Hubert Vermeersch

Quantitative Tumor Apoptosis Imaging Using Technetium-99m–HYNIC Annexin V Single Photon Emission Computed Tomography

PURPOSE Radiolabeled annexin V may allow for repetitive and selective in vivo identification of apoptotic cell death without the need for invasive biopsy. This study reports on the relationship between quantitative technetium-99m- (99mTc-) 6-hydrazinonicotinic (HYNIC) radiolabeled annexin V tumor uptake, and the number of tumor apoptotic cells derived from histologic analysis. PATIENTS AND METHODS Twenty patients (18 men, two women) suspected of primary (n = 19) or recurrent (n = 1) head and neck carcinoma were included. All patients underwent a spiral computed tomography (CT) scan, 99mTc-HYNIC annexin V tomography, and subsequent surgical resection of the suspected primary or recurrent tumor. Quantitative 99mTc-HYNIC annexin V uptake in tumor lesions divided by the tumor volume, derived from CT, was related to the number of apoptotic cells per tumor high-power field derived from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assays performed on sectioned tumor slices. RESULTS Diagnosis was primary head and neck tumor in 18 patients, lymph node involvement of a cancer of unknown primary origin in one patient, and the absence of recurrence in one patient. Mean percentage absolute tumor uptake of the injected dose per cubic centimeter tumor volume derived from tomographic images was 0.0003% (standard deviation [SD], 0.0004%) at 1 hour postinjection (PI) and 0.0001% (SD, 0.0000%) at 5 to 6 hours PI (P =.012). Quantitative 99mTc-HYNIC annexin V tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered. CONCLUSION In the absence of necrosis, absolute 99mTc-HYNIC annexin V tumor uptake values correlate well with the number of apoptotic cells derived from TUNEL assays.

An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways.

PURPOSE To develop a protocol for the irradiation of ethmoid sinus cancer, with the aim of sparing binocular vision; of developing a strategy of intensity-modulated radiation therapy (IMRT) planning that produces dose distributions that (1) are consistent with the protocol prescriptions and (2) are deliverable by static segmental IMRT techniques within a 15-minute time slot; of fine tuning the implementation strategy to a class solution approach that is sufficiently automated and efficient, allowing routine clinical application; of reporting on the early clinical implementation involving 11 patients between February 1999 and July 2000. patients and methods: Eleven consecutive T1-4N0M0 ethmoid sinus cancer patients were enrolled in the study. For Patients 1-8, a first protocol was implemented, defining a planning target volume prescription dose of 60 to 66 Gy in 30-33 fractions and a maximum dose (Dmax) of 50 Gy to optic pathway structures and spinal cord and limit of 60 Gy to brainstem. For Patients 9-11, an adapted (now considered mature) protocol was implemented, defining a (planning target volume) prescription dose of 70 Gy in 35 fractions and a Dmax to optic pathway structures and brainstem of 60 Gy and to spinal cord of 50 Gy. RESULTS The class solution-directed strategy developed during this study reduced the protocol translation process from a few days to about 2 hours of planner time. The mature class solution involved the use of 7 beam incidences (20-37 segments), which could be delivered within a 15-minute time slot. Acute side effects were limited and mild. None of the patients developed dry eye syndrome or other visual disturbances. The follow-up period is too short for detection of retinopathy or optic nerve and chiasm toxicity. CONCLUSION Conventional radiotherapy of ethmoid sinus tumors is associated with serious morbidity, including blindness. We hypothesize that IMRT has the potential to save binocular vision. The dose to the optic pathway structures can be reduced selectively by IMRT. Further enrollment of patients and longer follow-up will show whether the level of reduction tested by the clinical protocol is sufficient to save binocular vision. An adaptive strategy of IMRT planning was too inefficient for routine clinical practice. A class solution-directed strategy improved efficiency by eliminating human trial and error during the IMRT planning process.

Postoperative intensity-modulated radiotherapy in sinonasal carcinoma - Clinical results in 39 patients

Carcinoma of the paranasal sinuses is rare. Standard therapeutic modalities consist of surgery and radiotherapy (RT). Because of the often advanced stage and the vicinity of optic structures, RT‐induced ocular toxicity is a feared side effect of conventional RT. Intensity‐modulated radiotherapy (IMRT) is a relatively new technique, which is implemented with the hypothesis that, compared with conventional RT, it would result in a lower rate of ocular toxicity for an equal local control (LC).

Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses: treatment results for 47 patients

PURPOSE Ethmoid sinus cancer is a rare malignancy. Treatment results are mostly reported together with other sinonasal tumors, grouping a wide range of different histologies and treatment approaches. This study reports on the treatment outcome of 47 patients diagnosed with adenocarcinoma of the ethmoid sinuses and treated with surgery and high-dose postoperative radiation therapy. METHODS AND MATERIALS Between September 1985 and October 2001, 51 patients with adenocarcinoma of the ethmoid sinuses were referred to the Ghent University Hospital. Four patients were treated with low-dose palliative radiation because of very extended inoperable disease or distant metastasis at the time of diagnosis. They were not included in this analysis. The other 47 patients, all staged as N0M0, were treated with surgery and postoperative high-dose radiation therapy. The median follow-up was 32 months. The T-stages were T1 for 2, T2 for 17, T3 for 11, and T4 for 17 patients. All 47 patients were staged as N0M0. RESULTS The 3-year, 5-year, and 7-year overall survival are respectively 71%, 60%, and 38%. The 3-year and 5-year disease-free survival are respectively 62% and 36%. The 3-year and 5-year disease-free survival for T1-T2 stages are respectively 87% and 55%, for T3 stages 57% and 28%, and for T4 stages 41% and 25%. The locoregional tumor control was 70% and 59% at respectively 3 and 5 years. Patients presenting with intracranial tumor invasion at the time of diagnosis relapsed within 7 months after the end of radiotherapy. Radiation-induced severe dry eye syndrome and optic neuropathy was observed in respectively 7 and 2 of the 47 cases. CONCLUSION Postoperative radiotherapy for adenocarcinoma of the ethmoid sinuses is associated with good local control rates. Crucial for a favorable prognosis is the absence of intracranial invasion. The rarity of these tumors makes it difficult to evaluate new therapeutic advances.

Intensity modulated radiation therapy for oropharyngeal and oral cavity tumors: clinical use and experience

Background and purpose. Intensity modulated radiation therapy (IMRT) offers an opportunity to generate dose distributions highly conformal to the target volume. Head and neck cancer patients, referred for radiotherapy, may be good candidates to benefit from IMRT. This paper discusses the clinical implementation of IMRT for oropharyngeal and oral cavity tumors, and reports the clinical results of the 14 patients treated with this technique at Ghent University Hospital (GUH). Patients and Methods. Between May 1999 and May 2001, 14 patients were treated with IMRT at GUH for oropharyngeal or oral cavity tumors. Two groups of patients can be distinguished. The first group consists of eight patients re-irradiated with IMRT for a locoregional relapse. The second group of six patients were treated with IMRT for a primary tumor. For the first group, IMRT was used to treat the relapse by generating a concave dose distribution, i.e. to combine a homogeneous target re-irradiation with a dose to the spinal cord as low as possible. For the second group, IMRT was applied in order to achieve a more homogeneous dose distribution inside the PTV and to preserve parotid gland function. Results. The majority of the patients of group 1 (6/8) relapsed in field within four months after the end of the re-irradiation, with a median overall survival of 7 months. For group 2, two patients died shortly after the end of the IMRT treatment, the other four patients are free of tumor relapse with a median follow-up of 5 months (1-13 months). The acute toxicity due to radiation was acceptable for both patient groups. Dysphagia and pain was more present in group 1. Regarding late complications for the group of re-irradiations (group 1), no myelitis, carotid rupture or cranial nerve palsy was observed. One patient of group 1 developed osteoradionecrosis of the mandible and feeding tube dependency was present for another patient. No fatal late complications were observed in this group. For the first two patients of group 2, sparing of the parotid function was not a treatment objective. For the other patients of group 2, the mean dose to the contralateral parotid gland ranged from 17 to 25 Gy, which resulted in a decrease of subjective symptoms of xerostomia compared to patients treated with conventional radiotherapy. Conclusions. The implementation of IMRT for oropharyngeal and oral cavity tumors results in a homogeneous target irradiation and allows to re-irradiate locoregional relapses with acceptable adverse effects. Sparing of the parotid gland by IMRT is feasible, although this may be significantly influenced by the delineation method of the elective lymph node regions.

Colonization of voice prostheses by albicans and non-albicans Candida species.

Objectives The purposes of the study were to assess the colonization of tracheoesophageal voice prostheses by albicans and non‐albicans Candida species and to determine their susceptibility for three antimycotics that are frequently used for prophylaxis or treatment of oral candidiasis (i.e., miconazole, fluconazole, and nystatin).

