laryngeal cancer

Laryngeal Cancer

Anh Q. TruongMS-4

University of Washington, SOM

Anatomy

Vaezi, MF . Nature Clinical Practice Gastroenterology & Hepatology (2005) 2, 595-603

Anatomy – cont’

Anatomy – subdivision

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

Most common head and neck CA (excluding skin) 12,250 new cases/yr Male : Female = 4 : 1 > 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

Incidence by Site

Supraglottic 40%

Glottic 59%

Subglottic 1%

Epidemiology

American Cancer Society: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008.

Tobacco smoking, bidi smoking, alcohol.

MJ smoking correlation HPV, GERD implicated Possibly perchloroethylene

Risk Factors

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

Clinical Presentation

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

Differential Diagnosis

Infectious Inflammatory Granulomatous disease (TB, sarcoidosis) Papillomatosis Lymphoma

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.

Biopsy and Histology

Direct laryngoscopy with biopsy Histologic subtypes

Squamous cell carcinoma > 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.

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.

Supraglottis Tis: CA in-situ T1: limited to subsite of

supraglots w/normal cord mobility

T2: invade mucosa of > 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


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


Staging• Nodes

– N0: no regional node mets– N1: single ipsilateral node, ≤ 3

cm– N2a: single ipsilateral node, > 3

cm, ≤ 6 cm– N2b: multiple ipsilateral nodes, ≤

6 cm– N2c: bilateral or contralateral

nodes, ≤ 6 cm– N3: node > 6 cm

• Mets– Mx: unknown– M0: no distant mets– M1: distant mets


Stage Grouping

Stage 0 Tis N0 M0

Stage I T1 N0 M0

Stage II T2 N0 M0

Stage IIIT3 N0 M0

T1-3 N1 M0

Stage IVAT4a N0-1 M0

T1-4a N2 M0

Stage IVBT4b any N M0

any T N3 M0

Stage IVC any T any N M1

Earlystage

Advanced stage

Surgery Microlaryngeal surgery Hemilargyngectomy Supraglottic laryngectomy Near-total laryngectomy Total laryngectomy

Photodynamic Therapy Radiation Chemothrapy

Cisplatin + 5-fluorouracil

Treatments – Options

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

Treatment – Early Stage (I/II)

Mendenhall WM et al., Cancer. 2004 May 1;100(9)

Dose Fractionation

Yu et al., 1997 [1] Retrospective study – 5 yr local ctr rate of XRT on T1 glottic CA Daily fx > 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 1;37(3):587-91.2www.rtog.org/members/protocols/95-12/95-12.pdf

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 1;64(1):77-82

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 1991;324:1685-90.

Treatment – Advanced Stage (III/IV) – VA Study cont’


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



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%)


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


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 2003;349:2091-8.

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



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%

Laryngeal Preservation


AForastiere AA et al, Journal of Clinical Oncology, Vol 24, No. 18S(June 20 Supplement),2006:5517.


2 yrs 5 yr updateA

- induction chemo XRT: 64% 54.9% - concurrent chemoXRT : 80% 68.8% - XRT alone : 58% 51%

Locoregional Control


AForastiere AA et al, Journal of Clinical Oncology, Vol 24, No. 18S(June 20 Supplement),2006:5517.


Concurrent chemoXRT

Induction chemo XRT

XRT alone

2 yrs 5 yrs 2 yrs 5 yrs 2 yrs 5 yrs

Dz Free SurvivalA

61% 36% 52% 38% 44% 27%

Overall SurvivalB

74% 54% 76% 55% 75% 56%

Distant metsC

8% 12% 9% 15% 16% 22%

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 differenceCDifference only significant comparing concurrent chemoXRT vs XRT alone.


Treatment – Advanced Stage (III/IV) – cont’


Hypothyroidism Mucositis Dermatitis Xerostomia Fibrosis Fistulas Dysgeusia

Anticipated Toxicities

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 > chemo XRT = XRT alone

Don’t smoke or drink too much alcohol

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

Questions?

laryngeal cancer

Health & Medicine

t1 n0 m0 stage

t2 n0 m0 stage

tis n0 m0 stage

andor subglottis

t3 n0 m0 t1

larynx t3

larynx t4b

cord t1a