]
Typical signs and symptoms characterize the clinical
presentation of RIT. Specifically, the primary manifestation
of RIT is restricted mouth opening, which
demonstrates a progressive nature in the absence of
promptly initiated treatment measures. It is regrettable
that, owing to its progressive fibrotic characteristics,
timely intervention may only decelerate rather than
arrest its advancement in severely affected patients.
Due to pain in the jaw muscles, temporomandibular
joint (TMJ), or surrounding areas, the patient has difficulty,
particularly when trying to open the mouth,
chew, or speak.[] Frequent jaw locking may cause
tension or stiffness in the muscles around the jaw region,
which may worsen over time. Difficulty chewing
is a common problem in RIT patients, mainly when
eating certain foods requiring a wide mouth opening.
In such cases, softer or liquid-based ingredients
may be preferred. Patients may also experience difficulties
with intelligible speech and articulation due
to restricted and painful jaw movements.[] Various
degrees of deformations in facial appearance may occur
if not treated on time, and, in severe cases, significant
asymmetry or changes in the facial structure may
result from persistent involuntary and painful muscle
contractures, stiffness, and atrophy. In some cases,
the affected individual may struggle to deal with the
problem, leading to depression and social withdrawal,
which may require psychiatric assistance. When confronted
with severely restricted mouth opening, challenges
relating to oral hygiene maintenance, halitosis,
and elevated susceptibility to periodontal and dental
issues may manifest commensurate with the severity
of the condition. Severe instances may experience
TMJ clicking, popping, or locking, culminating in discomfort
and constrained jaw mobility. These complications
may further worsen the afflicted individual's
psychological well-being and intimate relationships.
[,] Therefore, prompt assistance from oral and
maxillofacial surgeons, general dentists, periodontologists,
dietitians, and psychiatrists would be highly
beneficial in nearly all cases of RIT, given its harmful
impact on all aspects of quality of life (QoL) measures.
RIT may affect up to 38% to 42% of HNC patients
undergoing oncological treatment; hence, its diagnosis
must be made timely and correctly for appropriate management,
considering its detrimental effects on patients"
life quality.[,] However, defining RIT with a universally
accepted maximum mouth opening (MMO) cutoff
value remains challenging due to the diverse methods
and threshold values RIT researchers utilize. The same
remark also applies to the grading of RIT.[]
The measurement methods initially used by some
researchers involved using calipers-one for individuals
with some or partial teeth using a prosthesis
and another for edentulous individuals not using a
prosthesis. Ensuring all patients maintain a stable and
neutral head position during such measurement is
essential. Then, patients are instructed to open their
mouths to their maximum extent while minimizing
discomfort.[] The "three-finger test" is a simple diagnostic
procedure for trismus, where the patient is
asked to insert three fingers into their mouth. A normal
mouth opening is determined by the ability to fit
all three fingers between the incisors. If fewer than
three fingers can be inserted, trismus is likely present.
[] An alternative modern approach involves using
the Therabite® range of motion scale (Atos Medical
AB, Hörby, Sweden). This method allows for convenient
and rapid assessments and, because it is disposable,
minimizes the risk of infection.[,] Patients
are instructed to fully extend their mouths using the
Therabite® range of motion scale to measure the gap
between the upper edge of one of the lower central incisors
and the lower edge of the corresponding upper
central incisor. It is imperative to consistently assess
the MMO in patients at risk of restricted mouth opening,
irrespective of the chosen assessment method. It
is recommended that these assessments be conducted
before treatment initiation and subsequently at 3, 6, 9,
and 12-month intervals, followed by biannual assessments
during the follow-up period. Regular monitoring
is of utmost importance in promptly identifying
restricted mouth opening, progression to RIT, and the
advancement of RIT to more severe grades (Fig. 1).
Fig. 1. The measurement methods of maximum mouth-opening.
Further examination of the current literature is
warranted to address the prevailing disparities in RIT
definitions, grading systems, and their practical applications
in clinical contexts. Previous investigations have
introduced varied MMO cutoff values for RIT, contingent
upon the dental condition of the subjects. Notably,
the study by Louise Kent et al.[] established an MMO
threshold of 35 mm for patients with teeth and 40 mm
for edentulous patients. In contrast, Lindblom et al.[]
utilized a 35 mm cutoff value for RIT. Nevertheless, the
authors underscored the necessity for a standard RIT
cutoff value by illustrating that applying a 20 mm cutoff
would encompass only 8% of their patient cohort in the
RIT classification. These findings underscore the imperative
for a universally acknowledged RIT cutoff and
emphasize the critical requirement to define a standard
cutoff value that can be widely applied to cancer patients
undergoing RT or C-CRT. Steiner et al.[] established a cutoff value of 35 mm for RIT and classified MMO
measurements of less than 25 mm as indicative of severe
trismus. Additionally, they employed grading systems to
assess trismus severity, with grades 2, 3, and 4 assigned
to MMOs of 10-20 mm, 5-10 mm, and less than 5 mm,
respectively.[] However, the utilization of diverse
MMO cutoff values in defining RIT in previous studies
lacks a systematic approach.[,] This is primarily
due to the absence of objective and reliable metric assessments
comparing MMO measurements before and
after RT. The application of variable RIT cutoff values
complicates the analysis of risk factors and the evaluation
of different therapeutic interventions for RIT. Nevertheless,
efforts have been made by Dijkstra et al.[] to
standardize the definition of trismus in HNC patients by
establishing a generally accepted MMO cutoff value of
35 mm or less. However, Dijkstra et al.[] widely accepted
RIT definition fails to consider the relative changes
between the pre-RT and post-RT measurements, as it
applies identical criteria to every patient with HNC.
The frequently cited risk factors associated with the
development of RIT encompass age, sex, genetic predisposition,
nutritional status, smoking, presence of chronic
inflammatory disorders, TMJ disorders, arthropathies,
history of prior trauma, fibrotic disorders, tumor
characteristics (such as location, size, and stage), the
involvement and location of neck nodes, prior surgical
interventions and their extent, the proximity of the RT
field to the masticatory muscles and TMJ, RT modality
and technique, as well as the inclusion of chemotherapy
in conjunction with RT and their administration sequence.[] Intensity-modulated radiotherapy (IMRT)
has improved the distribution of radiation doses to the
tumor, neck, and high-risk regions compared to previous
methods, reducing radiation doses to at-risk organs.
[] Consequently, individuals who undergo IMRT
treatment are anticipated to have a reduced occurrence of RIT in comparison to those treated with conventional
methods. As an example, Chen et al.[] documented
an RIT prevalence of only 5.7% in patients with
nasopharyngeal cancer who had treatment with IMRT.
Moreover, proton therapy appears to result in the lowest
RIT rates, according to its exceptional tissue-sparing capabilities.
While there is insufficient long-term evidence
on the rates of RIT, particularly for proton treatment,
preliminary studies indicate that the occurrence of RIT
may be reduced compared to IMRT, perhaps less than
5%. Traditional RT modalities have been shown to have
higher incidences of RIT, ranging from 25% to 40%. On
the other hand, IMRT has lower rates of trismus, ranging
from 5% to 15%. Proton therapy, however, has the
lowest rates of trismus, less than 5%. This comparison
emphasizes the benefits of IMRT and proton therapy in
minimizing the likelihood of RIT in patients receiving
RT for HNC. Nevertheless, the availability of advanced
technologies such as IMRT and proton therapy might
provide an obstacle for countries with limited funds, a
drawback of these technologies.[]
CCRT poses a higher risk for RIT development than
RT alone. Borges et al.[] recently addressed this issue
in a meta-analysis of eight articles and 2332 patients:
chemoradiotherapy (n=1474) and RT alone (n=858).
The results of this meta-analysis demonstrated that
the addition of chemotherapy to RT increases the RIT
prevalence by a factor of 2.55 (p=0.0003). Therefore,
the risk of RIT must be assessed on a per-patient basis
by considering the significant variabilities among numerous
factors predisposing to RIT in HNC patients,
which may be beneficial in the early arrangement of
preventive measures for high-risk patients.
RIT is more likely to occur when the radiation
doses to the masticatory muscles, namely the masseter,
pterygoid, and temporalis muscles, or the TMJ, surpass
60 Gy.[] Although a prescription dose of >60 Gy is often reported as the threshold dose for RIT development,
the fundamental determinant of the RIT risk is
not the total dose received by the tumor but the doses
received by the masticatory muscles and TMJ.[] This
is because the doses delivered to the masticatory apparatus
may be significantly lower or higher than the
prescribed doses to the tumor, depending on factors
such as the size of the irradiated volume, its proximity
to these structures, the location of the hot spot
doses, the radiation modality, and the technique used.
[] For instance, Somay et al.[] administered 70.0,
59.4, and 54.0 Gy for high-risk, intermediate-risk, and
low-risk planning target volumes (PTVs) using the simultaneous
integrated boost IMRT technique in 230
locally advanced nasopharynx (LA-NPC) patients who
underwent C-CRT. However, the authors found that a
mean masticatory apparatus dose (MAD) of >37.2 Gy
(p<0.05) and the MAD V53.2 Gy>38.6% (p<0.05) were
the threshold values associated with a significantly increased
risk of RIT development, even though these
values are much lower than the prescribed doses to the
PTVs. Consequently, the mean and Vx (percentage receiving
X Gy or higher) doses of MAD emerge as more
reliable indicators of the extent of injury to the masticatory
apparatus and, hence, the risk of RIT in HNC
patients undergoing RT or C-CRT. This assertion accords
well with the anatomical structure and functional
characteristics of the masticatory apparatus, which
operates as a parallel organ when irradiated.[] Despite
the lack of reliable outcomes from well-structured
large-scale studies providing adequate data to formulate
definitive recommendations for threshold doses in
routine RT planning, it is savvy to minimize the mean
MAD and MAD Vx doses without compromising tumor
control rates to mitigate the risk of RIT.[]
Acute effects such as inflammation, edema, and
muscle spasms may occur during or immediately after
RT before RIT manifests. Depending on the dose and
fractionation schedule applied, long-term effects such as
fibrosis and scarring may also develop.[] The primary
step in managing these effects is to control the disabling
pain with analgesic medications, such as non-steroidal
anti-inflammatory drugs. Patients should be encouraged
to initiate jaw movements and physiotherapy.[]
Alternatively, botulinum toxin has been suggested for
pain control. However, injections into the TMJ region are
only effective in relieving radiation-induced pain caused
by radiation-induced fibrosis syndrome, and additional
injections are needed later to relieve recurrent masseter
muscle pain. Moreover, no reliable evidence suggests
that the administration of botulinum toxin significantly
improves the severity of RIT.[] Although there is no
consensus on whether starting exercise before RT or CCRT
will improve mouth opening after treatment, it has
been reported that the incidence of RIT is low in patients
with high pre-treatment MMO measures.[] Additionally,
jaw exercise therapy before treatment is reported to
increase MMO, reduce symptoms associated with radiation-
induced trismus, and improve health-related quality
of life. Therefore, it is recommended that jaw exercise
therapy be initiated early, structured, and continued in
the long term, making jaw exercises essential (Fig. 2).[]
Fig. 2. Jaw opening and stretching exercises applied to patients in our clinic: (a) Exercises that assist in opening the
mouth. (b) Perform self-mouth opening exercises, also known as mouth-open-wide exercises: a. Maintain the
position for a duration of 7-10 seconds; b. Repeat the exercise 10 times, with 2 repetitions for each set. (c) Jaw
resistance (Using one hand, gently grasp the chin with the index finger and thumb; apply pressure by closing your
mouth while providing gentle downward force on the chin): a. Maintain for 7-10 seconds; b. Repeat 10 times,
with 2 sets; (d) Forward jaw displacement: Move the upper jaw forward so that the lower teeth are positioned in
front of the upper teeth: a. Hold for 7-10 seconds; b. Repeat 10 times, with 2 sets); (e) Perform lateral jaw movement
by moving the jaw from side to side with a slightly open mouth: a. Maintain this position for 7-10 seconds.
b. Repeat this action 10 times, with two sets of repetitions.
In addition to the non-invasive measures, oral and
maxillofacial surgeons can perform various intraoperative
interventions to minimize trismus, one of which is
the prophylactic excision of the adjacent coronoid process
(the insertion site of the temporalis muscle) in cases
of cancer in the mandibular ramus area, temples, or
zygomatic arch.[] Surgeons can also perform various
intraoperative interventions to minimize RIT incidence
or alleviate RIT-related symptoms and functional losses.
One of these interventions is the prophylactic excision
of the adjacent coronoid process, which is the insertion
site of the temporalis muscle, in cases of cancer in the
mandibular ramus area, temples, or zygomatic arch.[]
Muscle myotomy is a preferred method to treat myofibrotic
contracture of the masticatory muscles that may
occur due to RT, surgical scarring, or immobilization.
Similarly, coronoidectomy may be considered an alternative
in temporalis muscle pathology cases.[] Surgical
excision of scar tissue and fibrotic bands and restoration
of tissue defects may improve trismus by alleviating
the restriction.[-] As the fibrosis in muscle tissue
due to surgery increases, there is a risk of further reduction
in MMO and the potential for persistent limited
mouth opening, which can lead to TMJ ankylosis.[]
It is vital to follow all release-reconstruction operations
with rigorous physical therapy regimens and select cooperative
and motivated patients for such procedures to
increase success rates in managing disabling RIT.
Early diagnosis of RIT is crucial, as it may threaten
the patient's life by making it difficult to keep the airway
open under emergency conditions. Imaging studies, such as magnetic resonance imaging and computed
tomography scans, are beneficial for assessing structural
changes in the TMJ, synovial fluid, and adjacent soft tissues.[] The aforementioned imaging modalities may
further facilitate the evaluation of the severity of secondary
complications, including fibrosis, joint abnormalities,
and osteoradionecrosis, all of which may exacerbate
RIT. Additionally, functional assessments, such
as electromyography, can yield a more comprehensive
understanding of the neuromuscular aspects of trismus,
ultimately contributing to a more thorough diagnostic
process.[,] The complex nature of RIT and the fact
that many aspects of the patient's condition can impact
the prognosis and effectiveness of treatment necessitate
a multidisciplinary evaluation process in which patients
are actively involved. This team typically includes radiation
oncologists, medical oncologists, dental oncologists,
oral and maxillofacial surgeons, periodontologists,
general dentistry specialists, physiotherapists, speech
therapists, psychiatrists, and dietitians, emphasizing
the need for tailored management of patients requiring
special care. Such comprehensive modern approaches
will undoubtedly reduce the RIT rates and improve the
prophylactic and treatment measures, with resultant advancements
in most aspects of QoL scores (Fig. 3).
Fig. 3. The key points of determination and management of radiation-induced trismus.
RIT: Radiation-induced trismus; HNC: Head and neck cancer; C-CRT: Concurrent chemoradiotherapy; IMRT: Intensity-modulated
radiotherapy; TMJ: Temporomandibular joint; MAD: Masticatory apparatus dose; V: Volume.
