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Laryngeal Cancer

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Laryngeal Cancer

  1. 1. Laryngeal Cancer Anh Q. Truong MS-4 University of Washington, SOM
  2. 2. Anatomy
  3. 3. Vaezi, MF . Nature Clinical Practice Gastroenterology & Hepatology (2005) 2 , 595-603 Anatomy – cont’
  4. 4. Anatomy – subdivision Source: AJCC Cancer Staging Manual, 6 th Ed (2002)
  5. 5. <ul><li>Most common head and neck CA (excluding skin) </li></ul><ul><li>12,250 new cases/yr </li></ul><ul><li>Male : Female = 4 : 1 </li></ul><ul><li>> 90% squamous cell cancer </li></ul><ul><li>Glottic CA more common in Caucasian (in US) </li></ul><ul><li>Glottic CA = supraglottic in African American (in US) </li></ul><ul><li>Variation of ratio around world </li></ul>Epidemiology American Cancer Society: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Incidence by Site Supraglottic 40% Glottic 59% Subglottic 1%
  6. 6. <ul><li>Tobacco smoking, bidi smoking, alcohol. </li></ul><ul><li>MJ smoking correlation </li></ul><ul><li>HPV, GERD implicated </li></ul><ul><li>Possibly perchloroethylene </li></ul>Risk Factors
  7. 7. <ul><li>Signs and symptoms </li></ul><ul><ul><li>Mass effect: hoarseness, dysphagia, hemoptysis, neck mass, airway compromise (difficulty breathing), aspiration </li></ul></ul><ul><ul><li>Throat pain, ear pain (referred through CN X branch) </li></ul></ul><ul><ul><ul><li>Suggests advanced stage </li></ul></ul></ul><ul><ul><li>Hoarseness = allow for early detection of glottic cancer </li></ul></ul><ul><ul><li>Supraglottic CA = tend to present later </li></ul></ul><ul><ul><ul><li>Usually present w/bulkier tumors before Si/Sx present </li></ul></ul></ul><ul><ul><ul><li>More likely to present w/node mets d/t richer lymphatics </li></ul></ul></ul><ul><ul><li>Weight loss </li></ul></ul>Clinical Presentation
  8. 8. Clinical Presentation – cont’ <ul><li>Physical Exam </li></ul><ul><ul><li>Complete head and neck exam </li></ul></ul><ul><ul><ul><li>Palpation for nodes; restricted laryngeal crepitus. </li></ul></ul></ul><ul><ul><li>Quality of voice </li></ul></ul><ul><ul><ul><li>Breathy voice = cord paralysis </li></ul></ul></ul><ul><ul><ul><li>Muffled voice = supraglottic lesion </li></ul></ul></ul><ul><ul><li>Laryngoscopy </li></ul></ul><ul><ul><ul><li>Laryngeal mirror </li></ul></ul></ul><ul><ul><ul><li>Fiberoptic exam (lack depth perception) </li></ul></ul></ul><ul><ul><ul><li>Note: contour, color, vibration, cord mobility, lesions. </li></ul></ul></ul><ul><ul><li>Stroboscopic video laryngoscopy </li></ul></ul><ul><ul><ul><li>Highlights subtle irregularities: vibration, periodicity, cord closure </li></ul></ul></ul>
  9. 9. Differential Diagnosis <ul><li>Infectious </li></ul><ul><li>Inflammatory </li></ul><ul><li>Granulomatous disease (TB, sarcoidosis) </li></ul><ul><li>Papillomatosis </li></ul><ul><li>Lymphoma </li></ul>
