cancers

Article
Quality of Life after Mandibular Reconstruction Using Free
Fibula Flap and Customized Plates: A Case Series
and Comparison with the Literature
Jorge Pamias-Romero 1,2 , Manel Saez-Barba 1,2 , Alba de-Pablo-García-Cuenca 1,2 , Pablo Vaquero-Martínez 1,2 ,
Joan Masnou-Pratdesaba 3 and Coro Bescós-Atín 1,2,4, *

1 Service of Oral and Maxillofacial Surgery, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona
Hospital Campus, Passeig Vall d’Hebron 119-129, E-08035 Barcelona, Spain;
[email protected] (J.P.-R.); [email protected] (M.S.-B.);
[email protected] (A.d.-P.-G.-C.); [email protected] (P.V.-M.)
2 CIBBM-Nanomedicine, Noves Tecnologies i Microcirurgia Craniofacial, Vall d’Hebron Institut de
Reserca (VHIR), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus,
E-08035 Barcelona, Spain
3 Radiology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus,
Passeig Vall d’Hebron 119-129, E-08035 Barcelona, Spain; [email protected]
4 Unitat Docent Vall d’Hebron, Facultat de Medicina UAB, Universitat Autònoma de Barcelona,
E-08035 Barcelona, Spain
* Correspondence: [email protected]

Simple Summary: The health-related quality of life was evaluated in 23 patients undergoing
mandibular reconstruction with free fibula flap and titanium customized plates. A computer-aided
Citation: Pamias-Romero, J.; design and computer-aided manufacturing technology were used. The University of Washington
Saez-Barba, M.; Quality of Life questionnaire for head and neck cancer patients is a widely used and validated
de-Pablo-García-Cuenca, A.; tool, which was self-completed by the patients after 12 months of surgery. In the 12 single question
Vaquero-Martínez, P.; domains, the highest scores were obtained in the domains of taste, shoulder function, anxiety, and
Masnou-Pratdesaba, J.; Bescós-Atín, pain. The lowest scores corresponded to chewing, appearance, saliva, and mood. The global quality
C. Quality of Life after Mandibular of life was rated as good, very good, or outstanding by 81% of patients. The present results compared
Reconstruction Using Free Fibula favorably with previous studies of mandibular reconstruction using the same questionnaire published
Flap and Customized Plates: A Case
in literature.
Series and Comparison with the
Literature. Cancers 2023, 15, 2582.
Abstract: A single-center retrospective study was conducted to assess health-related quality of life
https://doi.org/10.3390/
(HRQoL) in 23 consecutive patients undergoing mandibular reconstruction using the computer-aided
cancers15092582
design (CAD) and computer-aided manufacturing (CAM) technology, free fibula flap, and titanium
Academic Editors: Remco De Bree, patient-specific implants (PSIs). HRQoL was evaluated after at least 12 months of surgery using
Carlo Lajolo, Gaetano Paludetti and the University of Washington Quality of Life (UW-QOL) questionnaire for head and neck cancer
Romeo Patini
patients. In the 12 single question domains, the highest mean scores were found for “taste” (92.9),
Received: 27 March 2023 “shoulder” (90.9), “anxiety” (87.5), and “pain” (86.4), whereas the lowest scores were observed for
Revised: 18 April 2023 “chewing” (57.1), “appearance” (67.9), and “saliva” (78.1). In the three global questions of the UW-
Accepted: 28 April 2023 QOL questionnaire, 80% of patients considered that their HRQoL was as good as or even better
Published: 30 April 2023 than it was compared to their HRQoL before cancer, and only 20% reported that their HRQoL had
worsened after the presence of the disease. Overall QoL during the past 7 days was rated as good,
very good or outstanding by 81% of patients, respectively. No patient reported poor or very poor
QoL. In the present study, restoring mandibular continuity with free fibula flap and patient-specific
Copyright: © 2023 by the authors.
titanium implants designed with the CAD-CAM technology improved HRQoL.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
Keywords: quality of life; mandibular reconstruction; free fibula flap; patient-specific implant; plates;
conditions of the Creative Commons University of Washington Quality of Life Questionnaire
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

Cancers 2023, 15, 2582. https://doi.org/10.3390/cancers15092582 https://www.mdpi.com/journal/cancers

