Organ Preservation Surgery for Laryngeal Cancer Following Failed Radiation Therapy

Hedyeh JavidniaJanuary 14th, 2008Grand RoundsUniversity of Ottawa Department of Otolaryngology and Head and Neck Surgery

Objectives

To evaluate a case of recurrent laryngeal cancer following radiotherapy.

To discuss the steps in diagnosis and preoperative assessment of recurrent laryngeal cancer following radiation.

To review the staging of laryngeal cancer

To discuss the evidence and literature for three common organ preservation surgeries for laryngeal cancer with regards to:

- Risks and benefits- Patient selection/indications/contraindications- Functional outcomes- Survival as compared to total laryngectomy

The Canadian perspective

Case of Mr. L

71 yo M presents with >1yr Hx of hoarseness He is a >25 pack year smoker who quit smoking 14 yrs ago FNL shows tumour involving the anterior 3/4 of the left

vocal cord and crossing over to involve the anterior commissure and the very anterior part of the right vocal cord. Some degree of subglottic extension is apparent. Vocal cord mobility is normal.

No apparent clinical lymphadenopathy

Case of Mr. L

CT proves less subglottic extension as believed on FNL and no lymphadenopathy and no metastasis.

Biopsy shows spindle cell carcinoma AKA sarcomatoid squamous cell carcinoma.

Due to anterior commissure involvement, a multidiciplinary decision is made with the patient to go ahead with radiotherapy in order to maximize voice preservation.

He recieves 5260 cGy in 20 fractions over four weeks.

Case of Mr. L

5 months post completion of radiation, on a routine follow-up there is evidence of recurrence

Anterior third of the right vocal cord involving the commissure without any bulk. There is normal cord mobility.

Repeat biopsy shows High-grade squamous intraepithelial lesion/squamous cell carcinoma in situ

Repeat CT shows no evidence of cartilage involvement, nodal, or distant metastasis.

Case of Mr. L

What are your management options?

Total Laryngectomy

OR OPS

Transoral Laser Surgery

Vertical Partial Laryngectomy

Supracricoid Partial Laryngectomy

What constitutes laryngeal organ preservation surgery?

The goal of any organ preservation surgery is to preserve function without compromising cure rate

Functions of the larynx:- Phonation - Respiration - Deglutition (swallowing)- Airway protection

The functions of the larynx must be maintained without the need for tracheostomy or feeding tube.

Principles of Organ Preservation Surgery 1

1. Local control

2. Accurate assessment of the 3D extent of tumor

3. Cricoarytenoid unit is the basic functional unit of the larynx

4. Resection of normal tissue to achieve an expected functional outcome

1. Tufano R. et. al. Organ preservation surgery for laryngeal cancer. Otolaryngol Clin N Am. 2008; 41: 741-755

Radiation failure & Total Laryngectomy

Radiotherapy reported failure rates of 9% - 21% in T1 and 28% - 37% in T2. 2

Total Laryngectomy post radiation has survival rates of 78% - 81% in T1 and 64% - 67% in T2. 3

2. Grisen O et. al. Consecutive series of patients with laryngeal carcinoma treated by primary irradiation. Acta Oncol 1997; 36:279-282 3. Hawkins NV et al. The treatment of glottic carcinoma: an analysis of 800 cases. Laryngoscope 1975; 85:1485-93

Anatomy

Anatomy

First step is identification: Challenges

Differentiation between cancer recurrence and sequelae of radiotherapy is often clinically and rediographically difficult. 4

Endoscopic evaluation followed by biopsies may exacerbate post-radiotherapy changes and initiate superimposed infection, perichondritis, healing failure, and further edema. 5

4. Zbaren P. et. al. Pretherapeutic staging of recurrent laryngeal carcinoma: clinical findings and imaging studies compared with histopathology. Otolaryngol Head and Neck Surg. 2007; 137:487-491.

5. De Bree R, et. al. A randomized trial of PET scanning to improve diagonostic yield of direct laryngoscopy in pateints with suspicion of recurrent laryngeal carcinoma after radiotherapy. Contemp Clin Trials 2007; 28:705-712

Diagnostic steps: Clinical

Careful evaluation of clinical records of prior diagnosis including staging, pathological slides, clinical examination, radiotherapy approach (technique, doses, courses).

Fiberoptic laryngoscopy

Video Stroboscopy (?)

Direct layngoscopy under GA

In advanced case fibroscopic evaluation of the esophagus to R/O synchronous malignancy. 6

6. Marioni et. al. Current opinion in diagnosis and treatment of laryngeal carcinoma. Cancer Treatment Rev. 2006; 32:504-515

Diagnostic steps: Radiographic

CT or MRI

Provide information regarding

primary tumor volume, cartilage

involvement, invasion of preepiglottic

space, extension beyond the larynx

and finally neck matastasis.

If cartilage invasion is suspected or imperative to be ruled out, MRI seems to be superior to CT. 7

7. Becker M. Neoplastic invasion of laryngeal cartilage: radiologic diagnosis and therapeutic implications. Eur J Radiol 2000; 33:216-229.

TNM DefinitionsAJCC 6th Ed. 2002

Primary tumor (T) TX: Primary tumor cannot be

assessed T0: No evidence of primary tumor Tis: Carcinoma in situ

Supraglottis

T1- Tumor limited to one subsite of supraglottis or glottis with normal vocal cord mobility

T2- Tumor invades more than one subsite of supraglottis with normal vocal cord mobility

T3- Tumor limited to larynx with vocal cord fixation or invades postcricoid area, medial wall of piriform sinus, or preepiglottic tissues

T4a- Tumor invades through thyroid cartilage or extends to other tissues beyond the larynx (e.g., to oropharynx, soft tissues of neck)

T4b- Tumor invades prevertebral space, encases the carotid artery, or invades the medistinal structures

Glottis

T1- Tumor limited to vocal cord(s) (may involve anterior or posterior commissures) with normal mobility

T2- Tumor extends to supraglottis or subglottis, or with impaired vocal cord mobility

T3- Tumor limited to the larynx with vocal cord fixation and/or paraglottic space involvement or minor thyroid cartilage invasion (inner cortex)

T4a- Tumor invades through thyroid cartilage or extends to other tissues beyond the larynx, (e.g., to oropharynx, soft tissues of neck)

T4b- Tumor invades prevertebral space, encases the carotid artery, or invades the mediastinal structures

Subglottis

T1- Tumor limited to the subglottis

T2- Tumor extends to vocal cord(s) with normal or impaired mobility

T3- Tumor limited to the larynx with vocal cord fixation

T4a- Tumor invades through cricoid or thyroid cartilage or extends to other tissues beyond the larynx (e.g., to oropharynx, soft tissues of neck)

T4b- Tumor invades prevertebral space, encases the carotid artery, or invades the medistinal structures

Regional lymph nodes (N)

NX: Regional lymph nodes cannot be assessed

N0: No regional lymph node metastasis

N1: Metastasis in a single ipsilateral lymph node ≤ 3 cm.

N2: Metastasis in a single ipsilateral lymph node > 3 cm but ≤ 6 cm, or in multiple ipsilateral lymph nodes ≤ 6 cm, or in bilateral or contralateral lymph nodes ≤ 6 cm.

N2a: Metastasis in a single ipsilateral node > 3 cm but ≤ 6 cm N2b: Metastasis in multiple ipsilateral nodes ≤ 6 cmN2c: Metastasis in bilateral or contralateral nodes ≤ 6 cm

N3: Metastasis in a lymph node > 6 cm

Distant metastasis (M)

MX- Distant metastasis cannot be assessed

M0- No distant metastasis

M1- Distant metastasis

AJCC Stage Groupings

Stage 0 Tis, N0, M0 Stage I T1, N0, M0 Stage II T2, N0, M0 Stage III T3, N0, M0 T1, N1, M0 T2, N1, M0 T3, N1, M0

Stage IVA T4a, N0, M0 T4a, N1, M0 T1, N2, M0 T2, N2, M0 T3, N2, M0 T4a, N2, M0 Stage IVB T4b, any N, M0 Any T, N3, M0 Stage IVC Any T, any N, M1

Back to Case of Mr. L

Anterior third of the right vocal cord involving the commissure without any bulk. There is normal cord mobility.

Repeat CT shows no evidence of cartilage involvement, nodal, or distant metastasis.

His AJCC Staging? T1, N0, M0 Stage I

Transoral Laser Surgery

Transoral Laser Surgery: Inclusion Criteria 8

Complete endoscopic visualization of the carcinoma

Tumor extension to the contralateral VC < 3mm

Absence of arytenoid involvement (except vocal process)

Subglottic extension < 5mm

Supraglottic extension no further than lateral extension of ventricle

Mobile vocal folds

No cartilage involvement

Strict correlation between recurrent lesion and 1° lesion before radiation.

8. Motamed M, et. al. Salvage conservation laryngeal surgery after irradiation failure for early laryngeal cancer. Laryngoscope 2006; 116:451-455

Transoral Laser Surgery: Reported advantages 9

Good voice quality Good swallowing Lower complications rates Lower costs Shorter hospitalization Tracheostomy and NG tubes not routinely

required

9. Piazza C, et. al. Salvage surgery after radiotherapy for laryngeal cancer: from endoscopic resections to open-neck partial and total laryngectomies. Arch Otolaryngol Head and Neck Surg 2007; 133:1037-1043

Transoral Laser Surgery: Operative considerations10

Increased difficulty in identification of recurrent carcinoma in irradiated tissue leads to routine use of frozen section

All margins to be confirmed by permanent section post-op

Strict follow-up with fibroscopic examination and serial imaging allowing early detection of recurrence

The use of CO2 laser excision after radiation failure does not preclude its use for persistent or multiple recurrent disease.

