1. In the name of God

2. Laryngeal Carcinoma M. H. Baradaranfar M.D professor of otolaryngology Head and Neck surgery Rhinologist

3. Overview 11,000 new cases of laryngeal cancer per year in the U.S. 11,000 new cases of laryngeal cancer per year in the U.S. Accounts for 25% of head and neck cancer and 1% of all cancers Accounts for 25% of head and neck cancer and 1% of all cancers One-third of these patients eventually die of their disease One-third of these patients eventually die of their disease Most prevalent in the 6 th and 7 th decades of life Most prevalent in the 6 th and 7 th decades of life

4. Overview 4:1 male predilection 4:1 male predilection Downward shift from 15:1 post WWII Downward shift from 15:1 post WWII Due to increasing public acceptance of female smoking Due to increasing public acceptance of female smoking More prevalent among lower socioeconomic class, in which it is diagnosed at more advanced stages More prevalent among lower socioeconomic class, in which it is diagnosed at more advanced stages

5. Subtypes Glottic Cancer: 59% Glottic Cancer: 59% Supraglottic Cancer: 40% Supraglottic Cancer: 40% Subglottic Cancer: 1% Subglottic Cancer: 1% Most subglottic masses are extension from glottic carcinomas Most subglottic masses are extension from glottic carcinomas

6. History The first laryngectomy for cancer of the larynx was performed in 1883 by Billroth The first laryngectomy for cancer of the larynx was performed in 1883 by Billroth Patient was successfully fed by mouth and fitted with an artificial larynx Patient was successfully fed by mouth and fitted with an artificial larynx In 1886 the Crown Prince Frederick of Germany developed hoarseness as he was due to ascend the throne. In 1886 the Crown Prince Frederick of Germany developed hoarseness as he was due to ascend the throne.

7. Crown Prince Frederick of Germany Crown Prince Frederick of Germany

8. History Was evaluated by Sir Makenzie of London, the inventor of the direct laryngoscope Was evaluated by Sir Makenzie of London, the inventor of the direct laryngoscope Frederick’s lesion was biopsied and thought to be cancer Frederick’s lesion was biopsied and thought to be cancer He refused laryngectomy and later died in 1888 He refused laryngectomy and later died in 1888

9. History Frederick was succeeded by Kaiser Wilhelm II, who along with Otto von Bismark militarized the German Empire and led them into WW I Frederick was succeeded by Kaiser Wilhelm II, who along with Otto von Bismark militarized the German Empire and led them into WW I Could an Otolaryngologist have prevented WW I? Could an Otolaryngologist have prevented WW I?

10. Risk Factors

11. Prolonged use of tobacco and excessive EtOH use primary risk factors Prolonged use of tobacco and excessive EtOH use primary risk factors The two substances together have a synergistic effect on laryngeal tissues The two substances together have a synergistic effect on laryngeal tissues 90% of patients with laryngeal cancer have a history of both 90% of patients with laryngeal cancer have a history of both

12. Risk Factors Human Papilloma Virus 16 &18 Human Papilloma Virus 16 &18 Chronic Gastric Reflux Chronic Gastric Reflux Occupational exposures Occupational exposures Prior history of head and neck irradiation Prior history of head and neck irradiation

13. Histological Types 85-95% of laryngeal tumors are squamous cell carcinoma 85-95% of laryngeal tumors are squamous cell carcinoma Histologic type linked to tobacco and alcohol abuse Histologic type linked to tobacco and alcohol abuse Characterized by epithelial nests surrounded by inflammatory stroma Characterized by epithelial nests surrounded by inflammatory stroma Keratin Pearls are pathognomonic Keratin Pearls are pathognomonic

14. Histological Types Verrucous Carcinoma Verrucous Carcinoma Fibrosarcoma Fibrosarcoma Chondrosarcoma Chondrosarcoma Minor salivary carcinoma Minor salivary carcinoma Adenocarcinoma Adenocarcinoma Oat cell carcinoma Oat cell carcinoma Giant cell and Spindle cell carcinoma Giant cell and Spindle cell carcinoma

15. Anatomy

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22. Anatomy

23. Natural History Supraglottic tumors more aggressive: Supraglottic tumors more aggressive: –Direct extension into pre-epiglottic space –Lymph node metastasis –Direct extension into lateral hypopharnyx, glossoepiglottic fold, and tongue base

24. Natural History Glottic tumors grow slower and tend to metastasize late owing to a paucity of lymphatic drainage Glottic tumors grow slower and tend to metastasize late owing to a paucity of lymphatic drainage They tend to metastasize after they have invaded adjacent structures with better drainage They tend to metastasize after they have invaded adjacent structures with better drainage Extend superiorly into ventricular walls or inferiorly into subglottic space Extend superiorly into ventricular walls or inferiorly into subglottic space Can cause vocal cord fixation Can cause vocal cord fixation

25. Natural History True subglottic tumors are uncommon True subglottic tumors are uncommon Glottic spread to the subglottic space is a sign of poor prognosis Glottic spread to the subglottic space is a sign of poor prognosis Increases chance of bilateral disease and mediastinal extension Increases chance of bilateral disease and mediastinal extension Invasion of the subglottic space associated with high incidence of stomal reoccurrence following total laryngectomy (TL) Invasion of the subglottic space associated with high incidence of stomal reoccurrence following total laryngectomy (TL)

26. Presentation Hoarseness Hoarseness –Most common symptom –Small irregularities in the vocal fold result in voice changes –Changes of voice in patients with chronic hoarseness from tobacco and alcohol can be difficult to appreciate

27. Presentation Patients presenting with hoarseness should undergo an indirect mirror exam and/or flexible laryngoscope evaluation Patients presenting with hoarseness should undergo an indirect mirror exam and/or flexible laryngoscope evaluation Malignant lesions can appear as friable, fungating, ulcerative masses or be as subtle as changes in mucosal color Malignant lesions can appear as friable, fungating, ulcerative masses or be as subtle as changes in mucosal color Videostrobe laryngoscopy may be needed to follow up these subtler lesions Videostrobe laryngoscopy may be needed to follow up these subtler lesions

28. Presentation Good neck exam looking for cervical lymphadenopathy and broadening of the laryngeal prominence is required Good neck exam looking for cervical lymphadenopathy and broadening of the laryngeal prominence is required The base of the tongue should be palpated for masses as well The base of the tongue should be palpated for masses as well Restricted laryngeal crepitus may be a sign of post cricoid or retropharyngeal invasion Restricted laryngeal crepitus may be a sign of post cricoid or retropharyngeal invasion

29. Presentation Other symptoms include: Other symptoms include: –Dysphagia –Hemoptysis –Throat pain –Ear pain –Airway compromise –Aspiration –Neck mass

30. Work up Biopsy is required for diagnosis Biopsy is required for diagnosis Performed in OR with patient under anesthesia Performed in OR with patient under anesthesia Other benign possibilities for laryngeal lesions include: Vocal cord nodules or polyps, papillomatosis, granulomas, granular cell neoplasms, sarcoidosis, Wegner’s granulomatosis Other benign possibilities for laryngeal lesions include: Vocal cord nodules or polyps, papillomatosis, granulomas, granular cell neoplasms, sarcoidosis, Wegner’s granulomatosis

31. Work up Other potential modalities: Other potential modalities: –Direct laryngoscopy –Bronchoscopy –Esophagoscopy –Chest X-ray –CT or MRI –Liver function tests with or without US –PET ?

