Back To Search Results

Total Laryngectomy

Editor: Jason Widrich Updated: 5/28/2023 10:40:39 AM

Introduction

The primary goal in treating laryngeal cancer is oncologic control of the disease. Secondary goals include preserving speech and swallowing functions and avoidance of tracheostomy. Treatment regimens for laryngeal carcinomas may include radiotherapy, chemotherapy, surgery, or a combination. The expertise of an interprofessional team, such as a tumor board or within a multidisciplinary clinic, often determines the treatment for laryngeal cancer. Treatment is based on the tumor type, location, function of the larynx, and medical and social comorbidities of the individual patient. Total laryngectomy is the standard of care for surgical salvage in laryngeal cancer that has failed or recurred after nonsurgical management; it is also performed routinely as a primary treatment for advanced-stage laryngeal malignancy.[1]

Several anatomic, physiologic, geographic, and vocational factors may affect treatment selection. The most important parameter influencing treatment selection is the stage of the malignancy; the location and extent of the primary tumor and the status of the regional lymph nodes determine the stage. Early-stage (I and II) tumors can be treated with single-modality therapy, which can be primary radiation therapy or surgery (cordectomy or partial laryngectomy). Advanced-stage (III and IV) tumors require multimodality treatment, which may consist of a combination of radiation therapy and chemotherapy or surgery followed by radiation therapy.[2]

In the last decade, the focus of therapeutic approaches for malignant laryngeal tumors has shifted to "organ preservation." Treatment modalities such as transoral laser microsurgery (TOLM) and transoral robotic surgery (TORS) have expanded surgical options and decreased the morbidity of partial laryngeal surgery. Radiation therapy remains an important, organ-preserving treatment option for Stage I and II laryngeal malignancy. Total laryngectomy remains a first-line therapeutic option for patients who are unsuitable for organ-preserving techniques or in the setting of treatment failures. More rarely, a total laryngectomy may be performed for chronic aspiration.[3]

Anatomy and Physiology

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Anatomy and Physiology

Anatomy of the Larynx

The larynx is found in the anterior neck, connecting the inferior portion of the pharynx with the cervical trachea. There are 6 cartilage subunits; 3 unpaired (thyroid, cricoid, epiglottic) and 3 paired (arytenoid, cuneiform, corniculate). Each cartilage is surrounded by connective and muscular tissue. Although the hyoid bone, attached to the thyroid cartilage through the thyrohyoid membrane, is not a part of the laryngeal framework, it plays a vital role in the swallowing function of the upper aerodigestive tract.[4] 

For classification purposes, the larynx is divided into 3 regions based on embryologic development. Each region includes several subsites:

  1. Supraglottis: The portion of the larynx superior to the apex of the ventricle. It includes the ventricle, false vocal folds, arytenoids, aryepiglottic folds, and epiglottis.
  2. Glottis: Comprises the true vocal folds from the anterior to posterior commissure; the region extends anteriorly to 10 mm inferior to the true vocal folds and posteriorly to 5 mm inferior to the true vocal folds.
  3. Subglottis: The portion of the larynx from the inferior border of the glottis to the lower border of the cricoid cartilage.

The surface mucosa of the larynx consists of squamous epithelium with interposed mucous glands. The true vocal cords are lined by stratified squamous epithelium.[5]

The internal branch of the superior laryngeal nerve provides the sensory innervation to the supraglottic larynx.[6] The mucosa of the true vocal cords derives dual sensory nerve supply from the superior laryngeal and recurrent laryngeal nerves. The subglottic larynx derives its sensory supply from the recurrent laryngeal nerve. The intrinsic musculature of the larynx derives its innervation from the recurrent laryngeal nerve except for the cricothyroid muscle, which is innervated by the external laryngeal branch of the superior laryngeal nerve (nerve of Galli-Curci).[6] The larynx derives its blood supply from branches of the superior and inferior thyroid arteries.

The supraglottic larynx has a rich lymphatic network initially draining into lymph nodes at levels II and III. The lymphatic network of the glottis is very sparse, especially the free edge of the true vocal cord, which is devoid of lymphatics. The subglottic larynx drains into the paratracheal and deep jugular lymph nodes at levels IV and VI.[7]

Function of the Larynx

The 2 principal functions of the larynx are respiration and phonation.