10. Bradley PJ, et. al. Options for salvage after failed initial treatment of anterior vocal commissure squamous carcinoma. Eur Arch Otorhinolaryngol 2006; 263:889-894

Transoral Laser Surgery: Outcomes

Steiner W, et. al. 11

One of the largest reported series of laser surgery post-radiation.

Adhered to selection criteria as above

Included 34 patients with early or advanced recurrent glottic CA after full course radiation. T1=11, T2=10, T3=10, T4=3

71% cure with one or more laser procedures.

Subsequent TL required in 21%

5 year disease-specific survival of 86%

Transoral Laser Surgery: Outcomes Steiner W, et. al. 11

38%

41%

3%

6%Total 71%

control with laser alone

Transoral Laser Surgery: Outcomes

Motamed et. al. 8

In 40% of cases more than one laser-assisted surgery was required Local control rate was 51-87% (Mean 65%) Subsequent total laryngectomy was necessary in 25% Overall control rate including those requiring total laryngectomy was

80-100% (Mean 83%)

Piazza et al. 9

5 year disease – specific survival 95% Disease-free survival 63% Laryngeal preservation 75%

Transoral Laser Surgery: Complications 8

Complication rates are <5% and from most to least common include:

Granuloma formation Laryngeal edema Laryngeal stenosis Chondronecrosis

Vertical Partial Laryngectomy

Vertical Partial Laryngectomy:

Removal of:

One vocal fold - from anterior commissure to vocal process

½ of opposite vocal fold may also be removed if involved

Ipsilateral false vocal cord

Ventricle

Paraglottic space (and overlying thyroid cartilage)

Vertical Partial Laryngectomy:Contraindications

Large T3 or any T4 lesion

Intrarytenoid or cricoarytenoid joint involvement

Bilateral arytenoid cartilage involvement or bilaterally diminished vocal cord mobility

Thyroid cartilage penetration

Supraglottic extension exceeding 10mm at the anterior commissure or 5mm at the vocal process of the arytenoid

Poor pulmonary function

Vertical Partial Laryngectomy:Operative Considerations

The use of intraoperative frozen sections is imperative for maximal local control 12

All margins should be confirmed with permanent section postoperatively

In the event of failure of salvage VPL total laryngectomy remains an option and this will not ultimately affect local control. 8

The use of bipedicled flaps of strap muscles to replace excised intralarygeal soft tissue may facilitate post-op rehabilitation 13

12. Sewnaik A. et. al. Partial Laryngectomy for recurrent glottic carcinoma after radiotherapy. Head and Neck 2005; 27:101-107.

Vertical Partial Laryngectomy:Outcomes 13

Yotakis et. al. Retrospective review of 27 patients with early glottic CA who

underwent partial laryngectomy for recurrence after radiation 18 patients had VPL (T1=13, T2=5) Cannulation time 6 – 17 days (Mean 11.5 days) NGT removal in 7 – 81 days Hospitalization time 10 – 40 days (Mean 25 days) Disease-specific survival was 88.8% (92.3% for T1 and 80%

for T2) Total laryngectomy was performed in 16.6% Laryngeal preservation rate was 77.8%

13. Yotakis et. al. Partial laryngectomy after irradiation failure. Otolaryngol Head and Neck Surg. 2003; 128: 200-209

Vertical Partial Laryngectomy:Outcomes 13

Meta-analysis performed in the same study showed:

Local control rate 50-100% (mean 78%) Approximately 15% of patients require

completion laryngectomy for second recurrence

Vertical Partial Laryngectomy: Complications

Early - generally tracheostomy related Infection Aspiration and dysphonia (should not persist for > 3 weeks)

Late Aspiration Chondritis Laryngeal stenosis (Must rule out local recurrence) Severe hoarseness Granulation tissue (CO2 laser and keel) Tumor recurrence

Supracricoid Laryngectomy

Supracricoid Laryngectomy

Removal of: Entire thyroid cartilage Bilateral true and false vocal cords Ventricles Paraglottic and Preepiglottic spaces Epiglottis Hyoid bone One arytenoid (may spare both if not involved)

- At least one arytenoid must be spared to preserve phonation and sphincter functions

Supracricoid Laryngectomy: Contraindications

Infiltration of both aryntenoid cartilages Infiltration of cricoarytenoid joint or inter-arytenoid region Subglottic extension >1cm below the vocal fold Extension to the glossoepiglottic valecula Major preepiglottic space invasion Hyoid bone invasion Invasion of outer perchondrium of thyroid cartilage Extra-laryngeal spread

Makeieff et. al. 14 Laryngoscope 2005 Retrospective series of 23 patients

with T1-2 Glottic CA post-radiation 6 (26%) went on to have TL Disease specific survival 74% 5 yr survival of 69% Mean cannulation time 28 days Mean NGT time 24 days Mean Hospitalization time 30 days

Pellini et. al. 15 Head and Neck 2007

A multi-institutional retrospective analysis of 78 patients T1=36, T2=33, T3=8, T4=1 5yr survival was 81.8% Disease-specific survival 95.5% Mean NGT time 15 days Swallowing was preserved in 97.4% 97.4% of patients were successfully decannulated 35.7% decannulated within 1 month, 92.3% within 3 months Mean hospitalization time 54 days

Supracricoid Laryngectomy: Outcomes 16

Disease-free survival 84.5% Of the 15.5% failure of SCL, 66.7%

successfully treated with Total laryngectomy 3 year survival rate of 80 -100% 5 year survival rate of 69.4 -100%

16. Marioni G, et. al. The role of supracricoid partial laryngectomy for glottic carcinoma recurrence after radiotherapy failure: A critical review. Acta Otolaryngol 2006; 126:1245-1251

Supracricoid Laryngectomy: Complications 16

Swallowing disorders are the most common in the short term

Voice quality is hoarse, rough, breathy but with acceptable intelligibility.

Aspiration Pneumonia is the most frequent complication (17.5%)

Neo-laryngeal edema

Overall Review

Motamed et. al. Laryngoscope 2006

Motamed et. al. 8 Laryngoscope 2006

Meta Analysis of 22 studies fulfilling criteria: Sample size >10 and F/U >24 mos

All retrospective for total of 552 cases Majority early stages (T1-2) 6 studies of TLS = 145 cases 13 studies of VPL = 357 cases 3 studies of SCPL = 50 cases

Motamed et. al. Laryngoscope 2006

TLS Local Control 51 – 87% = 65% overall Required >1 procedure = 14.5% Required total Layngectomy = 25% Ultimate local control = 83 %

Motamed et. al. Laryngoscope 2006

VPL Local Control 56 – 100% = 84% overall Required total Layngectomy = 15.6% Ultimate local control = 91%

Motamed et. al. Laryngoscope 2006

SCPL Local Control 66 – 100% = 83% overall Required total Layngectomy = 2.4% Ultimate local control = 91%

Horizontal Partial Laryngectomy

Shaw et. al. in 1987 showed high rates of morbidity and mortality with HPL following radiation

Since then, there has been very limited use of this technique in this scenario and as such very limited studies.

Data is therefore inconclusive.

Complications of partial laryngectomies exacerbated by previous radiation

Delayed wound healing, infection, fistula formation, and aspiration pneumonia in up to 25% of cases 5

Less commonly laryngeal stenosis, larygeal edema or granuloma formation, perichondritis, and surgical emphysema

Neck Management Neck dissection must be performed in all cases of

laryngeal carcinoma recurrence with clinical/cytological evidence of regional matastasis 17

Elective neck dissection in patients with N0 prior to salvage laryngeal surgery is controversial 18

The decision for elective neck dissection must be based on T staging, supraglottic or subglittic extension, and extralaryngeal involvement of recurrence.

17. Farrang et. al. Neck management in patients undergoing postradiotherapy slavage laryngeal surgery for recurrenc/persistent laryngeal cancer. Laryngoscope 2006; 116:1864-1866

18. Ganly I. et. al. Results of surgical salvage after failure of definitive radiation therapy for early stage squamous cell carcinoma of the glottic larynx. Arch otolaryngol Head and Neck Surg 2006; 132:59-66

Back to Case of Mr. L

T1, N0, M0 Stage I

Management Options:

Meets all criteria for TLS Local Control = 65% May required >1 procedure Total Layngectomy remains a viable option Ultimate local control = 83 %

The Canadian Perspective

Taylor M et. al. Journal of Otolaryngology – Head & Neck Surgery 2008

Retrospective series of 36 patients who underwent transoral laser surgery for early glottic CA

Tis=7, T1=17, T2=12 2 year disease-free survival of 89% 60% of patients had no voice complaints

Conclusion

Conservation laryngeal surgery is a safe and effective treatment for recurrent localized disease after radiotherapy.

This however is predicated on meticulous patient selection for the most appropriate procedure.

Local control may be achieved without sacrifice of laryngeal function.

Total laryngectomy may be held in reserve as the ultimate option for salvage without compromising ultimate survival.