33. Staging- Primary Tumor (T) TX Minimum requirements to assess primary tumor cannot be met T0 No evidence of primary tumor Tis Carcinoma in situ

34. Staging- Supraglottis T1 Tumor limited to one subsite of supraglottis with normal vocal cord mobility T2 Tumor involves mucosa of more than one adjacent subsite of supraglottis or glottis, or region outside the supraglottis (e.g. mucosa of base of the tongue, vallecula, medial wall of piriform sinus) without fixation T3 Tumor limited to larynx with vocal cord fixation and or invades any of the following: postcricoid area, preepiglottic tissue, paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) T4a Tumor invades through the thyroid cartilage and/or invades tissue beyond the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

35. Staging- Glottis T1 Tumor limited to the vocal cord (s) (may involve anterior or posterior commissure) with normal mobilty T1a Tumor limited to one vocal cord T1b Tumor involves both vocal cords T2 Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility T3 Tumor limited to the larynx with vocal cord fixation and/or invades paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) T4a Tumor invades through the thyroid cartilage, and/or invades tissues beyond the larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

36. Staging- Subglottis T1 Tumor limited to the subglottis T2 Tumor extends to vocal cord (s) with normal or impaired mobility T3 Tumor limited the larynx with vocal cord fixation T4a Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

37. Staging- Nodes N0 No cervical lymph nodes positive N1 Single ipsilateral lymph node ≤ 3cm N2a Single ipsilateral node > 3cm and ≤6cm N2b Multiple ipsilateral lymph nodes, each ≤ 6cm N2c Bilateral or contralateral lymph nodes, each ≤6cm N3 Single or multiple lymph nodes > 6cm

38. Staging- Metastasis M0 No distant metastases M1 Distant metastases present

39. Stage Groupings 0TisN0M0 IT1N0M0 IIT2N0M0 IIIT3N0M0 T1-3N1M0 IVAT4aN0-2M0 T1-4aN2M0 IVBT4b Any N M0 Any T N3M0 IVC Any N M1

40. Treatment Premalignant lesions or Carcinoma in situ can be treated by surgical stripping of the entire lesion Premalignant lesions or Carcinoma in situ can be treated by surgical stripping of the entire lesion CO2 laser can be used to accomplish this but makes accurate review of margins difficult CO2 laser can be used to accomplish this but makes accurate review of margins difficult

41. Treatment Early stage (T1 and T2) can be treated with radiotherapy or surgery alone, both offer the 85-95% cure rate. Early stage (T1 and T2) can be treated with radiotherapy or surgery alone, both offer the 85-95% cure rate. Surgery has a shorter treatment period, saves radiation for recurrence, but may have worse voice outcomes Surgery has a shorter treatment period, saves radiation for recurrence, but may have worse voice outcomes Radiotherapy is given for 6-7 weeks, avoids surgical risks but has own complications Radiotherapy is given for 6-7 weeks, avoids surgical risks but has own complications

42. Treatment XRT complications include: XRT complications include: –Mucositis –Odynophagia –Laryngeal edema –Xerostomia –Stricture and fibrosis –Radionecrosis –Hypothyroidism

43. Treatment Advanced stage lesions often receive surgery with adjuvant radiation Advanced stage lesions often receive surgery with adjuvant radiation Most T3 and T4 lesions require a total laryngectomy Most T3 and T4 lesions require a total laryngectomy Some small T3 and lesser sized tumors can be treated with partial larygectomy Some small T3 and lesser sized tumors can be treated with partial larygectomy

44. Treatment Adjuvant radiation is started within 6 weeks of surgery and with once daily protocols lasts 6-7 weeks Adjuvant radiation is started within 6 weeks of surgery and with once daily protocols lasts 6-7 weeks Indications for post-op radiation include: T4 primary, bone/cartilage invasion, extension into neck soft tissue, perineural invasion, vascular invasion, multiple positive nodes, nodal extracapsular extension, margins<5mm, positive margins, CIS margins, subglottic extension of primary tumor. Indications for post-op radiation include: T4 primary, bone/cartilage invasion, extension into neck soft tissue, perineural invasion, vascular invasion, multiple positive nodes, nodal extracapsular extension, margins<5mm, positive margins, CIS margins, subglottic extension of primary tumor.

45. Treatment Chemotherapy can be used in addition to irradiation in advanced stage cancers Chemotherapy can be used in addition to irradiation in advanced stage cancers Two agents used are Cisplatinum and 5- flourouracil Two agents used are Cisplatinum and 5- flourouracil Cisplatin thought to sensitize cancer cells to XRT enhancing its effectiveness when used concurrently. Cisplatin thought to sensitize cancer cells to XRT enhancing its effectiveness when used concurrently.

