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Title: SU-F-T-118: Characterization of Change in Fractional Anisotropy After Radiation Therapy: Does Nearby Disruption Predict for White Matter Damage?

Abstract

Purpose: We investigated predictors of fractional anisotropy (FA) change in the corticospinal white matter tract (CST) following radiation therapy (RT). Methods: Diffusion tensor imaging (DTI) is a non-invasive modality which models water diffusion properties. FA quantifies the extent of directional bias—a decrease indicates disrupted white matter integrity. Fifteen patients with high-grade glioma underwent DTI scans before, and ten months after RT to 59.4–60 Gy. The CST was segmented using an automated atlas-based algorithm on all DTI images. Treatment planning CT and DTI images were aligned using non-linear registration allowing for baseline FA, follow-up FA, and absorbed dose to be determined in each voxel. Relative FA change was dichotomized into a binary outcome using 25% decrease as cutoff. Three metrics were assessed as predictors: voxel dose, distance from the voxel to the center of the CST (Rc), and the number of neighboring voxels (Nadj from 0 to 26) with ≥25% decrease in FA. Logistic regression and the area under the receiver-operating characteristics curve (AUC) analysis were performed for each patient. Results: Median age of the cohort was 59 years (range: 40–85). The average number of voxels in the CST amongst all patients was 1181 (±172, SD). In logistic regression, the probabilitymore » of FA change was highly associated with Nadj in all 15 patients with corresponding AUCs between 0.81 and 0.97. With all three metrics included in the logistic regression models, Nadj was highly significant (p<0.001) in all patients, voxel dose significant (p<0.05) in 3/15 patients, and Rc significant in 12/15 patients (p<0.05). Conclusion: The number of neighboring voxels with change in FA was the dominant predictor of FA change at any given voxel. This suggests that the microenvironment of surrounding white matter disruption after radiation therapy may drive local effects along a white matter tract. Pettersson and Cervino are funded by a Varian Medical Systems grant.« less

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;  [1]
  1. University of California, San Diego, La Jolla, CA (United States)
Publication Date:
OSTI Identifier:
22642360
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ABSORBED RADIATION DOSES; ANISOTROPY; BIOMEDICAL RADIOGRAPHY; IMAGES; NONLINEAR PROBLEMS; PATIENTS; RADIOTHERAPY