  10. 10. Imaging <ul><li>CT or MRI </li></ul><ul><ul><li>Evaluate pre-epiglottic or paraglottic space </li></ul></ul><ul><ul><li>Laryngeal cartilage erosion </li></ul></ul><ul><ul><li>Cervical node mets </li></ul></ul><ul><li>PET </li></ul><ul><ul><li>Role under investigation, currently not standard of care </li></ul></ul><ul><ul><li>Specific application </li></ul></ul><ul><ul><ul><li>Identifying occult nodal mets </li></ul></ul></ul><ul><ul><ul><li>Distinguish recurrence vs radionecrosis or other prior tx sequalae </li></ul></ul></ul><ul><li>Ultrasound </li></ul><ul><ul><li>In Europe: used to identify cervical mets and laryngeal abn. </li></ul></ul>
  11. 11. Biopsy and Histology <ul><li>Direct laryngoscopy with biopsy </li></ul><ul><li>Histologic subtypes </li></ul><ul><ul><li>Squamous cell carcinoma </li></ul></ul><ul><ul><ul><li>> 90% of causes </li></ul></ul></ul><ul><ul><ul><li>Characterized by nl  hyperplasia  dysplasia  CIS  invasive CA </li></ul></ul></ul><ul><ul><ul><li>Invasive CA characterized by: well, moderately, or poorly differentiated </li></ul></ul></ul><ul><ul><ul><ul><li>Nest of malig epi cells, desmoplastic & inflammatory stroma, keratin pearls (in well and mod dif CA). </li></ul></ul></ul></ul><ul><ul><ul><li>Linked to tobacco and excessive alcohol </li></ul></ul></ul><ul><ul><ul><li>Variance: verrucous, spindle cell carcinoma, & basaloid. </li></ul></ul></ul>
  12. 12. Biopsy and Histology – cont’ <ul><li>Histologic subtypes - cont’ </li></ul><ul><ul><li>Salivary gland </li></ul></ul><ul><ul><ul><li>Adenoid cystic carcinoma </li></ul></ul></ul><ul><ul><ul><li>Mucoepidermoid carcinoma </li></ul></ul></ul><ul><ul><ul><li>Surgery is preferred w/guidelines for adjuvant XRT </li></ul></ul></ul><ul><ul><li>Sarcomas (mainly chondrosarcoma) </li></ul></ul><ul><ul><ul><li>Most commonly from cricoid cartilage </li></ul></ul></ul><ul><ul><ul><li>Nonaggressive, preferably tx with partial laryngeal surgery </li></ul></ul></ul><ul><ul><ul><li>XRT viewed as ineffective </li></ul></ul></ul><ul><ul><li>Others: carcinoid tumors, lymphoma, mets. </li></ul></ul>
  13. 13. <ul><li>Supraglottis </li></ul><ul><ul><li>Tis: CA in-situ </li></ul></ul><ul><ul><li>T1: limited to subsite of supraglots w/normal cord mobility </li></ul></ul><ul><ul><li>T2: invade mucosa of > 1 subsite of supraglottis, glottis, or outside of supraglottis w/out fixation of the larynx </li></ul></ul><ul><ul><li>T3: limited to larynx w/vocal cord fixation and/or invades postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosion </li></ul></ul><ul><ul><li>T4a: invades thyroid cartilage and/or tissues beyond larynx </li></ul></ul><ul><ul><li>T4b: invades prevertebral space, encases carotid artery, or invades mediastinal structures </li></ul></ul><ul><li>Glottis </li></ul><ul><ul><li>Tis: CA in-situ </li></ul></ul><ul><ul><li>T1: limited to cord; </li></ul></ul><ul><ul><li>T1a : one cord; T1b : two cords </li></ul></ul><ul><ul><li>T2: extends to supraglottis, and/or subglottis, and/or w/impaired cord mobility </li></ul></ul><ul><ul><li>T3: limited to larynx w/vocal cord fixation and/or invades paraglottic space, and/or minor thyroid cartilage erosion </li></ul></ul><ul><ul><li>T4a: invades thyroid cartilage and/or tissues beyond larynx </li></ul></ul><ul><ul><li>T4b: invades prevertebral space, encases carotid artery, or invades mediastinal structures </li></ul></ul><ul><li>Subglottis </li></ul><ul><ul><li>Tis: CA in-situ </li></ul></ul><ul><ul><li>T1: limited to subglottis </li></ul></ul><ul><ul><li>T2: extends to vocal cord with normal or impaired mobility </li></ul></ul><ul><ul><li>T3: limited to larynx w/vocal cord fixation </li></ul></ul><ul><ul><li>T4a: invades cricoid or thyroid cartilage, and/or invades tissues beyond the larynx </li></ul></ul><ul><ul><li>T4b: invades prevertebral space, encases carotid artery, or invades mediastinal structures </li></ul></ul>Staging Source: AJCC Cancer Staging Manual, 6 th Ed (2002)
  14. 14. <ul><li>Subglottis </li></ul><ul><ul><li>Tis: CA in-situ </li></ul></ul><ul><ul><li>T1: limited to subglottis </li></ul></ul><ul><ul><li>T2: extends to vocal cord with normal or impaired mobility </li></ul></ul><ul><ul><li>T3: limited to larynx w/vocal cord fixation </li></ul></ul><ul><ul><li>T4a: invades cricoid or thyroid cartilage, and/or invades tissues beyond the larynx </li></ul></ul><ul><ul><li>T4b: invades prevertebral space, encases carotid artery, or invades mediastinal structures </li></ul></ul>Staging <ul><li>Nodes </li></ul><ul><ul><li>N0: no regional node mets </li></ul></ul><ul><ul><li>N1: single ipsilateral node, ≤ 3 cm </li></ul></ul><ul><ul><li>N2a: single ipsilateral node, > 3 cm, ≤ 6 cm </li></ul></ul><ul><ul><li>N2b: multiple ipsilateral nodes, ≤ 6 cm </li></ul></ul><ul><ul><li>N2c: bilateral or contralateral nodes, ≤ 6 cm </li></ul></ul><ul><ul><li>N3: node > 6 cm </li></ul></ul><ul><li>Mets </li></ul><ul><ul><li>Mx: unknown </li></ul></ul><ul><ul><li>M0: no distant mets </li></ul></ul><ul><ul><li>M1: distant mets </li></ul></ul>Source: AJCC Cancer Staging Manual, 6 th Ed (2002)
  15. 15. Stage Grouping Early stage Advanced stage Stage 0 Tis N0 M0 Stage I T1 N0 M0 Stage II T2 N0 M0 Stage III T3 N0 M0 T1-3 N1 M0 Stage IVA T4a N0-1 M0 T1-4a N2 M0 Stage IVB T4b any N M0 any T N3 M0 Stage IVC any T any N M1
  16. 16. <ul><li>Surgery </li></ul><ul><ul><li>Microlaryngeal surgery </li></ul></ul><ul><ul><li>Hemilargyngectomy </li></ul></ul><ul><ul><li>Supraglottic laryngectomy </li></ul></ul><ul><ul><li>Near-total laryngectomy </li></ul></ul><ul><ul><li>Total laryngectomy </li></ul></ul><ul><li>Photodynamic Therapy </li></ul><ul><li>Radiation </li></ul><ul><li>Chemothrapy </li></ul><ul><ul><li>Cisplatin + 5-fluorouracil </li></ul></ul>Treatments – Options
  17. 17. <ul><li>Current therapeutic options </li></ul><ul><ul><li>Laser microsurgery (transoral) </li></ul></ul><ul><ul><li>Open partial laryngectomy </li></ul></ul><ul><ul><li>Radiation therapy </li></ul></ul><ul><li>No RCT to compare surgery w/XRT </li></ul><ul><li>Rate of local control similar between surgery and radiation </li></ul><ul><li>Current recommendations, XRT with surgery reserved for salvage therapy with local recurrence </li></ul>Treatment – Early Stage (I/II) Mendenhall WM et al., Cancer. 2004 May 1;100(9)
