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\begin{document}

\title{Multidisciplinary Team Role in Cochlear Implantation after Radiotherapy
and Chemotherapy in Nasopharyngeal Carcinoma Patients}



\author[1]{Yue Liang}%
\author[1]{Fanqin Wei}%
\author[1]{Huiwen Zhuang}%
\author[1]{Jincangjian Sun}%
\author[1]{Liping Xie}%
\author[1]{Kaitian Chen}%
\author[1]{Guanxia Xiong}%
\affil[1]{Sun Yat-sen University First Affiliated Hospital}%


\vspace{-1em}



  
  \date{June 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objectives: To explore the role of multidisciplinary team (MDT) in
perioperative safety and feasibility evaluation and postoperative effect
prediction of cochlear implantation (CI) in patients with bilateral
profound sensorineural hearing loss (SNHL) after radiotherapy and
chemotherapy for nasopharyngeal carcinoma (NPC). Methods: From 2017 to
2022, 11 patients with bilateral profound SNHL after radiotherapy and
chemotherapy for NPC received CI in our department. MDT formulated
diagnosis and treatment plan for all patients during their perioperative
period. The MDT participants were from the following departments:
otorhinolaryngology, radiology, radiotherapy, neurology, psychiatry,
anesthesiology, and audiology and speech rehabilitation. Several hearing
examinations were tested during the follow-up to dynamically observe the
effectiveness of the hearing and speech rehabilitation in the patients.
Results: Based on the MDT conclusion and decision, five patients
underwent routine CI, two patients underwent simultaneously extended
radical mastoidectomy and CI, and four patients underwent simultaneously
subtotal petrosectomy, external auditory canal elimination, mastoid
cavity obliteration by fat graft or musculoperiosteal flaps and CI. The
pure tone average of all 11 patients was 39.5 \selectlanguage{ngerman}± 5.0 dB and the average
speech discrimination score was 95.0 ± 9.7\% postoperatively. One
patient underwent a second surgery for the cochlear electrode prolapsed
postoperatively. Conclusion: To some extent, CI is risky for patients
after chemoradiotherapy for NPC. However, the MDT approach can reduce
the risk fast, predict the auditory effect after implantation early, as
well as predict and prevent the occurrence of postoperative
complications. Therefore, MDT exerts a positive effect on the outcome of
the relatively safe and feasible application of CI in these patients.
Keywords: Multidisciplinary team, nasopharyngeal carcinoma, cochlear
implantation.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{TITLE}

Multidisciplinary Team Role in Cochlear Implantation after Radiotherapy
and Chemotherapy in Nasopharyngeal Carcinoma Patients

\textbf{ABSTRACT}

\textbf{Objectives:} To explore the role of multidisciplinary team (MDT)
in perioperative safety and feasibility evaluation and postoperative
effect prediction of cochlear implantation (CI) in patients with
bilateral profound sensorineural hearing loss (SNHL) after radiotherapy
and chemotherapy for nasopharyngeal carcinoma (NPC).

\textbf{Methods:} From 2017 to 2022, 11 patients with bilateral profound
SNHL after radiotherapy and chemotherapy for NPC received CI in our
department. MDT formulated diagnosis and treatment plan for all patients
during their perioperative period. The MDT participants were from the
following departments: otorhinolaryngology, radiology, radiotherapy,
neurology, psychiatry, anesthesiology, and audiology and speech
rehabilitation. Several hearing examinations were tested during the
follow-up to dynamically observe the effectiveness of the hearing and
speech rehabilitation in the patients.

\textbf{Results:} Based on the MDT conclusion and decision, five
patients underwent routine CI, two patients underwent simultaneously
extended radical mastoidectomy and CI, and four patients underwent
simultaneously subtotal petrosectomy, external auditory canal
elimination, mastoid cavity obliteration by fat graft or
musculoperiosteal flaps and CI. The pure tone average of all 11 patients
was 39.5 \selectlanguage{ngerman}± 5.0 dB and the average speech discrimination score was 95.0 ±
9.7\% postoperatively. One patient underwent a second surgery for the
cochlear electrode prolapsed postoperatively.