46. Treatment Induction chemotherapy with definitive radiation therapy for advanced stage cancer is another option Induction chemotherapy with definitive radiation therapy for advanced stage cancer is another option Studies have shown similar survival rates as compared to total laryngectomy with adjuvant radiation but with voice preservation. Studies have shown similar survival rates as compared to total laryngectomy with adjuvant radiation but with voice preservation. Role in treatment still under investigation Role in treatment still under investigation

47. Treatment Modified or radical neck dissections are indicated in the presence of nodal disease Modified or radical neck dissections are indicated in the presence of nodal disease Neck dissections may be performed in patients with supra or subglottic T2 tumors even in the absence of nodal disease Neck dissections may be performed in patients with supra or subglottic T2 tumors even in the absence of nodal disease N0 necks can have a selective dissection sparing the SCM, IJ, and XI N0 necks can have a selective dissection sparing the SCM, IJ, and XI N1 necks usually have a modified dissection of levels II-IV N1 necks usually have a modified dissection of levels II-IV

48. Surgical Options

49. Hemilaryngectomy No more than 1cm subglottic extension anteriorly or 5mm posteriorly No more than 1cm subglottic extension anteriorly or 5mm posteriorly Mobile affected cord Mobile affected cord Minimal anterior contralateral cord involvement Minimal anterior contralateral cord involvement No cartilage invasion No cartilage invasion No neck soft tissue invasion No neck soft tissue invasion

50. Supraglottic laryngectomy T1,2, or 3 if only by preepiglottic space invasion T1,2, or 3 if only by preepiglottic space invasion Mobile cords Mobile cords No anterior commissure involvement No anterior commissure involvement FEV1 >50% FEV1 >50% No tongue base disease past circumvallate papillae No tongue base disease past circumvallate papillae Apex of pyriform sinus not invloved Apex of pyriform sinus not invloved

51. Supracricoid Laryngectomy Resection of true vocal cords, supraglottis, thyroid cartilage Resection of true vocal cords, supraglottis, thyroid cartilage Leave arytenoids and cricoid ring intact Leave arytenoids and cricoid ring intact Half of patients remain dependent on tracheostomy Half of patients remain dependent on tracheostomy

52. Total Larygectomy Indications: Indications: –T3 or T4 unfit for partial –Extensive involvement of thyroid and cricoid cartilages –Invasion of neck soft tissues –Tongue base involvement beyond circumvallate papillae

53. Total Laryngectomy

57. Voice Rehabilitation Tracheostomal prosthesis Tracheostomal prosthesis Electrolarynx Electrolarynx Pure esophageal speech Pure esophageal speech

58. Complications Inaccurate staging Inaccurate staging Infection Infection Voice alterations Voice alterations Swallowing difficulties Swallowing difficulties Loss of taste and smell Loss of taste and smell Fistula Fistula Tracheostomy dependence Tracheostomy dependence Injury to cranial nerves: VII, IX, X, XI, XII Injury to cranial nerves: VII, IX, X, XI, XII Stroke or carotid “blowout” Stroke or carotid “blowout” Hypothyroidism Hypothyroidism Radiation induced fibrosis Radiation induced fibrosis

59. Prognosis After initial treatment patients are followed at 4- 6 week intervals. After first year decreases to every 2 months. Third and fourth year every three months, with annual visits after that After initial treatment patients are followed at 4- 6 week intervals. After first year decreases to every 2 months. Third and fourth year every three months, with annual visits after that 5 year survival Stage I >95% Stage II 85-90% Stage III 70-80% Stage IV 50-60%

60. Prognosis Patients considered cured after being disease free for five years Patients considered cured after being disease free for five years Most laryngeal cancers reoccur in the first two years Most laryngeal cancers reoccur in the first two years Despite advances in detection and treatment options the five year survival has not improved much over the last thirty years Despite advances in detection and treatment options the five year survival has not improved much over the last thirty years