsequent adjustments needed to the 
mandibular/fibular osteotomies, drill holes and/or the plate itself.  
 
To further evaluate the efficiency of either surgical technique (and any potential 
‘learning curve’ effect), the surgeon and scrub nurse will be asked to provide a 5-
point Likert scale rating for the following criteria at the end of the operation: 
• Ease of use 
• Confidence in performing the technique 
• Immediate satisfaction with reconstructive component of surgery 
 
In the immediate postoperative (inpatient) phase of recovery, dates of stay in the 
intensive care unit (ITU), high dependency unit (HDU) and/or the inpatient ward 
will be recorded, along with a final discharge date.  During this period, any 
postoperative complications are to be recorded if/as they occur. 
4.5.3 6 weeks follow up 
 
This will include reporting of any complications since discharge from hospital, as 
well as repetition of some data collected in the baseline assessment, using the “6 
weeks case report form” (CRF03).  Specific data to be collected includes: 
 
• 
Physical assessment (BMI, oral hygeine status, report on wound healing). 
• 
University of Washington QoL questionnaire. 
• 
Short-form Derriford appearance scale (DAS24). 
• 
Liverpool oral rehabilitation questionnaire. 
• 
Report on complications. 
• 
Stereophotogrammetry (3D photography) of the head and neck. 
4.5.3 6 months follow up 
 
The “6 months case report form” (CRF04) will be used to collect identical data to 
that collected at 6 weeks follow-up.  This follow up point is selected as in the case 
of cancer surgery, it is a standard follow-up point for assessment of signs of early 
disease recurrence.  For this reason, routine medical CT scanning to evaluate for 
disease recurrence is performed.  A 3D render of DICOM data from this clinical 
scan can be used to dimensionally and volumetrically compare the actual bony 
reconstruction with the preoperative plan, evaluating overall accuracy and 
precision of the reconstructive technique used.  Furthermore, CT assessment of 
bony union will be performed using a quantitative numerical rating score, 
adapted from Akashi et al.(Akashi et al., 2015) 
4.5.4 1 year follow up 
 

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15 
The “1 year care report form” (CRF05) will be used to collect identical data to 
that collected at 6 weeks follow-up.  Furthermore, in some cases routine clinical 
and radiographic (cone beam CT) dental assessment is performed 1 year 
postoperatively with a view to further dental rehabilitation (with dental 
implants in some patients).  From this dental assessment, we would aim to 
evaluate the clinician’s opinion (using a 5 point Likert scale) of the patient 
participant’s overall suitability for dental rehabilitation (if not already in place) 
with a variety of possible prosthetic solutions: 
• Simple dentures 
• Bridge 
• (Multiple) single tooth implants 
• Implant retained bridge 
• Implant retained dentures 
 
Dental radiology (cone beam CT) if used as part of this routine dental assessment 
will also be analysed to further evaluate any bony 
(dimensional/volumetric/healing) changes that occur over time.  
Post-surgical dental occlusion would clinically routinely be evaluated with a bite 
registration. This can be compared to the pre-surgical bite registration to 
evaluate the impact of the reconstructive surgery on dental occlusion.  
5.0 Risk management 
 
All clinical testing (physical, serological and radiological) performed within this 
study is within the remit of standard clinical care and therefore the study itself 
will not put the participant at additional risk of medical complications or side-
effects.  
 
For qualitative data collection, validated scoring tools will be used wherever 
possible.  
 
Both treatment pathways (A & B) observed in this study constitute routine 
surgical practice, with both techniques routinely used at ABMUHB.  Both are 
gold-standard treatment with subtle differences in technique; neither is 
experimental in any way.  Consequently any clinical complications can be dealt 
with in the normal clinical manner, regardless of the study. 
 
It will be made clear to participants from the start of their involvement that they 
are free to withdraw from the study at any time, without any reason and without 
any impact upon their standard of care.  Participants will be given the contact 
details for the study team, with their primary link being their centre’s PI who will 
supervise both their clinical care and data collection throughout the study 
period.   
 
Should clinical need require deviation from the study protocol and subsequent 
exclusion as to avoid confounding effects on study results, this will be disclosed 
and reported in the results.  Where it is felt that any data collected was 
unaffected by this process, it will be used wherever feasible.  

JaW PrinT Protocol v1.8_22.12.2017 
16 
6.0 Statistical analysis 
 
Data will be collated and analyzed using a statistical software package.  
Descriptive statistics will be used for baseline measures, categorical statistics for 
questionnaire outcome data, and relationships will be evaluated using tests of 
correlation and comparison, along with regressional analysis.  
7.0 Data management and quality control 
 
Data will be collated and stored in compliance with the Data Protection Act 1998 
and the ABMUHB data protection policy.  All data used beyond the participant’s 
immediate clinical environment will be anonymized accordingly.   
 
The study team will meet throughout the study with quarterly meetings to 
discuss and audit participant recruitment, data collection and any issues with the 
study protocol that may arise.  
 