Cancers 2023, 15, 2582 2 of 13

1. Introduction
Refinements in surgical techniques have led to significant improvement in oncological,
functional, and aesthetic outcomes in oral cancer. Currently, one of the main goals of
mandibular defect reconstruction is to provide patients with the best possible health-
related quality of life (HRQoL) [1]. Assessment of results of treatment is a key aspect for
the accurate selection of patients and the choice of the most appropriate reconstruction
technique [2,3].
The microvascular or free fibula flap, originally described by Hidalgo et al. [4] in 1989,
is considered the “gold standard” flap for the reconstruction of mandibular defects. More re-
cently, the use of computer-aided design (CAD) and computer-aided manufacturing (CAM)
(CAD-CAM) technology [5] promoted a paradigm shift in the diagnostic and therapeutic
approach of defects in the maxillofacial region. Further introduction of 3D-printed titanium
using direct metal laser sintering (DMLS) as an additive manufacturing technique allowed
the development of custom-made plates or patient-specific implants (PSIs), improving
accuracy and efficiency in mandibular reconstruction procedures. PSIs could provide the
missing link in the digital flow process for mandibular reconstruction, and in doing so
they would avoid potential shortcomings that are inherent to pre-modelled reconstruction
plates and improve final precision [6,7]. Thus, computer-generated PSIs would be the next
logical step in the digital planning and design flow rather than an independent device, as
they represent the metallic cast that accurately reflects the surface of the reconstructed bone
compounds and keeps geometry stable [8].
The evidence of PSI printed titanium implants for reconstruction of mandibular conti-
nuity defects is scarce. In a systematic review of the literature of 31 clinical studies with
139 patients, benefits identified included finite element analysis of the digital design, di-
mensional accuracy, shorter duration of surgery, augmenting dental/masticatory function,
and capacity for dental implant rehabilitation, although the evidence predominantly was
low level and at moderate-to-high risk of bias [9]. The published articles provided valuable
evidence of the use of 3D-printed titanium PSIs with reported benefits seemingly outweigh-
ing their limitations and of the important role to be played by such implants in mandibular
reconstruction for improving patient outcomes. However, in none of the studies included
in the review was HRQoL evaluated. Improvements in different domains of HRQoL and
patient satisfaction after free fibula flap reconstruction of segmental mandibulectomy have
been rarely reported [10–15], but as far as we are aware, no studies have specifically as-
sessed HRQoL outcomes in the setting of mandibular reconstruction using free fibula flaps
combined with 3D-customized titanium plates.
Therefore, the aim of this study was to assess the impact of using free fibula flaps
associated with CAD-CAM technology and PSI titanium plates on HRQoL in patients with
mandibular pathology undergoing reconstruction for continuity defects.

2. Materials and Methods

2.1. Study Design and Participants
This was a retrospective study of all consecutive patients undergoing mandibular
reconstruction with free fibula flaps using CAD-CAM technology and titanium PSI for the
repair of mandibular defects of malignant or benign etiology operated on at the Service
of Oral and Maxillofacial Surgery of Hospital Universitari Vall d’Hebron in Barcelona
(Spain) between October 2015 and July 2019. Inclusion criteria were as follows: adult
patients scheduled for primary or secondary mandibular reconstruction due to benign
or malignant pathology, whether diseases had been treated previously or not; use of
CAD-CAM technology including virtual planning, mandibular resection, fibula cutting
guides for modelling, and PSI; use of free fibula flap for the reconstruction of the mandibular
bone defect; and follow-up for at least 1 year after surgery. Patients were excluded if one or
several components of the CAD-CAM technology were lacking (such as virtual planning,
mandibular resection guides, fibula cutting guides for modelling), PSI was not used, or the
free fibula flap failed.
 Cancers 2023, 15, x FOR PEER REVIEW 3 of 13

Cancers 2023, 15, x FOR PEER REVIEW 3 of 13

mandibular resection guides, fibula cutting guides for modelling), PSI was not used, or
Cancers 2023, 15, 2582 the free fibula flap failed. 3 of 13
mandibular resection guides, fibula cutting guides for modelling), PSI was not used, or
The study protocol was approved by the Clinical Research Ethics Committee of
the free fibula flap failed.
Hospital Universitari Vall d’Hebron (codes PR(AG)93/2016, approval date 1 March
The study protocol was approved by the Clinical Research Ethics Committee of
2016) (Barcelona, Spain). Written informed consent was obtained from all participants.
The study
Hospital protocolVall
Universitari wasd’Hebron
approved(codes
by thePR(AG)93/2016,
Clinical Research Ethics Committee
approval date 1 Marchof Hos-
2016)pital Universitari
(Barcelona, Vall
Spain). d’Hebron
Written (codes
informed PR(AG)93/2016,
consent was obtainedapproval
from alldate 1 March 2016)
participants.
2.2. Protocol for Mandibular Reconstruction with Free Fibula Flap
(Barcelona, Spain). Written informed consent was obtained from all participants.
Briefly,
2.2. Protocol the presurgical
for Mandibular stage included
Reconstruction the following
with Free Fibula Flapsteps: (a) virtual planning (image
2.2. Protocol segmentation,
processing, for Mandibular resection,
Reconstruction withand
cutting, Freereconstruction
Fibula Flap planning); (b) CAD (man-
Briefly, the presurgical stage included the following steps: (a) virtual planning (image
dibular resection
Briefly, guides, fibula
the presurgical stagecutting guides,
included custom-made
the following steps:reconstruction plates, (im-
(a) virtual planning and
processing, segmentation, resection, cutting, and reconstruction planning); (b) CAD (man-
custom-made prostheses); and (c) manufacturing stage (polyamide models
age processing, segmentation, resection, cutting, and reconstruction planning); (b) CAD from Stereo-
dibular resection guides, fibula cutting guides, custom-made reconstruction plates, and
Litography (STL)
(mandibular file format
resection forfibula
guides, resection andguides,
cutting cuttingcustom-made
guides for thereconstruction
mandible and plates,
fibula,
custom-made prostheses); and (c) manufacturing stage (polyamide models from Stereo-
STL custom-made
and model for theprostheses);
mandible, 3D andprinting and manufacturing
(c) manufacturing titaniummodels
stage (polyamide platesfrom
[PSI],Stere-
and
Litography (STL) file format for resection and cutting guides for the mandible and fibula,
custom-made(STL)
oLitography polyetheretherketone [PEEK]
file format for resection andprosthesis) (Figure
cutting guides for 1).
the Custom-made plates
mandible and fibula,
STL model for the mandible, 3D printing and manufacturing titanium plates [PSI], and
weremodel
STL manufactured using direct
for the mandible, 3Dmetal laserand
printing sintering using an EOSINT
manufacturing titaniumM270 system
plates [PSI],(EOS
and
custom-made polyetheretherketone [PEEK] prosthesis) (Figure 1). Custom-made plates
GmbH, Electropolyetheretherketone
custom-made Optical Systems Company, [PEEK]Munich, Germany).
prosthesis) (Figure 1). Custom-made plates
were manufactured using direct metal laser sintering using an EOSINT M270 system (EOS
were manufactured using direct metal laser sintering using an EOSINT M270 system (EOS
GmbH, Electro Optical Systems Company, Munich, Germany).
GmbH, Electro Optical Systems Company, Munich, Germany).