Citation Formats

Pettersson, N, Karunamuni, R, Connor, M, Moiseenko, V, Dale, A, Bartsch, H, Brewer, J, Krishnan, A, Kuperman, J, Hagler, D, McDonald, C, Farid, N, White, N, Hattangadi-Gluth, J, and Cervino, L. SU-F-T-118: Characterization of Change in Fractional Anisotropy After Radiation Therapy: Does Nearby Disruption Predict for White Matter Damage?. United States: N. p., 2016. Web. doi:10.1118/1.4956254.
Pettersson, N, Karunamuni, R, Connor, M, Moiseenko, V, Dale, A, Bartsch, H, Brewer, J, Krishnan, A, Kuperman, J, Hagler, D, McDonald, C, Farid, N, White, N, Hattangadi-Gluth, J, & Cervino, L. SU-F-T-118: Characterization of Change in Fractional Anisotropy After Radiation Therapy: Does Nearby Disruption Predict for White Matter Damage?. United States. doi:10.1118/1.4956254.
Pettersson, N, Karunamuni, R, Connor, M, Moiseenko, V, Dale, A, Bartsch, H, Brewer, J, Krishnan, A, Kuperman, J, Hagler, D, McDonald, C, Farid, N, White, N, Hattangadi-Gluth, J, and Cervino, L. 2016. "SU-F-T-118: Characterization of Change in Fractional Anisotropy After Radiation Therapy: Does Nearby Disruption Predict for White Matter Damage?". United States. doi:10.1118/1.4956254.
@article{osti_22642360,
title = {SU-F-T-118: Characterization of Change in Fractional Anisotropy After Radiation Therapy: Does Nearby Disruption Predict for White Matter Damage?},
author = {Pettersson, N and Karunamuni, R and Connor, M and Moiseenko, V and Dale, A and Bartsch, H and Brewer, J and Krishnan, A and Kuperman, J and Hagler, D and McDonald, C and Farid, N and White, N and Hattangadi-Gluth, J and Cervino, L},
abstractNote = {Purpose: We investigated predictors of fractional anisotropy (FA) change in the corticospinal white matter tract (CST) following radiation therapy (RT). Methods: Diffusion tensor imaging (DTI) is a non-invasive modality which models water diffusion properties. FA quantifies the extent of directional bias—a decrease indicates disrupted white matter integrity. Fifteen patients with high-grade glioma underwent DTI scans before, and ten months after RT to 59.4–60 Gy. The CST was segmented using an automated atlas-based algorithm on all DTI images. Treatment planning CT and DTI images were aligned using non-linear registration allowing for baseline FA, follow-up FA, and absorbed dose to be determined in each voxel. Relative FA change was dichotomized into a binary outcome using 25% decrease as cutoff. Three metrics were assessed as predictors: voxel dose, distance from the voxel to the center of the CST (Rc), and the number of neighboring voxels (Nadj from 0 to 26) with ≥25% decrease in FA. Logistic regression and the area under the receiver-operating characteristics curve (AUC) analysis were performed for each patient. Results: Median age of the cohort was 59 years (range: 40–85). The average number of voxels in the CST amongst all patients was 1181 (±172, SD). In logistic regression, the probability of FA change was highly associated with Nadj in all 15 patients with corresponding AUCs between 0.81 and 0.97. With all three metrics included in the logistic regression models, Nadj was highly significant (p<0.001) in all patients, voxel dose significant (p<0.05) in 3/15 patients, and Rc significant in 12/15 patients (p<0.05). Conclusion: The number of neighboring voxels with change in FA was the dominant predictor of FA change at any given voxel. This suggests that the microenvironment of surrounding white matter disruption after radiation therapy may drive local effects along a white matter tract. Pettersson and Cervino are funded by a Varian Medical Systems grant.},
doi = {10.1118/1.4956254},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • 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 samemore » radiation dose, and the ratio between them were quantified and denoted as FFA, PFA, and FA{sub f/p}, respectively. The Mann-Whitney U test was used to test for significant differences of FFA, PFA, and FA{sub 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{sub 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.« less
  • Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gymore » (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.« less
  • Purpose: To examine the association between hospital surgical volume and the use of radiation therapy (RT) after breast-conserving surgery (BCS) in Taiwan. Methods and Materials: We used claims data from the National Health Insurance program in Taiwan (1997-2005) in this retrospective population-based study. We identified patients with breast cancer, receipt of BCS, use of radiation, and the factors that could potentially associated with the use of RT from enrollment records, and the ICD-9 and billing codes in claims. We conducted logistic regression to examine factors associated with RT use after BCS, and performed subgroup analyses to examine whether the associationmore » differs by medical center status or hospital volumes. Results: Among 5,094 patients with newly diagnosed invasive breast cancer who underwent BCS, the rate of RT was significantly lower in low-volume hospitals (74% vs. 82%, p < 0.01). Patients treated in low-volume hospitals were less likely to receive RT after BCS (odds ratio = 0.72, 95% confidence interval = 0.62-0.83). In addition, patients treated after the implementation of the voluntary pay-for-performance policy in 2001 were more likely to receive RT (odds ratio = 1.23; 95% confidence interval = 1.05-1.45). Subgroup analyses indicated that the high-volume effect was limited to hospitals accredited as non-medical centers, and that the effect of the pay-for-performance policy was most pronounced among low-volume hospitals. Conclusions: Using population-based data from Taiwan, our study concluded that hospital surgical volume and pay-for-performance policy are positively associated with RT use after BCS.« less
  • Purpose: To determine whether childhood medulloblastoma and acute lymphoblastic leukemia (ALL) survivors have decreased white matter fractional anisotropy (WMFA) and whether WMFA is related to the speed of processing and motor speed. Methods and Materials: For this study, 17 patients (6 medulloblastoma, 5 ALL treated with high-dose methotrexate (MTX) (4 x 5 g/m{sup 2}) and 6 with low-dose MTX (3 x 2 g/m{sup 2})) and 17 age-matched controls participated. On a 3.0-T magnetic resonance imaging (MRI) scanner, diffusion tensor imaging (DTI) was performed, and WMFA values were calculated, including specific regions of interest (ROIs), and correlated with the speed ofmore » processing and motor speed. Results: Mean WMFA in the patient group, mean age 14 years (range 8.9 - 16.9), was decreased compared with the control group (p = 0.01), as well as WMFA in the right inferior fronto-occipital fasciliculus (IFO) (p = 0.03) and in the genu of the corpus callosum (gCC) (p = 0.01). Based on neurocognitive results, significant positive correlations were present between processing speed and WMFA in the splenium (sCC) (r = 0.53, p = 0.03) and the body of the corpus callosum (bCC) (r = 0.52, p = 0.03), whereas the right IFO WMFA was related to motor speed (r = 0.49, p < 0.05). Conclusions: White matter tracts, using a 3.0-T MRI scanner, show impairment in childhood cancer survivors, medulloblastoma survivors, and also those treated with high doses of MTX. In particular, white matter tracts in the sCC, bCC and right IFO are positively correlated with speed of processing and motor speed.« less
  • Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less