All clinical records will remain within ABMUHB and stored within the patient’s 
clinical records in the normal manner.  Case Report Forms (CRFs) will be kept in 
the PI’s office in a locked cabinet.  To maintain anonymity from the earliest stage, 
recruited participants will be assigned a numeric identity code (instead of 
identifiable information such as age or date of birth) from the beginning.  Once 
anonymised, patient data will be stored electronically on a password-protected 
laptop computer and backed-up on an external hard drive on a daily basis.   
 
As anonymised raw data, CRFs will be physically stored for 15 years beyond the 
termination of the study by the PI (as the data custodian).  This strategy is based 
upon the recommendations of the ABMUHB research and development 
department (where local policy advises a data storage period of 5 to 15 years 
following termination of the study) and the UK Policy Framework for health and 
social care research(Health_Research_Authority, 2017).  Identifiable data that 
requires storage for clinical reasons alone, will only be stored in the usual NHS 
clinical manner according to NHS Wales policy 
(The_National_Assembly_For_Wales, 2000).  
8.0 Ethical considerations 
 
All treatments provided to study participants are normal, routine clinical 
practice at ABMUHB.   
 
Apart from HRQOL questionnaires and gaining informed written consent for the 
research study, all investigations/tests in this study are routine clinical practice 
at ABMUHB for patients undergoing jaw reconstruction surgery.  With regards to 
some specific tests: 
 

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17 
• Clinical 3D photography (stereophotogrammetry) is routinely available 
and commonly used for ABMUHB patients undergoing facial 
reconstructive surgery, although not routinely in all cases.  In this study, 
stereophotogrammetry (3D photos) will be obtained at baseline 
(preoperatively), as well as 6 weeks, 6 months and 1 year post 
operatively.  This has been discussed with the Medical Illustration 
department at Morriston Hospital.  
 
• Dental bite registrations are routinely performed after jaw reconstruction 
surgery in order to plan the patient for rehabilitation with dental 
prostheses.  In some, dental impressions and bite registrations are 
obtained prior to the surgery as well but not in all cases.  In this study, we 
plan to obtain dental impressions (immediately before surgery whilst 
under general anaesthesia) as well as several months later (as per routine 
practice).  The study team felt that collecting the preoperative dental 
impressions at the beginning of the participant’s surgery provides an 
opportunistic, efficient, safe and controlled setting in which to do this.  
 
The above items are explained fully (in lay terms) in the patient information 
sheet.  
9.0 Funding 
 
This study is funded externally through KESS, in partnership with Renishaw plc 
and the University of South Wales and includes the cost of 
consumables/equipment and other incidental costs relating to the study itself.  
 
Knowledge Economy Skills Scholarships (KESS) is a pan-Wales higher level skills 
initiative led by Bangor University on behalf of the HE sector in Wales. It is part 
funded by the Welsh Government’s European Social Fund (ESF) convergence 
programme for West Wales and the Valleys.  
10.0 Study timeline 
 
 
The study timeline is illustrated in the following Gantt chart (figure 2).  

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11.0 References 
 
AKASHI, M., HASHIKAWA, K., KAKEI, Y., SAKAKIBARA, A., HASEGAWA, T., 
MINAMIKAWA, T. & KOMORI, T. 2015. Sequential evaluation for bone 
union of transferred fibula flaps in reconstructed mandibles: panoramic 
X-ray versus computed tomography. Int J Oral Maxillofac Surg, 44, 942-
947. 
ALLUM, S. 2008. Immediately loaded full-arch provisional implant restorations 
using CAD/CAM and guided placement: maxillary and mandibular case 
reports. . Br Dent J., 204, 377-381. 
BROWN, J., BARRY, C., HO, M. & SHAW, R. 2016. A new classification for 
mandibular defects after oncological resection. Lancet Oncol, 17, e23-30. 
BUTTERWORTH, C., MCCAUL, L. & BARCLAY, C. 2016. Restorative dentistry and 
oral rehabilitation: United 
Kingdom National Multidisciplinary Guidelines. JLO, 130, 41-44. 
CANCER_RESEARCH_UK Oral cancer incidence statistics. 
CARR, T., MOSS, T. & HARRIS, D. 2005. The DAS24: A short form of the Derriford 
Appearance Scale (DAS59) to measure individual responses to living with 
problems of appearance. British Journal of Health Psychology, 10, 285-298. 
CHEN, S., CHEN, H., HORNG, S., TAI, H., HSIEH, J., YEONG, E., CHENG, N., HSIEH, T., 
CHIEN, H. & TANG, Y. 2014. Reconstruction for osteoradionecrosis of the 
mandible: superiority of free iliac bone flap to fibula flap in postoperative 
infection and healing. Ann Plast Surg, 73, 18-26. 
DJAN, R. & PENINGTON, A. 2013. A systematic review of questionnaires to 
measure the impact of appearance on quality of life for head and neck 
cancer patients. J Plast Reconstr Aesthet Surg, 66, 647-659. 
GIL, R., ROIG, A., ARRANZ OBISPO, C., MORLA, A., MARTI PAGES, C. & LLOPIS 
PEREZ, J. 2015. Surgical planning and microvascular reconstruction of the 
mandible with a fibular flap using computer-aided design and rapid 
prototype modelling, and precontoured titanium reconstruction plates: a 
prostpective study. . Br J Oral Maxillofac Surg, 53, 49-53. 
Quarter 
1st  
2nd  
3rd  
4th 
(1 yr) 
5th  
6th  
7th  
8th 
(2 
yrs) 
9th  
10th  
End of Study 
Participants 
recruited 
 
 
 
 
- 
Unblinding of 
study participants 
 
- 
Dissemination of 
data 
 
- 
Peer-reviewed 
publication 
 
- 
Presentation 
Participants 
complete 
study 
 
 
Landmark 
events 
Study 
team 
meet 
Study 
team 
meet 
Study 
team 
meet 
Study 
team 
meet 
Study 
team 
meet 
 
First 
particip
ant 
comple
tes 
study 
Study 
team 
meet 
Study 
team 
meet 
Study 
team 
meet 
Study 
team 
meet 
Study 
team 
meet 
 
Last 
particip
ant 
comple
tes 
study 
Figure 2.  Gantt chart illustrating the study timeline 

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HEALTH_RESEARCH_AUTHORITY 2017. UK Policy Framework for health and 
social care research v3.3. 
KOKOSIS, G., SCHMITZ, R., POWERS, D. & ERDMANN, D. 2016. Mandibular 
Reconstruction Using the Free Vascularized Fibula Graft: An Overview of 
Different Modifications. Arch Plast Surg, 43, 3-9. 
LYONS, A. & BRENNAN, P. 2014. Osteoradionecrosis a new classification. Br J 
Oral Maxillofac Surg, 52, e64-e65. 
NICR 2016. Northern Ireland Cancer Registry, Queens University Belfast, 
Incidence by stage 2010-2014. 
NUTTING, C. 2016. Radiotherapy in head and neck cancer management: United 
Kingdom National Multidisciplinary Guidelines. JLO, 130, 66-67. 
PACE-BALZAN, A., CAWOOD, J., HOWELL, R., BUTTERWORTH, C., LOWE, D. & 
ROGERS, S. 2006. The further development and validation of the 
Liverpool Oral Rehabilitation Questionnaire: A cross-sectional survey of 
patients attending for oral rehabilitation and general dental practice. Int J 
Oral Maxillofac Surg, 35, 72-78. 
PARK, S., LEE, D., LEE, J., KIM, Y., KIM, L. & NOH, G. 2016. Stability of the 
permanently bent plates used in mandibular reconstructive surgery. 2016 
38th Annual International Conference of the IEEE Engineering in Medicine 
and Biology Society (EMBC). Orlando, FL. 
PARTHASARATHY, J. 2014. 3D modeling, cusom implants and its future 
perspectives in craniofacial surgery. Annals of Maxillofacial Surgery, 4, 9-
18. 
ROGERS, S., GWANNE, S., LOWE, D., HUMPRHIS, G., YUEH, B. & WEYMULLER, E. 
2002. The addition of mood and anxiety domains to the University of 
Washington Quality of Life Scale. Head & Neck, 24, 521-529. 
STEINBACHER, D. 2015. Three-Dimensional Analysis and Surgical Planning in 
Craniomaxillofacial Surgery. J Oral Maxillofac Surg, 73, S40-S56. 
SU, Y. 2017. Three-Dimensional Printing of Patient-Specific Titanium Plates in Jaw 
Surgery: A Pilot Study [Online]. 
https://clinicaltrials.gov/ct2/show/NCT03057223: U.S. National 
Institutes of Health.  [Accessed 2/4/17 2017]. 
TARSITANO, A., BATTAGLIA, S., CRIMI, S., CIOCCA, L., SCOTTI, R. & MARCHETTI, 
C. 2016. Is a computer-assisted design and computer-assisted 
manufacturing method for mandibular reconstruction economically 
viable? J Craniomaxillofac Surg, 44, 795-799. 
THE_NATIONAL_ASSEMBLY_FOR_WALES 2000. For the record - Managing 
Records in NHS Trusts and Health Authorities. Welsh Health Circular. 
WANG, Y., ZHANG, S., FAN, S., ZHANG, D., HUANG, Z., CHEN, W., YE, J. & LI, J. 2016. 
Mandibular reconstruction with the vascularised fibula flap: comparison 
of virtual planning surgery and conventional surgery. . int J Oral 
Maxillofac Surg, 45, 1400-1405. 

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12.0 Appendices 
Appendix A 
 

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Appendix B 
 
 

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