Fluorescence spectroscopy as a diagnostic tool in HNSCC

Program Oral Presentations

Factors predictive of severity of ORN of the mandible Shamit Chopra, MBBS (presenter); Dev P Kamdar, MD; Ozlem Tulunay, MD; Mark Marunick, DDS, MS; Ho-Sheng Lin, MD; John Jacobs, MD; Harold Kim, MD OBJECTIVES: 1) Determine risk factors associated with severe osteoradionecrosis (ORN) of the mandible. 2) Aid future ORN management and prophylaxis based on results of the study. METHODS: We retrospectively analyzed 40 ORN patients diagnosed between June 2002 and November 2008. Of those, 92.5% were squamous cell cancers, 85% were oral cavity or oropharyngeal tumors, and 92.5% had mandibular ORN. All received 3D conformal radiation therapy (RT) or intensitymodulated RT, with 60 Gy median dose. 22.5% and 77.5% received primary and postoperative RT respectively. 75% received chemotherapy (CT), mostly concurrent (97%) and platinum-based (95%). ORN was staged based on Store-Boysen scores of 0-3. 90% of patients received antibiotics, and 32.5% hyperbaric oxygen. Debridement, plate removal, flap repair and external fixation were done in 87.5%, 42.5%, 22.5% and 7.5% patients respectively. RESULTS: Median time to ORN was 7.5 months (range,183). All primary RT, 96% Stage IV and 94% T4a patients had Stage 2/3 ORN. Secondary infection predicted Stage 3 ORN significantly (p⫽0.0001). Differences between proportions of Stage 3 patients with greater than, vs less than, or equal to 40 pack-year smoking history; and those who had primary surgery versus none, were significant (p⫽0.00001, 0.004 respectively). No significant association existed between ORN severity and CT, RT modality and dose, primary site, dental extractions, and alcohol intake. At 37 months average follow-up, 5%, 27.5%, 5% and 7.5% patients developed new primaries, local, regional and distant relapse respectively. CONCLUSIONS: Secondary infection, smoking, primary RT, surgery, T and overall stage were predictive of severity, and can potentially guide prophylaxis and management of mandibular osteoradionecrosis. Fluorescence lifetime imaging microscopy in oral cancer Jeremy D Meier, MD (presenter); D Gregory Farwell, MD; Yinghua Sun;

Jennifer Phipps; Nisa Hatami; Laura Marcu; Yang Sun OBJECTIVES: 1) Investigate fluorescence lifetimes in oral cavity carcinoma. 2) Evaluate a fluorescence lifetime imaging microscopy (FLIM) apparatus as an aid in the intra-operative assessment of oral carcinoma. METHODS: Case series at a university-based medical center from 2008-2009. Ten patients with oral cavity squamous cell carcinoma who underwent intraoperative biopsy or resection were included. A novel FLIM apparatus was utilized allowing remote image collection. Tissue autofluorescence was induced with a nitrogen pulse laser (337 nm, 700 ps pulse width). The fluorescence images were magnified by a 20x microscope objective and recorded using a compact gated ICCD camera. Images of carcinoma, surrounding normal mucosa, and at the transition zone between normal and malignant tissue were recorded. The images were compared to histopathology slides. A total of 27 sites were imaged. RESULTS: The fluorescence intensity dropped significantly (over 30%) and was associated with the decrease of fluorescence lifetime from 1.55 ns to 1.35 ns at 460/60 nm in malignant lesions compared with normal healthy tissue. The fluorescence lifetimes were generally decreased in carcinoma but the values varied by the location within the oral cavity. This was consistent with previous reports from our hamster model. The time-resolved images were minimally affected by the irregular tissue surface, the non-uniform illumination, and the presence of endogenous absorbers. CONCLUSIONS: These results demonstrate differences in fluoresce intensity and lifetime between malignant and normal tissue in the oral cavity. FLIM has potential as a noninvasive and intraoperative imaging technique for oral cavity carcinoma. Fluorescence spectroscopy as a diagnostic tool in HNSCC Jeremy D Meier, MD (presenter); D Gregory Farwell, MD; Yinghua Sun; Nisa Hatami; Laura Marcu; Yang Sun; Hongtao Xie OBJECTIVES: 1) Determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract. 2) Evaluate the potential of time-resolved laserinduced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC). METHODS: Case series at a university-based medical center from 2008-2009. Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 900 ps pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared to the histopathology at each site. A total

ORALS

vival of patients with primary metastases after therapy compared with patients with non-primary metastases gives cause to define two different follow-up periods. The results underscore the relevance of postoperative ultrasound investigations and short follow-up intervals to identify patients that could benefit from a second time surgery in connection with improved survival.

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Otolaryngology-Head and Neck Surgery, Vol 141, No 3S1, September 2009

of 64 sites were measured. The fluorescence parameters that provided the most discrimination were determined. RESULTS: Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than the normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360⬃660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7⫹/-0.06 ns for normal and 1.3⫹/0.06 ns for tumor, p⫽0.0025), and the Laguerre coefficients, LEC-2 (i.e., at 460 nm: 0.135⫹/-0.001 for normal and 0.155⫹/-0.007 for tumor, p⬍0.05). CONCLUSIONS: These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a non-invasive diagnostic technique for HNSCC. Free-flap reconstruction for osteoradionecrosis of the jaws Steven B Cannady, MD (presenter); Eben Rosenthal, MD; Nichole Renae Dean, DO; Andrew Kroeker; Mark K Wax, MD OBJECTIVES: 1) Elucidate predictive factors for free flap success in advanced osteoradionecrosis. 2) Present a dualinstitution experience with free tissue reconstruction of the jaws for ORN. METHODS: A dual institution retrospective review was conducted between 2000 and 2009. Univariate analysis of overall and flap complications was performed for patient demographic, original treatment, ORN presentation, flap surgery details, and surgical complications. The effect of time to ORN (tXO) and ORN to reconstruction (tOR) on overall and flap complication rates as well as length of bone replaced was evaluated. RESULTS: Fifty-five free flaps were performed on 53 patients for ORN of the mandible and maxilla, with a 90% resolution rate. Univariate parameter analysis was significant for in-field mandibulotomy (p ⫽ 0.008 for overall complications and 0.04 for flap loss). Increased time from XRT to ORN development significantly predicted for flap specific complications and flap loss (p ⬍ 0.05). Increased time from ORN diagnosis to flap surgery resulted in greater length of bone involvement (p⫽ 0.01). Fifty-three percent of patients developed a major complication (fistula, native skin necrosis, hardware exposure or fracture, or other complications requiring surgical intervention). CONCLUSIONS: In-field mandibulotomy, increased tXO, and increased tOR result in greater soft tissue fibrosis, potentially explaining the associated complication risk or disease progression. Thus, in patients developing ORN long after treat-

ment, or longer interval from diagnosis to flap surgery, surgery should be accordingly more aggressive. Functional outcomes after paraganglioma resections are independent David M Neskey, MD (presenter); Zoukaa Sargi, MD; Georges Hatoum; Rishi Modh; Gregg Goldin OBJECTIVES: Paragangliomas of the head and neck are derived from a collection of neuroendocrine tissues associated with the paraganglionic system. The most common paraganglioma of the head and neck is the carotid body tumor (CB) followed by glomus jugulare (GJ), glomus tympanicum, and glomus vagale. Although most of these tumors are benign, patients frequently present with cranial nerve palsies secondary to mass effect and surgical resection is generally considered the treatment of choice. The objective of this study is to determine the incidence of severe functional impairment after surgery, measured retrospectively by PEG /trach dependence. METHODS: A retrospective analysis of patients treated at the University of Miami from 1998 to 2008 for paraganglioma. The primary endpoints collected were the type of paraganglioma and the presence of pre- and postoperative cranial neuropathies. Additional endpoints were outcomes measures assessing post operative function including PEG tube and/or tracheostomy dependence along with pathologic and radiographic review of the neoplasms. RESULTS: Sixty-five patients were identified which included, 29 carotid body tumors, 25 glomus jugulare, 8 glomus tympanicum, and 3 glomus vagale. The presence of preoperative cranial neuropathies was 7% and 40% for CB tumors and GJ respectively. Post-operative cranial nerve dysfunction increased to 17% and 76% for CB tumors and GJ respectively. Of the 19 patients with GJ and postoperative cranial neuropathies only four were PEG dependent. Alternatively, of the five patients with CB tumors and postoperative CN dysfunction, three were PEG tube dependent. None of the patients in our study were tracheostomy dependent. CONCLUSIONS: Cranial nerve deficits occur less frequently in CB tumors compared with GJ tumors. However, when cranial nerve dysfunction is present, patients with CB tumors are more likely to be PEG tube dependent implying that patients with progressive preoperative neuropathies are able to compensate better than patients with acute surgically acquired neuropathies. Functional outcomes after transoral robotic surgery Brian D Kulbersh, MD (presenter) OBJECTIVES: 1) Understand the use of transoral robotic surgery for head and neck cancer. 2) Learn functional outcomes of transoral robotic surgery.