Pulmonary embolism: radiation dose with multi-detector row CT and digital angiography for diagnosis.

PURPOSE: To compare radiation dose delivered at four- and 16-detector row computed tomography (CT) with a dose-modulation program and that delivered at digital angiography for evaluation of pulmonary embolism (PE). MATERIALS AND METHODS: The part of the study involving patients (seven women, four men; mean age, 62 years +/- 16 [standard deviation]; range, 41-85 years) was approved by the institutional review board. Patients gave written informed consent. Exposure was performed with an anthropomorphic phantom with thermoluminescent dosimeters for four-detector row CT without the dose-modulation program and 16-detector row CT without and with the dose-modulation program with standard protocols for pulmonary CT angiography (120 kV, 144 mAs, four and 16 detector rows with 1.00- and 0.75-mm section thickness, respectively). Digital angiograms were acquired with four standard projections at 80 kV. For digital angiography, radiation dose was calculated according to phantom measurements and adapted to acquisition and fluoroscopy times. Distribution of dose was compared for CT and digital angiography. RESULTS: During pulmonary CT angiography, mean radiation dose delivered at middle of chest was 21.5, 19.5, and 18.2 mGy for four-detector row CT and for 16-detector row CT without and with dose-modulation program, respectively. At the same level, a mean dose of 91 mGy was delivered with digital angiography. The dose adjusted to clinical conditions was 139.0 mGy for digital angiography and could be reduced after technical adjustment. Ratios of maximum dose to mean dose were 1.15 and 2.96 for CT and digital angiography, respectively. With application of the dose-modulation program at 16-detector row CT, radiation dose was reduced 15%-20% at the upper chest. CONCLUSION: Multi-detector row CT delivers a lower radiation dose, with better spatial distribution of dose, than does pulmonary CT angiography. With 16-detector row CT and a dose-modulation program, radiation dose is decreased during PE work-up

Comparison of setup accuracy of three different thermoplastic masks for the treatment of brain and head and neck tumors.

PURPOSE: Setup accuracy is an important factor influencing the definition of the planning target volume (PTV). The purpose of this study was to compare the setup accuracy of three different thermoplastic masks used for immobilization of patients with brain or head and neck tumors. MATERIALS AND METHODS: Thirty patients with brain or head and neck tumors were consecutively assigned to one of three different thermoplastic masks (Posifix): head mask with three fixation points (3 FP, ten patients), head and shoulder mask with four fixation points (4 FP, ten patients), head and shoulder mask with five fixation points (5 FP, four fixations plus an additional one on the top of head, ten patients). Once a week, during the session with a 6 MV linac (Elekta), orthogonal (antero-posterior and lateral) portal images were acquired for three fictitious isocenters placed during the simulation at the level of the head, the neck and the shoulders. Portal images and digitized simulator films were compared using the PIPS pro software, and displacements in antero-posterior (A-P), cranio-caudal (C-C) and medio-lateral (M-L) directions were calculated. From these displacements, 2D or 3D errors were also calculated. RESULTS: A total of 915 portal images were obtained, of which 98% could be analyzed. For the whole population, total displacements reached a standard deviation (SD) of 2.2 mm at the level of the head and the neck. Systematic and random displacements were in the same order of magnitude and reached a SD of 1.8 mm. Patient setup was slightly worse at the shoulder level with a total displacement of 2.8 mm (1 SD) for both the C-C and the M-L directions. There again, the systematic and the random components were in the same order of magnitude below 2.4 mm (+/-SD). For isocenters in the head and in the neck, there was no substantial difference in the setup deviation between the three masks. The setup reproducibility was found to be significantly worse (P=0.01) at the level of the shoulders with the 3 FP mask. For the 2D random error, 1 SD of 2.3 mm was observed compared to 0.8 and 1.2 mm for the 4 and 5 FP masks, respectively. Lastly, 90% of the 3D total deviations were below 4.5 mm for the head and the neck. In the shoulder region, 90% of the 2D total deviations were below 5.5 mm. CONCLUSION: Thermoplastic masks provide an accurate patient immobilization. At the shoulder level, setup variations are reduced when 4 or 5 FP masks are used. These data could be used for the assessment of margins for the PTV

Role of 2'-2' difluorodeoxycytidine (gemcitabine)-induced cell cycle dysregulation in radio-enhancement of human head and neck squamous cell carcinomas.