\textbf{Conclusion:} To some extent, CI is risky for patients after
chemoradiotherapy for NPC. However, the MDT approach can reduce the risk
fast, predict the auditory effect after implantation early, as well as
predict and prevent the occurrence of postoperative complications.
Therefore, MDT exerts a positive effect on the outcome of the relatively
safe and feasible application of CI in these patients.

\textbf{Keywords:} Multidisciplinary team, nasopharyngeal carcinoma,
cochlear implantation.

\textbf{Key points:}

\begin{enumerate}
\tightlist
\item
  Hearing loss is a major adverse effect of the treatment of an NPC
  patient and cochlear implantation is an effective method for the
  recovery of the hearing of patients suffering from severe to profound
  hearing loss.
\item
  This is the \selectlanguage{english}first study applying multidisciplinary team method to face
  the long-term complications after chemoradiotherapy for NPC patients,
  including limitation of the mouth opening, caused by temporomandibular
  joint dysfunction, osteoradionecrosis of the temporal bone, chronic
  otitis media and radioactive encephalopathy.
\item
  Our study showed that MDT has an important role in the whole process
  of diagnosis and treatment, which can rapidly reduce the perioperative
  risk, effectively predict the postoperative auditory effect, and
  prevent the occurrence of postoperative complications.
\item
  Based on the results of the MDT discussion, surgeons employed
  different operative approaches depending on the patient's situation,
  including the extent of ORNTB and the intactness of tympanic membrane.
\item
  Our study showed that the application of CI in patients who underwent
  chemoradiotherapy for NPC is relatively safe and feasible.
\end{enumerate}

\textbf{INTRODUCTION}

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor that
originates from the nasopharynx, which is highly prevalent in East and
Southeast Asia, especially in South
China.\textsuperscript{1}Intensity-modulated radiotherapy (IMRT) alone
or in combination with chemotherapy is recommended for the treatment of
NPC.\textsuperscript{2}In the course of treatments, the hearing
apparatus, including the tympanic membrane, eustachian tube, and cochlea
are damaged by radiation and the adjuvant chemotherapy drugs. Hearing
loss was reported was a major adverse effect of the treatment of an NPC
patient.\textsuperscript{3} Hearing loss seriously and negatively
affects patients' daily communication and quality of life, further
leading to a decline in patients' cognitive function. In contrast to the
insufficient compensation effect of hearing aids (HA), cochlear
implantation (CI) is an effective method for the recovery of the hearing
of patients suffering from severe to profound SNHL.\textsuperscript{4,5}

However, long-term complications after chemoradiotherapy, including
limitation of the mouth opening, caused by temporomandibular joint
dysfunction, neck fibrosis, osteoradionecrosis of the temporal bone
(ORNTB), chronic otitis media, eustachian tube dysfunction, radioactive
encephalopathy (REP), and radioactive paranasal sinusitis affect
perioperative safety and surgical
feasibility.\textsuperscript{6,7}Although previous evidence has shown
that CI can significantly improve the hearing of patients with severe or
profound SNHL after chemoradiotherapy for NPC, the perioperative safety
and feasibility, as well as surgical effect of CI remain key
issues.\textsuperscript{8}Therefore, we propose the introduction of the
multidisciplinary team (MDT) discussion approach of the above issues.

MDT is a clinical treatment mode in which experts from different
specialties form relatively fixed expert groups that regularly schedule
discussion concerning the diagnosis and treatment for a certain organ or
system disease. Currently, MDT is widely implemented in the field of
malignant tumor therapy.\textsuperscript{9} In our department, MDT is
often used in the comprehensive treatment of head and neck tumors.
Experts from various departments jointly evaluate and plan interventions
of specific patients. Hence, optimal treatment plans are assigned to
patients according to the particular clinical needs.

