Daniel Tatro
University of Michigan
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Journal of Clinical Oncology | 2005
Edgar Ben-Josef; Daniel P. Normolle; William D. Ensminger; Suzette Walker; Daniel Tatro; Randall K. Ten Haken; James A. Knol; Laura A Dawson; Charlie Pan; Theodore S. Lawrence
PURPOSE A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies. PATIENTS AND METHODS Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients. The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10% to 15%. The study design provided more than 80% power to detect a two-fold increase in median survival compared with historical controls at a 5% significance level. RESULTS The median radiation dose delivered was 60.75 Gy (1.5-Gy fractions bid). At a median follow-up time of 16 months (26 months in patients who were alive) the median survival was 15.8 months (95% CI, 12.6 to 18.3 months), significantly longer than in the historical control. The actuarial 3-year survival was 17%. The total dose was the only significant predictor of survival. Primary hepatobiliary tumors had a significantly greater tendency to remain confined to the liver than did colorectal cancer metastases. Overall toxicity was acceptable, with 27 patients (21%) and 11 patients (9%) developing grade 3 and 4 toxicity, respectively, and one treatment-related death. CONCLUSION The results suggest that, compared with historical controls, high-dose focal liver irradiation with hepatic artery floxuridine prolongs survival in patients with unresectable chemotherapy-refractory metastatic colorectal cancer and primary hepatobiliary tumors. This provides a rationale for intensification of local therapy for unresectable hepatobiliary cancers and integration of this regimen with newer systemic therapy for patients with colorectal cancer.
Journal of Clinical Oncology | 2005
Yue Cao; Christina Tsien; Z. Shen; Daniel Tatro; Randall K. Ten Haken; Marc L. Kessler; Thomas L. Chenevert; Theodore S. Lawrence
PURPOSE For chemotherapy to act synergistically and safely with radiation against high-grade gliomas, drugs must pass the endothelial junctions of the blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood-brain barrier (BBB) to cause toxicity to normal brain. The objective of this study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during a course of radiotherapy of high-grade gliomas. PATIENTS AND METHODS Sixteen patients with grade 3 or 4 supratentorial malignant glioma receiving conformal radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) uptake index was analyzed with respect to the tumor and RT dose received. RESULTS In the nonenhanced tumor region, contrast uptake increased significantly after the receipt of approximately 10 Gy (P < .01), and reached a maximum after the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor region, contrast uptake decreased over the course of RT and became significant after completion of RT in patients without progressive disease. The healthy brain showed only nonsignificant changes during and after irradiation. CONCLUSION Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced tumor region but not in the remaining brain during the course of RT, suggesting opening of the BTB. This finding suggests that the effect of conformal radiation is more selective on the BTB than the BBB, and there may be a window extending from 1 week after the initiation of radiotherapy to 1 month after the completion of treatment during which a pharmaceutical agent has maximum access to high-grade gliomas.
International Journal of Radiation Oncology Biology Physics | 2009
Orit Gutfeld; Annette E. Kretzler; Rojano Kashani; Daniel Tatro; James M. Balter
PURPOSE To evaluate the impact of rotational setup errors on dose distribution in spinal stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS Thirty-nine cone beam computed tomography (CBCT) scans from 16 SBRT treatment courses were analyzed. Alignment (including rotation) to the treatment planning computed tomography was performed, followed by translational alignment that reproduced the actual positioning. The planned fluence was then applied to determine the delivered dose to the targets and organs at risk. RESULTS The mean planning target volume (PTV) was 71.01 mL (SD +/- 60.05; range, 22.62-250.65 mL). Prescribed dose (to the 62-82% isodose) was 14-30 Gy in one to six fractions. The average rotational displacements were 0.38 +/- 1.21, 1.12 +/- 1.82, and -0.51 +/- 2.0 degrees with maximal rotations of -4.29, 5.76, and -6.64 degrees along the x (pitch), y (yaw), and z (roll) axes, respectively. PTV coverage changed by an average of -0.07 Gy (SD +/- 0.20 Gy) between the rotated and the original plan, representing 0.92% of prescription dose (SD +/- 2.65%). For the spinal cord, planned with 2-mm expansion to create a planning organ at risk volume (PRV), the difference in minimum dose to the upper 10% of the PRV volume was 0.03 +/- 0.3 Gy (maximum, 0.9 Gy). Other organs at risk saw insignificant changes in dose. CONCLUSIONS PRV expansion generally assures safe treatment delivery in the face of typically encountered rotations. Given the variability of delivered dose within this expansion for certain cases, caution should be taken to properly interpret doses to the cord when considering clinical dose limits.