Figure 1. Patient-specific implant (PSI): a) screw hole with thread; it contains information on the
screw angle;
Figure b) an enveloping
1. Patient-specific design
implant to help
(PSI): placehole
(a) screw the plate
within the optimal
thread; position;
it contains and c) patient’s
information on the
Figure 1. Patient-specific implant (PSI): a) screwPositioning
hole with thread; it contains information on thebone
screw angle; (b) an enveloping design to help place the plate in the optimal position; andhealthy
information code (left). PEEK prosthesis. of the PSI in the remaining (c) patient’s
screw angle; b) an enveloping design to help place the plate in the optimal position; and c) patient’s
(right).
information
information codecode (left).
(left). PEEKPEEK prosthesis.Positioning
prosthesis. Positioningof
of the
the PSI
PSI in
inthetheremaining
remaining healthy bone
healthy (right).
bone
(right). The surgical procedure (Figure 2) included the following steps: (1) mandibular resec-
The surgical procedure (Figure 2) included the following steps: (1) mandibular re-
tion using
section resection
using guides;
resection (2) modelling
guides; (2) modelling of the
offibula flap using
the fibula cutting
flap using guidesguides
cutting and place-
and
The surgical procedure (Figure 2) included the following steps: (1) mandibular resec-
ment of immediate implants (if required); (3) plate binding in the donor
placement of immediate implants (if required); (3) plate binding in the donor zone before zone before sec-
tion using resection guides; (2) modelling of the fibula flap using cutting guides and place-
tioning thethe
sectioning vascular
vascularpedicle; (4)(4)positioning
pedicle; positioningand andbinding
bindingofofthe
theflap
flap in
in the mandibular
ment of immediate implants (if required); (3) plate binding in the donor zone before sec-
defect; (5)
defect; (5) microsurgical
microsurgical anastomosis;
anastomosis; (6) (6) positioning
positioning andand binding
binding of the PEEK prosthesis
tioning the vascular pedicle; (4) positioning and binding of the flap in the mandibular
with miniplates
with miniplates and
and screws
screws (if
(if required);
required); andand (7)
(7) final
final repositioning
repositioning of of soft
soft tissues
tissues and
and
defect; (5) microsurgical anastomosis; (6) positioning and binding of the PEEK prosthesis
wound closure.
wound closure. All plates were customized
customized for each each patient.
patient. In all cases, PSI
PSI modelling
modelling
with miniplates and screws (if required); and (7) final repositioning of soft tissues and
was performed
was performed inin the
the limb
limb while
while the the flap
flap remained
remained vascularized.
vascularized.
wound closure. All plates were customized for each patient. In all cases, PSI modelling
was performed in the limb while the flap remained vascularized.

Figure 2. Details
Figure Detailsofofthe surgical
the procedure:
surgical a) mandibular
procedure: resection;
(a) mandibular b) fibula
resection; (b) flap modelling;
fibula c) plate
flap modelling;
binding
(c) in the donor
plate binding in thezone; andzone;
donor d) positioning and binding
and (d) positioning andofbinding
the flap of
in the
the flap
mandibular defect.
in the mandibular
Figure 2. Details of the surgical procedure: a) mandibular resection; b) fibula flap modelling; c) plate
defect.
binding in the donor zone; and d) positioning and binding of the flap in the mandibular defect.
Anatomical models, surgical guides, and custom-made plates were designed using
the specific design software “D-matic Medical ® 10.0 by Materialise”. Biomodels were
manufactured directly using a rapid prototyping machine that used tridimensional solid
Cancers 2023, 15, 2582 4 of 13

support technology (Stratasys, Eden Prairie, MN, USA). Plates were manufactured using
direct sintering with metal laser using an EOSINT M270 system (Electro-Optical Systems,
GmbH, Munich, Germany).

2.3. Evaluation and Follow-up

Patients were visited postoperatively by the same investigator (J.P.-R.) during their stay
in the hospital, after 1 week of hospital discharge, and at 1, 3, 6, and 12 months thereafter.
Postoperative complications were evaluated using the Clavien–Dindo classification [16].
Complications related to PSI (presence or absence of intraoral or extraoral exposure) and
the PEEK prosthesis (stability) were evaluated clinically. Prosthesis failure was determined
when the prosthesis was extra-orally exposed and had to be removed. Other variables
were evaluated by orthopantomography and computed tomography (CT) scan performed
at least 6 months after mandibular reconstruction, including merging of fibula fragments
(between different fibula fragments and between the fibula fragments and the remaining
mandible), stability of screws, plate adjustment (defined as the presence of close contact
between the PSI, the fibula, and the mandible), and presence or absence of PSI fracture.
Esthetical evaluation included photographs of the patients before and after surgery.
Additionally, pre- and post-surgical panoramic radiographs and 3D-cone-beam computed
tomography (CBCT) scans were acquired, and image superposition was used to assess the
correlation between virtual planning and the results obtained.

