Improving dose homogeneity in large breasts by IMRT: efficacy and dosimetric accuracy of different techniques.

PURPOSE: Evaluation of a simplified intensity-modulated irradiation (IMRT), a three-field (MFT), and a conventional two-tangential-field technique regarding dose homogeneity, target coverage, feasibility and, for the first time, dosimetric reliability in patients with large breasts treated postoperatively for breast cancer on a low-energy linac. MATERIAL AND METHODS: CT datasets of ten patients with relatively large breast volumes treated for breast cancer were selected. For each patient, four treatment plans were created: low-energy conventional (C-LE), high-energy conventional (C-HE), three-field (MFT), and a two-field aperture-based IMRT technique. Apertures for the IMRT and MFT were created with the aid of a three-dimensional dose display. Dosimetric accuracy of each technique was evaluated in an anthropomorphic thorax/breast phantom. RESULTS: The mean of planning target volumes receiving < 95% or > 105% of the prescribed total dose was reduced from 16.0% to 13.9% to 10.4% to 8.9% in the C-LE, C-HE, MFT, and IMRT plans, respectively. Phantom dose measurements agreed well with the calculated dose within the breast tissue. CONCLUSION: Aperture-based IMRT using two tangential incident beam directions, as well as a three-field technique with inverse optimization, provide a better alternative to the standard wedged tangential beams for patients with large breasts treated on low-energy linacs while maintaining the efficiency of the treatment-planning and delivery process.

Phantom and in-vivo measurements of dose exposure by image-guided radiotherapy (IGRT): MV portal images vs. kV portal images vs. cone-beam CT.

PURPOSE: Positioning verification is usually performed with treatment beam (MV) portal images (PI) using an electronic portal imaging device (EPID). A new alternative is the use of a low energy photon source (kV) and an additional EPID mounted to the accelerator gantry. This system may be used for PI or--with rotating gantry--as cone-beam CT (CBCT). The dose delivered to the patient by different imaging processes was measured. METHODS AND MATERIALS: A total of 15 in-vivo dose measurements were done in five patients receiving prostate IMRT. For anterior-posterior (AP) and lateral PI with MV and kV photons measurement points were inside the rectum and at the patient's skin. Dose for CBCT was measured in the rectum. Additional measurements for CBCT were done in a cylindrical CT-dose-index (CTDI) phantom to determine peripheral, central and weighted CTDI. RESULTS: The dose for AP MV PI was 57.8 mGy at the surface and 33.9 mGy in the rectum, for lateral MV PI 69.4 mGy and 31.7 mGy, respectively (5 MU/exposure). The dose for AP kV PI was 0.8 mGy at the surface and 0.2 mGy in the rectum, for lateral PI 1.1 mGy and 0. 1 mGy, respectively. For a CBCT the rectal dose was 17.2 mGy. The peripheral CTDI was 23.6 mGy and the center dose was 10.2 mGy, resulting in a weighted CTDI of 19.1 mGy in the phantom and an estimated surface dose of < or =28 mGy. CONCLUSIONS: Even taking into account an RBE (Relative Biological Effectiveness) of 2 for kV vs. MV radiation, for kV PI the delivered dose is lower and image quality is better than for MV PI. CBCT provides a 3D-image dataset and dose exposure for one scan is lower than for two MV PI, thus rendering frequent volume imaging during a fractionated course of radiotherapy possible.

Repositioning accuracy of two different mask systems-3D revisited: comparison using true 3D/3D matching with cone-beam CT.

PURPOSE: The repositioning accuracy of mask-based fixation systems has been assessed with two-dimensional/two-dimensional or two-dimensional/three-dimensional (3D) matching. We analyzed the accuracy of commercially available head mask systems, using true 3D/3D matching, with X-ray volume imaging and cone-beam CT. METHODS AND MATERIALS: Twenty-one patients receiving radiotherapy (intracranial/head-and-neck tumors) were evaluated (14 patients with rigid and 7 with thermoplastic masks). X-ray volume imaging was analyzed online and offline separately for the skull and neck regions. Translation/rotation errors of the target isocenter were analyzed. Four patients were treated to neck sites. For these patients, repositioning was aided by additional body tattoos. A separate analysis of the setup error on the basis of the registration of the cervical vertebra was performed. The residual error after correction and intrafractional motility were calculated. RESULTS: The mean length of the displacement vector for rigid masks was 0.312 +/- 0.152 cm (intracranial) and 0.586 +/- 0.294 cm (neck). For the thermoplastic masks, the value was 0.472 +/- 0.174 cm (intracranial) and 0.726 +/- 0.445 cm (neck). Rigid masks with body tattoos had a displacement vector length in the neck region of 0.35 +/- 0.197 cm. The intracranial residual error and intrafractional motility after X-ray volume imaging correction for rigid masks was 0.188 +/- 0.074 cm, and was 0.134 +/- 0.14 cm for thermoplastic masks. CONCLUSIONS: The results of our study have demonstrated that rigid masks have a high intracranial repositioning accuracy per se. Given the small residual error and intrafractional movement, thermoplastic masks may also be used for high-precision treatments when combined with cone-beam CT. The neck region repositioning accuracy was worse than the intracranial accuracy in both cases. However, body tattoos and image guidance improved the accuracy. Finally, the combination of both mask systems with 3D image guidance has the potential to replace therapy simulation and intracranial stereotaxy.

Radiation enhancement by gemcitabine-mediated cell cycle modulations.

The purpose of this study was to investigate the exact dose dependency and time dependency of the radiation-enhancing effect of gemcitabine (2',2'difluoro desoxycytidine [dFdC]) in in vitro experiments (HeLa cells: cancer of the uterine cervix, #4197 cells: oropharyngeal squamous cell carcinoma), and to correlate this effect with the underlying changes in cell cycle distribution. Cell viability was determined fluorometrically after exposure to dFdC (0-20.0 micro mol/l), irradiation (0-37.5 Gy), and both modalities. Combining both therapies, cells were exposed to dFdC (0-10.0 micro mol/l) for 24 hours before further treatment and irradiated (0-30 Gy) immediately afterwards with or without removal of dFdC. For cell cycle analysis by flow cytometry, cells were irradiated (0-40 Gy) or treated with dFdC (0.012-1.0 micro mol/l, 24-48 hours). Additionally, cells were exposed to dFdC (2.0 micro mol/l, 0-4 hours). Cell cycle kinetics were evaluated using bromodeoxyuridine (BrdU) (10 micro mol/l) S-phase labeling, given either 30 minutes before or in the last hour of dFdC treatment (2.0 micro mol/l, 0-6 hours). The fluorometric assay revealed that dFdC enhances radiation-induced cytotoxicity at marginally toxic or nontoxic concentrations (<37 nmol/l). Radiation resulted in the anticipated G2/M arrest already at 2 Gy. DFdC induced concentration and exposure time-dependent cell cycle changes that were better resolved using BrdU, demonstrating a pronounced S-phase arrest already at 12 nmol/l. BrdU-pulse labeling revealed that the cell cycle block occurred at the G1/S boundary. Our data reconfirm the already known radiation enhancement, the S-phase specific activities of dFdC, and the relevance of the synchronized progression of cells through the S-phase with regard to the radiosensitizing properties of low-dose dFdC. However, we could demonstrate that before progressing in the S-phase, cells were blocked and partially synchronized at the more radiosensitive G1/S boundary. Furthermore, cells progressing past the block might accumulate proapoptotic signals caused by both radiation and dFdC, which will also results in cell death.

[Combined radiotherapy and gemcitabine. Evaluation of clinical data based on experimental knowledge]. / Kombination von Radiotherapie und Gemcitabine. Bewertung der klinischen Daten auf der Basis experimenteller Erkenntnisse.

BACKGROUND: In experimental studies the nucleoside analog Gemcitabine (2',2' difluorodesoxycytidine) clearly demonstrates radiation enhancing properties. After describing the pharmacological Gemcitabine-related data and the clinical studies regarding combined radiochemotherapy and taking under consideration the in-vitro data and the results provided by animal models, this overview is aimed to draw clinically relevant conclusions, resulting in the improvement of treatment approaches. MATERIALS AND METHODS: The available literature data regarding the metabolism and the mechanism of action, the evaluation of possible schedules of administration, and combined radiochemotherapy including Gemcitabine has been reviewed. Publications reporting experimental data in vitro and in vivo as well as our own experimental results have been incorporated. RESULTS: In clinical phase I and II studies, the favorable tumor response is accompanied by a high incidence of grade III-IV toxicities whereby the maximum-tolerated dose (MTD) of the various schedules of administration used is always lower compared to the MTD of single-agent treatment. In in-vitro and in-vivo data addressing the description and the evaluation of the radiation enhancing mechanism (especially influence on cell cycle, depletion of the dATP pool, induction of apoptosis, inhibition of DNA synthesis, reduction of DNA repair) this effect is already observed with non and moderately toxic Gemcitabine concentrations and depends on drug concentration and exposure time. Independent of the fractionation effect of radiotherapy, the radiation enhancement is persistent for at most 72 hours after the end of drug exposure. Taking under consideration the single dose per day and the target volume, a prolonged infusion and/or a twice-weekly administration of Gemcitabine at low concentration each and simultaneous radiotherapy are presumably considered to resemble the experimental data. CONCLUSION: It is without doubt that data provided by clinical studies are of highest relevance for the evaluation of an optimized radiochemotherapy with Gemcitabine. However, although it is often difficult to transfer experimental data into the clinical situation, these data offer the possibility to develop an improved schedule of administration in patient treatment based on rational evidence in tumor biology.