In this study, we applied MDT to the whole process, including the
perioperative and postoperative period. Our study showed that the role
of MDT in CI after chemoradiotherapy of NPC patients is of considerable
significance.

\textbf{MATERIALS AND METHODS}

In this study, we reviewed the data of 11 patients with bilateral
profound SNHL after radiotherapy and chemotherapy for NPC who underwent
CI in our department ``Blinded for review'' from 2017 to 2022.

\emph{Evaluation of the perioperative safety and feasibility through
MDT}

Currently, our hospital ``Blinded for review'' has established MDT,
whose core is the Department of Otorhinolaryngology, combined with the
Departments of Radiology, Radiotherapy, Neurology, Psychiatry,
Anesthesiology.

Radiotherapists, radiologists, and otorhinolaryngologists evaluated the
tumor control situation to exclude tumor residue, local recurrence, and
distant metastasis

According to the Chinese Society of Clinical Oncology (CSCO) clinical
guidelines for the diagnosis and treatment of NPC, nasopharyngoscopy and
nasopharyngeal and neck magnetic resonance imaging (MRI) scan were
employed to assess the local lesions. Besides, chest computed tomography
(CT) scan, abdominal ultrasound or upper abdominal CT, whole-body bone
scan, and detection of Epstein-Barr virus (EBV) DNA copy number in
peripheral blood were used to exclude distant post-treatment metastases.
When necessary, PET-CT examination should be
considered.\textsuperscript{2}

Radiologists and otorhinolaryngologists assessed the severity of ORNTB
and otitis media

ORNTB was characterized as either localized or diffuse based on Ramsden
classification: 1) localized type: mostly limited to the external
auditory canal (EAC) without invading the mastoid bone of the middle
ear; 2) diffuse type: predominantly diffuse necrosis of the temporal
bone with a high risk of involvement of adjacent structures, in
particular the brain, labyrinth, and the facial nerve and to a lesser
extent the temporomandibular joint and the parotid
gland.\textsuperscript{10-13} Based on the Ramsden classification, the
surgeons and the radiologists planned the application of three different
surgical methods by assessing the intactness of the tympanic membrane
(TM) and the thickness and integrity of the cortical bone of the
posterior and upper wall of the EAC through the temporal bone CT
thin-layer scan on the horizontal section from the facial recess to the
base turn of cochlea.

Radiologists diagnosed radiation encephalopathy (REP) and assessed the
severity of REP; neurologists and psychologists evaluated patients'
cognitive function and psychological status.

Focal cerebral radiation necrosis, which is a type of REP, can occur
after incidental irradiation of the brain during NPC
treatment.\textsuperscript{14} The diagnosis of REP is based mainly on
NPC radiotherapy history, imaging examinations, clinical symptoms, and
cognitive functions. However, the clinical presentation of focal
radiation necrosis is a subacute space-occupying lesion, which is
nonspecific. Therefore, imaging examinations, such as standard MRI
scans, are the main diagnostic methods for REP (Fig.
1).\textsuperscript{15} The radiologists diagnosed REP and assessed the
severity of REP by MRI. Meanwhile, neurologists and psychologists
assisted in judging whether epilepsy and cognitive dysfunction caused by
REP were contraindications.

Anesthesiologists should evaluate patients' perioperative situation and
the risk of anesthesia.

One of the most common complications after radiotherapy for NPC is
limitation of the mouth opening, which increases the difficulty of
endotracheal intubation and thus increases the risk of anesthesia. The
anesthesiologists used the modified Mallampati scores to divide the
patients into four classes. Nasotracheal intubation should be considered
in grades III and IV patients, whereas orotracheal intubation was
applied in grade I and II patients.\textsuperscript{16}

Otorhinolaryngologists and audiologists evaluated the patients'
remaining hearing and speech abilities and predicted the postoperative
results.

All patients underwent preoperative audiological examination evaluation
for cochlear implant candidacy. Intraoperative audiologists routinely
performed neural response telemetry (NRT). Postoperative routine
reexamination of temporal bone CT was conducted to confirm the
electrode's position in order to exclude the possibility of electrode
fracture, partial electrode implantation or implantation failure.