BACKGROUND AND PURPOSE: To try to get a better insight on the interaction between dFdC and ionizing radiation at the cellular level, we examined in vitro the effect of dFdC on the cell cycle of two human head and neck squamous cell carcinoma cell lines (SQD9 and SCC61). PATIENTS AND METHODS: Experimental conditions yielding radio-enhancement were used. Confluent cells were incubated with dFdC (5 microM) for different incubation times, washed, pulse-labeled with BrdUrd (10 microM), fixed and then processed for flow cytometry analysis. Alternatively, cells preincubated or not with dFdC were irradiated (5Gy) in drug-free medium, incubated at 37 degrees C for various times and then processed for flow cytometry analysis. RESULTS: In both cell lines, dFdC incubated between 1 and 6 h induced a DNA synthesis inhibition with accumulation of cells in the G1-S boundary followed, when DNA reinitiated, by a synchronous progression of cells throughout the cycle. A slightly different kinetics was observed in the two cell lines. A weak correlation between dFdC radio-enhancement and distribution of cells in the cell cycle was observed. It was also observed that for longer dFdC incubation times, DNA synthesis could reinitiate while cells were still incubated with dFdC. This reinitiation could be correlated with a decrease in the intracellular dFdCTP pool to non-inhibitory levels. Finally in both cell lines, dFdC modified neither the importance nor the kinetics of the radiation-induced G1 delay. CONCLUSIONS: This study provides evidence that gemcitabine used at radio-enhancing concentration induces alteration of cell kinetics and cell redistribution throughout the cell cycle. This effect is cell line-dependent. However, the weak correlation between dFdC radio-enhancement and cell cycle distribution suggests that the cell cycle effect does not constitute the most important mechanism of interaction with ionizing radiation. Our study also indicated that in the two cell lines studied, a modulation of the G1-S checkpoint was not implicated in enhancement of radiation response by dFdC

Effect of gemcitabine on the tolerance of the lung to single-dose irradiation in C3H mice

In an early phase II trial combining gemcitabine (dFdC) and radiotherapy for lung carcinomas, severe pulmonary toxicity was observed. In this framework, the objective of this study was to investigate the effect of dFdC on the tolerance of the lungs of C3H mice to single-dose irradiation. The thoraxes of C3H mice were irradiated with a graded single dose of 8 MV photons; dFdC (150 mg/kg) or saline (control animals) was administered i.p. 3 or 48 h prior to irradiation. Lung tolerance was assessed by the LD50 at 7-180 days after irradiation. For irradiation alone, the LD50 reached 14.45 Gy (95% CI 13.33-15.66 Gy). With a 3-h interval between administration of dFdC and irradiation, the LD50 reached 13.29 (95% CI 12.26-14.44 Gy); the corresponding value with a 48-h interval reached 13.01 Gy (95% CI 11.92-14.20 Gy). Our data also suggested a possible effect of dFdC on radiation-induced esophageal toxicity. dFdC has a minimal effect on lung tolerance after single-dose irradiation. However, a proper phase I-II trial should be designed before any routine use of combined dFdC and radiotherapy in the thoracic region

Role of deoxycytidine kinase (dCK) activity in gemcitabine's radioenhancement in mice and human cell lines in vitro.

