Image-guided radiotherapy for left-sided breast cancer patients: geometrical uncertainty of the heart.

Purpose: To quantify the geometrical uncertainties for the heart during radiotherapy treatment of left-sided breast cancer patients and to determine and validate planning organ at risk volume (PRV) margins.

Methods And Materials: Twenty-two patients treated in supine position in 28 fractions with regularly acquired cone-beam computed tomography (CBCT) scans for offline setup correction were included. Retrospectively, the CBCT scans were reconstructed into 10-phase respiration correlated four-dimensional scans.

Image-guided radiotherapy for breast cancer patients: surgical clips as surrogate for breast excision cavity.

Purpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam radiotherapy for breast cancer patients, using cone beam computed tomography (CBCT) scans.

Methods And Materials: Twenty-one breast cancer patients with surgical clips placed in the breast excision cavity were treated in a supine position with 28 daily fractions. CBCT scans were regularly acquired for a setup correction protocol.

Breast-conserving therapy: radiotherapy margins for breast tumor bed boost.

Purpose: To quantify the interfraction position variability of the excision cavity (EC) and to compare the rib and breast surface as surrogates for the cavity. Additionally, we sought to determine the required margin for on-line, off-line and no correction protocols in external beam radiotherapy.

Methods And Materials: A total of 20 patients were studied who had been treated in the supine position for 28 daily fractions.

Development of luciferase tagged brain tumour models in mice for chemotherapy intervention studies.

The blood-brain barrier (BBB) is considered one of the major causes for the low efficacy of cytotoxic compounds against primary brain tumours. The aim of this study was to develop intracranial tumour models in mice featuring intact or locally disrupted BBB properties, which can be used in testing chemotherapy against brain tumours. These tumours were established by intracranial injection of suspensions of different tumour cell lines.

A model to predict bladder shapes from changes in bladder and rectal filling.

The purpose of this study is to develop a model that quantifies in three dimensions changes in bladder shape due to changes in bladder and/or rectal volume. The new technique enables us to predict changes in bladder shape over a short period of time, based on known urinary inflow. Shortly prior to the treatment, the patient will be scanned using a cone beam CT scanner (x-ray volume imager) that is integrated with the linear accelerator.

Modulation of the blood-brain barrier in oncology: therapeutic opportunities for the treatment of brain tumours?

Systemically administered chemotherapy is not very effective in the treatment of primary or metastatic brain tumours. An important reason for this low efficacy is insufficient drug delivery to the tumour site due to the presence of the blood-brain barrier (BBB). In this review, we give an overview of strategies that were tested to bypass the BBB or to increase its permeability for anticancer drugs.

Improved penetration of docetaxel into the brain by co-administration of inhibitors of P-glycoprotein.

P-glycoprotein (Pgp) in the blood-brain barrier limits the brain's uptake of many anticancer drugs. We have investigated whether the Pgp inhibitors cyclosporin A, valspodar (PSC833) and elacridar (GF120918) increase the accumulation of docetaxel in the brain. Pgp knockout mice served as a reference model for the complete absence or complete inhibition of Pgp.

Incidence and treatment of recurrent plantar fibromatosis by surgery and postoperative radiotherapy.

Background: The incidence of plantar fibromatosis (PF) is unknown. Sometimes PF tends to recur repetitively after surgical treatment. In our institute we have used postoperative radiotherapy in an attempt to diminish the change on recurrence.

Bioanalysis of zosuquidar trihydrochloride (LY335979) in small volumes of human and murine plasma by ion-pairing reversed-phase high-performance liquid chromatography.

We have developed and validated a sensitive and selective method for the quantitative determination of the P-glycoprotein inhibitor zosuquidar (LY335979) in human and murine plasma using only 50 microl sample volumes. Sample pretreatment involved liquid-liquid extraction with tert-butyl methyl ether. Zosuquidar and the internal standard chlorpromazine were separated using a narrow bore column (2.

The influence of the P-glycoprotein inhibitor zosuquidar trihydrochloride (LY335979) on the brain penetration of paclitaxel in mice.

We determined the effect of zosuquidar.3HCl, an inhibitor of P-gp, on the penetration of the anticancer drug paclitaxel into the brain. Zosuquidar.

Serum S100B is suitable for prediction and monitoring of response to chemoimmunotherapy in metastatic malignant melanoma.

Serum S100B and lactate dehydrogenase (LDH) levels were evaluated for their ability to predict response in patients with metastatic malignant melanoma and to determine their usefulness in monitoring the results of chemoimmunotherapy. Levels were studied in 53 patients with metastatic malignant melanoma receiving chemoimmunotherapy and in 19 control patients with metastatic renal cell carcinoma receiving a similar immunotherapy regimen. The serum S100B level was elevated in 81% of the patients before treatment.

Margins for translational and rotational uncertainties: a probability-based approach.

Purpose: To define margins for systematic rotations and translations, based on known statistical distributions of these deviations.

Methods And Materials: The confidence interval-based expansion method for translations, known as the "rolling ball algorithm," was extended to include rotations. This new method, which we call the Rotational and Translational Confidence Limit (RTCL) method, is exact for a point with arbitrary rotations and translations or for a finite shape with rotations only.

Entrapment by Cremophor EL decreases the absorption of paclitaxel from the gut.

