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Biomedical subjects

Marc D Coltrera

Publications and source records attributed to Marc D Coltrera.

6 recordsLinked to original sources

FDG-PET/CT imaging for preradiotherapy staging of head-and-neck squamous cell carcinoma.

PURPOSE: Image localization of head-and-neck squamous cell carcinoma lags behind current techniques to deliver a precise radiation dose with intensity-modulated radiotherapy. This pilot study prospectively examined the use of registered 18-F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT for preradiotherapy staging of the neck. METHODS AND MATERIALS: Sixty-three patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx were enrolled into an institutional FDG-PET imaging protocol between September 2000 and June 2003. Of these patients, 20 went on to immediate neck dissection surgery and were studied further. Of these 20, 17 (85%) had American Joint Committee on Cancer Stage III or IV disease. All patients underwent preoperative FDG-PET and contrast-enhanced CT of the head and neck. FDG-PET/CT images were created using a nonrigid image registration algorithm developed at the University of Washington. Alternate primary and nodal gross tumor volumes were contoured with radiotherapy treatment planning software, blinded to each other and to the pathology results. One set of volumes was designed with CT guidance alone and the other with the corresponding FDG-PET/CT images. Neck dissection specimens were subdivided into surgical nodal levels intraoperatively, and the histopathologic findings were correlated with the CT and FDG-PET/CT nodal level findings. RESULTS: FDG-PET/CT detected 17 of 17 heminecks and 26 of 27 nodal zones histologically positive by dissection (100% and 96% sensitivity, respectively). The nodal level staging sensitivity and specificity for FDG-PET/CT was 96% (26 of 27) and 98.5% (68 of 69), respectively. FDG-PET/CT correctly detected nodal disease in 2 patients considered to have node-negative disease by CT alone. Agreement between the imaging results and pathology findings was stronger for FDG-PET/CT (kappa 0.95, 95% confidence interval 0.82-0.99) than for CT alone (kappa 0.81, 95% confidence interval 0.63-0.91; p = 0.06 by two-sided McNemar's testing). CONCLUSION: These early findings suggest that FDG-PET/CT is superior to CT alone for geographic localization of diseased neck node levels. Confirmatory trials to substantiate the accuracy of FDG-PET/CT neck staging should be prioritized.

Adult↗

FDG-PET/CT-guided intensity modulated head and neck radiotherapy: a pilot investigation.

BACKGROUND: 2-deoxy-2[(18)F]fluoro-D-glucose-positron emission tomography (FDG-PET) imaging can be registered with CT images and can potentially improve neck staging sensitivity and specificity in patients with head and neck squamous cell cancer. The intent of this study was to examine the use of registered FDG-PET/CT imaging to guide head and neck intensity modulated radiotherapy (IMRT) planning. METHODS: Twenty patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx underwent FDG-PET and contrast-enhanced CT imaging of the head and neck before neck dissection surgery. Combined FDG-PET/CT images were created by use of a nonrigid image registration algorithm. All IMRT plans were theoretical and were not used for treatment. We prescribed 66 Gy in 30 fractions to FDG-avid CT abnormalities and nodal zones directly involved with disease, without prophylactic coverage of uninvolved neck levels. Matched CT-guided IMRT plans designed according to the specifications of Radiation Therapy Oncology Group (RTOG) H-0022 were available for comparison. We investigated the feasibility of FDG-PET/CT-directed IMRT dose escalation in five patients with FDG-avid disease located away from critical normal structures. After 66 Gy, FDG-avid disease with 0.5-cm margins was boosted in 220 cGy increments until dose-limiting criteria were reached. RESULTS: Elimination of prophylactic coverage to FDG-PET/CT-negative neck levels markedly reduced mean dose (Dmean) to the contralateral parotid gland (p < .001) and Dmean to the laryngeal cartilage (p = .001). No FDG-PET/CT-directed plan missed pathologically verified nodal disease. During the dose escalation exercise, we successfully increased the dose to 95% of the planning target volume (PTV95%) to a mean of 7490 cGy (range, 7153-8098 cGy). CONCLUSIONS: We demonstrate early proof of the principle that FDG-PET/CT-guided IMRT planning can selectively target and intensify treatment of head and neck disease while reducing critical normal tissue doses. Routine clinical use of such planning should not be engaged until the accuracy of FDG-PET/CT is fully validated. Future directions, including refinement of treatment to gross disease and radiologically uninvolved neck nodal levels, are discussed.

Adult↗

FDG-PET prediction of head and neck squamous cell cancer outcomes.

OBJECTIVE: To confirm that high pretreatment uptake of 2-deoxy-2[(18)F]fluoro-d-glucose (FDG) detected by positron emission tomography (PET) measured at the primary head and neck squamous cell carcinoma (HNSCC) and at metastatic nodal disease predicts poor outcomes for HNSCC. DESIGN AND PATIENTS: We enrolled 63 consecutive patients with a histological diagnosis of HNSCC (including tumors of the oral cavity, oropharynx, larynx, and hypopharynx) from September 2000 through June 2003, into a prospective institutional imaging trial. Fifty-four patients (86%) underwent a baseline FDG-PET scan before curative treatment and were eligible for analysis. RESULTS: A primary tumor standardized uptake value (SUV) of greater than 9.0 predicted inferior local recurrence-free survival (P = .02) and disease-free survival (P = .03). Nodal SUV dichotomized according to the cohort median of 6.1 did not predict for either disease outcome (P = .71 and P = .98, respectively). On proportional hazards analysis, local recurrence and disease event hazard ratios for a primary tumor SUV of 9.0 or greater remained significant or at borderline significance when adjusted for nodal SUV or other clinical covariates. CONCLUSIONS: Our findings support an association between baseline primary tumor FDG SUV and HNSCC outcomes. In contrast, nodal FDG SUV was not predictive. Primary tumor FDG SUV is a promising prognostic factor and may establish the need for intensified locoregional therapy in individual patients. Multi-institutional imaging trials and further characterization of the biology responsible for elevated FDG uptake in HNSCC will be necessary to confirm the prognostic utility of FDG-labeled PET.

Carcinoma, Squamous Cell↗

Round window gentamicin application: an inner ear hair cell damage protocol for the mouse.

It is important to develop an inner ear damage protocol for mice that avoids systemic toxicity and produces damage in a relatively rapid fashion, allowing for study of early cellular and molecular mechanisms responsible for hair cell death and those that underlie the lack of hair cell regeneration in mammals. Ideally, this damage protocol would reliably produce both partial and complete lesions of the sensory epithelium. We present a method for in vivo induction of hair cell damage in the mouse via placement of gentamicin-soaked Gelfoam in the round window niche of the inner ear, an adaptation of a method developed to study hair cell regeneration in chicks. A total of 82 subjects underwent the procedure. Variable doses of gentamicin were used (25, 50, 100 and 200 microg). Saline-soaked Gelfoam, sham-operations and the contralateral, non-operated cochlea were used as controls. Survival periods were 1, 3 and 14 days. Damage was assessed on scanning electron microscopy. We found that this method produces relatively rapid hair cell damage that varies with dose and can extend the entire length of the sensory epithelium. In addition, this protocol produces no systemic toxicity and preserves the contralateral ear as a control.

Animals↗

Organ preservation strategies in the treatment of laryngeal cancer.

For most patients, a total laryngectomy should not be used as the initial treatment for any stage laryngeal tumor. The goal in treating a patient with laryngeal cancer must be not only to cure but also to provide the best functional outcome for the patient. In the United States, the treatment of laryngeal cancer has moved from radical surgery toward a more conservative approach involving definitive radiotherapy and chemotherapy, with extirpative surgery held in reserve for salvage. In Europe, there has been increasing reliance on limited endoscopic cordectomy procedures for early tumors and the use of function-preserving surgical approaches for more advanced lesions. Careful monitoring of the conservatively treated patient is mandatory to allow for early salvage of failures to the original therapy. Because of the high costs of hospitalization, the direct medical costs attributable to conservative approaches are equal to or less than the costs for more radical surgical resections. Even if survivals are only equivalent, organ preservation approaches should be the treatment of choice for most patients.

Combined Modality Therapy↗

Designing clinical databases.

Evidence-based medicine has always relied on databases. Anyone who needs to know anything about the outcome of a treatment needs a database, but individual practitioners may feel that database design is beyond them for various reasons. Effective database design does not require complexity. This article seeks to be a practical guide for those who are contemplating development of their own database.

Computer Security↗