Radiotherapy With 4 Gy × 5 Versus 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression: Final Results of the SCORE-2 Trial (ARO 2009/01).

PURPOSE: To compare short-course radiotherapy (RT) (4 Gy × 5) to longer-course RT (3 Gy × 10) for metastatic epidural spinal cord compression (MESCC). PATIENTS AND METHODS: Two-hundred three patients with MESCC and poor to intermediate expected survival were randomly assigned to 4 Gy × 5 in 1 week (n = 101) or 3 Gy × 10 in 2 weeks (n = 102). Patients were stratified according to ambulatory status, time developing motor deficits, and primary tumor type. Seventy-eight and 77 patients, respectively, were evaluable for the primary end point, 1-month overall response regarding motor function defined as improvement or no further progression of motor deficits. Other study end points included ambulatory status, local progression-free survival, and overall survival. End points were evaluated immediately after RT and at 1, 3, and 6 months thereafter. RESULTS: At 1 month, overall response rates regarding motor function were 87.2% after 4 Gy × 5 and 89.6% after 3 Gy × 10 (P = .73). Improvement rates were 38.5% and 44.2%, respectively, no further progression rates 48.7% and 45.5%, respectively, and deterioration rates 12.8% and 10.4%, respectively (P = .44). Ambulatory rates at 1 month were 71.8% and 74.0%, respectively (P = .86). At other times after RT, the results were also not significantly different. Six-month local progression-free survival was 75.2% after 4 Gy × 5 and 81.8% after 3 Gy × 10 (P = .51); 6-month overall survival was 42.3% and 37.8% (P = .68). CONCLUSION: Short-course RT with 4 Gy × 5 was not significantly inferior to 3 Gy × 10 in patients with MESCC and poor to intermediate expected survival.

Stereotactic imaging for radiotherapy: accuracy of CT, MRI, PET and SPECT.

CT, MRI, PET and SPECT provide complementary information for treatment planning in stereotactic radiotherapy. Stereotactic correlation of these images requires commissioning tests to confirm the localization accuracy of each modality. A phantom was developed to measure the accuracy of stereotactic localization for CT, MRI, PET and SPECT in the head and neck region. To this end. the stereotactically measured coordinates of structures within the phantom were compared with their mechanically defined coordinates. For MRI, PET and SPECT, measurements were performed using two different devices. For MRI, T1- and T2-weighted imaging sequences were applied. For each measurement, the mean radial deviation in space between the stereotactically measured and mechanically defined position of target points was determined. For CT, the mean radial deviation was 0.4 +/- 0.2 mm. For MRI, the mean deviations ranged between 0.7 +/- 0.2 mm and 1.4 +/- 0.5 mm, depending on the MRI device and the imaging sequence. For PET, mean deviations of 1.1 +/- 0.5 mm and 2.4 +/- 0.3 mm were obtained. The mean deviations for SPECT were 1.6 +/- 0.5 mm and 2.0 +/- 0.6 mm. The phantom is well suited to determine the accuracy of stereotactic localization with CT, MRI, PET and SPECT in the head and neck region. The obtained accuracy is well below the physical resolution for CT, PET and SPECT, and of comparable magnitude for MRI. Since the localization accuracy may be device dependent, results obtained at one device cannot be generalized to others.

The bootstrap and cross-validation in neuroimaging applications: estimation of the distribution of extrema of random fields for single volume tests, with an application to ADC maps.

We discuss the assessment of signal change in single magnetic resonance images (MRI) based on quantifying significant departure from a reference distribution estimated from a large sample of normal subjects. The parametric approach is to build a test based on the expected distribution of extrema in random fields. However, in conditions where the variance is not uniform across the volume and the smoothness of the images is moderate to low, this test may be rather conservative. Furthermore, parametric tests are limited to datasets for which distributional assumptions hold. This paper investigates resampling methods that improve statistical tests for signal changes in single images in such adverse conditions, and that can be used for the assessment of images taken for clinical purposes. Two methods, the bootstrap and cross-validation, are compared. It is shown that the bootstrap may fail to provide a good estimate of the distribution of extrema of parametric maps. In contrast, calibration of the significance threshold by means of cross-validation (or related sampling without replacement techniques) address three issues at once: improved power, better voxel-by-voxel estimate of variance by local pooling, and adaptation to departures from ideal distributional assumptions on the signal. We apply the cross-validated tests to apparent diffusion coefficient maps, a type of MRI capable of detecting changes in the microstructural organization of brain parenchyma. We show that deviations from parametric assumptions are strong enough to cast doubt on the correctness of parametric tests for these images. As case studies, we present parametric maps of lesions in patients suffering from stroke and glioblastoma at different stages of evolution.

A radioprotective effect of imatinib (Gleevec) in human squamous carcinoma cells.

PURPOSE: To study the radiation response-modifying effect of imatinib (Gleevec) in a squamous cell carcinoma line, PECA. MATERIAL AND METHODS: Cytotoxicity was determined by colony forming and multiplying capacity. Drug stability was shown by HPLC. Multidrug resistance phenotype was studied by rhodamine-123 efflux. Cell-cycle responses were measured by flow cytometry. Homologous recombination repair was determined by Rad51 immunohistochemistry. RESULTS: Inactivating 50% of the PECA cells required approximately 7 microM imatinib. The drug did not decay nor was it degraded during test periods. Drug efflux occurred only to a minor extent. Multiplying capacity but not survival fractions revealed a radioprotective effect of imatinib. There were only minor cell-cycle alterations in the presence of imatinib but the rate of Rad51-positive repair foci was significantly increased. CONCLUSION: PECA cells apparently lack a highly specific target for imatinib. In cells surviving at high drug concentrations, imatinib may exert a radioprotective effect on multiplying capacity by inducing DNA repair. Under prolonged exposure, drug-resistant cells may show an accelerated recovery from acute or delayed radiation damage.