The larynx represents the cephalad aperture of the respiratory tree, joining the upper digestive tract in the oropharynx. Three laryngeal structures protect the trachea and lower airways: the true vocal folds, the false vocal folds, and the epiglottis. The true and false vocal folds abduct during inhalation and exhalation to minimize airflow turbulence and maximize air exchange. Sensory branches of the superior laryngeal nerve create a cough reflex, rapidly closing the true and false vocal folds and increasing intra-thoracic pressure with any unexpected stimulation of the supraglottis or glottis during respiration. This helps prevent foreign material from passing into the lower airways.[8] The larynx elevates during deglutition, allowing the epiglottis to act as a cap overtop of the laryngeal inlet and diverting oropharyngeal contents laterally and posteriorly into the pyriform sinuses and cervical esophagus, decreasing the likelihood of material passing into the larynx inlet and lower airway. This also allows the vocal folds to remain open even when swallowing if normal sensation is intact, facilitating the suck-swallow-breathe pattern seen in nursing infants.[9]

The true vocal folds are the structures responsible for producing a normal voice. To do so, they must fully adduct and meet in the midline of the larynx. Air is propelled from the lungs into the trachea, then up through the vocal folds, which vibrate in a fluid wave, owing to their unique structure.[10] If the mobility of a vocal fold is impaired, as seen in vocal fold paralysis, the fold will not move completely to the midline. This causes a 'breathy' voice and compromises the protective function of the vocal folds. Disruptions to the mucosa or the submucosal structures of the true vocal folds impair vibration and will result in hoarseness. These disruptions may occur in many clinical conditions: with benign mucosal neoplasms such as papillomas, in the presence of vocal fold nodules, due to reactive changes from laryngopharyngeal reflux, in the presence of malignant neoplasms, or due to scarring from autoimmune diseases or trauma. As such, hoarseness is a very nonspecific sign.[11]

Laryngeal Anatomy and Function Post-Laryngectomy

The respiratory and digestive tracts normally meet in the oropharynx and hypopharynx. The posterior wall of the larynx is normally shared with the anterior wall of the esophagus, and both the laryngeal and esophageal introitus form the inferior boundaries of the hypopharynx. This anatomy allows for breathing via the nose and mouth and swallowing via the mouth.

A total laryngectomy eliminates this communication. After a laryngectomy, the entirety of the trachea is diverted to a stoma in the anterior neck, and the pharyngeal remnant is closed on itself to form a neo-pharynx. Thus there is a complete separation of the respiratory and digestive tracts. Breathing through the nose or mouth is no longer possible, as both now connect to the esophagus only. All respiration, including any needed oxygen supplementation or intubation, is via the anterior neck stoma, now an unprotected route to the trachea and lower airways. Similarly, while it is now impossible to aspirate via the nose or mouth, patients must take great care to avoid open water and be mindful of other foreign objects that can now be aspirated directly from the surface of the anterior neck.[12]

Indications

Total laryngectomy may be indicated in various circumstances.[13] Indications for total laryngectomy include:

  • Advanced laryngeal or hypopharyngeal malignancies with the invasion of thyroid or cricoid cartilage and extra laryngeal soft tissue
  • Failed response to primary radiotherapy or chemoradiotherapy
  • Extensive tumors of histologic entities not suitable for conservative treatment
  • Histopathological subtypes of tumors that have proven resistant to radiotherapy, such as soft tissue sarcomas, chondrosarcomas, melanomas, adenocarcinomas, large cell neuroendocrine tumors, and tumors of the minor salivary glands
  • Severe laryngeal trauma prohibiting functional reconstruction of the organ
  • Patients who have no voice and have chronic aspiration due to palsy of cranial nerves IX, X, or XI
  • Recurrent laryngeal papillomatosis with an increased risk of tracheal invasion

Contraindications

Contraindications to total laryngectomy include the presence of a surgically unresectable tumor, distant metastases, a condition resulting in high anesthetic risk, a tumor encasing the common or internal carotid artery, or a tumor invading the profound parts of the tongue. While tumors invading the profound parts of the tongue are technically resectable, such procedures are rarely performed except in extreme circumstances; procedure-associated morbidity is high.[14]

Equipment

  • Standard head and neck soft tissue set
  • Laryngoscopy set
  • Cautery: monopolar or bipolar diathermy, a harmonic scalpel
  • Nasogastric tube, if a concurrent gastrostomy is not planned
  • Tracheoesophagealgeal prosthesis and puncture kit, if planned

Personnel

  • Surgeon
  • Surgical first assistant
  • Anesthetist
  • Circulator or operating room nurse
  • Surgical technologist or operating room nurse

Preparation

The patient is placed on the operating table under general endotracheal anesthesia through an orotracheal tube. If difficult intubation is anticipated due to airway compromise, a planned awake fiberoptic intubation or preoperative tracheotomy can be performed with local anesthesia and vasoconstrictor preparation. 

Many surgeons plan on an immediate direct laryngoscopy after the airway has been secured to confirm the location and extent of the tumor and to plan the location of the initial pharyngotomy during the laryngectomy (into the pyriform versus the vallecula).

Technique or Treatment

A standard total laryngectomy procedure encompasses the entire larynx with its attached prelaryngeal strap muscles, the hyoid bone, the thyroid lobe ipsilateral to the tumor, and the lymph nodes in the anterior or pretracheal compartment (level VI). Unilateral or bilateral neck dissections are frequently performed concurrently with total laryngectomy to remove the lateral cervical lymph nodes at levels II-IV, sometimes to include levels I and V.

The most commonly used skin incision for total laryngectomy is the Gluck - Sorenson U-shaped incision (also termed the 'apron' or 'utility' incision). The starting point of the incision is located at the tip of the mastoid, continued on the anterior border of the sternocleidomastoid muscle up to 1 to 2 cm above the upper edge of the sternal notch, and it is continued in the same way on the opposite side. If a tracheotomy were performed before this procedure, the tracheal stoma would be included in the skin incision. Flap elevation should be in the subplatysmal plane, immediately above the anterior and external jugular veins, and deep to the muscle. The vascularisation of the flap is guaranteed by the rich subdermal plexus located superficial to the muscle. The upper and lower skin flaps are elevated to get exposure from the hyoid to the suprasternal notch.

If concurrent neck dissections are planned, these are typically performed first. The digastric tendon is identified and traced anteriorly to level Ia and posteriorly to the mastoid insertion. The marginal mandibular nerve is then identified and elevated sharply off the underlying submandibular gland to preserve it. This is then performed on the contralateral side. Level Ib nodes may be removed for oncologic indication, to facilitate microvascular access to the facial vessels, or to facilitate pharyngeal closure.

Mobilization of the larynx begins superiorly by detaching the muscles attached to the upper surface of the hyoid bone. Dissection proceeds to isolate the superior thyroid artery and its superior laryngeal branch. Identification, dissection, and ligation of these vessels will minimize hemorrhage during mobilization of the larynx. The stylohyoid attachment is released, and blunt dissection of the pyriform mucosa off the deep surface of the lesser cornua of the hyoid is performed to preserve as much pharyngeal mucosa as possible. 

Inferior release of the larynx is performed, with the sternohyoid and sternothyroid muscles divided as low in the neck as possible. The sternal heads of the sternocleidomastoid muscle are released to facilitate stomal care postoperatively. After dividing and ligating the inferior thyroid artery ipsilateral to the tumor, the thyroid isthmus is divided using two clamps and tied. This leaves the ipsilateral thyroid lobe attached to the laryngeal specimen to be included in the resection. Division of the isthmus exposes the cervical trachea allowing the release of the contralateral thyroid lobe, which is left in situ in the neck with its superior and inferior blood supply intact. The inferior constrictor muscle is detached bilaterally from the posterior edge of the thyroid cartilage using electrocautery. A Freer elevator is used to dissect in a sub-perichondrial plane on the deep surface of the thyroid cartilage to release and preserve as much mucosa as possible.