BACKGROUND: Gemcitabine (dFdC, 2',2'-difluorodeoxycytidine) is a deoxycytidine nucleoside analog which has a marked effect on several enzymes involved in DNA synthesis and repair. Gemcitabine has been tested as a radiosensitizer in various biological models, and radiation dose modification factors (DMF) have been reported in the range between 1.1 and 2.4. Gemcitabine is a prodrug that requires intracellular activation by phosphorylation into its active triphosphate dFdCTP form. Deoxycytidine kinase (dCK) is the enzyme involved in the first phosphorylation cascade, and several observations have suggested that dCK was a limiting factor for the cytotoxic activity of gemcitabine. OBJECTIVE: In the present article, we investigated the relationship between dCK activity and gemcitabine's radiosensitization in four mice and two human cell lines. MATERIALS AND METHODS: Four mice and two human tumor cell lines were investigated. Radiosensitization was assessed on confluent cell incubated with 5 microM gemcitabine for 3 h prior to a single radiation dose. Enzymatic activity was assessed using deoxycytidine as substrate with (specific activity) or without (total activity) inhibition of thymidine kinase 2 activity. dCK protein level was assessed by immunoblotting using a rabbit anti-human dCK antibody. mRNA expression was assessed with Northern blot using beta-actin as internal control. RESULTS: Gemcitabine's radiosensitization was heterogeneous with DMF ranging from 0.8 to 1.5. A good correlation was observed between the specific dCK activity and the protein level or the mRNA expression indicating that in our cell systems no post-transcriptional or post-translational activation occurred. An excellent correlation (r = 0.99) was observed between the specific enzymatic activity and gemcitabine's radiosensitization. Cell lines that expressed a high enzymatic activity were the more radiosensitized by gemcitabine. This correlation holds when radiosensitization was plotted against the dCK mRNA expression and protein level. CONCLUSIONS: The present study has suggested the role of dCK activity in gemcitabine's radioenhancement in human and mice cell lines. The study suggests that determination of the enzymatic activity prior to a concurrent gemcitabine and radiotherapy treatment might represent a good predictive assay for tumor response. Such concept should deserve further testing in pre-clinical and clinical settings

RBE variation as a function of depth in the 200-MeV proton beam produced at the National Accelerator Centre in Faure (South Africa)

BACKGROUND AND PURPOSE: Thorough knowledge of the RBE of clinical proton beams is indispensable for exploiting their full ballistic advantage. Therefore, the RBE of the 200-MeV clinical proton beam produced at the National Accelerator Centre of Faure (South Africa) was measured at different critical points of the depth-dose distribution. MATERIAL AND METHODS: RBEs were determined at the initial plateau of the unmodulated and modulated beam (depth in Perspex = 43.5 mm), and at the beginning, middle and end of a 7-cm spread-out Bragg peak (SOBP) (depths in Perspex = 144.5, 165.5 and 191.5 mm, respectively). The biological system was the regeneration of intestinal crypts in mice after irradiation with a single fraction. RESULTS: Using 60Co gamma-rays as the reference, the RBE values (for a gamma-dose of 14.38 Gy corresponding to 10 regenerated crypts) were found equal to 1.16 +/- 0.04, 1.10 +/- 0.03, 1.18 +/- 0.04, 1.12 +/- 0.03 and 1.23 +/- 0.03, respectively. At all depths, RBEs were found to increase slightly (about 4%) with decreasing dose, in the investigated dose range (12-17 Gy). No significant RBE variation with depth was observed, although RBEs in the SOBP were found to average a higher value (1.18 +/- 0.06) than in the entrance plateau (1.13 +/- 0.04). CONCLUSION: An RBE value slightly larger than the current value of 1.10 should be adopted for clinical application with a 200-MeV proton beam

Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer : the RadiOxCape study

BACKGROUND: Preoperative radiotherapy has been shown to decrease the local recurrence rate of patients with locally advanced rectal cancer. Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer and have radiosensitizing properties. Therefore, these drugs would be expected to improve effectiveness of preoperative radiotherapy in terms of local control and prevention of distant metastases. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4 and/or N+) received radiotherapy (1.8 Gy, 5 days a week over 5 weeks, total dose 45 Gy, 3D conformational technique) in combination with intravenous oxaliplatin 50 mg/m2 once weekly for 5 weeks and oral capecitabine 825 mg/m2 twice daily on each day of radiation. Surgery was performed 6-8 weeks after completion of radiotherapy. The main end points were safety and efficacy as assessed by the pathological complete response (pCR). RESULTS: The most frequent grade 3/4 adverse event was diarrhea, occurring in 30% of patients. pCR was found in five (14%) patients. According to Dworak's classification, good regression was found in six (18%) additional patients. CONCLUSIONS: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer