Perry W Grigsby

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (325)1178.26 Total impact

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    ABSTRACT: To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.
    International journal of radiation oncology, biology, physics 01/2014; · 4.59 Impact Factor
  • International journal of radiation oncology, biology, physics 01/2014; · 4.59 Impact Factor
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    ABSTRACT: Background Clinical outcome of papillary thyroid carcinoma (PTC) in children differs significantly from that of adults. There is no clear explanation of this difference although previous studies have demonstrated a lower prevalence of the BRAFV600E mutation in PTC of children. However, data are limited due to the rarity of this diagnosis. BRAFV600E mutation prevalence and its relationship with outcome in pediatric PTC remain unclear.ProcedureBRAFV600E mutational status was determined in 27 PTC patients less than 22 years of age using restriction fragment length polymorphism (RFLP) analysis. The relationship between BRAFV600E mutation status, patient and tumor characteristics as well as progression-free survival (PFS) were analyzed.ResultsBRAFV600E was present in 63% of patients and occurred more often in male patients versus females (P = 0.033). Presence of the mutation did not correlate with any difference in extent of disease at diagnosis, tumor size, capsular invasion, vascular invasion, soft tissue invasion, or margin status. At 10 years, PFS for BRAFV600E positive versus negative patients was 55.5% versus 70.0%, respectively (P = 0.48). Overall survival was 100% and median follow-up was 13.9 years.Conclusions This study of pediatric PTC demonstrates that BRAFV600E mutations occur in children at a rate comparable to adults. We found a correlation of BRAFV600E with the male gender, but no evidence that the mutation correlates with more extensive or aggressive disease. This analysis suggests that differences in disease course of PTC in children versus adults are not strongly dependent upon the presence of the BRAFV600E mutation. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 01/2014; · 2.35 Impact Factor
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    ABSTRACT: PI3K/AKT pathway alterations are associated with incomplete response to chemoradiation in human cervical cancer. This study was performed to test for mutations in the PI3K pathway and to evaluate the effects of AKT inhibitors on glucose uptake and cell viability. Mutational analysis of DNA from 140 pretreatment tumor biopsies and 8 human cervical cancer cell lines was performed. C33A cells (PIK3CAR88Q and PTENR233*) were treated with increasing concentrations of two allosteric AKT inhibitors (SC-66 and MK-2206) with or without the glucose analogue 2-deoxyglucose (2-DG). Cell viability and activation status of the AKT/mTOR pathway were determined in response to the treatment. Glucose uptake was evaluated by incubation with 18F-fluorodeoxyglucose (FDG). Cell migration was assessed by scratch assay. Activating PIK3CA (E545K, E542K) and inactivating PTEN (R233*) mutations were identified in human cervical cancer. SC-66 effectively inhibited AKT, mTOR and mTOR substrates in C33A cells. SC-66 inhibited glucose uptake via reduced delivery of Glut1 and Glut4 to the cell membrane. SC-66 (1 µg/ml-56%) and MK-2206 (30 µM-49%) treatment decreased cell viability through a non-apoptotic mechanism. Decreases in cell viability were enhanced when AKT inhibitors were combined with 2-DG. The scratch assay showed a substantial reduction in cell migration upon SC-66 treatment. The mutational spectrum of the PI3K/AKT pathway in cervical cancer is complex. AKT inhibitors effectively block mTORC1/2, decrease glucose uptake, glycolysis, and decrease cell viability in vitro. These results suggest that AKT inhibitors may improve response to chemoradiation in cervical cancer.
    PLoS ONE 01/2014; 9(4):e92948. · 3.73 Impact Factor
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    Frank J Brooks, Perry W Grigsby
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    ABSTRACT: Translational relevance: Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology.Purpose: We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas.Experimental design: We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (zeta) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally, we observed that S is strongly dependent upon tumor volume and that zeta moderately correlates with mean FDG uptake. FDG uptake heterogeneity did not indicate patients with differing prognoses. Apparent heterogeneity differences between clinical groups may be an artifact arising from either the dependence of some image metrics upon other factors such as tumor volume or upon the underlying variations in the patient populations compared.