An incision is made in the anterior tracheal wall at a level dictated by the lower extent of the tumor. The trachea is divided obliquely, leaving a short anterior wall and a long posterior wall; this bevels the lateral tracheal walls superiorly to enlarge the final stoma. Next, the distal trachea is sutured to the skin edges of the chest with interrupted nylon sutures. Some surgeons will also place a permanent suture from the anterior trachea to the manubrium to relieve tension on the stomal suture line. Finally, the party wall between the proximal trachea and larynx is dissected from the cervical esophagus by sharp dissection up to the cricoid cartilage.

Lastly, entry is made in the pharynx through either the vallecula or the pyriform sinus opposite the tumor, depending on the tumor localization determined by imaging and preoperative laryngoscopy. After opening the mucosa to enter the pharynx, the mucosal incision is continued along the periphery of the larynx until the opening is large enough to permit the introduction of a retractor in the pharynx. Subsequent mucosal cuts are made under direct visualization with Metzenbaum scissors, leaving a gross margin from the visible tumor. Circumferential mucosal margins are sent for a frozen section to confirm oncologic resection.

If planned, a tracheoesophageal puncture (TEP) is performed at this time; otherwise, a cricopharyngeal myotomy is performed to maximize postoperative swallowing. If the patient does not have a gastrostomy tube, a nasogastric tube is passed under direct visualization from a naris into the pharynx and into the esophagus. This is sutured to the membranous nasal septum using a 3-0 silk. The pharyngeal defect is closed, preferably in a transverse fashion; if there is sufficient mucosa to close the neo-pharynx over the nasogastric tube, the neo-pharynx will be of sufficient caliber to permit swallowing once healed.

A continuous Connell inverting suture (true or modified) with 3-0 Vicryl closes the pharyngeal defect beginning inferiorly. Many surgeons will test for watertight closure at this time by instilling methylene blue-impregnated saline into the oropharynx with an Asepto syringe. Any leaks will be visualized and should be repaired immediately; meticulous attention at this step is required. After the closure of the pharynx, suction drains are placed lateral to the pharynx, the platysma is closed with interrupted Vicryl sutures, and the skin is closed with interrupted nylon sutures or staples.[15][16][17]

Complications

Early complications after total laryngectomy include bleeding, postoperative edema, and airway compromise. The patient should be carefully monitored for these complications in the immediate postoperative period. The patient should be on a postoperative ward familiar with laryngectomy care, as the stoma will need frequent suctioning in the first few days. Signs should be placed at the head of the bed and the room door indicating that the patient is a permanent neck breather and cannot be intubated orally or nasally.

A postoperative hematoma will present as a firm or fluctuant swelling and may result in purplish discoloration of the overlying skin; this should be promptly recognized and surgically evacuated. Wound infection is minimized using broad-spectrum antibiotic coverage for oral and oropharyngeal flora; this is continued until the drains are removed.

Pharyngocutaneous fistula is a complex and common complication of total laryngectomy due to dehiscence of the pharyngeal suture line. If left untreated, this can progress to pharyngocutaneous fistula. Initial presentation is typically between postoperative days four and five, with neck swelling and erythema of the overlying flaps. If drains are in place and functioning, saliva or mucopurulent fluid may be seen in the drain. The incidence of fistula formation depends on tension on the pharyngeal suture line, previous radiotherapy or chemoradiotherapy, nutritional status of the patient, and the presence of a medical comorbidity such as diabetes.

Overall primary pharyngeal leak rates for non-radiated patients are near 10% but rise to greater than 30% in patients undergoing a post-radiation laryngectomy.[18] Support of the pharyngeal suture line with a vascularized, non-radiated flap is a valuable measure that may reduce the risk and severity of a pharyngocutaneous fistula. This can be a free or regional pedicled flap and is a planned part of salvage laryngectomy in many centers.[19] 

Late complications of total laryngectomy include pharyngoesophageal stenosis, stoma stenosis, and hypothyroidism.[20]

Clinical Significance

Surgical management remains the mainstay for treating Stage T4 laryngeal cancers and select Stage T3 cancers where the larynx is nonfunctional.[21] Total laryngectomy remains the most commonly-employed treatment for persistent or recurrent disease after primary radiation therapy. While the patient must adapt to significant life changes regarding the loss of the natural voice and protective mechanisms of the lower airway, many patients achieve long-term survival with good quality of life.

Enhancing Healthcare Team Outcomes

Total laryngectomy represents a well-codified ablative surgical procedure. Expertise and knowledge from an interprofessional healthcare team will likely require input from a head and neck surgeon, a pulmonologist, an oncologist, a radiologist, a radiotherapist, and a pathologist. In addition, the team must consider the biological behavior of laryngeal cancer and the anticipated responses to different therapies.

Additional support from speech and swallowing therapists, respiratory therapists, nutritionists, psychiatrists, and expert nursing staff is essential in the treatment program. Interprofessional dialogue is critical in the management of laryngeal cancer.

References


[1]

Obid R, Redlich M, Tomeh C. The Treatment of Laryngeal Cancer. Oral and maxillofacial surgery clinics of North America. 2019 Feb:31(1):1-11. doi: 10.1016/j.coms.2018.09.001. Epub     [PubMed PMID: 30449522]


[2]

Jones TM, De M, Foran B, Harrington K, Mortimore S. Laryngeal cancer: United Kingdom National Multidisciplinary guidelines. The Journal of laryngology and otology. 2016 May:130(S2):S75-S82     [PubMed PMID: 27841116]


[3]

Forastiere AA, Ismaila N, Lewin JS, Nathan CA, Adelstein DJ, Eisbruch A, Fass G, Fisher SG, Laurie SA, Le QT, O'Malley B, Mendenhall WM, Patel S, Pfister DG, Provenzano AF, Weber R, Weinstein GS, Wolf GT. Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 Apr 10:36(11):1143-1169. doi: 10.1200/JCO.2017.75.7385. Epub 2017 Nov 27     [PubMed PMID: 29172863]

Level 1 (high-level) evidence

[4]

Inamoto Y, Saitoh E, Okada S, Kagaya H, Shibata S, Baba M, Onogi K, Hashimoto S, Katada K, Wattanapan P, Palmer JB. Anatomy of the larynx and pharynx: effects of age, gender and height revealed by multidetector computed tomography. Journal of oral rehabilitation. 2015 Sep:42(9):670-7. doi: 10.1111/joor.12298. Epub 2015 Apr 18     [PubMed PMID: 25892610]


[5]

Noordzij JP, Ossoff RH. Anatomy and physiology of the larynx. Otolaryngologic clinics of North America. 2006 Feb:39(1):1-10     [PubMed PMID: 16469651]


[6]

Marchese-Ragona R, Restivo DA, Mylonakis I, Ottaviano G, Martini A, Sataloff RT, Staffieri A. The superior laryngeal nerve injury of a famous soprano, Amelita Galli-Curci. Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale. 2013 Feb:33(1):67-71     [PubMed PMID: 23620644]


[7]

Kakodkar KA, Schroeder JW Jr, Holinger LD. Laryngeal development and anatomy. Advances in oto-rhino-laryngology. 2012:73():1-11. doi: 10.1159/000334108. Epub 2012 Mar 29     [PubMed PMID: 22472221]

Level 3 (low-level) evidence

[8]

Young VN, Kidane J, Gochman GE, Bracken DJ, Ma Y, Rosen CA. Abnormal Laryngopharyngeal Sensation in Adductor Laryngeal Dystonia Compared to Healthy Controls. The Laryngoscope. 2022 Oct 22:():. doi: 10.1002/lary.30462. Epub 2022 Oct 22     [PubMed PMID: 36271910]


[9]

Vilensky JA, Henton P, Suárez-Quian CA. Infants can breathe and swallow at the same time? Clinical anatomy (New York, N.Y.). 2022 Mar:35(2):174-177. doi: 10.1002/ca.23799. Epub 2021 Oct 18     [PubMed PMID: 34636089]


[10]

Jiang W, Farbos de Luzan C, Wang X, Oren L, Khosla SM, Xue Q, Zheng X. Computational Modeling of Voice Production Using Excised Canine Larynx. Journal of biomechanical engineering. 2022 Feb 1:144(2):. doi: 10.1115/1.4052226. Epub     [PubMed PMID: 34423809]


[11]

Groenewald NE, Du Toit M, Graham MA, Swanepoel C, Maartens G, Van der Linde J. Reflux symptoms and vocal characteristics in adults with non-organic voice disorders. The South African journal of communication disorders = Die Suid-Afrikaanse tydskrif vir Kommunikasieafwykings. 2022 Oct 26:69(1):e1-e9. doi: 10.4102/sajcd.v69i1.935. Epub 2022 Oct 26     [PubMed PMID: 36331218]


[12]

Sethia R, Alfayez Y, VanKoevering KK, Seim NB. Altered Airway Anatomy Course Using 3D-Printed Models for Medical Students. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2023 Apr:168(4):714-719. doi: 10.1177/01945998221117507. Epub 2023 Jan 28     [PubMed PMID: 35943806]


[13]

Verma SP, Mahboubi H. The changing landscape of total laryngectomy surgery. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2014 Mar:150(3):413-8. doi: 10.1177/0194599813514515. Epub 2013 Dec 16     [PubMed PMID: 24343024]

Level 2 (mid-level) evidence

[14]

Ceachir O, Hainarosie R, Zainea V. Total laryngectomy - past, present, future. Maedica. 2014 Jun:9(2):210-6     [PubMed PMID: 25705281]


[15]

van der Kamp MF, Rinkel RNPM, Eerenstein SEJ. The influence of closure technique in total laryngectomy on the development of a pseudo-diverticulum and dysphagia. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2017 Apr:274(4):1967-1973. doi: 10.1007/s00405-016-4424-4. Epub 2016 Dec 21     [PubMed PMID: 28004260]


[16]

Stell PM. Total laryngectomy. Clinical otolaryngology and allied sciences. 1981 Oct:6(5):351-60     [PubMed PMID: 7318230]


[17]

Maclean J, Cotton S, Perry A. Variation in surgical methods used for total laryngectomy in Australia. The Journal of laryngology and otology. 2008 Jul:122(7):728-32. doi: 10.1017/S0022215108002119. Epub 2008 Apr 11     [PubMed PMID: 18405403]


[18]

Patel UA, Moore BA, Wax M, Rosenthal E, Sweeny L, Militsakh ON, Califano JA, Lin AC, Hasney CP, Butcher RB, Flohr J, Arnaoutakis D, Huddle M, Richmon JD. Impact of pharyngeal closure technique on fistula after salvage laryngectomy. JAMA otolaryngology-- head & neck surgery. 2013 Nov:139(11):1156-62. doi: 10.1001/jamaoto.2013.2761. Epub     [PubMed PMID: 23576219]

Level 2 (mid-level) evidence

[19]

Goepfert RP, Hutcheson KA, Lewin JS, Desai NG, Zafereo ME, Hessel AC, Lewis CM, Weber RS, Gross ND. Complications, hospital length of stay, and readmission after total laryngectomy. Cancer. 2017 May 15:123(10):1760-1767. doi: 10.1002/cncr.30483. Epub 2016 Dec 27     [PubMed PMID: 28026864]


[20]

Leong SC, Kartha SS, Kathan C, Sharp J, Mortimore S. Outcomes following total laryngectomy for squamous cell carcinoma: one centre experience. European annals of otorhinolaryngology, head and neck diseases. 2012 Dec:129(6):302-7. doi: 10.1016/j.anorl.2011.10.012. Epub 2012 Aug 24     [PubMed PMID: 22921300]

Level 2 (mid-level) evidence

[21]

Yamauchi M, Minesaki A, Ishida T, Sato Y, Okamura S, Shuto H, Tanaka N, Hatayama E, Shibamiya N, Kuratomi Y. Induction Chemotherapy With 5-Fluorouracil, Cisplatin, and Cetuximab in Advanced Head and Neck Squamous Cell Carcinoma. In vivo (Athens, Greece). 2023 May-Jun:37(3):1275-1280. doi: 10.21873/invivo.13205. Epub     [PubMed PMID: 37103108]