Anti-Angiogenesis

Ann Otol Rhinol Laryngol Suppl. 2009 Sep;201:1-13.

Microlarngoscopic and office-based injection of bevacizumab (Avastin) to enhance 532-nm pulsed KTP laser treatment of glottal papillomatosis.

Zeitels SM<>, Lopez-Guerra G<>, Burns JA<>, Lutch M<>, Friedman AM<>, Hillman RE<>.

Department of Surgery, Harvard Medical School, Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

OBJECTIVES: Photoangiolytic lasers effectively treat glottal papillomatosis, but do not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the effect on disease recurrence and phonatory function.

METHODS: A retrospective investigation was done in a pilot group of 10 adult patients with bilateral glottal papillomatosis who had prior angiolytic laser treatment with established patterns of recurrence. The patients underwent 5 bevacizumab injections (5 to 10 mg) into the diseased vocal folds along with 532-nm pulsed KTP laser photoangiolysis treatments 4 to 6 weeks apart. Their disease resolution was compared to findings from prior laser treatment alone, and objective measures of vocal function (acoustic, aerodynamic, Voice-Related Quality of Life survey) were obtained.

RESULTS: All 10 patients had a greater than 90% reduction in recurrence. Four of the 10 had resolution. Four of the 10 have limited recurrent or persistent disease, receive injections of bevacizumab at 8- to 12-week intervals, and have not required laser treatment. Two of the 10 have ongoing periodic office-based KTP laser treatment along with bevacizumab injections. No patient has required microlaryngeal surgery with general anesthesia, and all 10 have had substantial improvement in vocal function.

CONCLUSIONS: This pilot investigation provides preliminary evidence that bevacizumab injections enhance photoangiolytic laser treatment of glottal papillomatosis while enhancing phonatory function. Coupling an antiangiogenesis agent with pulsed KTP laser photoangiolysis is conceptually promising, since the mechanisms of action are complementary.

Ann Otol Rhinol Laryngol Suppl. 2008 Jul;199:3-24.

Photoangiolytic laser treatment of early glottic cancer: a new management strategy.

Zeitels SM<>, Burns JA<>, Lopez-Guerra G<>, Anderson RR<>, Hillman RE<>.

Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.

The 532 nm pulsed KTP (potassium titanyl phosphate) laser and the 585 nm pulsed dye laser (PDL) are photoangiolytic lasers that have been demonstrated to be effective for managing vocal fold dysplasia. The putative mechanism of action is selective photoangiolysis of the sublesional microcirculation. On the basis of this experience, early glottic cancers were treated by selectively targeting the intralesional and sublesional microvasculature. This approach was derived from Folkman’s concepts of neoplastic growth resulting from tumor angiogenesis. Staged microlaryngeal treatment was adopted, because it facilitated optimal functional results, and was considered safe, because early glottic cancer rarely metastasizes. Furthermore, intercurrent disease during conventional incremental radiotherapy is typical in treating early glottic cancer. A pilot group of 22 patients with early glottic cancer (13 T1, 9 T2) were treated with a fiber-based angiolytic laser. Eleven of the 22 had unilateral disease and were entirely treated by laser photoangiolysis as a sole modality. Eleven of the 22 had bilateral disease; 5 of the 11 were treated entirely (bilaterally) by laser photoangiolysis, and 6 of the 11 only underwent laser treatment of the less involved vocal fold, with conventional resection being done on the dominant side of the cancer. The initial 8 of the 22 were treated with the PDL, and the latter 14 of the 22 were treated with the pulsed KTP laser. No patient has cancer presently, and none have undergone posttreatment radiotherapy or open surgery. The mean follow-up is 27 months, 13 of the 22 patients have at least 2 years of follow-up, and the first patient was treated just over 5 years ago. Objective measures of vocal function revealed that photoangiolytic treatment of early glottic cancer resulted in significant postoperative improvements despite the fact that half of the patients had bilateral disease. Angiolytic lasers effectively involuted early glottic cancer, with microsurgically directed nonionizing radiation of the dense neoplastic blood supply resulting in complete tumor regression. This approach is conceptually attractive, because it is repeatable, it preserves all conventional cancer treatment options, and it results in excellent vocal function by improving phonatory mucosal wave vibration. Observations from this investigation suggest that this new and novel cancer treatment strategy is effective; however, larger patient cohorts, longer follow-up, and multi-institutional confirmation will be necessary to establish incontrovertible oncological efficacy.

Laryngoscope. 2007 Aug;117(8):1500-4.

532 nm pulsed potassium-titanyl-phosphate laser treatment of laryngeal papillomatosis under general anesthesia.

Burns JA<>, Zeitels SM<>, Akst LM<>, Broadhurst MS<>, Hillman RE<>, Anderson R<>.

Department of Surgery, Harvard Medical School, Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. Burns.james@mgh.harvard.edu

OBJECTIVES: Angiolytic lasers have been shown to be an effective treatment strategy for laryngeal papillomatosis. These lasers precisely target hemoglobin within the microcirculation of papillary lesions. We have previously demonstrated the advantages of the fiber-based pulsed 532-nm potassium-titanyl-phosphate (KTP) laser in an office setting (with local anesthesia). This investigation provides the first report of the pulsed-KTP laser during microlaryngoscopy under general anesthesia.

STUDY DESIGN: A prospective pilot study was performed in 55 adult patients with laryngeal papillomatosis to determine disease response.

METHODS: During suspension microlaryngoscopy, a solid-state 532 nm pulsed-KTP laser was used (15 ms pulse width, 5.25-7.5 J/pulse maximum output, 2 Hz repetition rate, 0.4 mm fiber, approximately 20-80 J/cm2 fluence) to treat laryngeal papillomatosis. All patients underwent postoperative videolaryngoscopy to assess disease regression based on a previously used rating scale.

RESULTS: Thirty-seven patients underwent 55 procedures during the 18-month study period. Near-term follow-up with an early postoperative evaluation was available in 23 patients (35 procedures). Fourteen patients (20 procedures) were geographically distant and only returned after developing symptoms with significant disease recurrence. Of the 35 procedures in which near-term follow-up was available, 90% or greater disease regression was achieved in 28 of 35 (80%), 75% to 89% disease regression was achieved in 4 of 35 (11%), and 50% to 74% disease regression in 3 of 35 (9%). Anterior-commissure disease was present in 51 of 55 (93%) cases, and no new webbing/synechia occurred. All patients reported that their vocal function improved after treatment.

CONCLUSIONS: The 532 nm pulsed-KTP laser was effective for treating recurrent respiratory papillomatosis, which was similar to our experience as an office-based procedure.