Discussion
In our experience, administration of systemic bevacizumab for RRP in children results in rapid improvement in voice quality, symptom relief and reduced need for surgical debridement. The treatment was well tolerated and side effects were minimal and included mild proteinuria and brief epistaxis. This is not surprising as the dose and frequency we use is lower than that used for treating children with cancer such as brain tumors. Although bevacizumab controls the growth of papillomas, it is unlikely that it will be curative. This raises concerns about long term use of bevacizumab in young children. The possible long-term effects of bevacizumab has to be balanced against the risks of repeated surgical procedures, anesthesia and lower voice quality. Our approach is to use the minimum dose and frequency necessary to avoid surgical debridements. To this end, we rapidly increase the interval between doses until papillomas recur or symptoms return.
The use of adjuvant therapies in the management of RRP has had mixed results1–5. A 2003 case series on the use of intralesional cidofovir on four children with RRP had heterogenous results with one of the patients achieving complete remission for 15 months5. A 2013 case series that evaluated the effects of three injections of intralesional bevacizumab in 10 children with RRP saw a median surgical procedure time increase of 5.9 weeks1. All three of our patients did not achieve significant benefit from use of intralesional cidofovir or bevacizumab.
Our case series is limited by a short follow up of patients which lessens our ability to determine long term efficacy as well as late side effects. Our patients lacked standardized surveys to assess symptom severity before and after starting treatment. HPV typing was not assessed which limited our ability to draw conclusions about the relationship between treatment response and HPV type.
Conflict of interest: Julina Ongkasuwan receives royalties from Springer and Elsevier. There are no other conflicts of interests to report.
Acknowledgements: There are no acknowledgements.
References
1. Rogers DJ, Ojha S, Maurer R, Hartnick CJ. Use of Adjuvant Intralesional Bevacizumab for Aggressive Respiratory Papillomatosis in Children. JAMA Otolaryngol Neck Surg . 2013;139(5):496-501. doi:10.1001/jamaoto.2013.1810
2. Derkay CS. Task force on recurrent respiratory papillomas. A preliminary report. Arch Otolaryngol Head Neck Surg . 1995;121(12):1386-1391. doi:10.1001/archotol.1995.01890120044008
3. Zur KB, Fox E. Bevacizumab chemotherapy for management of pulmonary and laryngotracheal papillomatosis in a child. The Laryngoscope . 2017;127(7):1538-1542. doi:10.1002/lary.26450
4. Mohr M, Schliemann C, Biermann C, et al. Rapid response to systemic bevacizumab therapy in recurrent respiratory papillomatosis. Oncol Lett . 2014;8(5):1912-1918. doi:10.3892/ol.2014.2486
5. Milczuk HA. Intralesional cidofovir for the treatment of severe juvenile recurrent respiratory papillomatosis: long-term results in 4 children. Otolaryngol Head Neck Surg . 2003;128(6):788-794. doi:10.1016/S0194-5998(03)00259-6
Figure Legends:
FIGURE 1 Laryngoscopy Before and After Bevacizumab in Patient 1. A-C show images from the last laryngoscopy performed before Bevacizumab. Figure A shows papilloma in epiglottis, figure B in glottis and figure C in trachea. Figures D to F show the first post bevacizumab laryngoscopy with minor papilloma laryngeal side of epiglottis (D), vocal folds (E) and a clear trachea. Figures G-I shows the most recent laryngoscopy showing minor papilloma in vocal folds (G) with persistently papilloma free trachea (H and I).
FIGURE 2 Laryngoscopy Before and After Bevacizumab in Patient 2. Figure A shows last laryngoscopy performed before procedure which shows bulky papilloma along entire length of vocal folds. Figures B-D show first laryngoscopy after bevacizumab which shows minimal papillomas on vocal folds. Figure E shows laryngoscopy performed after 4 cycles which does not show any papillomas. Picture F shows flexible nasolaryngoscopy obtained after 8 cycles of bevacizumab which also shows no papillomas.