    Radiation Oncology 12/2013; 8(1):294. · 2.11 Impact Factor
  • Frank J Brooks, Perry W Grigsby
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    ABSTRACT: The number of studies in the literature involving quantification of the metabolic heterogeneity seen in (18)F-FDG PET images has increased sharply over recent years. We hypothesized that inclusion of very small regions of interest as unique data points will have deleterious effects on these studies. Using a combination of probability theory and clinical (18)F-FDG PET data, we numerically calculated the curve describing the probability a given tumor volume is large enough to adequately sample the underlying tumor biology assayed via a PET/CT scanner at a planar resolution of 4 mm and transaxial resolution of 4 mm (64 mm(3) voxel size). We then used a computer simulation to isolate the effects of tumor volume on the image local entropy. We computed the underlying global intensity distribution for 70 cervical cancer tumors ranging from 4 to 248 cm(3)), which were ensemble-averaged over the same intensity scale. From this distribution, we determined that about 700 total voxels (45 cm(3)) are required to give 95% certainty that the global intensity distribution has been sufficiently sampled for common statistical comparisons of individual tumor intensity distributions to be made canonically. We demonstrated that one previously suggested measure of heterogeneity is dependent on tumor volume and that measurement of heterogeneity is about 5 times more sensitive to volume changes for volumes below the proposed minimum than for those above it. Inclusion of tumor volumes below 45 cm(3) can profoundly bias comparisons of intratumoral uptake heterogeneity metrics derived from data from the current generation of whole-body (18)F-FDG PET scanners.
    Journal of Nuclear Medicine 11/2013; · 5.77 Impact Factor
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    ABSTRACT: OBJECTIVE: Aim of this study was to report clinical outcomes of cervical cancer patients treated with weekly cisplatin chemo-radiation therapy (chemoRT) stratified by pre-treatment cisplatin in vitro chemosensitivity. METHODS: This was a retrospective analysis of patients with cervical cancer seen at our institution between May 2009 and August 2011. Patients underwent pre-treatment in vitro chemoresponse testing (Precision Therapeutics, Inc.) and were treated with concurrent weekly cisplatin chemoRT. The study consisted of 33 patients with FIGO tumor stages Ib2 to IIIb. Pre-treatment cisplatin chemoresponse of individual patient tumors was determined from chemoresponse dose response curves and scored as responsive (R), intermediate response (IR), or nonresponsive (NR). RESULTS: There were 28 patients with squamous cell carcinoma and 5 with adenocarcinoma. Cisplatin chemosensitivity was R and IR in 18 patient specimens and NR in 15. The 2-year recurrence-free survivals (RFS) were 87% for patients whose specimens tested R+IR to cisplatin compared to 58% for those whose specimens were NR (p=0.036). The 2-year RFS was 86% for the R+IR group compared to 46% for the NR group for patients with tumors that were squamous cell histology (p=0.009). Stepwise proportional hazards modeling for RFS demonstrated that chemoresponsiveness to cisplatin (p=0.029) and FDG-PET lymph node status (p=0.011) were the only independent predictors of RFS for patients with squamous cell histology. CONCLUSION: Pre-treatment in vitro cisplatin chemoresponse testing of cervix cancer biopsies was technically feasible and prognostic of RFS in patients treated with weekly cisplatin chemoRT.