International Journal of Radiation Oncology Biology Physics | 2013
J. Wang; Jianzhong Cao; S. Yuan; Wei Ji; Douglas A. Arenberg; Jianrong Dai; P. Stanton; Daniel Tatro; Randall K. Ten Haken; Feng Ming Kong
PURPOSE Poor pulmonary function (PF) is often considered a contraindication to definitive radiation therapy for lung cancer. This study investigated whether baseline PF was associated with radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) receiving conformal radiation therapy (CRT). METHODS AND MATERIALS NSCLC patients treated with CRT and tested for PF at baseline were eligible. Baseline predicted values of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and diffusion capacity of lung for carbon monoxide (DLCO) were analyzed. Additional factors included age, gender, smoking status, Karnofsky performance status, coexisting chronic obstructive pulmonary disease (COPD), tumor location, histology, concurrent chemotherapy, radiation dose, and mean lung dose (MLD) were evaluated for RILT. The primary endpoint was symptomatic RILT (SRILT), including grade ≥2 radiation pneumonitis and fibrosis. RESULTS There was a total of 260 patients, and SRILT occurred in 58 (22.3%) of them. Mean FEV1 values for SRILT and non-SRILT patients were 71.7% and 65.9% (P=.077). Under univariate analysis, risk of SRILT increased with MLD (P=.008), the absence of COPD (P=.047), and FEV1 (P=.077). Age (65 split) and MLD were significantly associated with SRILT in multivariate analysis. The addition of FEV1 and age with the MLD-based model slightly improved the predictability of SRILT (area under curve from 0.63-0.70, P=.088). CONCLUSIONS Poor baseline PF does not increase the risk of SRILT, and combining FEV1, age, and MLD may improve the predictive ability.
Medical Dosimetry | 2009
Jonathan G. Thomas; Rojano Kashani; James M. Balter; Daniel Tatro; Feng Ming Kong; Charlie C. Pan
The purpose of this study was to determine the intra and interfraction motion of mediastinal lymph node regions. Ten patients with nonsmall-cell lung cancer underwent controlled inhale and exhale computed tomography (CT) scans during two sessions (40 total datasets) and mediastinal nodal stations 1-8 were outlined. Corresponding CT scans from different sessions were registered to remove setup error and, in this reference frame, the centroid of each nodal station was compared for right-left (RL), anterior-posterior (AP), and superior-inferior (SI) displacement. In addition, an anisotropic volume expansion encompassing the change of the nodal region margins in all directions was used. Intrafraction displacement was determined by comparing same session inhale-exhale scans. Interfraction reproducibility of nodal regions was determined by comparing the same respiratory phase scans between two sessions. Intrafraction displacement of centroid varied between nodal stations. All nodal regions moved posteriorly and superiorly with exhalation, and inferior nodal stations showed the most motion. Based on anisotropic expansion, nodal regions expanded mostly in the RL direction from inhale to exhale. The interpatient variations in intrafraction displacement were large compared with the displacements themselves. Moreover, there was substantial interfractional displacement ( approximately 5 mm). Mediastinal lymph node regions clearly move during breathing. In addition, deformation of nodal regions between inhale and exhale occurs. The degree of motion and deformation varies by station and by individual. This study indicates the potential advantage of characterizing individualized nodal region motion to safely maximize conformality of mediastinal nodal targets.
Medical Physics | 2006
Mihaela Rosu; Indrin J. Chetty; Daniel Tatro; R.K. Ten Haken
Purpose: To investigate the relative magnitudes and clinical importances of the dosimetric effects related to 4D breathing motion and tissue heterogeneity for thoracic tumorstreatment planning.Methods: Scans were acquired at normal exhale/inhale breathing phases. The target was the union of the exhale and inhale GTVs, uniformly expanded by 5mm(ITV). Patients were planned with both AP/PA and 3‐D conformal plans using the exhale (“static”) dataset, assuming unit density, for 100±5% ITV dose coverage. Each of these plans was further used to calculate: (a) heterogeneous “static” dose; (b) homogeneous cumulative dose; (c) heterogeneous cumulative dose. The same number of MU were used for each of the calculations and was based on the homogeneous “static” plan. Cumulative dose distributions consisted of a time‐weighted sum of exhale and inhale doses. Doses were calculated using the DPM_MC code which includes secondary electrontransport for the heterogeneous computations. Results: Relative to unit‐density plans, tumor EUD, and lung NTCP increased in the heterogeneity corrected plans; primarily due to the reduced beam attenuation through lungs and the larger than coin‐size tumors investigated. In comparing 4D cumulative dose plans with static plans, clinical EUD and NTCP estimates were relatively unchanged. The insignificant tumor EUD change was a consequence of good target design, while the small lung NTCP change was due to its large volume effect. Accounting for tissue heterogeneity resulted in average changes of 10% in MLD. Accounting for 4D breathing motion effects resulted in <1% changes in MLD from the static value. The magnitude of these effects was not correlated with the dose distribution conformality. Conclusions: In this study we found that tissue heterogeneity effects are likely to have a larger clinical significance on tumor (if ITV is properly designed) and normal lung clinical treatment evaluation metrics than occurs with 4‐D respiratory‐induced changes. Supported by P01‐CA59827, R01‐CA106770.
Radiology and Oncology | 2014
Aron Popovtzer; Mohannad Ibrahim; Daniel Tatro; Felix Y. Feng; Randall K. Ten Haken; Avraham Eisbruch
Abstract Background. Magnetic resonance imaging (MRI) has been found to be better than computed tomography for defining the extent of primary gross tumor volume (GTV) in advanced nasopharyngeal cancer. It is routinely applied for target delineation in planning radiotherapy. However, the specific MRI sequences/planes that should be used are unknown. Methods. Twelve patients with nasopharyngeal cancer underwent primary GTV evaluation with gadolinium-enhanced axial T1 weighted image (T1) and T2 weighted image (T2), coronal T1, and sagittal T1 sequences. Each sequence was registered with the planning computed tomography scans. Planning target volumes (PTVs) were derived by uniform expansions of the GTVs. The volumes encompassed by the various sequences/planes, and the volumes common to all sequences/planes, were compared quantitatively and anatomically to the volume delineated by the commonly used axial T1-based dataset. Results. Addition of the axial T2 sequence increased the axial T1-based GTV by 12% on average (p = 0.004), and composite evaluations that included the coronal T1 and sagittal T1 planes increased the axial T1-based GTVs by 30% on average (p = 0.003). The axial T1-based PTVs were increased by 20% by the additional sequences (p = 0.04). Each sequence/plane added unique volume extensions. The GTVs common to all the T1 planes accounted for 38% of the total volumes of all the T1 planes. Anatomically, addition of the coronal and sagittal-based GTVs extended the axial T1-based GTV caudally and cranially, notably to the base of the skull. Conclusions. Adding MRI planes and sequences to the traditional axial T1 sequence yields significant quantitative and anatomically important extensions of the GTVs and PTVs. For accurate target delineation in nasopharyngeal cancer, we recommend that GTVs be outlined in all MRI sequences/planes and registered with the planning computed tomography scans.
Medical Physics | 2009
F. Kong; S. Yuan; Jean M. Moran; Daniel Tatro; C Lochart; R.K. Ten Haken
Purposes: This study aimed to assess the changes of lung ventilation (V) and perfusion (Q) function by single photon emission tomography (V/Q SPECT) at 45 Gy during radiation therapy (RT), and determine if V/Q SPECT during‐RT can be used to decrease dose to the functioning lung.Methods: V/Q SPECT‐CT and FDG‐PET‐CT were performed prior and during‐RT (@45Gy) for patients enrolled in prospective clinical trials for stage I–III NSCLC. The V and Q functions were assessed using a semi‐quantitative system. An adaptive plan was generated after RT of 45 Gy to the target based on the during‐RT FDG‐PET‐CT. The during‐RT SPECT was used to optimize the plan to minimize dose to the functioning lung.Results: Of 45 patients analyzed, 100% had lung functional defects at or around the primary tumor and the majority of them have defects in the remaining lung. The V/Q defects were mismatched in 40% and 50% patients for pre‐ and during‐RT SPECT, respectively. After 45 Gy, the global and local lung function improved in one third patients. Specifically, there was a significant improvement in V scores in ipsilateral lung (P=0.002), while there was no significant changes in V scores of the contralateral lung and Q scores of the ipsilateral lung at or around the tumor at 45 Gy during‐RT. Using V/Q SPECT at 45 Gy for voxel based optimization, the mean dose to the functioning lung decreased remarkably while maintaining the physical dose to the target and the physical dose based lung normal tissue complication probability. Conclusion: V/Q SPECT‐CT acquired during the course of treatment has a potential to escalate the tumordose and or decrease the dose to the functioning lung. Clinical trials are ongoing to assess if the therapeutic ratio (long‐term survival over lung toxicity) will improve in patients with NSCLC.
Medical Physics | 2006
F. Kong; Kirk A. Frey; Milton D. Gross; M. Feng; Shaneli Fernando; Marc L. Kessler; Indrin J. Chetty; R.K. Ten Haken; Daniel L. McShan; Daniel P. Normolle; Daniel Tatro; J.A. Hayman; Gregory P. Kalemkerian; Theodore S. Lawrence; A. Eisbruch
Background/purpose: To determine the changes in tumor and lung function during the course of radiation and their potentials in adaptive radiation therapy for non‐small cell lungcancer(NSCLC).Materials/Methods: FDG‐PET‐CT and Ventilation/perfusion (V/Q) SPECT were acquired prior to and after the delivery of 45 Gy during the course of radiation in 15 patients with NSCLC.Tumor activity was measured by relative standard uptake value (RSUV). V/Q SPECT was evaluated blindly by radiobiologist, through comparing to healthy normal controls. Results: After 45 Gy radiation, the mean RSUV decreased from 4.6±1.9 to 2.1±1.0 for primary tumors (p<0.0001) and from 3.2+1.3 to 1.7+0.5 for nodal diseases (p=0.0008). Mean reduction in PET tumor volume was 78% (67–100%). There was 28% (4/15) and 0% (0/15) complete responders on PET and CT, respectively. Three patients achieved a complete CT response at 3 month follow‐up, all of them were PET complete responders at 45 Gy. Boosting after 45 Gy, normal tissue complication probability (NTCP) could be reduced by 50%, V20 by 28%, and mean lungdose by 29% while keeping the total dose constant. Keeping the NTCP constant, dose could be escalated by 50%. Lung functional mapping also changed remarkably at 45 Gy during radiation. Fifteen of 15 patients had V/Q defects at or adjacent to tumor on the baseline SPECT, while 14/15 patients had at least one defect located remotely from tumor. For those defects located adjacent to tumor, 79% improved remarkably, while only 7.9% of the others had notable change (p<0.001). Lung NTCP adjusted by V/Q SPECT obtained during radiation was significantly different from those generated from the pretreatment V/Q SPECT and simulating CT.Conclusions:Tumor and lung functional imaging during the course of radiation may provide useful information for adaptive radiation therapy in patients with NSCLC.
International Journal of Radiation Oncology Biology Physics | 2006
Ming Chen; James A. Hayman; Randall K. Ten Haken; Daniel Tatro; Shaneli Fernando; Feng Ming Kong