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Comprehensive Diagnostic Approach to Head and Neck Masses

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Abstract

Head and neck masses are a significant diagnostic challenge and differential diagnoses range from inflammatory, infectious, and neoplastic conditions. Timely, accurate evaluation is essential for optimal patient outcomes. This review highlights a systematic approach to diagnosing head and neck masses through comprehensive history, physical examination, and a variety of diagnostic tools. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound are integral in diagnosis. Fine-needle aspiration (FNA) biopsy is a minimally invasive option for a preliminary diagnosis. However, in cases where it may be inconclusive or when extensive tissue sampling is needed to confirm a diagnosis, open tissue biopsy is considered. Collaboration among a multidisciplinary team (surgeons, radiologists, and pathologists) is vital in developing an effective individualized treatment plan. Early detection and accurate diagnosis of head and neck masses are critical for achieving favorable clinical outcomes.
Citation: Chowdhury, R.; Turkdogan,
S.; Alsayegh, R.; Almhanedi, H.; Al
Majid, D.; Le Blanc, G.; Gerardis, G.;
Himdi, L. Comprehensive Diagnostic
Approach to Head and Neck Masses.
J. Otorhinolaryngol. Hear. Balance Med.
2024,5, 17. https://doi.org/10.3390/
ohbm5020017
Academic Editor: Jeroen C. Jansen
Received: 23 September 2024
Revised: 7 November 2024
Accepted: 14 November 2024
Published: 19 November 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Technical Note
Comprehensive Diagnostic Approach to Head and Neck Masses
Raisa Chowdhury 1, Sena Turkdogan 2, Raihanah Alsayegh 3, Hamad Almhanedi 3, Dana Al Majid 3,
Gabriella Le Blanc 3, George Gerardis 3and Lamiae Himdi 3, *
1Faculty of Medicine and Health Science, McGill University, Montreal, QC H3G 2M1, Canada
2Department of Otolaryngology Head & Neck Surgery, University of British Columbia,
Victoria, BC V5Z 1M9, Canada
3Department of Otolaryngology Head & Neck Surgery, McGill University Health Centre,
Montreal, QC H4A 3J1, Canada
*Correspondence: lamiae.himdi@mcgill.ca
Abstract: Head and neck masses are a significant diagnostic challenge and differential diagnoses range
from inflammatory, infectious, and neoplastic conditions. Timely, accurate evaluation is essential
for optimal patient outcomes. This review highlights a systematic approach to diagnosing head and
neck masses through comprehensive history, physical examination, and a variety of diagnostic tools.
Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and
ultrasound are integral in diagnosis. Fine-needle aspiration (FNA) biopsy is a minimally invasive
option for a preliminary diagnosis. However, in cases where it may be inconclusive or when extensive
tissue sampling is needed to confirm a diagnosis, open tissue biopsy is considered. Collaboration
among a multidisciplinary team (surgeons, radiologists, and pathologists) is vital in developing an
effective individualized treatment plan. Early detection and accurate diagnosis of head and neck
masses are critical for achieving favorable clinical outcomes.
Keywords: head and neck masses; imaging modalities; fine-needle aspiration; multidisciplinary
management; patient outcomes
1. Case Scenario
Mr. P, a 55-year-old man, presents to the clinic with a gradually enlarging swelling on
the left side of his neck, which he first noticed a few weeks ago. He describes the mass as
painless and primarily noticeable when he touches his neck or turns his head. He denies
any difficulty swallowing, changes in voice, or discomfort while chewing. He also reports
no recent illnesses, fevers, chills, night sweats, unintentional weight loss, or trauma to the
neck. Mr. P’s medical history is unremarkable, and he is not on any regular medications.
On examination, a firm, non-tender, well-defined mass is palpated in the left anterior
cervical region, just below the angle of the mandible. The mass is non-fluctuant and not
warm to the touch. There are no palpable lymph nodes in the surrounding area, and the
overlying skin is intact, showing no signs of inflammation or discoloration.
Given the clinical presentation, differential diagnoses could include benign causes (e.g.,
benign salivary gland tumor) or malignant conditions (e.g., lymphadenopathy secondary
to metastatic disease, lymphoma). A systematic approach is essential to determine the
underlying cause, guiding subsequent management.
