Laryngeal Cancer

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Laryngeal Cancer

• Anh Q. Truong
• MS-4
• University of Washington, SOM

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Anatomy
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Anatomy cont
Vaezi, MF . Nature Clinical Practice
Gastroenterology Hepatology (2005) 2, 595-603
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Anatomy subdivision
Source AJCC Cancer Staging Manual, 6th Ed (2002)
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Epidemiology

• Most common head and neck CA (excluding skin)
• 12,250 new cases/yr
• Male Female 4 1
• gt 90 squamous cell cancer
• Glottic CA more common in Caucasian (in US)
• Glottic CA supraglottic in African American (in
  US)
• Variation of ratio around world

American Cancer Society Cancer Facts and Figures
2008. Atlanta, Ga American Cancer Society, 2008.
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Risk Factors

• Tobacco smoking, bidi smoking, alcohol.
• MJ smoking correlation
• HPV, GERD implicated
• Possibly perchloroethylene

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Clinical Presentation

• Signs and symptoms
• Mass effect hoarseness, dysphagia, hemoptysis,
  neck mass, airway compromise (difficulty
  breathing), aspiration
• Throat pain, ear pain (referred through CN X
  branch)
• Suggests advanced stage
• Hoarseness allow for early detection of glottic
  cancer
• Supraglottic CA tend to present later
• Usually present w/bulkier tumors before Si/Sx
  present
• More likely to present w/node mets d/t richer
  lymphatics
• Weight loss

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Clinical Presentation cont

• Physical Exam
• Complete head and neck exam
• Palpation for nodes restricted laryngeal
  crepitus.
• Quality of voice
• Breathy voice cord paralysis
• Muffled voice supraglottic lesion
• Laryngoscopy
• Laryngeal mirror
• Fiberoptic exam (lack depth perception)
• Note contour, color, vibration, cord mobility,
  lesions.
• Stroboscopic video laryngoscopy
• Highlights subtle irregularities vibration,
  periodicity, cord closure

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Differential Diagnosis

• Infectious
• Inflammatory
• Granulomatous disease (TB, sarcoidosis)
• Papillomatosis
• Lymphoma

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Imaging

• CT or MRI
• Evaluate pre-epiglottic or paraglottic space
• Laryngeal cartilage erosion
• Cervical node mets
• PET
• Role under investigation, currently not standard
  of care
• Specific application
• Identifying occult nodal mets
• Distinguish recurrence vs radionecrosis or other
  prior tx sequalae
• Ultrasound
• In Europe used to identify cervical mets and
  laryngeal abn.

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Biopsy and Histology

• Direct laryngoscopy with biopsy
• Histologic subtypes
• Squamous cell carcinoma
• gt 90 of causes
• Characterized by nl ? hyperplasia ? dysplasia ?
  CIS ? invasive CA
• Invasive CA characterized by well, moderately,
  or poorly differentiated
• Nest of malig epi cells, desmoplastic
  inflammatory stroma, keratin pearls (in well and
  mod dif CA).
• Linked to tobacco and excessive alcohol
• Variance verrucous, spindle cell carcinoma,
  basaloid.

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Biopsy and Histology cont

• Histologic subtypes - cont
• Salivary gland
• Adenoid cystic carcinoma
• Mucoepidermoid carcinoma
• Surgery is preferred w/guidelines for adjuvant
  XRT
• Sarcomas (mainly chondrosarcoma)
• Most commonly from cricoid cartilage
• Nonaggressive, preferably tx with partial
  laryngeal surgery
• XRT viewed as ineffective
• Others carcinoid tumors, lymphoma, mets.