\emph{Evaluation of postoperative effects through MDT}

These postoperative patients were followed up by the hearing and speech
rehabilitation team. During the follow-up, professional audiologists
assessed the cochlear implanters' postoperative hearing and speech
function recovery by Category of Auditory Performance (CAP), Speech
Intelligibility Rating (SIR), pure tone average (PTA) and speech
discrimination score (SDS). If MDT team noticed the occurrence of
postoperative complications, such as infection, electrode array
extrusion, facial paralysis, and device failure, they would immediately
inform the attending surgeons and provide relevant treatment.

\emph{Statistical analysis}

SPSS software (Version 20.0; SPSS, IBM Corp., Armonk, NY, USA) was used
to analyze the data in this study, a paired T-test was used to assess
the preoperative and postoperative data results. \emph{P} \textless{}
.05 was considered to indicate a statistically significant difference.

\textbf{RESULTS}

In this study, a total number of 11 patients (4 males and 7 females)
aged from 36 to 69 years, with bilateral severe or profound SNHL after
chemoradiotherapy for NPC, who underwent CI, were enrolled. All patients
had suffered from hearing loss after standard chemoradiotherapy prior to
CI. All patients were regularly followed up postoperatively, with a
follow-up duration ranging from 6 to 60 months, with an average of 29
months (Table 1).

\emph{MDT discussion results}

All patients participated in a perioperative MDT discussion for the
evaluation of the safety and feasibility of surgery, preliminarily
prediction of the postoperative effects, and prevention of the
occurrence of postoperative complications. The following results were
obtained: 1) All primary lesions were completely controlled after
comprehensive treatment without signs of residues, recurrence, or
metastasis; 2) All patients were classified into three different
classes. Five patients of grade (a), whose ORNTB were localized by an
intact TM and continuous cortical bone of the posterior and superior
walls of the EAC, were accepted for routine CI (Fig. 2a). Two patients
of grade (b) with diffuse ORNTB and an intact TM and a continuous
cortical bone of the posterior and superior walls of the EAC were
subjected to simultaneous extended radical mastoidectomy and CI (Fig.
2b). The other four patients of grade (c) simultaneously underwent
subtotal petrosectomy (STP), external auditory canal elimination,
mastoid cavity obliteration by fat graft or musculoperiosteal flaps and
CI because of their diffuse ORNTB with perforate TM and defects in the
posterior and upper walls of the EAC (Fig. 2c); 3) Radiologists
diagnosed five patients who had different levels of REP depending on
standard MRI and CT. Neurologists and psychiatrists found that four of
them had no abnormal neurological symptoms or clinical signs due to REP.
It is worth noting that a patient had been diagnosed with REP on the
bilateral temporal lobe after epileptic seizures in 2012 and underwent
partial radiation lesion resection of the right temporal lobe. Because
the epilepsy was well controlled and the patient did not occur any
seizure over a year, MDT team did not regard REP as a surgical
contraindication. But REP was predicted to probably affect postoperative
hearing recovery; 4) According to modified Mallampati scores,
anesthesiologists classified four patients into grade IV, characterized
by difficult airway passage, thus nasotracheal intubation under
fiberoptic bronchoscopy was considered, combined with preparation of
emergency measures such as tracheotomy before anesthesia.

\emph{Operative approach}

Based on the results of the MDT discussion, surgeons employed different
operative approaches depending on the patient's situation. However, the
surgeon planned to perform the grade (c) surgery method in one of the
patients. However, this patient could not accept the symptom of aural
fullness, and thus grade (b) surgery method was adopted. The other
patients agreed with the results of the MDT discussion and accepted the
surgical methods. The intraoperative time fluctuated 3.2 +- 1.0 hours.
Intraoperative neural response telemetry (NRT) showed that the surgery
of all cochlear implant was performed successfully. Smooth anesthesia
and operation without complications were achieved in all patients (Table
2).