Mr. P’s age (55 years) increases the likelihood of malignancy, particularly in cases of
metastatic disease or lymphoma. Other risk factors like human papilloma virus (HPV)
infection, smoking, and alcohol consumption cancers should be considered if present. Also,
screening for head and neck malignancies is essential, particularly when there are risk
factors or concerning features such as a hard or fixed mass.
The following stages in assessing Mr. P’s neck tumor should adhere to a systematic
clinical decision-making framework. First, a detailed history and examination should be
J. Otorhinolaryngol. Hear. Balance Med. 2024,5, 17. https://doi.org/10.3390/ohbm5020017 https://www.mdpi.com/journal/ohbm
J. Otorhinolaryngol. Hear. Balance Med. 2024,5, 17 2 of 8
performed. The presence of a painless, slowly developing mass with no high-risk symptoms
suggests a benign cause but malignancy needs to be ruled out first. Imaging studies can
help characterize the structural assessment of the mass as well as guide FNA biopsy if the
mass is small or difficult to palpate. Fine-needle aspiration is generally considered the best
next step for a definitive diagnosis. It provides a minimally invasive means of assessing
cytology, differentiating the benign lesion from a malignancy. It is important to note that if
FNA is not feasible due to the mass being highly vascular or the presence of infection, core
biopsy or excisional biopsy may be considered, with additional imaging if necessary. The
American Academy of Otolaryngology guidelines emphasize early imaging and FNA in
patients with persistent neck masses.
Given Mr. P’s presentation of a painless, gradually enlarging neck mass without
associated systemic symptoms, the next step in management should focus on determining
the underlying cause to guide appropriate patient care.
Question: What is the most appropriate next step in management for this patient?
(A)
Order a complete blood count (CBC) and comprehensive metabolic panel (CMP)
(B)
Perform fine-needle aspiration (FNA) biopsy of the mass
(C)
Refer the patient for imaging studies (e.g., ultrasound, CT scan)
(D)
Start empiric antibiotic therapy
(E)
Reassure the patient and schedule a follow-up appointment in six months
Answer
B. Perform fine-needle aspiration (FNA) biopsy of the mass. FNA is the preferred next
step as it is minimally invasive and often sufficient for the initial evaluation of a painless
neck mass. This procedure allows for the collection of tissue samples from the mass, which
can then be examined microscopically to differentiate between benign and malignant
lesions, guiding further management decisions. Imaging (Option C) can complement
FNA by providing an anatomical extension of the lesion but does not provide a definite
diagnosis. An empiric antibiotic therapy (Option D) is not indicated, as there are no signs
of infection, and reassurance with delayed follow-up (Option E) would be inappropriate
without further evaluation.
2. Initial Approach
2.1. Overview of Head and Neck Mass
Head and neck masses are abnormal growths or lumps found between the base of the
skull and the collarbone. They can arise from various conditions, including inflammation,
congenital abnormalities, benign growths, or malignancies. In adults, these masses should
be considered potentially malignant until proven otherwise. The diagnostic sequence
begins with a thorough history and physical examination. Significant advances in diagnosis
(i.e., rapid FNA biopsy following initial imaging) have improved initial assessment accuracy.
These steps are crucial to ensure early diagnosis, appropriate management, and timely
intervention by a multidisciplinary team [14].
2.2. History Taking
A detailed history is essential when evaluating a patient with a head or neck lump.
Clinicians should assess the onset and duration of the presenting mass, and associated
symptoms such as pain, difficulty swallowing, voice changes, fever, night sweats, uninten-
tional weight loss, or recent trauma. Additionally, inquire about the patient’s past medical
history, including previous surgeries, chronic conditions, and current medications. Lifestyle
factors, such as smoking, alcohol use, and occupational exposures, should also be discussed.
Understanding family history, particularly regarding head and neck cancers, is crucial.
This comprehensive history helps in forming a differential diagnosis and determining
the need for further evaluation [
5
]. High-risk history (pain, short duration, weight loss)
may prompt an immediate FNA for early cytological assessment, while low-risk history
(painless, chronic, trauma) may justify observation.
J. Otorhinolaryngol. Hear. Balance Med. 2024,5, 17 3 of 8
2.3. Physical Examination
Physical examination is a critical component in assessing head and neck masses. In
adults, a cautious approach is to consider neck masses as malignant until proven otherwise.
It aims to characterize mass features such as size, mobility, and consistency. Specific
physical exam findings, such as fixation to surrounding tissues, firmness, size greater than
1.5 cm, or skin ulceration, may indicate a higher risk of cancer [1,4].
Neurological assessment is crucial in evaluating head and neck masses, helping to
identify neurologic pathologies and refine differential diagnoses. This includes a thorough
examination of the cranial nerves, which are vital for head and neck function. Imag-
ing studies further assist in differentiating benign from malignant lesions, aiding in the
development of treatment strategies [6] (Table 1).
Table 1. Physical examination of head and neck mass. Adapted from [69].
Examination Component Details
Assessment of Mass Location and Size Determine the exact location, size, and any changes over time.
Evaluation of Skin Color and Texture
Observe for discoloration, redness, or changes in skin texture over the mass.
Palpation for Tenderness or Firmness Assess the mass for tenderness, firmness, and consistency.
Assessment of Mass Mobility Evaluate whether the mass is mobile or fixed to surrounding tissues.
Examination of Surrounding Lymph Nodes Check for enlargement or tenderness in regional lymph nodes.
Assessment of Cranial Nerve Function Test the functionality of cranial nerves to detect any neurological deficits.
Evaluation of Voice Quality and Swallowing Assess for hoarseness, voice changes, or difficulty swallowing.
Inspection of Oral Cavity and Oropharynx Examine the mouth, throat, and oropharynx for any abnormalities.
Examination of Nasal Cavity and Sinuses Check for obstructions, masses, or signs of infection in the nasal passages.
Assessment of Thyroid Gland (if applicable) Evaluate for enlargement, nodules, or tenderness of the thyroid gland.
Inspection of Ear Canal and Tympanic Membrane Examine the ear canal and eardrum for abnormalities or fluid.
2.4. Differential Diagnosis
Cervical masses are frequently encountered in adult patients by general practitioners.
A thorough medical history and comprehensive physical examination are paramount.
Considerations include patient age and characteristics of the mass, such as location, size,
and duration. In young children, inflammatory and infectious causes like cervical adenitis
and cat-scratch disease are common, whereas congenital anomalies like branchial cleft
cysts and thyroglossal duct cysts should be considered. In older adults, the differential
diagnosis is broader, where both benign and malignant neoplastic causes (lymphoma,
squamous cell carcinoma, and metastatic tumors) are more prevalent [
8
]. In these cases,
the mass’s characteristics (such as being firm, fixed, or progressively enlarging) often raise
suspicion for malignancy. Current guidelines suggest observation for low-risk masses
(mobile, soft, small size), and a conservative approach (observation or antibiotic course)
may be suitable. But in high-risk masses (fixed, firm, larger than 1.5 cm), a combination of
FNA and imaging is suggested to confirm the diagnosis, allowing for early detection and
timely treatment [1,4].
2.5. Investigations
Imaging studies are essential in evaluating head and neck masses, providing critical
information about their nature and extent [
10
,
11
]. First-line investigations for all adults
at risk of malignancy consist of CT of the neck with contrast and fine-needle aspiration.
These two investigations provide complementary information, including primary tumor
histopathological detection, anatomical localization, and nodal staging. Simultaneously
arranging these investigations prevents delays in diagnosis and treatment [4].
2.5.1. Computed Tomography (CT) of Neck with Intravenous Contrast
It is the preferred initial imaging modality for staging head and neck masses. It
effectively delineates bony invasion, evaluates nodal basins, and is the first-line choice for
lesions in the oral, oropharyngeal, laryngeal, and hypopharyngeal regions [
11
14
]. Also, a
CT scan can help differentiate benign processes, such as salivary calculi or dental infections.
J. Otorhinolaryngol. Hear. Balance Med. 2024,5, 17 4 of 8
While generally safe, CT scans may be contraindicated due to contrast use, in patients with
kidney impairment or iodine allergy [1,7].
2.5.2. Fine-Needle Aspiration Biopsy
It is a vital diagnostic tool for non-thyroidal head and neck lesions. It provides
clinicians with key insights into tissue composition and pathology, and determines the
nature (benign or malignant) of the suspicious masses. FNA biopsy is valued for its
accessibility, cost-effectiveness, and clinical utility [
11
,
13
]. The procedure involves the
extraction of cellular material from suspicious masses, enabling cytological examination to
determine the underlying pathology. When correlated with subsequent excisional biopsy
results, FNA significantly enhances diagnostic accuracy and aids in treatment planning
for patients with head and neck masses [
15
]. However, it is contraindicated in vascular
lesions due to inadequate sampling because of risk of bleeding. Despite this, FNA and
contrast-enhanced CT scanning are optimal for assessing these masses. Persistent neck
masses beyond one course of broad-spectrum antibiotics over four to six weeks warrant
referral to otolaryngology for endoscopic evaluation and possible excisional biopsy [6,8].
2.5.3. Other Investigations
Ultrasound imaging is the preferred initial modality for assessing thyroid, salivary
gland, lymph node, muscle, and soft tissue pathologies within the head and neck region.
It is also helpful in ultrasound guided-FNA in cases where the mass is very small or
deep within the skin, which makes it difficult to palpate. Improved visualization through
ultrasound allows for better sample collection [10,12].
Magnetic resonance imaging (MRI) is particularly useful for assessing soft tissue
involvement and detecting small tumors [
10
,
12
]. MRI excels in detecting sinonasal, na-
sopharyngeal, and salivary gland tumors. However, it has some drawbacks which include
more motion artifacts, longer scan times, and generally poorer availability and tolerability
compared to CT. Therefore, CT remains the preferred primary imaging modality for head
and neck pathologies [4].
Positron emission tomography (PET) with CT utilizing the fluorodeoxyglucose tracer
has demonstrated high sensitivity and specificity in the detection of primary and recurring
head and neck tumors. As a result, PET/CT is becoming increasingly important in the
evaluation of head and neck tumors, particularly in the diagnosis of residual or recurrent
tumors following treatment. However, due to its restricted availability, PET/CT is not
suitable as a first-line imaging investigation [4,1114].
Ultrasonography is invaluable for differentiating between cystic from solid lesions and
evaluating lymph nodes in head and neck masses. They offer a detailed assessment of nodal
size, distribution, internal structure, and vascular patterns. Doppler and contrast-enhanced
ultrasonography provide additional insights into lymph node perfusion and differentiate
high-flow from low-flow vascular malformations [
9
]. Ultrasonography can also help guide
FNA for nonpalpable or tiny superficial lesions. Although CT and ultrasonography have
equal capabilities, ultrasonography is frequently preferred initially in younger patient
populations to limit radiation exposure [16].
Elastography allows for both qualitative and quantitative assessment of lymph node
stiffness. Due to its reliability and cost-effectiveness, ultrasonography is an excellent
screening method for detecting malignant lymph nodes, with higher sensitivity compared
to other imaging modalities [
9
]. Laryngeal sonography has evolved as an important
imaging method, particularly during the SARS-CoV-2 epidemic. It is quick, non-invasive,
and allows for repeated real-time evaluation of the patient, which might be advantageous in
some diagnostic settings. However, head and neck sonography is still operator-dependent,
which affects diagnostic sensitivity and specificity [
17
]. The investigation of head and neck
masses is based on excluding malignancy. The course of investigation is determined by an
assessment of the indications and symptoms, as well as the results of prior investigations.
An approach to investigation is shown in Figure 1.
J. Otorhinolaryngol. Hear. Balance Med. 2024,5, 17 5 of 8
J.Otorhinolaryngol.Hear.BalanceMed.2024,5,xFORPEERREVIEW5of9
Elastographyallowsforbothqualitativeandquantitativeassessmentoflymphnode
stiness.Duetoitsreliabilityandcost-eectiveness,ultrasonographyisanexcellent
screeningmethodfordetectingmalignantlymphnodes,withhighersensitivitycompared
tootherimagingmodalities[9].Laryngealsonographyhasevolvedasanimportant
imagingmethod,particularlyduringtheSARS-CoV-2epidemic.Itisquick,non-invasive,
andallowsforrepeatedreal-timeevaluationofthepatient,whichmightbeadvantageous
insomediagnosticseings.However,headandnecksonographyisstilloperator-
dependent,whichaectsdiagnosticsensitivityandspecicity[17].Theinvestigationof
headandneckmassesisbasedonexcludingmalignancy.Thecourseofinvestigationis
determinedbyanassessmentoftheindicationsandsymptoms,aswellastheresultsof
priorinvestigations.AnapproachtoinvestigationisshowninFigure1.
Figure1.Flowchartfortheassessmentofadultswithaheadandneckmass.Adiagramillustrating
thesequenceofclinicalevaluationanddiagnosticprocedures.CT:computedtomography;FNA:
ne-needleaspiration.AdaptedfromtheAmericanAcademyofOtolaryngology[1].