2.4. Health-Related Quality of Life

At least 12 months after surgery, patients were contacted by phone and were appointed
for a face-to-face visit to assess HRQoL. After signing the informed consent, they completed
the University of Washington Quality of Life Questionnaire (UW-QOL v4) for head and
neck cancer patients [17,18]. A Spanish validation version of the UW-QOL instrument was
used [19]. The UW-QOL is a self-administered questionnaire specifically for head and neck
cancer patients that measures health and quality of life (QoL) over the past 7 days. The
questionnaire includes 12 single question domains (pain, appearance, activity, recreation,
swallowing, chewing, speech, shoulder function, taste, saliva, mood, and anxiety) and
3 global questions, one about how patients feel relative to before they developed their
cancer, one about their HRQoL, and one about their overall QoL. A free-text box is also
included, so that the patient may write down any other comment he or she wishes to
make on QoL that had not come forth in the previous questions. Domains are scaled from
0 (worst possible response) to 100 (best possible response). Domain scores include the
mean (SD), the percentage of patients selecting the best possible response (100), and the
percentage of patients choosing each domain. The domains can also be ranked by order.

2.5. Study Outcomes

The primary outcome was HRQoL assessed by means of the UW-QOL questionnaire
at least 12 months after mandibular reconstruction using free fibula flap and titanium PSI
based on the CAD-CAM technology. Secondary outcomes were complications related to
the PSI and the PEEK prosthesis.

2.6. Statistical Analysis

Categorical variables are expressed as frequencies and percentages, and continuous
variables are expressed as mean and standard deviation (SD) or median and interquartile
range (IQR) (25th–75th percentile) or range (maximum–minimum). The chi-square test
or the Fisher’s exact test were used for the comparison of categorical variables, and the
Student’s t-test or the Mann–Whitney U test were used for the comparison of quantitative
variables according to conditions of application. Statistical significance was set at p < 0.05.
Cancers 2023, 15, 2582 5 of 13

3. Results
3.1. Clinical and Surgical Characteristics
The study population consisted of 23 patients (56.5% men) with a mean age of
52.8 (14.2) years. Fifteen patients (65.2%) had malignant tumors and locally advanced disease.
Four patients had received neoadjuvant radiotherapy or combined radiochemotherapy.
Central defects according to the classification of Boyd et al. [20] were the most common
(56.5%). PSIs were inserted in the occlusal zone in 15 patients and in the basal zone in
the remaining 8. The skin flap was used as an internal intraoral layer in 20 patients, as an
external skin layer in 2, and both as internal and external layers in 1. One patient required
bilateral nasolabial flaps because of a defect that involved a large amount of soft tissue.
Arterial anastomosis was most frequently performed with the facial artery and venous
anastomosis with the thyrolinguofacial trunk. Osseointegrated dental implants were placed
immediately in 2 patients and in a second step in 3.
The mean (SD) ischemia time was 122 (4) minutes, and the mean duration of surgery
was 10.2 (1.4) hours. Immediate postoperative complications were recorded in 11 patients,
which were classified as grade I in 7 and grade IIIb in 4 (2 cases of cervical bleeding and
2 of compartment syndromes in the donor limb). These 4 patients were reoperated under
general or local anesthesia. In all cases, complications were solved. The mean length
of hospital stay was 23 days (range 10–55 days), without significant differences between
patients without and with complications (17 [4.4] vs. 26.3 [12.9] days, p = 0.062).
The microvascular fibula flap survived in 100% of the patients. Postoperatively,
12 patients received chemotherapy and/or radiotherapy adjuvant treatment. Table 1 shows
the main clinical characteristics of patients and surgery-related data.

Table 1. Clinical and surgical data of the 23 patients included in the study.

Variables Number (%)

Men/women 13 (56.5)/10 (43.5)
Age, years, mean (SD) 52.8 (14.2)
Type of pathology
Malignant 15 (65.2)
Benign 8 (34.8)
Histological type
Oral squamous cell carcinoma 10 (43.5)
Odontogenic tumors (benign and malignant) 7 (30.4)
Sarcoma 2 (8.7)
Secondary deformity 1 (4.3)
Osteoradionecrosis 1 (4.3)
Infiltrating verrucous carcinoma 1 (4.3)
TNM stage of malignant tumors 15 (65.2)
T4N0 9 (39.1)
T4N1 3 (13.0)
T4N2a 3 (13.0)
Neoadjuvant treatment (RT or QT/RT) 4 (17.4)
Mandibular defect
Type C (LCL, CL, LC, and CH) 13 (56.5)
Type H 4 (17.4)
Type L 6 (26.1)
Cancers 2023, 15, 2582 6 of 13

Table 1. Cont.

Variables Number (%)

Fibula skin flap positioning
Intraoral internal 20 (87.0)
Extraoral external 3 (13.0)
Closure of the lower limb defect
Direct 3 (13.0)
Skin graft 20 (87.0)
Postoperative complications (Clavien–Dindo)
Grade I 7 (30.4)
Grade IIIb 4 (17.4)
Adjuvant treatment 12 (52.2)
SD: standard deviation; TNM: tumor node metastasis; T: tumor; N: node; RT: radiotherapy; CT: chemotherapy;
type C: defect consisting of the entire central segment containing four incisors and two canines; LCL: lateral
defect-to-bilateral angle defect; CL, LC: lateral angle-to-bilateral canines; CH: lateral segment defect including
the condyle and central defect; type H: lateral defect of any length, including the condyle but not significantly
crossing the midline; type L: defect of the same type without the condyle.