  18. 18. Dose Fractionation <ul><li>Yu et al., 1997 [1] </li></ul><ul><ul><li>Retrospective study – 5 yr local ctr rate of XRT on T1 glottic CA </li></ul></ul><ul><ul><li>Daily fx > 2 Gy (50 Gy/2.5Gy QD & 65.25Gy/2.25 Gy QD) had 5 yr local ctr rate of 84% </li></ul></ul><ul><ul><li>Daily fx = 2 Gy had 5 yr local ctr 65.6% </li></ul></ul><ul><li>Andy Trotti, RTOG 95-12 – closed [2] </li></ul><ul><ul><li>Randomized pts with T2 glottic cancer to 70Gy/2Gy QD vs 79.2 Gy/1.2 Gy BID </li></ul></ul>1 Yu E. et al., Int J Radiat Oncol Biol Phys. 1997 Feb 1;37(3):587-91. 2 www.rtog.org/members/protocols/95-12/95-12.pdf
  19. 19. Dose Fractionation <ul><li>Yamazaki et al., 2006 </li></ul><ul><ul><li>RTC – 5 yr local ctr rate of XRT on T1 glottic CA </li></ul></ul><ul><ul><li>2 Gy/fx (60Gy/30 fx or 66Gy/33fx): 5 yr local ctr rate = 77% </li></ul></ul><ul><ul><li>2.25 Gy/fx (56.25Gy/25fx or 63 Gy/28fx): 5 yr local ctr rate = 92% </li></ul></ul>Yamazaki H et al., Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):77-82
  20. 20. Treatment – Advanced Stage (III/IV) – VA Study <ul><li>Dept of VA Laryngeal CA Study Group, 1991 </li></ul><ul><ul><li>RCT: Induction chemo  XRT vs laryngectomy  post-op XRT </li></ul></ul><ul><ul><ul><li>Chemo arm = cisplatin + 5-FU x 2c  if partial/complete response  3 rd cycle  XRT*, else  salvage surgery </li></ul></ul></ul><ul><ul><ul><li>Surgery arm = total laryngectomy (partial if poss)  XRT* </li></ul></ul></ul><ul><ul><ul><li>*XRT = definitive: 66 Gy – 76 Gy; post-op: 50.4Gy (+10Gy if high risk of local recurrence) </li></ul></ul></ul>Department of Veterans Affairs Laryngeal Cancer Study Group, N Engl J Med 1991;324:1685-90.
  21. 21. Treatment – Advanced Stage (III/IV) – VA Study cont’ Department of Veterans Affairs Laryngeal Cancer Study Group, N Engl J Med 1991;324:1685-90. Overall Survival Surg + XRT Chemo + XRT 2 yr OS = 68% in both groups, P = 0.9846 Surg + XRT Chemo + XRT Chem + XRT shorter disease free interval, but dif not significant Disease Free Survival
  22. 22. Treatment – Advanced Stage (III/IV) – VA Study cont’ Department of Veterans Affairs Laryngeal Cancer Study Group, N Engl J Med 1991;324:1685-90. Site of recurrence Surgery (N = 166) Chemotherapy (N=166) Primary 4 (2%) 20 (12%) Regional 9 (5%) 14 (8%) Distant 29 (17%) 18 (11%) All 42 (25%) 52 (31%) No difference in rate of recurrence, significant difference in site of recurrence, significant difference in development of a 2nd primary CA (surg 6%, chemo 2%)
  23. 23. Treatment – Advanced Stage (III/IV) – VA Study cont’ Of the 166 pts in the chemo arms - 107 (64%) patients had preserved larynx - 30 patients (18%)  laryngectomy before definitive XRT - 29 patients (18%)  laryngectomy after definitive XRT Department of Veterans Affairs Laryngeal Cancer Study Group, N Engl J Med 1991;324:1685-90.
  24. 24. Treatment – Advanced Stage (III/IV) – RTOG 91-11 Study <ul><li>Forastiere et al, (RTOG 91-11), 2003 </li></ul><ul><ul><li>RCT: XRT alone vs induction chemo  XRT vs concurrent chemoXRT, primary endpoint = larynx perservation </li></ul></ul><ul><ul><ul><li>XRT: 70Gy/35fx in all arms </li></ul></ul></ul><ul><ul><ul><li>Induction – cisplatin + 5 FU x 2c  if complete or partial response, w/out neck progression  3 rd cycle  XRT; else  laryngectomy  XRT </li></ul></ul></ul><ul><ul><ul><li>Concurrent – cisplatin x 3c + XRT </li></ul></ul></ul>Forastiere AA et al, N Engl J Med 2003;349:2091-8.