3.BeyondtheInitialApproach
3.1.MultidisciplinaryApproach
Acomprehensive,multidisciplinaryapproach(pathologists,surgeons,radiologists,
andoncologists)iscrucialforeectivelymanagingpatientswithheadandneckmasses.
Radiologistsuseimagingmodalitiestohelpindiagnosisandstagingbydeterminingthe
preciselocationofthetumorandsurroundinganatomicalstructures.Pathologistsmake
thenaldiagnosisbyhistologicalexamination,remarkingontheprecisenatureofthe
mass,anditsspreadtoneighbouringstructures.Surgeonsplayanimportantroleintumor
removalusingconservativeorthoroughexcisionalbiopsiesofthemass.Medicaland
radiationoncologistsplanandadministerchemotherapyandradiationtherapy,
especiallyinthetreatmentofmalignantheadandneckmalignancies.Thiscollaborative
strategyensuresthoroughassessment,accuratediagnosis,andimprovedtreatment
outcomesbyadheringtoestablishedclinicalprotocolsandfosteringparticipationin
researchinitiatives.Multidisciplinaryteamsareinstrumentalinshapingdiagnosticand
Figure 1. Flowchart for the assessment of adults with a head and neck mass. A diagram illus-
trating the sequence of clinical evaluation and diagnostic procedures. CT: computed tomography;
FNA: fine-needle aspiration. Adapted from the American Academy of Otolaryngology [1].
3. Beyond the Initial Approach
3.1. Multidisciplinary Approach
A comprehensive, multidisciplinary approach (pathologists, surgeons, radiologists,
and oncologists) is crucial for effectively managing patients with head and neck masses.
Radiologists use imaging modalities to help in diagnosis and staging by determining the
precise location of the tumor and surrounding anatomical structures. Pathologists make
the final diagnosis by histological examination, remarking on the precise nature of the
mass, and its spread to neighbouring structures. Surgeons play an important role in tumor
removal using conservative or thorough excisional biopsies of the mass. Medical and
radiation oncologists plan and administer chemotherapy and radiation therapy, especially
in the treatment of malignant head and neck malignancies. This collaborative strategy
ensures thorough assessment, accurate diagnosis, and improved treatment outcomes by
adhering to established clinical protocols and fostering participation in research initiatives.
Multidisciplinary teams are instrumental in shaping diagnostic and therapeutic strategies,
particularly for patients newly diagnosed with head and neck malignancies [1821].
3.2. Surgical Intervention
Surgical management remains a viable and effective option for treating head and
neck masses. The size of the tumor, its location, and the patient’s overall health deter-
mine surgical candidacy. Over recent decades, the development of minimally invasive,
endoscopically-assisted transoral approaches (transoral robotic surgery and transoral laser
microsurgery) has gained popularity due to their enhanced cosmetic and functional out-
comes. These approaches allow for adequate mass excision with minimal external incisions,
making it ideal for early-stage or benign tumors with limited vascular involvement [
22
].
However, minimally invasive techniques for emergent bleeding offer limited survival
benefits. Larger invasive tumors or those involving vital structures often require traditional
open surgery, which may be combined with reconstruction for optimal functional and
J. Otorhinolaryngol. Hear. Balance Med. 2024,5, 17 6 of 8
aesthetic outcomes [
23
,
24
]. Surgery is still the preferred treatment option due to complete
removal and lower chances of recurrence [16].
3.3. Non-Surgical Treatment
Non-surgical treatments (radiotherapy and chemotherapy) are frequently recom-
mended for patients who have contraindications to surgery, such as those with advanced
disease, a high anesthesia risk, or those who value functional preservation. Patient factors
such as age, comorbidities, and the presence of metastatic disease also influence surgical
decisions, as older patients or those with advanced disease may derive more benefit from
non-surgical therapies. Radiotherapy is particularly suited for patients with localized tu-
mors where organ preservation is desired. Conversely, chemotherapy is typically indicated
in advanced or metastatic cases, where it may help control disease progression and improve
survival [16].
3.3.1. Radiation Therapy
Radiation therapy is a common treatment modality for head and neck masses, either
as a standalone treatment or in combination with chemotherapy. Standard radiation
doses for primary treatment typically range between 60 and 70 Gy, delivered using high-
energy photons via external beam radiation. Given the complex anatomy of the head and
neck, meticulous planning is required to minimize potential adverse effects. Innovative
techniques such as intensity-modulated radiation therapy (IMRT) and magnetic resonance-
guided high-intensity focused ultrasound (MRg-HIFU) are being explored to enhance
treatment efficacy while reducing side effects [25,26].