Image superposition studies showed a high correlation (greater than 92% in most
patients) between preoperative virtual surgical plan and the results obtained.
The mean length of follow-up was 26 months (range 12–50 months). Twenty-two
patients (95.6%) were alive at 12 months after surgery. One patient developed a recurrence
of their oral cancer and the other patient died due to cancer progression.

3.2. Health-Related Quality of Life

Twenty-one patients (91.3%) completed the UW-QOL questionnaire, after a median of
27 months (IQR 19–41 months) after primary surgery. Two patients did not complete the
questionnaire; one patient had an advanced stage of the oral cancer due to recurrence, and
the other patient had died.
Table 2 shows the results obtained in the 12 single question domains of the UW-QOL
questionnaire. The highest mean scores were found for “taste” (92.9 [13.1]), “shoulder”
(90.9 [18.4]), “anxiety” (87.5 [24.5]), and “pain” (86.4 [12.8]). In contrast, the lowest mean
scores were observed in the domains of “chewing” (57.1 [39.6]), “appearance” (67.9 [19.6]),
and “saliva” (78.1 [27.3]).

Table 2. Results obtained in the 12 single question domains of the UW-QOL questionnaire.

% Best
Patients Mean Median Importance Rank
Domain Score
Number (SD) (Range) of Domain * Order
(of 100)
Pain 21 86.9 (12.8) 75 (75–100) 48 10 6
Appearance 21 67.9 (19.6) 75 (25–100) 10 48 2
Activity 21 83.3 (16.5) 75 (50–100) 43 29 4
100
Recreation 21 84.5 (20.1) 52 5 7
(25–100)
100
Swallowing 21 84.5 (20.1) 67 10 6
(30–100)
Chewing 21 57.1 (39.6) 50 (0–100) 38 62 1
Speech 20 83.0 (19.5) 85 (30–100) 50 43 3
100
Shoulder 21 90.9 (18.4) 76 5 7
(30–100)
Cancers 2023, 15, 2582 7 of 13

Table 2. Cont.

% Best
Patients Mean Median Importance Rank
Domain Score
Number (SD) (Range) of Domain * Order
(of 100)
100
Taste 21 92.9 (13.1) 76 10 6
(70–100)
100
Saliva 21 78.1 (27.3) 52 24 5
(30–100)
87.5
Mood 20 82.6 (21.6) 50 24 5
(25–100)
100
Anxiety 20 87.5 (24.5) 70 10 6
(25–100)
* This asks about which three domain issues were the most important during the past 7 days, and results expressed
as the percentage of patients choosing each domain.

The highest percentages of patients selecting the best possible response (100) were
76% for “shoulder” and “taste”, 70% for “anxiety”, 67% for “swallowing”, and 52% for
“recreation” and “saliva”. The lowest percentages corresponded to 10% for “appearance”,
38% for “chewing”, and 43% for “activity”.
In relation to importance of domain, “chewing”, “appearance”, and “speech” were
selected by 62%, 48%, and 43% of patients, respectively. “Recreation” and “shoulder” were
chosen by only 5% of patients, respectively. The rank order of domains was consistent with
the importance already assigned to the different domains.
In the three global questions of the UW-QOL questionnaire (Table 3), 80% of patients
considered that their HRQoL was as good as or even better than it was compared with
their HRQoL before cancer, and only 20% reported that their HRQoL had worsened after
the presence of the disease. Additionally, HRQoL and overall QoL during the past 7 days
were rated as good, very good, or outstanding by 81% of patients, respectively. No patient
reported poor or very poor QoL.

Table 3. Responses to three global questions of the UW-QOL questionnaire.

Questions Mean (SD) % Best Scores *

A. Health-related QoL compared to month before had cancer 60.0 (34.8) 80
B. Health-related QoL during the past 7 days 73.3 (22.2) 81
C. Overall QoL during the past 7 days 71.4 (22.4) 81
Key to ratings: A: (0) much worse, (25) somewhat worse, (50) about the same, (75) somewhat better, (100) much
better. B: (0) very poor, (20) poor, (40) fair, (60) good, (80) very good, (100) outstanding. C: (0) very poor, (20) poor,
(40) fair, (60) good, (80) very good, (100) outstanding. * Best scores: A = % of scoring 50, 75, or 100; B and C = %
scoring 60, 80, or 100.

Thirteen patients (61.9%) provided an answer in the free-text box of the questionnaire.
Four patients explicitly stated their satisfaction with the outcomes of surgery, but 9 patients
would like to undergo dental rehabilitation for improving chewing and aesthetic functions.
Other complaints were the possibility of a secondary reconstruction to improve appearance
(3 cases), reduction in the extension of mouth opening (1 case), decreased saliva output
and taste alterations (1 case), paresthesia (1 case), and delayed wound healing and/or
paresthesia in the graft area of the lower limb.

3.3. PSI-Related Complications

At 6 months after surgery, 22 out of 23 patients (95.6%) underwent clinical and radi-
ological assessment. One patient moved to another city and was lost to follow-up. The
fibula fragments were properly consolidated in all 22 patients. In 19 patients (86.4%), PSI-
related complications did not occur, whereas complications were recorded in the remaining
Cancers 2023, 15, 2582 8 of 13

3 patients (13.6%). Extraoral and intraoral exposure of the PSI was clinically documented
in 2 patients, and in both cases, the plate was removed, but the segments of the microvas-
cularized fibula flap were found to be well consolidated. In the remaining patient, there
was a lack of consolidation between the fibula and the remaining mandible, with screw
instability and plate mobility. In this patient, removal of both the plate and the remaining
segment of the mandibular ramus were performed.

3.4. PEEK Prosthesis-Related Complications

A PEEK prosthesis for the reconstruction of the mandibular inferior border was
performed in 14 patients (60.9%) (immediate reconstruction in 13 cases and at a later stage
in 1). In 6 patients (42.8%), the prosthesis became exposed and had to be removed. Five
of these 6 patients had received radiotherapy (RT) in the neoadjuvant or adjuvant setting.
Removal of the PEEK prosthesis was significantly more common in patients treated with
RT than in those who had not received RT (83.3% vs. 16.7%, p = 0.031).

4. Discussion
This study shows that in patients undergoing extensive mandibular resection leading
to wide mandibular continuity defects, the use of a surgical procedure based on CAD-
CAM technology with free fibula flap and titanium PSI was associated with high scores
in the UW-QOL questionnaire at least 12 months after surgery. In the 12 single question
domains, mean scores were higher than 80 (with 100 being the highest possible response)
in 9 domains (75%), with only 3 domains scoring below 80%. In the three global questions
of the UW-QOL instrument, HRQoL before diagnosis of malignancy and overall QoL in
the previous 7 days, high scores were achieved, as 80% and 81% of patients selected the
options of much better and good, very good, or outstanding, respectively.
Assessment of QoL is a clinically relevant outcome in monitoring the treatment suc-
cess and the sequelae of illness in patients with oral cancer. Subjective measures of health
status can be evaluated by generic or disease-specific instruments, but due to the complex
anatomy of the oral cavity, it is desirable to use specific HRQoL measures. These measures
are more sensitive in assessing the impact of oral conditions on daily life activities. The
relatively large number of questionnaires that are specific for diseases of the oral cavity (e.g.,
14-item Oral Health Impact Profile [OHIP-14], Oral Impacts on Daily Performances [OIDP],
Oral Health-Related Quality of Life [OHRQoL], European Organization for Research and
Treatment of Cancer Head and Neck cancer questionnaire [EORTC-H&N35]) [21], under-
scores the fact that there is no gold standard tool. The UW-QOL instrument is one of
the most used and validated questionnaires for patients with head and neck cancer and
has shown good psychometric properties that have been specifically developed for this
pathology [17,18]. Furthermore, the incorporation of importance-rating domains makes
UW-QOL unique among head and neck cancer instruments [22,23]. The Spanish version of
this questionnaire was validated by Nazar et al. [19] in 2010. In fact, the following character-
istics of the UW-QOL questionnaire stand out: (1) it provides a specific “appearance” item
related to disfigurement; (2) it allows for the evaluation of appearance problems through
“recreation”, “anxiety”, and “mood” domains; and (3) it is quick and simple for patients to
complete (it may take 5 minutes) and is easy to process.
Despite the advantages of the UW-QOL questionnaire, few studies have used this
instrument for assessing HRQoL after mandibular reconstruction using free fibula flaps.
In 2019, Petrovic et al. [24] conducted a systematic review of the literature and found only
6 studies in which QoL outcomes following mandible reconstruction using free fibula flap
had been evaluated using the UW-QOL questionnaire. All these studies were retrospective
case series. Apart from these 6 publications, we did not find any subsequent publication of
the use of this questionnaire after free fibula flap reconstruction of the mandible. Therefore,
the present results are compared with data reported in these 6 studies [14,15,25–28]. As
shown in Table 4, mean scores obtained in our study were higher than those reported by
Cancers 2023, 15, 2582 9 of 13

others, except for “appearance”. Overall, “chewing” was the domain with the lowest mean
values in all studies followed by “appearance”, “anxiety”, “speech”, and “swallowing”.

Table 4. Mean scores of the 12 single question domains of the UW-QOL questionnaire.

First Author, Year [Reference] (Number of Patients)

Domain Present Li et al., Yang et al., Zhu et al., Luo et al., Zhang Wang
Series 2014 [15] 2014 [27] 2014 [25] 2014 [28] 2013 [14] 2009 [26]
(n = 21) (n = 35) (n = 34) (n = 33) (n = 32) (n = 31) (n = 15)
Pain 86.9 (12.8) 82.2 (5.8) 67.4 (7.5) 76.4 (6.5) 80.6 (7.5) 87.6 (10.2) 86.7 (16.0)
Appearance 67.9 (19.6) 78.1 (11.6) 70.1 (6.6) 74.6 (9.6) 76.3 (8.7) 58.5 (2.1) 66.7 (29.4)
Activity 83.3 (16.5) 69.5 (7.6) 56.5 (9.1) 64.1 (8.3) 66.2 (9.1) 72.4 8.5) 76.7 (22.1)
Recreation 84.5 (20.1) 68.2 (10.6) 60.1 (9.1) 65.6 (8.7) 69.4 (7.1) 75.9 (6.1) 65.0 (33.8)
Swallowing 84.5 (20.1) 77.3 (6.8) 52.8 (9.0) 79.2 (7.2) 78.1 (5.1) 83.7 (1.6) 48.7 (26.9)
Chewing 57.1 (39.6) 28.5 (3.2) 33.1 (16.1) 32.4 (1.8) 30.3 (2.7) 42.2 (2.6) 36.7 (22.8)
Speech 83.0 (19.5) 71.3 (12.6) 55.3 (10.3) 68.8 (9.9) 66.4 (7.8) 47.9 (1.2) 53.3 (34.1)
Shoulder 90.9 (18.4) 80.3 (9.0) 65.9 (7.1) 81.1 (5.5) 82.3 (3.1) 92.4 (3.1) 82.0 (15.2)
Taste 92.9 (13.1) 71.2 (8.8) 55.6 (6.0) 80.5 (5.5) 78.7 (7.5) 90.3 (1.9) 80.7 (24.9)
Saliva 78.1 (27.3) 60.0 (7.6) 47.8 (8.9) 75.0 (9.7) 74.1 (8.0) 70.8 (1.5) 58.7 (28.2)
Mood 82.6 (21.6) 67.1 (1.2) 73.4 (11.5) 67.1 (1.2) 60.1 (3.0) 85.3 (7.9) 71.7 (31.1)
Anxiety 87.5 (24.5) 55.8 (8.2) 50.8 (14.3) 65.2 (8.6) 45.3 (9.6) 69.8 (6.3) 64.7 (66.7)
SD: standard deviation.

In relation to the domains in which the best score (of 100) was obtained, data were
reported in four studies, with “pain”, “shoulder function”, “activity”, and “recreation” as
those with the most favorable evaluation (Table 5).

Table 5. Best scores obtained in the 12 single question domains of the UW-QOL questionnaire.

First Author, Year [Reference] (Number of Patients)

Domain Present Li et al., Zhu et al., Luo et al., Wang

Series 2014 [15] 2014 [25] 2014 [28] 2009 [26]
(n = 21) (n = 35) (n = 33) (n = 32) (n = 15)
Pain 48 43 42 44 53
Appearance 10 26 36 31 20
Activity 43 9 6 NR 40
Recreation 52 0 3 6 33
Swallowing 67 29 49 28 7
Chewing 38 0 0 0 0
Speech 50 23 15 3 20
Shoulder 76 40 46 44 40
Taste 76 26 33 40 53
Saliva 52 42 42 22 13
Mood 50 11 9 3 40
Anxiety 70 0 0 6 40
Data as % best score (of 100) for each domain; NR: not reported.

A remarkable finding was that the “chewing” domain had the lowest score both in our
study and in the 6 studies analyzed. Additionally, this domain showed a rate of importance
Cancers 2023, 15, 2582 10 of 13

of 62% in the present study as compared with 76.8% in the remaining studies. On the
other hand, when considering the rank order assigned to the different domains, “chewing”
ranked first in all studies but one (Table 6).

Table 6. Importance of domain and rank order assigned to the 12 single question domains of the
UW-QOL questionnaire.

First Author, Year [Reference] (Number of Patients)

Domain Present Li et al., Yang et al., Zhu et al., Luo et al., Zhang Wang
Series 2014 [15] 2014 [27] 2014 [25] 2014 [28] 2013 [14] 2009 [26]
(n = 21) (n = 35) (n = 34) (n = 33) (n = 32) (n = 31) (n = 15)
Pain 10% (6) 0% (11) 5.9% (9) 0% (9) 0% (8) 7% (8) 7% (6)
Appearance 48% (2) 49% (3) 18% (7) 67% (2) 50% (3) 55% (3) 20% (5)
Activity 29% (4) 17% (7) 41% (4) 58% (3) 38% (4) 0% (11) 0% (8)
Recreation 5% (7) 14% (8) 0% (10) 15% (7) 13% (6) 0% (11) 0% (8)
Swallowing 10% (6) 6% (10) 47% (3) 0% (9) 3% (7) 13% (7) 93% (1)
Chewing 62% (1) 77% (1) 71% (1) 76% (1) 94% (1) 90% (1) 53% (2)
Speech 43% (3) 54% (2) 53% (2) 30% (4) 25% (5) 68% (2) 46% (3)
Shoulder 5% (7) 0% (11) 0% (10) 0% (9) 0% (8) 3% (9) 0% (8)
Taste 10% (6) 11% (9) 29% (5) 0% (9) 3% (7) 3% (9) NR
Saliva 24% (5) 23% (5) 24% (6) 12% (8) 0% (8) 26% (4) 40% (4)
Mood 24% (5) 20% (6) 0% (10) 18% (6) 13% (6) 16% (6) 0% (8)
Anxiety 10% (6) 29% (4) 12% (8) 24% (5) 63% (2) 19% (5) 7% (6)
Data as percentage of patients choosing which three domains were the most important during the past 7 days.
Rank order of domains in parenthesis; NR: not reported.

Chewing has been shown to score worse after segmental mandibulectomy and recon-
struction using composite free tissue transfer [29]. In these patients, rehabilitation with
implant-supported prosthesis appears to improve QoL outcomes [30–32]. In a pilot study of
10 patients of early loaded implant-supported fixed dental prosthesis following mandibular
reconstruction, patient satisfaction improved significantly after dental rehabilitation as
compared to mandibular reconstruction alone [33]. Dental implants were placed in only
5 patients in our series, but 9 of the 13 patients (69.2%) reported the desire to undergo
dental rehabilitation for improving chewing and aesthetic functions in the free-text box.
Prosthetic rehabilitation, however, should be indicated on a case-by-case basis [31]. This
decision should be based on several considerations including the medical history, prognosis,
comorbidities and, particularly, the patient’s desires and expectations. In addition, special
attention should be paid to the surgical planning of implants, soft tissue management, and
prosthodontics in order to avoid complications and achieve stable long-term results. We
also believe that tests of swallowing function could help identify patients with a preserved
swallowing function, which are in fact those who would benefit most from this kind of
rehabilitation.
“Appearance” in the preceding 7 days was another domain selected as one of the most
important by 48% of our patients, which is consistent with percentages between 49% and
67% reported in other studies [14,15,25,28]. Although “appearance” was considered an
important factor, 71.4% of our patients stated in the questionnaire that their appearance had
suffered slight or no changes, 19% a moderate change, and only 9.5% (2 patients) reported
feeling disfigured. However, appearance did not seem to be a reason for social isolation,
as “recreation” was rated as only 5% in the importance of domain and in the 7th position
of the rank order. As for the overall QoL during the past 7 days, 81% reported that it was
good, very good, or outstanding, and only 4 patients (20%) considered that QoL was fair.
Poor or very poor ratings were not observed.
Cancers 2023, 15, 2582 11 of 13

In relation to secondary outcomes, only 3 patients presented PSI-related complications,

with a rate of 13.6%, which is consistent with 12.2% reported in the systematic review of
Goodson et al. [9]. Plate removal was required by only 2 patients because of exposure, but
no deficiencies in the consolidation process between the fibula fragment and the mandible
were found.
A PEEK prosthesis was used in 14 patients for the correction of mandibular asymmetry
after free fibula flap reconstruction [34]. In 6 patients (42.8%), the prosthesis was exposed
and had to be removed. It should be noted that 5 of these 6 patients had received RT for
the treatment of their oncological disease. Patients in whom the PEEK prosthesis was not
exposed to RT did not present complications, with satisfactory aesthetic results and stability
of the mandibular contour.
Esthetical evaluation was performed using pre- and post-surgical photographs, panoramic
radiographs, and 3D-CBCT scans showing a high correlation between virtual surgical plan and
the results obtained. Other techniques, such as cephalometric analysis and photogrammetry,
were not used as the study was focused on the assessment of QoL as a primary subjective
domain.
Limitations of the study include the single-center characteristics, retrospective design,
and a small study population. Additionally, patients with malignant and benign conditions
were included, which may have different risk factors related to QoL, particularly the use
of radiation therapy and chemotherapy. However, the aim of the study was to assess
the impact of the reconstructive process of the mandible (CAD-CAM, free fibula flap,
and customized titanium plates) on QoL rather than the pathology itself, and in this
respect, the population was homogeneous. Patients included in other series reported in
the literature with which a comparison was made (Table 6) also included patients with
ameloblastoma, osteoradionecrosis, and oral squamous cell carcinoma. Preoperative data
of HRQoL using the same UW-QOL questionnaire was not obtained, so a within-group
comparison of QoL before and after surgery was not feasible. Although only 4 patients
received neoadjuvant or adjuvant RT and/or chemotherapy, the impact of this oncological
treatment (e.g., impairment of salivary gland, trismus, mucositis, mouth opening limitation,
etc.) was not evaluated. Other risk factors, such as oral health status, smoking, or age
were not evaluated either. However, the use of a validated HRQoL instrument, such
as the UW-QOL questionnaire, after a period of at least 12 months after surgery is a
strength of this study. Moreover, a detailed comparison of the present findings with other
studies published in the literature in which the UW-QOL questionnaire was completed by
patients undergoing similar mandibular reconstruction procedures with free fibula flap is
an interesting and distinctive aspect of the study.

5. Conclusions
Restoring mandibular continuity with free fibula flap and patient-specific titanium
implants designed with the CAD-CAM technology improved HRQoL. High scores in most
specific domains of the UW-QOL questionnaire were obtained at 12 months after surgery,
except for “chewing” which had the lowest score. The global QoL was considered good,
very good, or outstanding by 81% of the patients. Further studies with a larger study
population are necessary to confirm the present findings.

Author Contributions: Conceptualization, J.P.-R. and C.B.-A.; methodology, J.P.-R.; software, J.P.-R.;
validation, J.P.-R. and C.B.-A.; formal analysis, J.P.-R.; investigation, J.P.-R., M.S.-B., A.d.-P.-G.-C.,
P.V-M., J.M.-P. and C.B.-A.; data curation, J.P.-R. and C.B.-A.; writing—original draft preparation,
C.B.-A.; writing—review and editing, J.P.-R., M.S.-B., A.d.-P.-G.-C. and P.V.-M.; supervision, J.P.-R.
The authors decline the use of artificial intelligence, language models, machine learning, or similar
technologies to create content or assist with writing or editing of the manuscript. All authors have
read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Cancers 2023, 15, 2582 12 of 13

Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki and approved by the Clinical Research Ethics Committee of Hospital Universitari Vall
d’Hebron (codes PR(AG)93/2016, approval date 1 March 2016), Barcelona, Spain.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the
study.
Data Availability Statement: Study data are available from the corresponding author upon request.
Acknowledgments: The authors thank Marta Pulido, for editing the manuscript and editorial assistance.
Conflicts of Interest: The authors declare no conflict of interest.

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