Deanna H. Pafundi
Mayo Clinic
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Featured researches published by Deanna H. Pafundi.
Neuro-oncology | 2013
Deanna H. Pafundi; Nadia N. Laack; Ryan S. Youland; Ian F. Parney; Val J. Lowe; Caterina Giannini; Brad Kemp; Michael P. Grams; Jonathan M. Morris; Jason M. Hoover; Leland S. Hu; Jann N. Sarkaria; Debra H. Brinkmann
BACKGROUND Delineation of glioma extent for surgical or radiotherapy planning is routinely based on MRI. There is increasing awareness that contrast enhancement on T1-weighted images (T1-CE) may not reflect the entire extent of disease. The amino acid tracer (18)F-DOPA (3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine) has a high tumor-to-background signal and high sensitivity for glioma imaging. This study compares (18)F-DOPA PET against conventional MRI for neurosurgical biopsy targeting, resection planning, and radiotherapy target volume delineation. METHODS Conventional MR and (18)F-DOPA PET/CT images were acquired in 10 patients with suspected malignant brain tumors. One to 3 biopsy locations per patient were chosen in regions of concordant and discordant (18)F-DOPA uptake and MR contrast enhancement. Histopathology was reviewed on 23 biopsies. (18)F-DOPA PET was quantified using standardized uptake values (SUV) and tumor-to-normal hemispheric tissue (T/N) ratios. RESULTS Pathologic review confirmed glioma in 22 of 23 biopsy specimens. Thirteen of 16 high-grade biopsy specimens were obtained from regions of elevated (18)F-DOPA uptake, while T1-CE was present in only 6 of those 16 samples. Optimal (18)F-DOPA PET thresholds corresponding to high-grade disease based on histopathology were calculated as T/N > 2.0. In every patient, (18)F-DOPA uptake regions with T/N > 2.0 extended beyond T1-CE up to a maximum of 3.5 cm. SUV was found to correlate with grade and cellularity. CONCLUSIONS (18)F-DOPA PET SUV(max) may more accurately identify regions of higher-grade/higher-density disease in patients with astrocytomas and will have utility in guiding stereotactic biopsy selection. Using SUV-based thresholds to define high-grade portions of disease may be valuable in delineating radiotherapy boost volumes.
Neuro-oncology | 2015
Chani M. Becker; Rajneet K. Oberoi; Stephan J. McFarren; Daniel Muldoon; Deanna H. Pafundi; Jenny L. Pokorny; Debra H. Brinkmann; John R. Ohlfest; Jann N. Sarkaria; David A. Largaespada; William F. Elmquist
BACKGROUND Targeting drug delivery to invasive glioma cells is a particularly difficult challenge because these cells lie behind an intact blood-brain barrier (BBB) that can be observed using multimodality imaging. BBB-associated efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) influence drug distribution to these cells and may negatively impact efficacy. To test the hypothesis that efflux transporters influence brain pharmacokinetics/pharmacodynamics of molecularly targeted agents in glioma treatment, we assessed region-specific penetrance and molecular-targeting capacity for a PI3K/mTOR kinase inhibitor that has high substrate affinity for efflux transporters (GDC-0980) and an analog (GNE-317) that was purposely designed to have reduced efflux. METHODS Brain tumor penetrance of GDC-0980 and GNE-317 was compared between FVB/n wild-type mice and Mdr1a/b(-/-)Bcrp(-/-) triple-knockout mice lacking P-gp and BCRP. C57B6/J mice bearing intracranial GL261 tumors were treated with GDC-0980, GNE-317, or vehicle to assess the targeted pharmacokinetic/pharmacodynamic effects in a glioblastoma model. RESULTS Animals treated with GNE-317 demonstrated 3-fold greater penetrance in tumor core, rim, and normal brain compared with animals dosed with GDC-0980. Increased brain penetrance correlated with decreased staining of activated p-Akt, p-S6, and p-4EBP1 effector proteins downstream of PI3K and mTOR. CONCLUSIONS GDC-0980 is subject to active efflux by P-gp and BCRP at the BBB, while brain penetrance of GNE-317 is independent of efflux, which translates into enhanced inhibition of PI3K/mTOR signaling. These data show that BBB efflux by P-gp and BCRP is therefore an important determinant in both brain penetrance and molecular targeting efficacy in the treatment of invasive glioma cells.
American Journal of Neuroradiology | 2015
Leland S. Hu; Zachary S. Kelm; Panagiotis Korfiatis; Amylou C. Dueck; Christian Elrod; Benjamin M. Ellingson; Timothy J. Kaufmann; Jennifer Eschbacher; John P. Karis; Kris A. Smith; Peter Nakaji; Debra Brinkman; Deanna H. Pafundi; Leslie C. Baxter; Bradley J. Erickson
BACKGROUND AND PURPOSE: Relative cerebral blood volume, as measured by T2*-weighted dynamic susceptibility-weighted contrast-enhanced MRI, represents the most robust and widely used perfusion MR imaging metric in neuro-oncology. Our aim was to determine whether differences in modeling implementation will impact the correction of leakage effects (from blood-brain barrier disruption) and the accuracy of relative CBV calculations as measured on T2*-weighted dynamic susceptibility-weighted contrast-enhanced MR imaging at 3T field strength. MATERIALS AND METHODS: This study included 52 patients with glioma undergoing DSC MR imaging. Thirty-six patients underwent both non-preload dose– and preload dose–corrected DSC acquisitions, with 16 patients undergoing preload dose–corrected acquisitions only. For each acquisition, we generated 2 sets of relative CBV metrics by using 2 separate, widely published, FDA-approved commercial software packages: IB Neuro and nordicICE. We calculated 4 relative CBV metrics within tumor volumes: mean relative CBV, mode relative CBV, percentage of voxels with relative CBV > 1.75, and percentage of voxels with relative CBV > 1.0 (fractional tumor burden). We determined Pearson (r) and Spearman (ρ) correlations between non-preload dose– and preload dose–corrected metrics. In a subset of patients with recurrent glioblastoma (n = 25), we determined receiver operating characteristic area under the curve for fractional tumor burden accuracy to predict the tissue diagnosis of tumor recurrence versus posttreatment effect. We also determined correlations between rCBV and microvessel area from stereotactic biopsies (n = 29) in 12 patients. RESULTS: With IB Neuro, relative CBV metrics correlated highly between non-preload dose– and preload dose–corrected conditions for fractional tumor burden (r = 0.96, ρ = 0.94), percentage > 1.75 (r = 0.93, ρ = 0.91), mean (r = 0.87, ρ = 0.86), and mode (r = 0.78, ρ = 0.76). These correlations dropped substantially with nordicICE. With fractional tumor burden, IB Neuro was more accurate than nordicICE in diagnosing tumor versus posttreatment effect (area under the curve = 0.85 versus 0.67) (P < .01). The highest relative CBV–microvessel area correlations required preload dose and IB Neuro (r = 0.64, ρ = 0.58, P = .001). CONCLUSIONS: Different implementations of perfusion MR imaging software modeling can impact the accuracy of leakage correction, relative CBV calculation, and correlations with histologic benchmarks.
Neuro-oncology | 2018
Jann N. Sarkaria; Leland S. Hu; Ian F. Parney; Deanna H. Pafundi; Debra H. Brinkmann; Nadia N. Laack; Caterina Giannini; Terence C. Burns; Sani H. Kizilbash; Janice K. Laramy; Kristin R. Swanson; Timothy J. Kaufmann; Paul D. Brown; Nathalie Y. R. Agar; Evanthia Galanis; Jan C. Buckner; William F. Elmquist
The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM. However, contrary to this view, overwhelming clinical evidence demonstrates that there is also a clinically significant tumor burden with an intact BBB in all GBM, and there is little doubt that drugs with poor BBB permeability do not provide therapeutically effective drug exposures to this fraction of tumor cells. This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated.
Practical radiation oncology | 2017
Robert W. Mutter; Nicholas B. Remmes; Mohamed M. Kahila; Kathy A. Hoeft; Deanna H. Pafundi; Yan Zhang; Kimberly S. Corbin; Sean S. Park; Elizabeth S. Yan; Valerie Lemaine; Judy C. Boughey; C Beltran
PURPOSE The feasibility of proton postmastectomy radiation therapy in patients reconstructed with expanders has not been previously reported, limiting treatment options. We analyzed the dosimetric impact of the metallic port contained within expanders on intensity modulated proton therapy (IMPT) and report our techniques and quality control for treating patients in this setting. METHODS AND MATERIALS Twelve patients with the same expander model underwent 2-field IMPT as part of a prospective registry. All planning dosimetry was checked with an in-house graphic processing unit--based Monte Carlo simulation. Proton ranges through the expander were validated using a sample implant. Dosimetric impact of setup metallic port position uncertainty was evaluated. Pre- and posttreatment photographs were obtained and acute toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS Nine patients had bilateral skin-sparing mastectomy with bilateral tissue expander reconstruction, and 3 patients had unilateral skin-sparing mastectomy and reconstruction. The left side was treated in 10 patients and the right side in 2. Target coverage and normal tissue dose uncertainties resulting from the expander were small and clinically acceptable. The maximum physician-assessed acute radiation dermatitis was grade 3 in 1 patient, grade 2 in 5 patients, and grade 1 in 6 patients. CONCLUSIONS Postmastectomy IMPT in breast cancer patients with expanders is feasible and associated with favorable clinical target volume coverage and normal tissue sparing, even when taking into account treatment uncertainties; therefore, these patients should be eligible to participate in clinical trials studying the potential role of proton therapy in breast cancer. We caution, however, that institutions should carry out similar analyses of the physical properties and dosimetric impact of the particular expanders used in their practice before considering IMPT.
Practical radiation oncology | 2014
Michael P. Grams; Lindsay C. Brown; Debra H. Brinkmann; Deanna H. Pafundi; Daniel W. Mundy; Yolanda I. Garces; Sean S. Park; Kenneth R. Olivier; Luis E. Fong de los Santos
PURPOSE To evaluate the dependence of an automatic match process on the size of the user-defined region of interest (ROI), the structure volume of interest (VOI), and changes in tumor volume when using cone-beam computed tomography (CBCT) for tumor localization and to compare these results with a gold standard defined by a physicians manual match. METHODS AND MATERIALS Daily CBCT images for 11 patients with lung cancer treated with conventionally fractionated radiation therapy were retrospectively matched to a reference CT image using the Varian On Board Imager software (Varian, Palo Alto, CA) and a 3-step automatic matching protocol. Matches were performed with 3 ROI sizes (small, medium, large), with and without a structure VOI (internal target volume [ITV] or planning target volume [PTV]) used in the last step. Additionally, matches were performed using an intensity range that isolated the bony anatomy of the spinal column. All automatic matches were compared with a manual match made by a physician. RESULTS The CBCT images from 109 fractions were analyzed. Automatic match results depend on ROI size and the structure VOI. Compared with the physicians manual match, automatic matches using the PTV as the structure VOI and a small ROI resulted in differences ≥ 5 mm in 1.8% of comparisons. Automatic matches using no VOI and a large ROI differed by ≥ 5 mm in 30.3% of comparisons. Differences between manual and automatic matches using the ITV as the structure VOI increased as tumor size decreased during the treatment course. CONCLUSIONS Users of automatic matching techniques should carefully consider how user-defined parameters affect tumor localization. Automatic matches using the PTV as the structure VOI and a small ROI were most consistent with a physicians manual match, and were independent of volumetric tumor changes.
Medical Physics | 2014
Lorraine A. Courneyea; John P. Mullins; Michelle Howard; C Beltran; Debra H. Brinkmann; Deanna H. Pafundi
Purpose: Evaluate an immobilization system to determine its adequacy for the reduced margins required for proton therapy. Methods: Twelve head-and-neck cancer patients were immobilized for conventional photon radiotherapy and imaged with pre- and post-treatment cone beam CTs (CBCTs) for each treatment fraction. To quantify the patient positioning reproducibility, each CBCT was registered to the simulation CT offline. Registrations were performed using auto-match tools and a matching volume-of-interest (VOI) consisting of a 5mm expansion around the mandible, occipital bone, C1/C2 and C7/T1. For each registration, the bony anatomy in the VOI was evaluated for agreement with the simulation position using 3 and 5mm margins. Registrations were initially restricted to translational corrections. If the bony anatomy did not agree with the simulation position to within 3mm or 5mm, the auto-match was repeated with 3 additional rotational corrections. Intrafraction motion was calculated as the difference between the pre- and post-treatment CBCT matches. Results: Pre-treatment patient positioning agreed with the simulation CT to within 3mm/5mm for 62%/86% of fractions using translational matching and 84%/100% of fractions when rotations were included. Intrafraction motion averaged 1.1±0.8mm, with 12% of fractions having >2mm intrafraction motion. Post-treatment positioning accuracy was 57%/84% and 80%/100% for registrations without/with rotations. For the mandible, positioning accuracy dropped from 93% pre-treatment to 82% post-treatment. Conclusion: If rotational corrections are available, the immobilization system studied created reproducible patient positioning to within 3mm for 84% of fractions. However, intrafraction motion caused additional anatomy to fall outside the 3mm margin by the end of treatment.
Medical Physics | 2014
M Hosotani; S M Lacey; Deanna H. Pafundi; John A. Antolak; Robert L. Foote; Michael G. Herman; Yolanda I. Garces; T B Daniels; Debra H. Brinkmann
PURPOSE To compare two protocols for head and neck immobilization device fabrication and simulation and their effect on daily setup deviation and intrafraction motion over the course of VMAT or static IMRT. METHODS Fifteen post-surgical bilateral head and neck patients were immobilized with a custom-fit dental mold attached to a 5-point thermoplastic mask and treated with VMAT or IMRT. After fabrication of the immobilization device, which included 5-10 minutes for mask hardening, the patient either was scanned immediately without any positioning adjustments (N = 10), or got off of the simulation table for approximately 1 minute and was repositioned in treatment position prior to scanning (N = 5). Patients were localized using kV orthogonal imaging matching to overall bony anatomy for 30-35 fractions. Translational setup deviations were determined retrospectively by matching pre- and post-treatment kV orthogonal images to reference DRRs using bony anatomy near isocenter (typically C4) as well as gold fiducial markers embedded in the dental mold. Intrafraction motion was determined based on comparison of pre-treatment kV orthogonal images with post-treatment kV orthogonal images for each fraction. Margins were calculated using the pre- and posttreatment setup deviation data of each patient cohort. RESULTS Treatment position repositioning prior to simulation scanning decreased the patient group mean intrafraction motion near the dental mold (P < 0.02) and near isocenter (P < 0.04), but did not statistically significantly change the group mean setup uncertainty. CONCLUSION Repositioning of the patient in treatment position prior to simulation reduced intrafraction motion, but did not affect patient setup uncertainty during head and neck treatment. These results indicate that on average repositioning the patient in treatment position decreases patient intrafraction motion over the course of treatment for post-surgical bilateral head and neck patients immobilized with dental molds attached to a thermoplastic mask.
Practical radiation oncology | 2018
Yan Zhang; Robert W. Mutter; Sean S. Park; Tina J. Hieken; Elizabeth S. Yan; Kimberly S. Corbin; Debra H. Brinkmann; Deanna H. Pafundi
PURPOSE We investigated the feasibility and accuracy of using carbon fiducials to localize the lumpectomy cavity with 2-dimensional kV imaging for early stage breast cancer radiation therapy. METHODS AND MATERIALS Carbon fiducials were placed intraoperatively in the periphery of the lumpectomy cavity. Nine patients received whole breast irradiation with a boost, and 2 patients received 3-dimensional conformal partial breast irradiation. A total of 89 fractions were assessed for setup errors relative to a predefined gold standard, cone beam computed tomography (CBCT) match to the lumpectomy cavity, using the following 4 setup methods: (1) Align skin tattoos with lasers; (2) match bone with 2-dimensional-2-dimensional (2D/2D) kV onboard imaging (OBI); (3) match the whole breast with CBCT; and (4) match carbon fiducials with 2D/2D kV OBI. The margin for the planning target volume (PTV) was calculated by 2 standard deviations of the setup errors, and compared among the 4 setup methods. Setup errors for patients treated with free breathing and patients with deep inspiration breath hold were also compared. RESULTS The carbon fiducials were sufficiently visible on OBI for matching and introduced minimal artifacts. Of the 4 alignment methods, 2D/2D OBI match to fiducials resulted in the smallest setup errors. The PTV margin was 12 mm for aligning skin tattoos using lasers, 9.2 mm for matching bone on OBI, 6.5 mm for matching breast on CBCT, and 3.5 mm for matching fiducials on 2D/2D OBI. Compared with free breathing, deep inspiration breath hold generally reduced the standard deviations of the setup errors, but further investigation would be needed. CONCLUSIONS Matching to carbon fiducials increased the localization accuracy to the lumpectomy cavity. This reduces residual setup error and PTV margins, facilitating tissue sparing without diminishing treatment efficacy.
Physics and Imaging in Radiation Oncology | 2018
Tomáš Kazda; Deanna H. Pafundi; Alan Kraling; Thomas Bradley; Val J. Lowe; Debra H. Brinkmann; Nadia N. Laack
Background and purpose The amino-acid positron emission tomography (PET) tracer 3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine (18F-DOPA) has increased sensitivity for detecting regions of biologically aggressive tumors compared to T1 contrast-enhanced (T1-CE) magnetic resonance imaging (MRI). We performed dosimetric evaluation of treatment plans prepared with and without inclusion of 18F-DOPA-based biological target volume (BTV) evaluating its role in guiding radiotherapy of grade III/IV gliomas. Materials and methods Eight patients (five T1-CE, three non-contrast-enhancing [NCE]) were included in our study. MRI only-guided anatomic plans and MRI+18FDOPA-PET-guided biologic plans were prepared for each patient, and dosimetric data for target volumes and organs at risk (OAR) were compared. High-dose BTV60Gy was defined as regions with tumor to normal brain (T/N) >2.0, while low-dose BTV51Gy was initially based on T/N >1.3, but refined per Nuclear Medicine expert. Results For T1-CE tumors, planning target volumes (PTV) were larger than MRI-only anatomic target volumes. Despite increases in size of both gross target volumes and PTV, with volumetric-modulated arc therapy planning, no increase of dose to OAR was observed while maintaining similar target dose coverage. For NCE tumors, MRI+18F-DOPA PET biologic imaging identified a sub-region of the large, T2-FLAIR abnormal signal which may allow a smaller volume to receive the high dose (60 Gy) radiation. Conclusions For T1-CE tumors, PTVs were larger than MRI-only anatomic target volumes with no increase of dose to OARs. Therefore, MRI+18F-DOPA PET-based biologic treatment planning appears feasible in patients with high-grade gliomas.