Organ Preservation Surgery for Laryngeal Cancer Following Failed Radiation Therapy

1. Organ Preservation Surgery for Laryngeal Cancer Following Failed Radiation Therapy Hedyeh Javidnia January 14th, 2008 Grand Rounds University of Ottawa Department of Otolaryngology and Head and Neck Surgery

2. 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

3. 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

4. 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.

5. 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.

6. Case of Mr. L • What are your management options? • Total Laryngectomy OR OPS • Transoral Laser Surgery • Vertical Partial Laryngectomy • Supracricoid Partial Laryngectomy

7. 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.

8. Principles of Organ Preservation Surgery 1 • Local control • Accurate assessment of the 3D extent of tumor • Cricoarytenoid unit is the basic functional unit of the larynx • 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

9. 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

10. Anatomy

11. Anatomy

12. 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

13. 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

14. 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.

15. TNM DefinitionsAJCC 6th Ed. 2002 • Primary tumor (T) • TX: Primary tumor cannot be assessed • T0: No evidence of primary tumor • Tis: Carcinoma in situ

16. 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

17. 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

18. 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

19. 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 cm • N2c: Metastasis in bilateral or contralateral nodes ≤ 6 cm • N3: Metastasis in a lymph node > 6 cm

20. Distant metastasis (M) MX- Distant metastasis cannot be assessed M0- No distant metastasis M1- Distant metastasis

21. 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

22. 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

23. Transoral Laser Surgery

24. Transoral Laser Surgery: Inclusion Criteria8 • 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

25. Transoral Laser Surgery: Reported advantages9 • 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

26. 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

27. 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%

28. Transoral Laser Surgery: OutcomesSteiner W, et. al. 11 38% 41% 3% 6% Total 71% control with laser alone

29. 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%

30. Transoral Laser Surgery: Complications 8 Complication rates are <5% and from most to least common include: • Granuloma formation • Laryngeal edema • Laryngeal stenosis • Chondronecrosis

31. Vertical Partial Laryngectomy

32. 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)

33. 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

34. 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.

35. 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

36. 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

37. 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

38. Supracricoid Laryngectomy

39. 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

40. 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

41. 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

42. 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

44. 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

45. 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

46. Overall Review Motamed et. al. Laryngoscope 2006

47. 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

48. 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 %

49. Motamed et. al. Laryngoscope 2006 VPL • Local Control 56 – 100% = 84% overall • Required total Layngectomy = 15.6% • Ultimate local control = 91%

50. Motamed et. al. Laryngoscope 2006 SCPL • Local Control 66 – 100% = 83% overall • Required total Layngectomy = 2.4% • Ultimate local control = 91%