Impact of thyroidectomy without laryngeal nerve injury on vocal quality characteristics: An objective multiparameter approach

The main purpose of this study was to determine the impact of thyroidectomy on the subjective and objective vocal quality using the Dysphonia Severity Index. It was hypothesized that objective measures of vocal function and other vocal characteristics would change (temporarily or permanently) from the presurgical to the postsurgical conditions, even with the entire preservation of the laryngeal nerve, due to the surgical approach and other influencing factors.

Validation of a high-performance liquid chromatographic method for the determination of doxycycline in turkey plasma

A high-performance liquid chromatographic method for the analysis of doxycycline in turkey plasma samples using demeclocycline hydrochloride as the internal standard was developed, optimized and validated. A one-step extraction procedure and an isocratic HPLC method with UV detection were used. No interferences with endogenous compounds or with the anticoagulant were observed. Linear calibration curves (r2 > 0.99) were obtained in water and plasma between 0 and 600 micrograms ml-1. Good recoveries for doxycycline (> 66%) and demeclocycline (> 72%) were seen both in water and in plasma. The coefficient of variation was < 9.86% for within-day reproducibility and < 7.53% for the between-day reproducibility. The deviation between the mean value found and the true value was < 14.5% (accuracy). The limit of detection was 0.1 microgram ml-1 in plasma samples. A good stability of doxycycline was observed in water and in plasma samples after storage for six months at -20 degrees C (recovery > 91%).

Nuclear medicine imaging for the assessment of primary and recurrent head and neck carcinoma using routinely available tracers

This article reviews the literature on the use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and thallium-201, technetium-99m sestamibi and technetium-99m tetrofosmin single-photon emission tomography (SPET) for the diagnosis and staging of primary and recurrent squamous cell carcinoma of the head and neck (SCCHN). A search of the MEDLINE and CancerLit databases covering articles entered between 1989 and February 2003 was performed. In the case of FDG PET, only full-ring PET studies that included comparison with conventional morphological imaging were considered. Due to the wide variation in methodology, a straightforward meta-analysis of FDG PET literature was impossible. Instead, indicative summary receiver-operating curves of FDG PET and morphological imaging techniques were generated and a paired comparison of the sensitivities and specificities of FDG PET and morphological imaging performed. Compared with conventional morphological imaging, FDG PET proved as sensitive and specific for the detection of primary SCCHN but more sensitive and specific for the detection of cervical lymph node involvement (CLNI) and recurrence of SCCHN. Additional studies addressing the role of FDG PET in screening for distant metastases and synchronous primary tumours are mandatory. Following negative conventional evaluations, FDG PET identifies occult primary tumours in 20–50% of patients presenting with CLNI. As regards the use of 201Tl, 99mTc-sestamibi and 99mTc-tetrofosmin, more studies are required to define whether these imaging agents could form part of the current diagnostic armamentarium in SCCHN patients. It is concluded that FDG PET either is superior to or offers added value when compared with conventional morphological imaging techniques for the purpose of diagnosis and staging of primary and recurrent SCCHN.

Liquid chromatographic separation of doxycycline and 4-epidoxycycline in a tissue depletion study of doxycycline in turkeys

Liver and muscle tissue residues of doxycycline in turkeys were determined following administration of 25 mg doxycycline x HCl/kg BW in the drinking water under field conditions. Quantitation was performed using a validated HPLC method with fluorescence detection. The method was able to separate doxycycline and its 4-epimer, 4-epidoxycycline. This epimer was found in both liver and muscle tissue. The detection limits of the method were estimated at 1.2 ng/g and 1.0 ng/g of doxycycline in liver and muscle tissue, respectively, using a signal-to-noise ratio of 3:1. The recovery of doxycycline was determined from spiked tissues and was 63+/-3.8% and 66+/-3.1% for liver and muscle, respectively (n = 6). Within-day and between-day imprecision, expressed as the R.S.D. was below 7.4%. Linear calibration curves (r>0.997) were obtained in spiked liver between 0 and 1500 ng/g and in spiked muscle between 0 and 500 ng/g. A good stability of doxycycline was observed in liver samples after storage for 22 days at -20 degrees C. The correlation between the residues in the liver and the muscle was expressed as the correlation coefficient r and was 0.9884. The depletion kinetics of doxycycline fitted a one-compartment model. The elimination half-life (T1/2) of doxycycline was 77.7 h and 78.0 h in muscle and liver, respectively. Furthermore, the residue depletion kinetics were used to establish a withdrawal period in conformity with official guidelines. The withdrawal times necessary to reach concentrations below maximum residue limits (MRLs), as imposed by the EU, were 12 days and 17 days for liver and muscle tissue, respectively.