  25. 25. Treatment – Advanced Stage (III/IV) – RTOG 91-11 Study <ul><li>Induction Chemotherapy </li></ul><ul><ul><li>173 assigned  168 completed chemo x 2c  144 complete or partial response  134  completed 3 rd chemo cycle </li></ul></ul><ul><ul><li>84% of pts received ≥ 67 Gy </li></ul></ul><ul><li>Concurrent Chemoradiation </li></ul><ul><ul><li>172 assigned  120 (70%) completed cisplatin x 3 cycle, 40 (23%) completed cisplatin x 2 cycles. </li></ul></ul><ul><ul><li>91% of pts received ≥ 67 Gy </li></ul></ul><ul><li>Radiation alone </li></ul><ul><ul><li>95% of pts received ≥ 67 Gy </li></ul></ul>Forastiere AA et al, N Engl J Med 2003;349:2091-8.
  26. 26. Treatment – Advanced Stage (III/IV) – RTOG 91-11 Study 2 yr 3.8 yr 5 yr update A - induction chemo  XRT: 75% 72% 70.5% - concurrent chemoXRT : 88%* 84%* 83.6% - XRT alone : 70% 67% 65.7% Laryngeal Preservation Forastiere AA et al, N Engl J Med 2003;349:2091-8. A Forastiere AA et al, Journal of Clinical Oncology , Vol 24, No. 18S(June 20 Supplement),2006:5517.
  27. 27. Treatment – Advanced Stage (III/IV) – RTOG 91-11 Study Locoregional Control Forastiere AA et al, N Engl J Med 2003;349:2091-8. A Forastiere AA et al, Journal of Clinical Oncology , Vol 24, No. 18S(June 20 Supplement),2006:5517. 2 yrs 5 yr update A - induction chemo  XRT: 64% 54.9% - concurrent chemoXRT : 80% 68.8% - XRT alone : 58% 51%
  28. 28. Treatment – Advanced Stage (III/IV) – RTOG 91-11 Study A Chemo therapy  significant decreased in dz free survival compared to XRT alone (P =0.02 compared w/induction, P = 0.06 compared w/conccurent Tx) B No significant difference C Difference only significant comparing concurrent chemoXRT vs XRT alone. Forastiere AA et al, N Engl J Med 2003;349:2091-8. Concurrent chemoXRT Induction chemo  XRT XRT alone 2 yrs 5 yrs 2 yrs 5 yrs 2 yrs 5 yrs Dz Free Survival A 61% 36% 52% 38% 44% 27% Overall Survival B 74% 54% 76% 55% 75% 56% Distant mets C 8% 12% 9% 15% 16% 22%
  29. 29. Treatment – Advanced Stage (III/IV) – cont’ Forastiere AA et al, N Engl J Med 2003;349:2091-8.
  30. 30. <ul><li>Hypothyroidism </li></ul><ul><li>Mucositis </li></ul><ul><li>Dermatitis </li></ul><ul><li>Xerostomia </li></ul><ul><li>Fibrosis </li></ul><ul><li>Fistulas </li></ul><ul><li>Dysgeusia </li></ul>Anticipated Toxicities
  31. 31. Take Home Points <ul><li>Most laryngeal CA are SCC </li></ul><ul><li>Low stage can be tx by different modalities </li></ul><ul><ul><li>Fraction size ≥ 2.25 Gy/fx may increase local ctr </li></ul></ul><ul><li>OS similar b/w surgery + XRT vs chemo + XRT in advanced stage, but organ preservation better with chemo + XRT </li></ul><ul><li>Organ preservation: concurrent XRT > chemo  XRT = XRT alone </li></ul><ul><li>Don’t smoke or drink too much alcohol </li></ul>
  32. 32. An Actual Picture of a Laryngeal Cancer (L) Source: http://www.medscape.com/content/2002/00/44/25/442595/442595_fig.html (R) Source: http://www.som.tulane.edu/classware/pathology/medical_pathology/New_for_98/Lung_Review/Lung-62.html
  33. 33. Questions?

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