    Gynecologic Oncology 04/2013; · 3.93 Impact Factor
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    Frank J Brooks, Perry W Grigsby
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    ABSTRACT: Background There has been much recent interest in the quantification of visually evident heterogeneity within functional grayscale medical images, such as those obtained via magnetic resonance or positron emission tomography. In the case of images of cancerous tumors, variations in grayscale intensity imply variations in crucial tumor biology. Despite these considerable clinical implications, there is as yet no standardized method for measuring the heterogeneity observed via these imaging modalities.Methods In this work, we motivate and derive a statistical measure of image heterogeneity. This statistic measures the distance-dependent average deviation from the smoothest intensity gradation feasible. We show how this statistic may be used to automatically rank images of in vivo human tumors in order of increasing heterogeneity. We test this method against the current practice of ranking images via expert visual inspection.Results We find that this statistic provides a means of heterogeneity quantification beyond that given by other statistics traditionally used for the same purpose. We demonstrate the effect of tumor shape upon our ranking method and find the method applicable to a wide variety of clinically relevant tumor images. We find that the automated heterogeneity rankings agree very closely with those performed visually by experts.Conclusions These results indicate that our automated method may be used reliably to rank, in order of increasing heterogeneity, tumor images whether or not object shape is considered to contribute to that heterogeneity. Automated heterogeneity ranking yields objective results which are more consistent than visual rankings. Reducing variability in image interpretation will enable more researchers to better study potential clinical implications of observed tumor heterogeneity.
    BMC Medical Imaging 03/2013; 13(1):7. · 1.09 Impact Factor
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    ABSTRACT: PURPOSE: The aim of this pilot study was to explore heterogeneity in the temporal behavior of intratumoral [(18)F]fluorodeoxyglucose (FDG) accumulation at a regional scale in patients with cervical cancer undergoing chemoradiotherapy. METHODS: Included in the study were 20 patients with FIGO stages IB1 to IVA cervical cancer treated with combined chemoradiotherapy. Patients underwent FDG PET/CT before treatment, during weeks 2 and 4 of treatment, and 12 weeks after completion of therapy. Patients were classified based on response to therapy as showing a complete metabolic response (CMR), a partial metabolic response (PMR), or residual disease and the development of new disease (NEW). Based on the presence of residual primary tumor following therapy, patients were divided into two groups, CMR and PMR/NEW. Temporal profiles of intratumoral FDG heterogeneity as characterized by textural features at a regional scale were assessed and compared with those of the standardized uptake value (SUV) indices (SUV(max) and SUV(mean)) within the context of differentiating response groups. RESULTS: Textural features at a regional scale with emphasis on characterizing contiguous regions of high uptake in tumors decreased significantly with time (P < 0.001) in the CMR group, while features describing contiguous regions of low uptake along with those measuring the nonuniformity of contiguous isointense regions in tumors exhibited significant temporal changes in the PMR/NEW group (P < 0.03) but showed no persistent trends with time. Both SUV indices showed significant changes during the course of the disease in both patient groups (P < 0.001 for SUV(max) and SUV(mean) in the CMR group; P = 0.0109 and 0.0136, respectively, for SUV(max) and SUV(mean) in the PMR/NEW group), and also decreased at a constant rate in the CMR group and decreased up to the 4th week of treatment and then increased in the PMR/NEW group. CONCLUSION: The temporal changes in the heterogeneity of intratumoral FDG distribution characterized at a regional scale using image-based textural features may provide an adjunctive or alternative option for understanding tumor response to chemoradiotherapy and interpreting FDG accumulation dynamics in patients with malignant cervical tumors during the course of the disease.