\emph{Postoperative hearing and speech performance}

During the follow-up visits, audiological examinations were performed to
observe the dynamics of all patients' postoperative hearing and speech
recovery. The encouraging audiological outcomes revealed that CI had
positive effect on hearing rehabilitation.

All 11 patients were diagnosed with profound bilateral SNHL before
surgery. The average hearing threshold was more than 80 dB, with mean
SDS scores with hearing aids of less than 70\%. The mean PTA and SDS
scores obtained at the last follow-up examination were 39.5 +- 5.0 dB and
95.0 +- 9.7\% (mean +- standard deviation), respectively.

The mean CAP and SIR scores obtained before CI and at the last follow-up
examination were 1.8 +- 1.0 versus 5.9 +- 0.8 and 1.5 +- 0.5 versus 4.1 +-
0.7, respectively, which were significantly better than the preoperative
ones (paired Wilcoxon signed-rank test, \emph{P} = 0.000 \textless{}
.05) (Table 3).

\emph{Incidence of postoperative complications}

None of the 11 patients had serious postoperative complications in the
short term. However, 2 patients had otitis externa mycotica, which was
detected during the follow-up examinations; their condition was relieved
by the application of anti-fungal topical ointment. The patient who
refused surgeon's advice was noted to have an exposed electrode in the
right external auditory canal 12 months postoperatively (Fig. 3a), and
the intracochlear electrode array was completely migrated 28 months
postoperatively (Fig. 3b). Therefore, the patient accepted and underwent
STP, external auditory canal elimination, mastoid cavity obliteration by
fat graft, and cochlear reimplantation during the second operation (Fig.
3c).

\textbf{DISCUSSION}

Hearing impairment remains the most common complication in long-term
survivors after comprehensive treatment for NPC. Currently, CI is the
only method implemented for the rehabilitation severe to profound SNHL
in cases of insufficient compensation effect of the HA. However, various
postradiotherapy complications increase the difficulties of surgery, and
have negative effect on postoperative recovery. Therefore, the
evaluation performed only by otorhinolaryngologists of the condition of
such patients was not sufficient, and thus MDT was used to make the
diagnosis and provide the treatment plan for each of the patients
included in the present study.

According to the CSCO clinical guidelines for NPC, post-treatment
follow-up of NPC is very important. In this study, the relevant
examinations were strictly completed following the guidelines, and MDT
evaluated the situation of tumor control jointly by specialists from
different departments. The results showed that NPC in all 11 patients
was controlled completely.

Huang et al.\textsuperscript{17} divided the postirradiated NPC patients
into three categories: mild, moderate and severe. Different from our
study, they recommended that patients of severe category underwent
subtotal temporal bone resection (STBR), external auditory canal
elimination, CI simultaneously or by stage because they suffered
recurrent suppurative otitis media and mastoiditis, combined with the
external moist EAC with defect of skin and bear dead bones, and serious
or severe radiation osteomyelitis by CT/MRI. The results showed that CI
for postirradiated ears of NPC is safe and feasible following specific
surgical methods aiming to three categories.

In this study, we classified ORNTB into localized type and diffuse type
referring to Ramsden classification.\textsuperscript{11} On the basis of
Ramsden classification, our center's experience demonstrated the
importance of the thickness and integrity of the cortical bone of the
posterior and superior wall of the EAC. This was due to the fact that
the intact EAC can protect the cochlear electrode array, preventing the
occurrence of infection and electrode exposure. Thus, we recommended
that the patients of grade (c) underwent STP, external auditory canal
elimination, mastoid cavity obliteration by fat graft or
musculoperiosteal flaps and CI simultaneously. Prasad et
al.\textsuperscript{18} reported that STP is indicated in
osteoradionecrosis while STBR is usually used on the temporal bone
malignancies. In the present study we initially excluded the residues,
recurrence, or metastasis of the primary lesion based on perioperative
MDT discussion. Therefore, STP was selected to eliminate potential
infection, reduce the risk of postoperative complications and achieve
rapid postoperative recovery. It is worth noticing that the
aforementioned cochlear implant was dysfunctional because of the total
detached electrode from the round window. Considering the history of
radiotherapy for NPC and diffuse ORNTB, conservative management would
have exposed the patient to a high risk of infection. Therefore, the
patient underwent a second surgery, as mentioned earlier. Chua et
al.\textsuperscript{19} performed conservative treatment with close
clinical surveillance as a reasonable option faced with electrode array
extrusion post-CI in a post-irradiated patient. In contrast, we suggest
a positive surgical treatment in case of electrode extrusion. Besides,
MDT precisely predicted the risk of electrode exposure in this patient,
reflecting the potential of MDT to reduce the incidence of medical
errors.