3.3.2. Chemotherapy
Chemotherapy regimens for head and neck cancer often include platinum-based
agents, antimetabolites like 5-fluorouracil (5-FU) and methotrexate, and taxanes. Targeted
therapies, such as anti-EGFR antibodies, may also be incorporated into treatment protocols.
Response rates to conventional treatments, such as 5-FU combined with cisplatin or carbo-
platin, generally range from 20 to 30%. Ongoing research is investigating the efficacy of
newer agents, including artemisinin derivatives and sGC activators, in the management of
head and neck malignancies [27,28] (Table 2).
Table 2. Management of head and neck mass. Adapted from [18,19,2328].
Management Approaches Description
Surgical Intervention Surgical removal of the head or neck mass, often aiming for complete excision.
Radiation Therapy High-energy radiation is used to target and destroy cancer cells.
Chemotherapy Administration of drugs to kill or inhibit the growth of cancer cells.
Targeted Therapy Focuses on specific molecules involved in cancer growth and progression.
Immunotherapy Enhances the body’s immune response to fight cancer more effectively.
Surveillance Monitoring Provides symptom relief and improves the comfort and quality of life for patients.
Supportive Care Provides symptom relief and improves the comfort and quality of life for patients.
Patient Education Informs patients about their condition, treatment options, and care strategies.
Referral to Specialist Directs patients to specialized healthcare professionals for advanced care.
Treatment Planning
Development of a personalized and comprehensive management plan tailored to the patient’s needs.
3.4. Follow-Up
The necessity for a routine follow-up beyond three years post-treatment in head and
neck cancer patients is debated, as only about 2% of recurrences are detected after this
period, all of which are symptomatic. For patients, additional visits as symptoms arise
may be sufficient for late-stage follow-up needs [
29
]. Recurrence rates are highest within
the first three years following treatment, with regular visits recommended during this
period, extending up to five years in some cases. Beyond this timeframe, the frequency
of follow-ups should be tailored to the individual patient’s needs, focusing on early de-
J. Otorhinolaryngol. Hear. Balance Med. 2024,5, 17 7 of 8
tection of recurrence, managing treatment-related complications, and providing ongoing
psychosocial support [29].
4. Limitations
However, the limitation of this study is the variability in diagnostic imaging modalities
that is used for better visualization and staging of the tumor. The choice of imaging
modality, especially between CT with contrast and MRI with contrast, makes a difference in
the information obtained in the tumor’s structure and extent, that may eventually influence
the staging outcome. While CT with contrast is useful for bony invasion, the extent of tumor
into soft tissue is visualized better with contrast of MRI, which provides more accurate
staging in specific cases. Thus, relying on a single imaging modality may limit the ability
to stage cases consistently.
5. Conclusions
Overall, adapting a standardized approach that aligns with current national and
international protocols is crucial. This will ensure better, early, and consistent diagnosis
and management of head and neck masses. As imaging and diagnostic modalities evolve,
the continued refinement of these protocols will enhance diagnostic accuracy and improve
patient outcomes.
Author Contributions: Conceptualization, R.C.; methodology, R.C.; validation, R.C., S.T., R.A., H.A.,
D.A.M., G.L.B., G.G. and L.H.; formal analysis, R.C.; investigation, R.C. and L.H.; data curation, R.C.;
writing—original draft preparation, R.C.; writing—review and editing, R.C., S.T., R.A., H.A., D.A.M.,
G.L.B., G.G. and L.H.; visualization, R.C.; supervision L.H.; project administration, R.C. All authors
have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflicts of interest.
List of Abbreviations
Abbreviation Full Term
5-FU 5-Fluorouracil
CBC Complete Blood Count
CT Computed Tomography
EGFR Epidermal Growth Factor Receptor
FNA Fine-Needle Aspiration
HPV Human Papilloma Virus
IMRT Intensity-Modulated Radiation Therapy
MRI Magnetic Resonance Imaging
MRg-HIFU Magnetic Resonance-Guided High-Intensity Focused Ultrasound
PET Positron Emission Tomography
sGC Soluble Guanylate Cyclase
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