Matthew T. Brigger, M.D. Massachusetts Eye and Ear Infirmary Harvard Medical School

1. The 585-nm Pulsed Dye Laser for Recurrent Respiratory Papillomatosis: A Randomized Controlled Trial in Children Matthew T. Brigger, M.D. Massachusetts Eye and Ear Infirmary Harvard Medical School

2. Overview: Current Trial • A multicenter effort to assess the benefit of using the 585-nm pulsed dye laser (PDL) in children with RRP • All children will be treated • No children will receive placebo • All will receive at least conventional treatment • The safety of the PDL has been established • Sites: Boston, San Diego, Birmingham, Cincinnati

3. Background • Surgical treatment of RRP • The Goal: Remove papillomas to the fullest extent as is safely possible • Balance the functions of the larynx • Airway, swallowing and voice • Preserve normal anatomy • Primary methods – microlaryngeal dissection, microdebrider, CO2 laser

4. The Problem • Surgical therapies involve mucosal disruption • Scarring potential • “Good surgical technique” • Do not disrupt opposing mucosal surfaces

5. The Problem • “Difficult to treat areas” • Anterior commissure, inter-arytenoid space and laryngeal ventricle • Often must leave gross papilloma • Notoriously poor voice outcomes due to scarring

6. Basic CO2 Laser Physics • “Hemostatic Cutting Laser” • Wavelength 10,600 nm in a continuous beam • Primarily absorbed by water within tissue • Water is heated to steam • Steam expands and microscopically tears tissue • Various ways to alter the degree of tissue damage • defocusing, adjusting fluence (energy density)

7. A Different Type of Laser • Early 1980’s: Simon Parrish and R. Rox Anderson develop the 585 nm pulsed dye laser based on the concept of selective photothermolysis • A novel treatment for cutaneous vascular lesion by atraumatically coagulating microvasculature of lesion while preserving the epithelium • Destroys the vessels within the lesion

8. Papilloma Histology • Highly vascular fibrous core covered by nonkeratinizing squamous epithelium

9. Why is the Histology Important? • The vascular core of papillomas is a prime target for selective photothermolysis • Destruction of papilloma vascular supply should result in involution with mucosal preservation • Allow a more complete debulking than traditional staged procedures • Potentially better vocal outcomes due to mucosal preservation of the vocal folds

10. Initial Data • 1993 - reports of efficacy in cutaneous papilloma demonstrated • 1997 - Bower presented a pilot study demonstrating efficacy in 9 children • 1998 & 2001 - McMillan and Shapshay demonstrated efficacy in 10 adults • anterior commissure treated in 6 patients

11. Adult Data • 2001: Franco et al 1st large series in adults • 23 adults (41 procedures on 78 true vocal folds over a period of 19 months under general anesthesia • 37 cases of bilateral treatment • Anterior commisure in 27 • Demonstrated feasibilty and safety in large population • Marked regression of lesions with no anterior glottic webbing • No objective data

12. Pediatric Data • 2007 Hartnick et al • 23 patients underwent 37 bilateral procedures at the anterior commissure • No episodes of vocal scarring or web formation were seen • Trend toward increased time between surgical interventions, • treatment group was uncontrolled and heterogenous

13. How it’s Done • Setup similar to conventional methods • General anesthesia with child in microlaryngeal suspension • Debulk exophytic lesions as needed • Use fiber through a long cannula or suction • Fiber is held 1 mm to 2 mm from tissue and laser is fired

18. Where To Go From Here? • Feasibility and safety has been clearly shown • Objective outcomes are lacking • Does a more complete excision result in less procedures? • Are voice outcomes truly better than conventional therapy?

19. Where To Go From Here? • A randomized controlled trial with clear objective outcomes • Severely affected children will be most likely to demonstrate effects • Sufficient power will likely require a multicenter effort

20. Current Multicenter RCT • Massachusetts Eye and Ear Infirmary, Boston • Rady Children’s Hospital, San Diego • The Children’s Hospital of Alabama, Birmingham • Cincinnati Children’s Hospital Medical Center

21. Objectives • Primary: Determine if the PDL can decrease the time interval between surgeries in children with RRP • Secondary: Determine if the PDL has improved voice outcomes and laryngoscopic severity scores

22. Patient Population • Inclusion Criteria • Immunocompetent children ages 1-12 with symptomatic JORRP who have required four or more surgeries in the past year • Exclusion Criteria • Children receiving adjuvant therapies during study period • Caregivers who are non-English speaking as the PVRQOL instrument has been validated only in the English language.

23. Patient Population • Control group: debridement of papillomas with a powered microdebrider or cold instrumentation without the use of any further methods or adjuvant therapies • Experimental group: Primary debridement of non critical regions with conventional methods, followed by treatment of the anterior commissure, inter-arytenoid space and laryngeal ventricle with the pulsed dye laser.

24. Outcomes • Follow all patients for 1 year • Time interval between treatments • Laryngoscopic staging and severity scores for children • Pediatric Voice Related Quality of Life (PVRQOL) measurements • A validated pediatric voice instrument

25. Important Points • ALL children will be treated • No placebo arm • If randomized to control arm, each child will still receive the benefits of conventional surgical treatment • The PDL has an excellent safety profile

26. Conclusion • PDL represents a potential advantage by allowing a more complete debridement of papillomas • Need more data to determine the role in routine practice to justify cost

27. Contact Information • Matthew_Brigger@meei.harvard.edu • 617-573-4206