G. Farwell

Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

PURPOSE We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. METHODS AND MATERIALS Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. RESULTS Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade </= 1) and short duration (</=1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. CONCLUSIONS In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction.

Differential response rates to irradiation among patients with human papillomavirus positive and negative oropharyngeal cancer

To evaluate the responsiveness of human papillomavirus (HPV) ‐positive and HPV‐negative oropharyngeal cancer to intensity‐modulated radiotherapy (IMRT), using axial imaging obtained daily during the course of image‐guided radiotherapy (IGRT).

Comparison of IMRT techniques in the radiotherapeutic management of head and neck cancer: is tomotherapy "better" than step-and-shoot IMRT?

Currently, the most common method of delivering intensity-modulated radiotherapy (IMRT) is through step-and-shoot, segmental multi-leaf collimator (SMLC)-based techniques. Although rotational delivery methods such as helical tomotherapy (HT) have been proposed as offering advantages in the treatment of head and neck cancer, a lack of clinical data exists on its potential utility. This study compared dosimetric, clinical, and quality-of-life endpoints among 149 patients treated by HT and SMLC-IMRT for head and neck cancer. Dosimetric analysis revealed that the use of HT resulted in significant improvements with respect to mean dose (23.5 versus 27.9 Gy, p = 0.03) and V30 (30.1 versus 43.9 Gy, p = 0.01) to the contralateral (spared) parotid gland. However, the incidence of grade 3+ xerostomia in the late setting was 10% and 8% among patients treated by HT and SMLC-IMRT, respectively (p = 0.46). There were no significant differences in any of the quality of life endpoints among patients treated by HT and SMLC-IMRT (p > 0.05, for all). Acknowledging the biases inherent in this retrospective analysis, we found that the dosimetric advantages observed with HT compared to SMLC-IMRT failed to translate into significant improvements in clinical outcome. Prospective studies are needed to further evaluate how HT may affect the therapeutic ratio.

Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer

Background We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan–Meier curves were used for survival analyses. Results Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09–2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11–2.86, p = 0.016). Conclusion Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC.

The current status of human laryngeal transplantation in 2017: A state of the field review

Human laryngeal allotransplantation has long been contemplated as a surgical option following laryngectomy, but there is a paucity of information regarding the indications, surgical procedure, and patient outcomes. Our objectives were to identify all human laryngeal allotransplants that have been undertaken and reported in the English literature and to evaluate the success of the procedure.

Three-dimensional online surface reconstruction of augmented fluorescence lifetime maps using photometric stereo (Conference Presentation)

Multi-Spectral Time-Resolved Fluorescence Spectroscopy (ms-TRFS) can provide label-free real-time feedback on tissue composition and pathology during surgical procedures by resolving the fluorescence decay dynamics of the tissue. Recently, an ms-TRFS system has been developed in our group, allowing for either point-spectroscopy fluorescence lifetime measurements or dynamic raster tissue scanning by merging a 450 nm aiming beam with the pulsed fluorescence excitation light in a single fiber collection. In order to facilitate an augmented real-time display of fluorescence decay parameters, the lifetime values are back projected to the white light video. The goal of this study is to develop a 3D real-time surface reconstruction aiming for a comprehensive visualization of the decay parameters and providing an enhanced navigation for the surgeon. Using a stereo camera setup, we use a combination of image feature matching and aiming beam stereo segmentation to establish a 3D surface model of the decay parameters. After camera calibration, texture-related features are extracted for both camera images and matched providing a rough estimation of the surface. During the raster scanning, the rough estimation is successively refined in real-time by tracking the aiming beam positions using an advanced segmentation algorithm. The method is evaluated for excised breast tissue specimens showing a high precision and running in real-time with approximately 20 frames per second. The proposed method shows promising potential for intraoperative navigation, i.e. tumor margin assessment. Furthermore, it provides the basis for registering the fluorescence lifetime maps to the tissue surface adapting it to possible tissue deformations.

Autofluorescence lifetime imaging during transoral robotic surgery: a clinical validation study of tumor detection (Conference Presentation)

Autofluorescence lifetime spectroscopy is a promising non-invasive label-free tool for characterization of biological tissues and shows potential to report structural and biochemical alterations in tissue owing to pathological transformations. In particular, when combined with fiber-optic based instruments, autofluorescence lifetime measurements can enhance intraoperative diagnosis and provide guidance in surgical procedures. We investigate the potential of a fiber-optic based multi-spectral time-resolved fluorescence spectroscopy instrument to characterize the autofluorescence fingerprint associated with histologic, morphologic and metabolic changes in tissue that can provide real-time contrast between healthy and tumor regions in vivo and guide clinicians during resection of diseased areas during transoral robotic surgery. To provide immediate feedback to the surgeons, we employ tracking of an aiming beam that co-registers our point measurements with the robot camera images and allows visualization of the surgical area augmented with autofluorescence lifetime data in the surgeon’s console in real-time. For each patient, autofluorescence lifetime measurements were acquired from normal, diseased and surgically altered tissue, both in vivo (pre- and post-resection) and ex vivo. Initial results indicate tumor and normal regions can be distinguished based on changes in lifetime parameters measured in vivo, when the tumor is located superficially. In particular, results show that autofluorescence lifetime of tumor is shorter than that of normal tissue (p < 0.05, n = 3). If clinical diagnostic efficacy is demonstrated throughout this on-going study, we believe that this method has the potential to become a valuable tool for real-time intraoperative diagnosis and guidance during transoral robot assisted cancer removal interventions.