Several studies have revealed marked improvements in the hearing of
cochlear implant recipients who had previously received radiotherapy for
head and neck cancers. In this regard, Soh et al.\textsuperscript{20},
Chang et al.\textsuperscript{21}, and Low et
al.\textsuperscript{22}established that there were no obvious
differences in the effectiveness of CI in post-irradiated NPC patients
with hearing impairment as compared with non-NPC patients with profound
SNHL. However, whether REP, which is regarded as a severe
post-irradiation complication, affects postoperative hearing outcome
remains unclear. Besides, there are no clear guidelines for the
diagnosis and treatment of REP. In our study, it was shown that the
postoperative hearing and speech rehabilitation effects of all 11
patients were significantly better than those before surgery, regardless
of the presence or absence of REP.

\textbf{CONCLUSION}

Our study showed that the application of CI in patients who underwent
chemoradiotherapy for NPC is relatively safe and feasible. The long-term
complications reported here, including mastoiditis, ORNTB, and REP, are
not absolute surgical contraindications. MDT has an important role in
the whole process of diagnosis and treatment, which can rapidly reduce
the perioperative risk, effectively predict the postoperative auditory
effect, and prevent the occurrence of postoperative complications.

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\textbf{Figure Legends}

\textbf{Figure 1.} MRI scan of cases with or without REP. Imaging of (a)
showed typical REP in bilateral temporal lobes. Imaging of (b) showed no
obvious sign of REP. MRI = magnetic resonance imaging; REP = radioactive
encephalopathy.

\textbf{Figure 2.} Endoscopic imaging and CT scan of preoperative
situation. Imaging of (a) showed intact TM and the posterior and upper
wall of EAC, and localized ORNTB. Imaging of (b) showed intact TM and
the posterior and upper wall of EAC, and diffuse ORNTB. Imaging of (c)
showed perforated TM and the defects on the posterior and upper wall of
EAC, and diffuse ORNTB. CT = computed tomography; TM = tympanic
membrane; EAC = external auditory canal; ORNTB = osteoradionecrosis of
the temporal bone.

\textbf{Figure 3.} Endoscopic imaging of electrode exposure and CT scan
of postoperative situation. Imaging of (a) showed an exposed electrode
in the right posterior wall of the external auditory canal 12 months
after surgery. Imaging of (b) showed that the intracochlear electrode
array was completely migrated 28 months after surgery. Imaging of (c)
showed the right electrode's position in cochlea with the protection of
abdominal fat graft.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/515475/articles/590827-multidisciplinary-team-role-in-cochlear-implantation-after-radiotherapy-and-chemotherapy-in-nasopharyngeal-carcinoma-patients}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/515475/articles/590827-multidisciplinary-team-role-in-cochlear-implantation-after-radiotherapy-and-chemotherapy-in-nasopharyngeal-carcinoma-patients}

\textbf{Hosted file}

\verb`Table 3.docx`  available at \url{https://authorea.com/users/515475/articles/590827-multidisciplinary-team-role-in-cochlear-implantation-after-radiotherapy-and-chemotherapy-in-nasopharyngeal-carcinoma-patients}

\selectlanguage{english}
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