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ABSTRACT: PURPOSE: To determine whether radiation-induced changes in white matter tracts are uniform across the brainstem. METHODS AND MATERIALS: We analyzed serial diffusion tensor imaging data, acquired before radiation therapy and over 48 to 72 months of follow-up, from 42 pediatric patients (age 6-20 years) with medulloblastoma. FSL software (FMRIB, Oxford, UK) was used to calculate fractional anisotropy (FA) and axial, radial, and mean diffusivities. For a consistent identification of volumes of interest (VOIs), the parametric maps of each patient were transformed to a standard brain space (MNI152), on which we identified VOIs including corticospinal tract (CST), medial lemniscus (ML), transverse pontine fiber (TPF), and middle cerebellar peduncle (MCP) at the level of pons. Temporal changes of DTI parameters in VOIs were compared using a linear mixed effect model. RESULTS: Radiation-induced white matter injury was marked by a decline in FA after treatment. The decline was often accompanied by decreased axial diffusivity, increased radial diffusivity, or both. This implied axonal damage and demyelination. We observed that the magnitude of the changes was not always uniform across substructures of the brainstem. Specifically, the changes in DTI parameters for TPF were more pronounced than in other regions (P<.001 for FA) despite similarities in the distribution of dose. We did not find a significant difference among CST, ML, and MCP in these patients (P>.093 for all parameters). CONCLUSIONS: Changes in the structural integrity of white matter tracts, assessed by DTI, were not uniform across the brainstem after radiation therapy. These results support a role for tract-based assessment in radiation treatment planning and determination of brainstem tolerance.
International journal of radiation oncology, biology, physics 03/2013; · 4.59 Impact Factor
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ABSTRACT: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy.
We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL.
Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%.
Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.
International journal of radiation oncology, biology, physics 04/2012; 84(4):990-5. · 4.59 Impact Factor
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ABSTRACT: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI).
We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis.
The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns.
Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.
International journal of radiation oncology, biology, physics 06/2011; 82(5):2047-54. · 4.59 Impact Factor
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ABSTRACT: Abdominal intensity-modulated radiation therapy and proton therapy require quantification of target and organ motion to optimize localization and treatment. Although addressed in adults, there is no available literature on this issue in pediatric patients. We assessed physiologic renal motion in pediatric patients.
Twenty free-breathing pediatric patients at a median age of 8 years (range, 2-18 years) with intra-abdominal tumors underwent computed tomography simulation and four-dimensional computed tomography acquisition (slice thickness, 3 mm). Kidneys and diaphragms were contoured during eight phases of respiration to estimate center-of-mass motion. We quantified center of kidney mass mobility vectors in three dimensions: anteroposterior (AP), mediolateral (ML), and superoinferior (SI).
Kidney motion decreases linearly with decreasing age and height. The 95% confidence interval for the averaged minima and maxima of renal motion in children younger than 9 years was 5-9 mm in the ML direction, 4-11 mm in the AP direction, and 12-25 mm in the SI dimension for both kidneys. In children older than 9 years, the same confidence interval reveals a widening range of motion that was 5-16 mm in the ML direction, 6-17 mm in the AP direction, and 21-52 mm in the SI direction. Although not statistically significant, renal motion correlated with diaphragm motion in older patients. The correlation between diaphragm motion and body mass index was borderline (r = 0.52, p = 0.0816) in younger patients.
Renal motion is age and height dependent. Measuring diaphragmatic motion alone does not reliably quantify pediatric renal motion. Renal motion in young children ranges from 5 to 25 mm in orientation-specific directions. The vectors of motion range from 5 to 52 mm in older children. These preliminary data represent novel analyses of pediatric intra-abdominal organ motion.
International journal of radiation oncology, biology, physics 05/2011; 82(5):1771-6. · 4.59 Impact Factor
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ABSTRACT: To provide a radiation pneumonitis risk estimate and investigate the correlation of clinical and dosimetric factors in pediatric patients receiving chest irradiation.
A total of 122 patients diagnosed with sarcoma or Hodgkin lymphoma who received radiotherapy to the chest were evaluated for symptomatic radiation pneumonitis (Common Toxicity Criteria Grade 1 with respiratory symptom or higher grade). Pneumonitis data were collected from either prospective toxicity screenings as part of a clinical trial or through chart review. Dosimetric parameters including V(10)-V(25), mean lung dose, binned lung dose, and tissue complication probability models were used, as well as clinical features to correlate with the development of pneumonitis.
The 1- and 2-year cumulative incidence of symptomatic radiation pneumonitis for all patients was 8.2% and 9.1%, respectively. Nine patients experienced symptomatic Grade 1 toxicity, and 2 experienced Grade 2. From univariate analysis, chemotherapy containing bleomycin (chi(2) test, p = 0.027) and V(24) (logistic regression, p = 0.019) were the clinical and dosimetric factors that resulted in statistically significant differences in the occurrence of pneumonitis. The probability of pneumonitis increased more dramatically with increasing V(24) in patients receiving bleomycin than in those who did not. Adult tissue complication models did not differentiate pediatric patients with radiation pneumonitis from those without.
The incidence of symptomatic radiation pneumonitis in pediatric patients is low and its severity mild. Parameters frequently used in adult radiation oncology provide some guidance as to risk, but pediatric patients warrant their own specific models for risk assessment, incorporating dosimetry and clinical factors.
International journal of radiation oncology, biology, physics 09/2010; 78(1):143-9. · 4.59 Impact Factor
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ABSTRACT: To determine the effect of cochlear dose on sensorineural hearing loss in pediatric patients with brain tumor treated by using conformal radiation therapy (CRT).
We studied 78 pediatric patients (155 ears) with localized brain tumors treated in 1997-2001 who had not received platinum-based chemotherapy and were followed up for at least 48 months. They were evaluated prospectively by means of serial pure-tone audiograms (250 Hz-8 kHz) and/or auditory brainstem response before and every 6 months after CRT.
Hearing loss occurred in 14% (11 of 78) of patients and 11% (17 of 155) of cochleae, with onset most often at 3-5 years after CRT. The incidence of hearing loss was low for a cochlear mean dose of 30 Gy or less and increased at greater than 40-45 Gy. Risk was greater at high frequencies (6-8 kHz). In children who tested abnormal for hearing, average hearing thresholds increased from a less than 25 decibel (dB) hearing level (HL) at baseline to a mean of 46 +/- 13 (SD) dB HL for high frequencies, 41 +/- 7 dB HL for low frequencies, and 38 +/- 6 dB HL for intermediate frequencies.
Sensorineural hearing loss is a late effect of CRT. In the absence of other factors, including ototoxic chemotherapy, increase in cochlear dose correlates positively with hearing loss in pediatric patients with brain tumor. To minimize the risk of hearing loss for children treated with radiation therapy, a cumulative cochlear dose less than 35 Gy is recommended for patients planned to receive 54-59.4 Gy in 30-33 treatment fractions.
International journal of radiation oncology, biology, physics 05/2008; 72(3):892-9. · 4.59 Impact Factor
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ABSTRACT: To describe and review the radiotherapy (RT) treatment planning and delivery techniques used for pediatric sarcoma patients at St. Jude Children's Research Hospital. The treatment characteristics serve as a baseline for future comparison with developing treatment modalities.
Since January 2003, we have prospectively treated pediatric and young-adult patients with soft-tissue and bone sarcomas on an institutional Phase II protocol evaluating local control and RT-related treatment effects from external-beam RT (conformal or intensity-modulated RT; 83.4%), low-dose-rate brachytherapy (8.3%), or both (8.3%). Here we describe the treatment dosimetry and delivery parameters of the initial 72 patients (median, 11.6 years; range, 1.4-21.6 years).
Cumulative doses from all RT modalities ranged from 41.4 to 70.2 Gy (median, 50.4 Gy). Median D(95) and V(95) of the planning target volume of external-beam RT plans were, respectively, 93.4% of the prescribed dose and 94.6% of the target volume for the primary phase and 97.8% and 99.2% for the cone-down/boost phase. The dose-volume histogram statistics for 27 critical organs varied greatly. The spinal cord in 13 of 36 patients received dose >45 Gy (up to 52 Gy in 1 cc) because of tumor proximity.
Planning and delivery of complex multifield external beam RT is feasible in pediatric patients with sarcomas. Improvements on conformity and dose gradients are still desired in many cases with sensitive adjacent critical structures. Long-term follow-up will determine the risk of local failure and the benefit of normal tissue avoidance for this population.
International Journal of Radiation OncologyBiologyPhysics 05/2008; 70(5):1598-606. · 4.11 Impact Factor
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ABSTRACT: To estimate potential differences in volumetric bone growth in children with sarcoma treated with intensity-modulated (IMRT) and conformal (CRT) radiation therapy using an empiric dose-effect model.
A random coefficient model was used to estimate potential volumetric bone growth of 36 pelvic bones (ischiopubis and ilium) from 11 patients 4 years after radiotherapy. The model incorporated patient age, pretreatment bone volume, integral dose >35 Gy, and time since completion of radiation therapy. Three dosimetry plans were entered into the model: the actual CRT/IMRT plan, a nontreated comparable IMRT/CRT plan, and an idealized plan in which dose was delivered only to the planning target volume. The results were compared with modeled normal bone growth.
The model predicted that by using the idealized, IMRT, and CRT approaches, patients would maintain 93%, 87%, and 84%, respectively (p = 0.06), of their expected normal growth. Patients older than 10 years would maintain 98% of normal growth, regardless of treatment method. Those younger than 10 years would maintain 87% (idealized), 76% (IMRT), or 70% (CRT) of their expected growth (p = 0.015). Post hoc testing (Tukey) revealed that the CRT and IMRT approaches differed significantly from the idealized one but not from each other.
Dose-effect models facilitate the comparison of treatment methods and potential interventions. Although treatment methods do not alter the growth of flat bones in older pediatric patients, they may significantly impact bone growth in children younger than age 10 years, especially as we move toward techniques with high conformity and sharper dose gradient.
International Journal of Radiation OncologyBiologyPhysics 03/2007; 67(2):552-8. · 4.11 Impact Factor
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D Michael Lovelock, Chiaho Hua,
Ping Wang,
Margie Hunt,
Nathalie Fournier-Bidoz,
Kamil Yenice,
Sean Toner,
Wendell Lutz,
Howard Amols,
Mark Bilsky,
Zvi Fuks,
Yoshiya Yamada
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ABSTRACT: Because of the proximity of the spinal cord, effective radiotherapy of paraspinal tumors to high doses requires highly conformal dose distributions, accurate patient setup, setup verification, and patient immobilization. An immobilization cradle has been designed to facilitate the rapid setup and radiation treatment of patients with paraspinal disease. For all treatments, patients were set up to within 2.5 mm of the design using an amorphous silicon portal imager. Setup reproducibility of the target using the cradle and associated clinical procedures was assessed by measuring the setup error prior to any correction. From 350 anterior/posterior images, and 303 lateral images, the standard deviations, as determined by the imaging procedure, were 1.3 m, 1.6 m, and 2.1 in the ant/post, right/left, and superior/inferior directions. Immobilization was assessed by measuring patient shifts between localization images taken before and after treatment. From 67 ant/post image pairs and 49 lateral image pairs, the standard deviations were found to be less than 1 mm in all directions. Careful patient positioning and immobilization has enabled us to develop a successful clinical program of high dose, conformal radiotherapy of paraspinal disease using a conventional Linac equipped with dynamic multileaf collimation and an amorphous silicon portal imager.
