Susceptibility of the optic nerve and the involvement of retrograde neuronal degeneration in a delayed radiation induced injury model: evidence from a diffusion tensor imaging study

Animal Models of White Matter Disease & Neurodegeneration: No. 469In the present study, we evaluated changes of multiple white matter tracts following radiation using diffusion tensor imaging. A novel finding of severe changes in FA in the contralateral optic nerve as compared to the ipsilateral optic nerve was observed, and these changes were confirmed by histological evaluation. These findings cannot be explained by difference in radiation dose and suggests, for the first time, an important role of retrograde neuronal degeneration in the underlying mechanism for radiation induced injury to the visual pathway. The results also suggest susceptibility of the optic nerve relative to the cerebral peduncle.postprin

Diffusion tensor imaging for the evaluation of treatment-induced neurotoxicity in childhood medulloblastoma

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Longitudinal diffusion tensor MR imaging study of radiation induced white matter damage in a rat model

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Factors associated with loss of white matter anisotropy in post-treatment medulloblastoma survivors

We evaluate effects of age at cranial irradiation, time interval since irradiation and irradiation dose on white matter anisotropy in childhood medulloblastoma survivors by computing white matter fractional anisotropy (WM FA) using SPM post-processing functions. Mean percentage change in WM FA of patients compared to controls was -4.4% (sd=7.6%). Using Spearmanís correlation, there were significant associations between percentage reduction of WM FA and age at cranial irradiation (r=0.673, p=0.002) and irradiation dose (r=-0.723, p=<0.001), but not with time interval since irradiation. Multivariate regression analysis confirmed that both factors correlated significantly with percentage reduction of WM FA (adjusted r2=0.516, p=0.001).published_or_final_versio

A new tool for dose conformity evaluation of radiosurgery treatment plans

Purpose: A novel method for dose conformity evaluation of treatment plans produced by the stereotactic radiosurgery treatment planning system is postulated. Methods and Materials: By consolidating the information contained in the integral dose-volume histogram and the treatment volume ratio, a plot of treatment volume ratio versus percentage dose may be considered as a useful tool for plan evaluation. To validate the suggested argument, two simple experiments simulating the conformal and nonconformal cases were conducted on the geometric phantom that is commercially available from Radionics. An actual patient treatment plan is also included to explore the effectiveness of the proposed parameters. It is an attempt to establish the baseline of a conformal plan. Results: A plot showed the ability to give the user an idea whether the size of the collimator was adequate to cover the delineated lesion when the user-defined criteria had been in place. Two parameters, namely take-off dose (TOD) and take-off volume (TOV) were defined. The former was defined as the maximum dose level found on the surface of the target volume. The TOD is also the maximum possible dose to be received by the adjacent normal tissue. The latter was defined as the percentage of the target volume that received the TOD. Another parameter, irradiated percentage volume (IPV), was defined here as the percentage of the target volume receiving at least the prescribed dose. When the prescribed dose is also the TOD, the IPV becomes the TOV. They were proved to be effective in evaluating the dose conformity. Another term known as equivalent fall-off distance (EFOD) was defined as the equivalent radial distance calculated between two isodose lines. In fact, the dose fall-off rate can also act as a measuring index for plan comparison, because a fast dose fall-off rate is often a requirement for radiosurgery in order to minimize the risk of radiation damage to the surrounding structures. The two phantom studies showed consistent results with the theoretical predictions. The ability of the plot was further explored in the patient treatment plan studies. It was demonstrated that the plot had a remarkable ability to check whether the hot spot is in the vicinity of the lesion. A baseline of a conformal plan was also established; for example, a plan is said to be conformal if its IPV has attained a value of not less than 95% and its associated TVR is not greater than 2. Conclusion: The proposed method has demonstrated the effectiveness in dose conformity evaluation. It supplements the integral dose-volume histogram to provide a complete information of a treatment plan in terms of dose uniformity and conformity

Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial

Purpose: To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC). Methods and Materials: Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H&N35) were completed at baseline and 2, 6, and 12 months after radiotherapy. Results: Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy. Conclusions: IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach. © 2006 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Peripheral Doses from Noncoplanar IMRT for Pediatric Radiation Therapy

The use of noncoplanar intensity-modulated radiation therapy (IMRT) might result in better sparing of some critical organs because of a higher degree of freedom in beam angle optimization. However, this can lead to a potential increase in peripheral dose compared with coplanar IMRT. The peripheral dose from noncoplanar IMRT has not been previously quantified. This study examines the peripheral dose from noncoplanar IMRT compared with coplanar IMRT for pediatric radiation therapy. Five cases with different pediatric malignancies in head and neck were planned with both coplanar and noncoplanar IMRT techniques. The plans were performed such that the tumor coverage, conformality, and dose uniformity were comparable for both techniques. To measure the peripheral doses of the 2 techniques, thermoluminescent dosimeters (TLD) were placed in 10 different organs of a 5-year-old pediatric anthropomorphic phantom. With the use of noncoplanar beams, the peripheral doses to the spinal cord, bone marrow, lung, and breast were found to be 1.8-2.5 times of those using the coplanar technique. This is mainly because of the additional internal scatter dose from the noncoplanar beams. Although the use of noncoplanar technique can result in better sparing of certain organs such as the optic nerves, lens, or inner ears depending on how the beam angles were optimized on each patient, oncologists should be alert of the possibility of significantly increasing the peripheral doses to certain radiation-sensitive organs such as bone marrow and breast. This might increase the secondary cancer risk to patients at young age. © 2010 American Association of Medical Dosimetrists.link_to_subscribed_fulltex

Diffusion Tensor Magnetic Resonance Imaging Finding of Discrepant Fractional Anisotropy Between the Frontal and Parietal Lobes After Whole-Brain Irradiation in Childhood Medulloblastoma Survivors: Reflection of Regional White Matter Radiosensitivity?

Purpose: To test the hypothesis that fractional anisotropy (FA) is more severely reduced in white matter of the frontal lobe compared with the parietal lobe after receiving the same whole-brain irradiation dose in a cohort of childhood medulloblastoma survivors. Methods and Materials: Twenty-two medulloblastoma survivors (15 male, mean [± SD] age = 12.1 ± 4.6 years) and the same number of control subjects (15 male, aged 12.0 ± 4.2 years) were recruited for diffusion tensor magnetic resonance imaging scans. Using an automated tissue classification method and the Talairach Daemon atlas, FA values of frontal and parietal lobes receiving the same radiation dose, and the ratio between them were quantified and denoted as FFA, PFA, and FA f/p, respectively. The Mann-Whitney U test was used to test for significant differences of FFA, PFA, and FA f/p between medulloblastoma survivors and control subjects. Results: Frontal lobe and parietal lobe white matter FA were found to be significantly less in medulloblastoma survivors compared with control subjects (frontal p = 0.001, parietal p = 0.026). Moreover, these differences were found to be discrepant, with the frontal lobe having a significantly larger difference in FA compared with the parietal lobe. The FA f/p of control and medulloblastoma survivors was 1.110 and 1.082, respectively (p = 0.029). Conclusion: Discrepant FA changes after the same irradiation dose suggest radiosensitivity of the frontal lobe white matter compared with the parietal lobe. Special efforts to address the potentially vulnerable frontal lobe after treatment with whole-brain radiation may be needed so as to balance disease control and treatment-related morbidity. © 2007 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Mapping radiation dose distribution on the fractional anisotropy map: Applications in the assessment of treatment-induced white matter injury

We describe a method to map whole brain radiation dose distribution on to diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its applications for studying dose-effect relationships and regional susceptibility in two childhood medulloblastoma survivors. To determine the FA changes voxel-by-voxel in white matter, the post-treatment follow-up FA maps were coregistered to baseline pre-treatment FA maps and automatic segmentation for white matter was carried out. ΔFA maps representing relative FA change in white matter were hence generated for visual inspection and quantitative analysis. The radiation dose distribution, calculated from radiotherapy plan and exported as images, was coregistered to baseline FA images. DT-MR imaging and processing noise was small with root mean square value of 1.49% for mean ΔFA. We evaluated the mean ΔFA changes of regions-of-interest according to radiation dose regions to provide an estimate of the dose-response and found increasing reduction in mean ΔFA with increasing radiation dose up to 45 Gy after which there was a reversal in the mean FA trend and mean FA approached baseline value. We also found more severe mean FA reduction in the frontal lobes compared to the parietal lobes despite the same radiation dose, suggesting regional susceptibility in the frontal lobe, and mean FA increase in the brainstem after radiation in both patients. We conclude that the method described may be useful in estimating dose-effect relationships and studying regional susceptibility of the brain to radiation in medulloblastoma survivors. © 2005 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex