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, CO 2 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 CO 2 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