Medical Physics 09/2005; 32(8):2606-14. · 2.83 Impact Factor
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ABSTRACT: Gantry-couch collision is a serious concern for treatment planning of the linear accelerator (linac) based stereotactic radiosurgery (SRS). The ability to detect collision at the time of planning eliminates the need for backup plans and preserves the useful beam angles that would be deemed unsafe and discarded otherwise. Most collision-detection schemes embedded in commercial planning software guard only against the most apparent collisions. On the other hand, a fool-proof collision-map or lookup table often requires detailed measurement of machine geometry and complex graphic operations. In this study, we have developed a simple analytical method for collision detection with the use of quick machine-specific measurements. The collision detection is mathematically solved by determining whether two facets in three-dimensional space, representing gantry and couch surfaces, intersect with each other. A computer code was implemented and tested on a Varian Clinac 600C linac equipped with a BrainLab micromultileaf collimator (MLC) device. To measure machine-specific parameters, the lesion isocenter was set to the origin of the stereotactic coordinate system. The reference coordinates of couch bracket corners and micro-MLC to the linac isocenter were measured only once in the treatment room before they were incorporated into the computer program. Couch, gantry, and collimator were subsequently translated and rotated to study the clearance of various beam arrangements and lesion locations. Predicted results were verified at the machine. Our method correctly confirmed clearance for a retrospective study of 54 previously treated SRS plans (76 isocenters). It also accurately predicted the collisions for all ten artificially created cases. In conclusion, we have developed an analytical method for SRS collision detection that is accurate, easy to implement, and computationally inexpensive.
Medical Physics 08/2004; 31(7):2128-34. · 2.83 Impact Factor
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ABSTRACT: Delivering high dose to prostate with external beam radiation has been shown to improve local tumor control. However, it has to be carefully performed to avoid partial target miss and delivering excessive dose to surrounding normal tissues. One way to achieve safe dose escalation is to precisely localize prostate immediately before daily treatment. Therefore, the radiation can be accurately delivered to the target. Once the prostate position is determined with high confidence, planning target volume (PTV) safety margin might be reduced for further reduction of rectal toxicity. A rapid computed tomography (CT)-based online prostate localization method is presented for this purpose.
Immediately before each treatment session, the patient is immobilized and undergoes a CT scan in the treatment position using a CT scanner situated in the treatment room. At the CT console, posterior, anterior, left, and right extents of the prostate are manually identified on each axial slice. The translational prostate displacements relative to the planned position are estimated by simultaneously fitting these identified extents from this CT scan to a template created from the finely sliced planning CT scan. A total of 106 serial CT scans from 8 prostate cancer patients were performed immediately before treatments and used to retrospectively evaluate the precision of this daily prostate targeting method. The three-dimensional displacement of the prostate with respect to its planned position was estimated.
Five axial slices from each treatment CT scan were sufficient to produce a reliable correction when compared with prostate center of gravity (CoG) displacements calculated from physician-drawn contours. The differences (mean +/- SD) between these two correction schemes in the right-left (R/L), posterior-anterior (P/A), and superior-inferior (S/I) directions are 0.0 +/- 0.4 mm, 0.0 +/- 0.7 mm, and -0.4 +/- 1.9 mm, respectively. With daily CT extent-fitting correction, 97% of the scans showed that the entire posterior prostate gland was covered by PTV given a margin of 6 mm at the rectum-prostate interface and 10 mm elsewhere. In comparison, only 74% and 65% could be achieved by the corrections based on daily and weekly bony matching on portal images, respectively.
Results show that daily CT extent fitting provides a precise correction of prostate position in terms of CoG. Identifying prostate extents on five axial CT slices at the CT console is less time-consuming compared with daily contouring of the prostate on many slices. Taking advantage of the prostate curvature in the longitudinal direction, this method also eliminates the necessity of identifying prostate base and apex. Therefore, it is clinically feasible and should provide an accelerated localization of the prostate immediately before daily treatment.
International Journal of Radiation OncologyBiologyPhysics 04/2003; 55(3):811-24. · 4.11 Impact Factor