    European Journal of Nuclear Medicine 01/2013; · 4.53 Impact Factor
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    ABSTRACT: BACKGROUND: For cervical cancer patients treated with MR-guided high dose rate brachytherapy, the accuracy of radiation delivery depends on accurate localization of both tumors and the applicator, e.g. tandem and ovoid. Standard T2-weighted (T2W) MRI has good tumor-tissue contrast. However, it suffers from poor uterus-tandem contrast, which makes the tandem delineation very challenging. In this study, we evaluated the possibility of using proton density weighted (PDW) MRI to improve the definition of titanium tandems. METHODS: Both T2W and PDW MRI images were obtained from each cervical cancer patient. Imaging parameters were kept the same between the T2W and PDW sequences for each patient except the echo time (90ms for T2W and 5.5ms for PDW) and the slice thickness (0.5cm for T2W and 0.25cm for PDW). Uterus-tandem contrast was calculated by the equation C = (Su-St)/Su, where Su and St represented the average signal in the uterus and the tandem, respectively. The diameter of the tandem was measured 1.5cm away from the tip of the tandem. The tandem was segmented by the histogram thresholding technique. RESULTS: PDW MRI could significantly improve the uterus-tandem contrast compared to T2W MRI (0.42+/-0.24 for T2W MRI, 0.77+/-0.14 for PDW MRI, p=0.0002). The average difference between the measured and physical diameters of the tandem was reduced from 0.20+/-0.15cm by using T2W MRI to 0.10+/-0.11cm by using PDW MRI (p=0.0003). The tandem segmented from the PDW image looked more uniform and complete compared to that from the T2W image. CONCLUSIONS: Compared to the standard T2W MRI, PDW MRI has better uterus-tandem contrast. The information provided by PDW MRI is complementary to those provided by T2W MRI. Therefore, we recommend adding PDW MRI to the simulation protocol to assist tandem delineation process for cervical cancer patients.
    Radiation Oncology 01/2013; 8(1):16. · 2.11 Impact Factor
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    ABSTRACT: PURPOSE: To determine if FDG-PET results can predict for outcome in thyroid cancer patients with elevated Tg and negative I-131 imaging. MATERIALS AND METHODS: We conducted a retrospective review of 76 patients who had elevated serum Tg and negative (131)I scintigraphy and who underwent FDG-PET. After FDG-PET, patients underwent neck dissection or radiation. RESULTS: The 51 patients with positive FDG-PET had a 5-year survival of 63% compared to 100% (p<0.049) for the 25 patients with negative PET. Patients with FDG-avid disease isolated to the lymph nodes had 5-year CSS of 91% compared to 32% (p=0.0033) for those with disease outside the regional lymph nodes. Twenty-nine patients with disease isolated to the regional lymph nodes underwent salvage neck dissection and 22 remain NED after 28months. CONCLUSIONS: Negative FDG-PET with elevated Tg predicts an excellent outcome. FDG-avid disease isolated to the regional lymph nodes had a low likelihood of death due to thyroid cancer.
    American journal of otolaryngology 10/2012; · 0.77 Impact Factor
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    ABSTRACT: Purpose: This work describes an independent method to use the TomoTherapy Hi-ART megavoltage CT imaging system for daily monitoring of anatomical changes of cancer patients whose anatomy extends beyond the imaging field of view.Methods: The imaging detector response to changes in attenuating media was measured using water-equivalent plastic. Weight loss was simulated using an anthropomorphic phantom and determining the system's ability to detect the weight loss. Layers of tissue-equivalent bolus were added to an anthropomorphic pelvis phantom and CT simulations of the phantom were conducted, one in which the phantom and bolus were both within the TomoTherapy imaging field of view, and another in which the couch was raised so that the bolus was outside the field of view. Gynecological treatment plans were developed using the TomoTherapy treatment planning system, and successive fractions of the plan were then delivered to the phantom. Weight loss was simulated by removing a 0.5 cm layer of bolus following each fraction. The exit detector sinograms were obtained from each fraction, and ratios of sinograms were calculated relative to a reference sinogram for which all bolus was in place. Histograms of ratio sinograms were determined and used to correlate with simulated weight loss. Exit detector sinograms and ratio histograms were also retrospectively analyzed for five patients all of whose anatomies extended beyond the imaging field of view and all of whom experienced weight variations exceeding 10% during treatment.Results: Exit detector signal is well correlated to changes in attenuator thickness as demonstrated in both slab and anthropomorphic phantom geometries. Measured and expected signal increases agreed to within less than 2% for simulated weight loss on the anthropomorphic phantom. Exit detector signals for pelvic patients with significant weight loss variations were consistent with phantom measurements.Conclusions: The analysis of the ratio sinograms for the phantom measurements and real patients indicated that exit detector sinograms can be used to detect relative changes in patient anatomy for each fraction as a means of in vivo quality assurance.
    Medical Physics 10/2012; 39(10):6407-19. · 2.91 Impact Factor
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    ABSTRACT: PURPOSE: To compare [(18) F]fluorodeoxyglucose (FDG) / positron emission tomography (PET) / computed tomography (CT) and magnetic resonance imaging (MRI) for evaluating patients with cervical cancer. We compared tumor characteristics on FDG-PET and apparent diffusion coefficient (ADC) maps on diffusion-weighted MRI (DWI) to evaluate concordance of two functional imaging techniques. MATERIALS AND METHODS: Twenty women with cervical cancer underwent pretreatment FDG-PET/CT and pelvic MRI. Images were rigidly fused by pelvic anatomy using coregistration software. Tumor contours on PET images were generated by autosegmentation of the region containing at least 40% of the maximum standardized uptake value (SUV). DWI contours were generated by manual segmentation. Tumor volume similarity was evaluated using the [PET]/[ADC] volume proportion, Dice's coefficient, and the mean SUV isothreshold at the surface of each ADC contour. Tumor subvolume similarity was evaluated with analysis of variance (ANOVA). RESULTS: The [PET]/[ADC] volume proportion was 0.88 ± 0.14. Dice's coefficient between PET and ADC tumor contours was 0.76 ± 0.06. The mean SUV isothreshold at the ADC-delineated tumor surface was 34 ± 4%. Subvolumes with increased metabolic activity on FDG-PET also had more restricted diffusion on DWI (P < 0.0001, ANOVA). CONCLUSION: Concordance of functional imaging was observed between FDG-PET and DWI for cervical cancer. Tumor subvolumes with increased metabolic activity on FDG-PET also have greater cell density by DWI. J. Magn. Reson. Imaging 2012. © 2012 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 09/2012; · 2.57 Impact Factor
  • Fei Yang, Perry W Grigsby
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    ABSTRACT: Potential benefits of administering nonuniform radiation dose to heterogeneous tumors imaged with FDG-PET have been widely demonstrated; whereas the number of discrete dose levels to be utilized and corresponding locations for prescription inside tumors vary significantly with current existing methods. In this paper, an automated and unsupervised segmentation framework constituted mainly by an image restoration mechanism based on variational decomposition and a voxel clustering scheme based on spectral clustering was presented towards partitioning FDG-PET imaged tumors into subvolumes characterized with the total intra-subvolume activity similarity and the total inter-subvolume activity dissimilarity being simultaneously maximized. Experiments to evaluate the proposed system were carried out with using FDG-PET data generated from a digital phantom that employed SimSET (Simulation System for Emission Tomography) to simulate PET acquisition of tumors. The obtained results show the feasibility of the proposed system in dividing FDG-PET imaged tumor volumes into subvolumes with intratumoral heterogeneity being properly characterized, irrespective of variation in tumor morphology as well as diversity in intratumoral heterogeneity pattern.
    European journal of radiology 07/2012; · 2.65 Impact Factor
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    ABSTRACT: We previously found several individual FDG/PET-based prognostic factors for cervical cancer, specifically cervical tumor SUVmax, tumor volume, and highest level of lymph node (LN) involvement. For this study, we evaluate the combined use of these three prognostic factors assessed on pretreatment FDG-PET for predicting recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). The study included 234 cervical cancer patients, FIGO stage Ib1-IVa, treated with definitive radiation or chemoradiation therapy. All patients underwent FDG-PET or FDG-PET/CT at diagnosis, from which cervical tumor volume, SUVmax, and LN status were recorded. Using these PET-based factors, prognostic nomograms were created for RFS, DSS, and OS, and their prediction accuracies were measured using the concordance index (c-statistic). Fifty-three percent of patients had FDG-avid LN on PET; the highest level of nodal involvement was pelvic in 84, para-aortic in 41, and supraclavicular in 10. The average cervix tumor SUVmax was 12.4 (range, 2.1-50.4) and PET tumor volume average was 66.4 cm3 (range, 3.0-535.7 cm3). The median follow-up was 40.7 months for patients alive at last follow-up. PET LN status had the greatest influence on outcome. The c-statistics for the 3 nomograms were 0.741 for RFS, 0.739 for DSS, and 0.658 for OS. The PET-based nomograms performed better than FIGO stage with c-statistics of 0.605, 0.600 and 0.559 for RFS, DSS and OS, respectively. Pretreatment FDG-PET LN status, cervical tumor SUVmax, and tumor volume combined in a nomogram create good models for predicting cervical cancer RFS, DSS, and OS.
    Gynecologic Oncology 06/2012; 127(1):136-40. · 3.93 Impact Factor
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    ABSTRACT: PURPOSE: This pilot study was performed to evaluate whether tumor uptake of (18)F-labeled 3'-deoxy-3'fluorothymidine (FLT), a proliferative radiotracer, at baseline and early during therapy, is predictive of outcome in locally advanced rectal cancer. PROCEDURES: Fourteen patients underwent positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) and FLT before therapy and PET with FLT approximately 2 weeks after initiating neoadjuvant chemoradiotherapy. FLT and FDG uptake were evaluated qualitatively and by maximum standardized uptake value (SUV(max)). Tumor FLT and FDG uptake were correlated with disease-free survival (DFS). RESULTS: Thirteen patients underwent surgery after therapy, one died before surgery with progressive disease. FDG-PET/computed tomography detected regional lymph node metastases in five and FLT-PET was positive in one. High pretherapy FDG uptake (SUV(max) ≥ 14.3), low during-therapy FLT uptake (SUV(max) < 2.2), and high percentage change in FLT uptake (≥60 %) were predictive of improved DFS (p < 0.05 for all three values). CONCLUSION: Pretherapy FDG uptake, during-therapy FLT uptake, and percentage change in FLT uptake were equally predictive of DFS.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 06/2012; · 2.47 Impact Factor
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    ABSTRACT: Purpose: To evaluate the accuracy of a real-time automated method of performing dosimetric quality assurance using Eclipse DICOM files for patients receiving HDR-brachytherapy and IMRT. Methods: GYN patients are treated with concurrent high-dose rate brachtherapy and IMRT. The dosimetric parameters were obtained through an in-house QA program developed using Matlab. The DICOM files containing DVH data for organsat-risk (OAR) were analyzed Dosimetric data for 7 patients (total 42 fractions) were collected for bladder, rectum and sigmoid. The accuracy of the dosimetric parameters was estimated by comparing the parameters obtained from the DICOM based QA program and those in BrachyVision. Results: The maximal dose values (Dmax) for the OARs obtained using the DICOM-based program are significantly smaller than those valued reported in BrachyVision by 36.2%-48.3%. The mean dose has a deviation from 1% - 2.4%. The dose for the volume of 2cc (D2cc) has a difference up to 7.6% for structures with the volume larger than 200 cc. The average difference of D2cc is 0.5% for structures less than 200 cc. We found that Eclipse BrachyVision only exports DVH data down to a volume equivalent to 1% of the maximum volume for a given structure. Therefore, the reported maximal dose values obtained from DICOM RT dose file do not accurately reflect the maximum dose in a treatment plan. This will also slightly affect the mean dose calculation and D2cc when the structure volume is larger than 200cc. Conclusions: The automatic QA tool based on DICOM files provides a quick retrieval of dose to organs-at-risk and coverage of targets. However, maximal dose to structures is not accurate due to the truncationof the DVH information contained in DICOM files.
    Medical Physics 06/2012; 39(6):3773. · 2.91 Impact Factor
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    ABSTRACT: PURPOSE: Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUV(max)) and the variability of uptake (FDG(hetero)), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUV(max) and FDG(hetero) during concurrent chemoradiation for cervical cancer and their association with post-treatment response. METHODS AND MATERIALS: Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUV(max), FDG(hetero), and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4 of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT. RESULTS: For all patients, the average pretreatment SUV(max) was 17.8, MTV was 55.4 cm(3), and FDG(hetero) was -1.33. A similar decline in SUV(max) was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDG(hetero) decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUV(max) had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUV(max), larger MTV, and greater heterogeneity at all 3 times. Week 4 SUV(max) (P=.037), week 4 FDG(hetero) (P=.005), pretreatment MTV (P=.008), and pretreatment FDG(hetero) (P=.008) were all significantly associated with post-treatment PET response. CONCLUSIONS: SUV(max) shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study, pretreatment and week 4 of treatment represent the best time points for prediction of response.
    International journal of radiation oncology, biology, physics 04/2012; · 4.59 Impact Factor
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    ABSTRACT: Cervical tumor response on posttherapy 2[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is predictive of survival outcome. The purpose of this study was to use gene expression profiling to identify pathways associated with tumor metabolic response. This was a prospective tissue collection study for gene expression profiling of 62 pretreatment biopsies from patients with advanced cervical cancer. Patients were treated with definitive radiation. Fifty-three patients received concurrent chemotherapy. All patients underwent a pretreatment and a 3-month posttherapy FDG-PET/computed tomography (CT). Tumor RNA was harvested from fresh frozen tissue and hybridized to Affymetrix U133Plus2 GeneChips. Gene set enrichment analysis (GSEA) was used to identify signaling pathways associated with tumor metabolic response. Immunohistochemistry and in vitro FDG uptake assays were used to confirm our results. There were 40 biopsies from patients with a complete metabolic response (PET-negative group) and 22 biopsies from patients with incomplete metabolic response (PET-positive group). The 3-year cause-specific survival estimates were 98% for the PET-negative group and 39% for the PET-positive group (P < 0.0001). GSEA identified alterations in expression of genes associated with the PI3K/Akt signaling pathway in patients with a positive follow-up PET. Immunohistochemistry using a tissue microarray of 174 pretreatment biopsies confirmed p-Akt as a biomarker for poor prognosis in cervical cancer. The phosphoinositide 3-kinase (PI3K) inhibitor LY294002 inhibited FDG uptake in vitro in cervical cancer cell lines. Activation of the PI3K/Akt pathway is associated with incomplete metabolic response in cervical cancer. Targeted inhibition of PI3K/Akt may improve response to chemoradiation.
    Clinical Cancer Research 03/2012; 18(5):1464-71. · 7.84 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy. This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03). p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.
    International journal of radiation oncology, biology, physics 02/2012; 84(1):153-7. · 4.59 Impact Factor

Publication Stats

7k Citations
1,178.26 Total Impact Points

Institutions

  • 1988–2014
    • Washington University in St. Louis
      • • Department of Radiation Oncology
      • • Department of Obstetrics and Gynecology
      • • Alvin J. Siteman Cancer Center
      San Luis, Missouri, United States
  • 1987–2013
    • University of Washington Seattle
      • • Department of Radiation Oncology
      • • Department of Obstetrics and Gynecology
      • • Department of Surgery
      Seattle, WA, United States
  • 2012
    • Stanford University
      • Department of Radiation Oncology
      Stanford, CA, United States
  • 2008–2009
    • Thomas Jefferson University
      • Department of Radiation Oncology
      Philadelphia, PA, United States
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 2007
    • Columbia University
      • Department of Obstetrics and Gynecology
      New York City, NY, United States
  • 2006
    • Dechert LLP
      New York City, New York, United States
    • Barnes Jewish Hospital
      • Department of Obstetrics and Gynecology
      San Luis, Missouri, United States
  • 2005
    • St. Luke's Hospital (MO, USA)
      Saint Louis, Michigan, United States
  • 1999–2004
    • University of Texas MD Anderson Cancer Center
      • • Division of Radiation Oncology
      • • Department of Gynecologic Oncology
      Houston, TX, United States
  • 2001
    • Hacettepe University
      • Department of Radiation Oncology
      Ankara, Ankara, Turkey
    • University of Iowa
      • Department of Electrical and Computer Engineering
      Iowa City, IA, United States
  • 1993
    • University of Louisville
      Louisville, Kentucky, United States