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Staging

• Supraglottis
• Tis CA in-situ
• T1 limited to subsite of supraglots w/normal
  cord mobility
• T2 invade mucosa of gt 1 subsite of supraglottis,
  glottis, or outside of supraglottis w/out
  fixation of the larynx
• T3 limited to larynx w/vocal cord fixation
  and/or invades postcricoid area, pre-epiglottic
  tissues, paraglottic space, and/or minor thyroid
  cartilage erosion
• T4a invades thyroid cartilage and/or tissues
  beyond larynx
• T4b invades prevertebral space, encases carotid
  artery, or invades mediastinal structures

• Glottis
• Tis CA in-situ
• T1 limited to cord
• T1a one cord T1b two cords
• T2 extends to supraglottis, and/or subglottis,
  and/or w/impaired cord mobility
• T3 limited to larynx w/vocal cord fixation
  and/or invades paraglottic space, and/or minor
  thyroid cartilage erosion
• T4a invades thyroid cartilage and/or tissues
  beyond larynx
• T4b invades prevertebral space, encases carotid
  artery, or invades mediastinal structures

• Subglottis
• Tis CA in-situ
• T1 limited to subglottis
• T2 extends to vocal cord with normal or impaired
  mobility
• T3 limited to larynx w/vocal cord fixation
• T4a invades cricoid or thyroid cartilage, and/or
  invades tissues beyond the larynx
• T4b invades prevertebral space, encases carotid
  artery, or invades mediastinal structures

Source AJCC Cancer Staging Manual, 6th Ed (2002)
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Staging

• Subglottis
• Tis CA in-situ
• T1 limited to subglottis
• T2 extends to vocal cord with normal or impaired
  mobility
• T3 limited to larynx w/vocal cord fixation
• T4a invades cricoid or thyroid cartilage, and/or
  invades tissues beyond the larynx
• T4b invades prevertebral space, encases carotid
  artery, or invades mediastinal structures

• Nodes
• N0 no regional node mets
• N1 single ipsilateral node, 3 cm
• N2a single ipsilateral node, gt 3 cm, 6 cm
• N2b multiple ipsilateral nodes, 6 cm
• N2c bilateral or contralateral nodes, 6 cm
• N3 node gt 6 cm
• Mets
• Mx unknown
• M0 no distant mets
• M1 distant mets

Source AJCC Cancer Staging Manual, 6th Ed (2002)
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Stage Grouping
Early stage
Advanced stage
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Treatments Options

• Surgery
• Microlaryngeal surgery
• Hemilargyngectomy
• Supraglottic laryngectomy
• Near-total laryngectomy
• Total laryngectomy
• Photodynamic Therapy
• Radiation
• Chemothrapy
• Cisplatin 5-fluorouracil

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Treatment Early Stage (I/II)

• Current therapeutic options
• Laser microsurgery (transoral)
• Open partial laryngectomy
• Radiation therapy
• No RCT to compare surgery w/XRT
• Rate of local control similar between surgery and
  radiation
• Current recommendations, XRT with surgery
  reserved for salvage therapy with local
  recurrence

Mendenhall WM et al., Cancer. 2004 May 1100(9)
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Dose Fractionation

• Yu et al., 1997 1
• Retrospective study 5 yr local ctr rate of XRT
  on T1 glottic CA
• Daily fx gt 2 Gy (50 Gy/2.5Gy QD 65.25Gy/2.25 Gy
  QD) had 5 yr local ctr rate of 84
• Daily fx 2 Gy had 5 yr local ctr 65.6
• Andy Trotti, RTOG 95-12 closed 2
• Randomized pts with T2 glottic cancer to 70Gy/2Gy
  QD vs 79.2 Gy/1.2 Gy BID

1Yu E. et al., Int J Radiat Oncol Biol Phys. 1997
Feb 137(3)587-91.
2www.rtog.org/members/protocols/95-12/95-12.pdf
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Dose Fractionation

• Yamazaki et al., 2006
• RTC 5 yr local ctr rate of XRT on T1 glottic CA
• 2 Gy/fx (60Gy/30 fx or 66Gy/33fx) 5 yr local
  ctr rate 77
• 2.25 Gy/fx (56.25Gy/25fx or 63 Gy/28fx) 5 yr
  local ctr rate 92

Yamazaki H et al., Int J Radiat Oncol Biol Phys.
2006 Jan 164(1)77-82
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Treatment Advanced Stage (III/IV) VA Study

• Dept of VA Laryngeal CA Study Group, 1991
• RCT Induction chemo ? XRT vs laryngectomy ?
  post-op XRT
• Chemo arm cisplatin 5-FU x 2c ? if
  partial/complete response ? 3rd cycle ? XRT,
  else ? salvage surgery
• Surgery arm total laryngectomy (partial if
  poss) ? XRT
• XRT definitive 66 Gy 76 Gy post-op 50.4Gy
  (10Gy if high risk of local recurrence)

Department of Veterans Affairs Laryngeal Cancer
Study Group, N Engl J Med 19913241685-90.
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Treatment Advanced Stage (III/IV) VA Study
cont
Department of Veterans Affairs Laryngeal Cancer
Study Group, N Engl J Med 19913241685-90.
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Treatment Advanced Stage (III/IV) VA Study
cont
Department of Veterans Affairs Laryngeal Cancer
Study Group, N Engl J Med 19913241685-90.
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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 19913241685-90.
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Treatment Advanced Stage (III/IV) RTOG 91-11
Study

• Forastiere et al, (RTOG 91-11), 2003
• RCT XRT alone vs induction chemo ? XRT vs
  concurrent chemoXRT, primary endpoint larynx
  perservation
• XRT 70Gy/35fx in all arms
• Induction cisplatin 5 FU x 2c ? if complete
  or partial response, w/out neck progression ? 3rd
  cycle ? XRT else ? laryngectomy ? XRT
• Concurrent cisplatin x 3c XRT

Forastiere AA et al, N Engl J Med 20033492091-8.
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Treatment Advanced Stage (III/IV) RTOG 91-11
Study

• Induction Chemotherapy
• 173 assigned ? 168 completed chemo x 2c ? 144
  complete or partial response ? 134 ? completed
  3rd chemo cycle
• 84 of pts received 67 Gy
• Concurrent Chemoradiation
• 172 assigned ? 120 (70) completed cisplatin x 3
  cycle, 40 (23) completed cisplatin x 2 cycles.
• 91 of pts received 67 Gy
• Radiation alone
• 95 of pts received 67 Gy

Forastiere AA et al, N Engl J Med 20033492091-8.
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Treatment Advanced Stage (III/IV) RTOG 91-11
Study
Laryngeal Preservation
2 yr
3.8 yr 5 yr updateA - induction chemo ?
XRT 75 72 70.5 - concurrent
chemoXRT 88 84 83.6 - XRT alone
70 67 65.7
Forastiere AA et al, N Engl J Med 20033492091-8.
AForastiere AA et al, Journal of Clinical
Oncology, Vol 24, No. 18S(June 20
Supplement),20065517.
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Treatment Advanced Stage (III/IV) RTOG 91-11
Study
Locoregional Control
Forastiere AA et al, N Engl J Med 20033492091-8.
AForastiere AA et al, Journal of Clinical
Oncology, Vol 24, No. 18S(June 20
Supplement),20065517.
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Treatment Advanced Stage (III/IV) RTOG 91-11
Study
AChemo therapy ? significant decreased in dz free
survival compared to XRT alone (P 0.02
compared w/induction, P 0.06 compared
w/conccurent Tx) BNo significant
difference CDifference only significant comparing
concurrent chemoXRT vs XRT alone.
Forastiere AA et al, N Engl J Med 20033492091-8.
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Treatment Advanced Stage (III/IV) cont
Forastiere AA et al, N Engl J Med 20033492091-8.
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Anticipated Toxicities

• Hypothyroidism
• Mucositis
• Dermatitis
• Xerostomia
• Fibrosis
• Fistulas
• Dysgeusia

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Take Home Points

• Most laryngeal CA are SCC
• Low stage can be tx by different modalities
• Fraction size 2.25 Gy/fx may increase local ctr
• OS similar b/w surgery XRT vs chemo XRT in
  advanced stage, but organ preservation better
  with chemo XRT
• Organ preservation concurrent XRT gt chemo ? XRT
  XRT alone
• Dont smoke or drink too much alcohol

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An Actual Picture of a Laryngeal Cancer
(L) Source http//www.medscape.com/content/2002/0
0/44/25/442595/442595_fig.html
(R) Source http//www.som.tulane.edu/classware/pa
thology/medical_pathology/New_for_98/Lung_Review/L
ung-62.html
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Questions?