Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]).

Purpose: Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain.

Patients And Methods: In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain.

Investigation of the pharmacokinetics of 3'-deoxy-3'-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer.

Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer.

Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET.

Kinetic analysis of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in head and neck cancer patients before and early after initiation of chemoradiation therapy.

Unlabelled: The purpose of this study was to investigate the kinetic behavior of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) before and early after initiation of chemoradiation therapy in patients with squamous cell head and neck cancer.

Methods: A total of 8 patients with head and neck cancer underwent (18)F-FLT PET scans (7 patients at baseline and after 5 d [10 Gy] of radiation therapy given with concomitant chemotherapy and 1 patient only at baseline). Dynamic PET images were obtained with concurrent arterial or venous blood sampling.

Cisplatin combined with zidovudine enhances cytotoxicity and oxidative stress in human head and neck cancer cells via a thiol-dependent mechanism.

Oxidative stress and mitochondrial dysfunction in cancer cells represent features that may be exploited therapeutically. We determined whether agents that induce mitochondrial dysfunction, such as zidovudine (AZT) and cisplatin (CIS), could enhance killing of human head and neck cancer cells via oxidative stress. AZT- and/or CIS-induced cytotoxicity was determined using clonogenic survival, mitochondrial membrane potential was analyzed to investigate mitochondrial function, and glutathione was measured to determine thiol metabolism perturbations.

2-Deoxy-D-glucose combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells.

Glucose deprivation has been hypothesized to cause cytotoxicity by inducing metabolic oxidative stress in human cancer cells. The current work tests the hypothesis that 2-deoxy-d-glucose (2DG) combined with cisplatin [cis-diamminedichloroplatinum(II)] can enhance cytotoxicity in human head and neck cancer cells (FaDu) by mechanisms involving oxidative stress. Exposure of FaDu cells to the combination of 2DG and cisplatin resulted in a significant decrease in cell survival when compared with 2DG or cisplatin alone.

The failure patterns of oral cavity squamous cell carcinoma after intensity-modulated radiotherapy-the university of iowa experience.

Purpose: Determine the failure patterns of oral cavity squamous cell carcinoma (SCC) treated with intensity-modulated radiotherapy (IMRT).

Methods And Materials: Between May 2001 and July 2005, 55 patients with oral cavity SCC were treated with IMRT for curative intent. Forty-nine received postoperative IMRT, 5 definitive IMRT, and 1 neoadjuvant.

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research.

Objective: Review the University of Iowa experience with intensity modulated radiation treatment (IMRT) in oropharyngeal squamous cell carcinoma.

Methods: From January 2000 to July 2004, 66 patients with oropharyngeal cancer were treated with IMRT, 62 with definitive IMRT and 4 postoperative IMRT. Three target volumes (CTV1, CTV2, and CTV3) were defined.

Base excision repair of both uracil and oxidatively damaged bases contribute to thymidine deprivation-induced radiosensitization.

Purpose: Increased cellular sensitivity to ionizing radiation due to thymidine depletion is the basis of radiosensitization with fluoropyrimidine and methotrexate. The mechanism responsible for cytotoxicity has not been fully elucidated but appears to involve both the introduction of uracil into, and its removal from, DNA. The role of base excision repair of uracil and oxidatively damaged bases in creating the increased radiosensitization during thymidine depletion is examined.

Long-term quality of life for surgical and nonsurgical treatment of head and neck cancer.

Objective: To compare the long-term, health-related quality-of-life outcomes in patients with advanced head and neck cancer (HNC) treated with surgery and postoperative radiation therapy (SRT) or concurrent chemotherapy and radiation therapy (CRT).

Design: Matched-pair study comparing patients with advanced HNC treated with SRT or CRT at least 12 months after treatment. Patients completed 2 validated surveys addressing HNC-specific outcomes and depressive symptoms and provided information on employment and tobacco and alcohol use.

Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma--the University of Iowa experience.

Purpose: To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma.

Methods And Materials: From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis.

The role of FDG PET in management of neck metastasis from head-and-neck cancer after definitive radiation treatment.

Purpose: The role of neck dissection after definitive radiation for head-and-neck cancer is controversial. We select patients for neck dissection based on postradiation therapy (post-RT), computed tomography (CT), and [18F] fluorodeoxyglucose positron emission tomography (FDG PET). We summarize the clinical outcomes of patients treated with this policy to further elucidate the role of FDG PET in decision making for neck dissection after primary radiotherapy.

Value of FDG PET in assessment of treatment response and surveillance in head-and-neck cancer patients after intensity modulated radiation treatment: a preliminary report.

Purpose: [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been shown to be valuable in early detection of persistent and recurrent head-and-neck cancer after treatment. Previous studies have reported its use in patients treated with conventional radiation. Many patients are now treated with intensity-modulated radiation treatment (IMRT).

The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies.

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS.

The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head-and-neck squamous cell carcinoma.

Purpose: The role of neck dissection after radiation therapy ([RT] with or without chemotherapy) for regionally advanced head and neck cancer is controversial. As much as 50% of residual lymphadenopathy after radiation has no viable tumor cells present on histopathologic analysis. [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging can detect metabolically active cancer.

Ex vivo gene therapy for skeletal regeneration in cranial defects compromised by postoperative radiotherapy.

Because radiation remains a common postoperative treatment for head and neck cancers, it is critical to determine whether new bone-regenerative approaches are effective for healing craniofacial defects challenged by therapeutic doses of radiation. The objective of this study was to determine whether the deleterious effects of radiotherapy could be overcome by ex vivo gene therapy to heal craniofacial defects. Rat calvarial critical-sized defects were treated with either an inlay calvarial bone graft or syngeneic dermal fibroblasts transduced ex vivo with an adenovirus engineered to express bone morphogenetic protein 7 (BMP-7), a morphogen known to stimulate bone formation.