Background: Recent studies in mice and patients have shown that the low oral bioavailability of paclitaxel can be increased by coadministration of P-glycoprotein blockers. However, in patients an increase in the oral paclitaxel dose from 60 to 300 mg/m(2) does not result in proportionally higher plasma levels. We hypothesized that the surfactant Cremophor EL, present in the formulation of paclitaxel, may be responsible for this nonlinear absorption by entrapping paclitaxel within the intestinal lumen, probably by inclusion in micelles.

Irradiation of paranasal sinus tumors, a delineation and dose comparison study.

Purpose: To determine the influence of observer variation and treatment planner variation on the dose delivered to the target and normal structures when irradiating paranasal sinus carcinomas.

Patients And Methods: Nine patients with paranasal sinus tumors underwent debulking surgery and subsequent radiation therapy. Two observers from two different institutions delineated the clinical target volumes (CTVs) for the elective and the boost volumes.

Bioanalysis and preliminary pharmacokinetics of the acridonecarboxamide derivative GF120918 in plasma of mice and humans by ion-pairing reversed-phase high-performance liquid chromatography with fluorescence detection.

We have developed and validated a sensitive and selective method for the determination of the P-glycoprotein modulator GF120918 in murine and human plasma. Chlorpromazine is used as internal standard. Sample pretreatment involves liquid-liquid extraction with tert-butyl methyl ether.

The importance of drug-transporting P-glycoproteins in toxicology.

The importance of specific transport in toxicology is becoming increasingly clear and the work on P-glycoprotein has certainly been a major contribution to these growing insights. P-Glycoproteins were discovered by their ability to confer multidrug resistance in mammalian tumour cells. They are localised in the cell membrane where they actively extrude a wide range of compounds including many anti-cancer drugs from the cell.

Planning, computer optimization, and dosimetric verification of a segmented irradiation technique for prostate cancer.

Purpose: To develop and verify a multisegment technique for prostate irradiation that results in better sparing of the rectal wall compared to a conventional three-field technique, for patients with a concave-shaped planning target volume (PTV) overlapping the rectal wall.

Methods And Materials: Five patients have been selected with various degrees of overlap between PTV and rectal wall. The planned dose to the ICRU reference point is 78 Gy.

Treatment of malignancy arising in pilonidal disease.

Background: Malignant degeneration is a rare complication of pilonidal disease and is associated with a high recurrence rate and poor prognosis compared with regular nonmelanoma skin cancer. Treatment in our departments and in the international literature was evaluated.

Methods: We analyzed the data from three patients with malignant degeneration who were treated in our departments and an additional 56 patients who were found after an extensive literature search.

Alkyl-lysophospholipids as anticancer agents and enhancers of radiation-induced apoptosis.

Synthetic alkyl-lysophospholipids (ALPs, also referred to as ether-phospholipids) have been studied as antitumor agents for more than a decade. Classical examples of these ALPs include 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH(3); Edelfosine) and hexadecylphosphocholine (HePC; Miltefosine). Unlike most currently available chemotherapeutic drugs that target the nuclear DNA, ALPs exert their action at the plasma membrane level, where they interfere with mitogenic signal transduction pathways.

A method to improve the dose distribution of interstitial breast implants using geometrically optimized stepping source techniques and dose normalization.

Background And Purpose: The standard linear source breast implant of our institution was compared with alternative linear source implant geometries and a stepping source implant, to evaluate the possibility of minimizing the treated volume. Normalization to a higher isodose than the conventional 85% of the mean central dose (MCD) was investigated for the stepping source implant to reduce the thickness of the treated volume and to increase dose uniformity. The purpose of this study was to develop an implant geometry yielding a high conformity and a more uniform dose distribution over the target volume.

Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein.

Previous studies in mice with disrupted mdr1a P-glycoprotein genes have shown that the oral bioavailability of paclitaxel is very low because of the presence of this drug-transporting protein in the intestinal wall. Additional studies with cyclosporin A have shown that this P-glycoprotein-inhibiting agent is able to increase the bioavailability of paclitaxel in mouse models and in patients. However, the potential immune-suppressive side effects of cyclosporin A renders this compound less suitable for chronic use in cancer patients.

Phantom materials for boron neutron capture therapy.

The aim of this work was to establish which reference phantom material is most suited for dosimetry under reference conditions of neutron beams for boron neutron capture therapy (BNCT). For this purpose, phantoms of dimensions 15 x 15 x 15 cm3 and 30 x 30 x 30 cm3, composed of water, tissue-equivalent (TE) liquid, polyethylene (PE), polymethyl methacrylate (PMMA) and water containing 10 microg g(-1) and 30 microg g(-1) 10B were irradiated using the Petten BNCT beam. Activation foils and a diode detector were used for the determination of the thermal neutron fluence rate.

An improved technique for breast cancer irradiation including the locoregional lymph nodes.

Purpose: To find an irradiation technique for locoregional irradiation of breast cancer patients which, compared with a standard technique, improves the dose distribution to the internal mammary-medial supraclavicular (IM-MS) lymph nodes. The improved technique is intended to minimize the lung dose and reduce the dose to the heart.

Methods And Materials: The standard technique consists of an anterior mixed electron/photon IM-MS field.

Inter-observer variation in delineation of bladder and rectum contours for brachytherapy of cervical cancer.

Background And Purpose: In 3D treatment planning of low dose rate brachytherapy of cervical carcinoma the dose in bladder and rectum can be estimated from dose-volume histograms (DVHs). In this study, the influence of inter-observer variation in delineation of bladder and rectum on DVHs and dose at specific bladder and rectum points was investigated.

Materials And Methods: Three observers delineated bladder and rectum on axial CT images of ten patients.