Laurel Beckett

University of California, Davis, Davis, California, United States

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Publications (205)1145.13 Total impact

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    ABSTRACT: Erlotinib marginally improves survival when administered continuously with gemcitabine to patients with advanced pancreatic cancer; however, preclinical data suggest that there is antagonism between chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors when these are delivered concurrently. We tested a pharmacodynamic separation approach for erlotinib plus gemcitabine and interrogated EGFR signaling intermediates as potential surrogates for the efficacy of this strategy.
    International Journal of Clinical Oncology 08/2014; · 1.73 Impact Factor
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    ABSTRACT: Regulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 07/2014; 10(4):421-429.e3. · 14.48 Impact Factor
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    ABSTRACT: Object The authors analyzed headache relief after anterior cervical discectomy. Headache may be relieved after anterior cervical discectomy, but the mechanism is unknown. If headaches were directly referred from upper cervical pathology, more headache relief would be expected from surgery performed at higher cervical levels. If spinal kinesthetics were the mechanism, then headache relief may differ between arthroplasty and fusion. Headache relief after anterior cervical discectomy was quantified by the operated disc level and by the method of operation (arthroplasty vs arthrodesis). Methods The authors performed a post hoc analysis of an artificial disc trial. Data on headache pain were extracted from the Neck Disability Index (NDI) questionnaire. Results A total of 260 patients underwent single-level arthroplasty or arthodesis. Preoperatively, 52% reported NDI headache scores of 3 or greater, compared with only 13%-17% postoperatively. The model-based mean NDI headache score at baseline was 2.5 (95% CI 2.3-2.7) and was reduced by 1.3 points after surgery (95% CI 1.2-1.4, p < 0.001). Higher cervical levels were associated with a greater degree of preoperative headache, but there was no association with headache relief. There was no significant difference in headache relief between arthroplasty and arthrodesis. Conclusions Most patients with symptomatic cervical spondylosis have headache as a preoperative symptom (88%). Anterior cervical discectomy with both arthroplasty and arthrodesis is associated with a durable decrease in headache. Headache relief is not related to the level of operation. The mechanism for headache reduction remains unclear.
    Journal of neurosurgery. Spine. 05/2014;
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    ABSTRACT: Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. Global amyloid-β load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-β load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-β-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to dementia patients. Amyloid-β pathology has different associations with cerebral blood flow and volume, and may cause more loss of blood flow in early stages, whereas volume loss dominates in late disease stages.
    Brain 03/2014; · 10.23 Impact Factor
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    ABSTRACT: The objective of this study was to identify and characterize echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase fusion (EML4-ALK+) cancers by variant-specific, quantitative reverse transcription polymerase chain reaction (RT-PCR) assays in a large cohort of North American non-small-cell lung cancer (NSCLC) patients. We developed a panel of single and multiplex RT-PCR assays suitable for rapid and accurate detection of the eight most common EML4-ALK+ variants and ALK gene expression in archival formalin-fixed, paraffin-embedded NSCLC specimens. EGFR and KRAS genotyping and thymidylate synthase RNA level by RT-PCR assays were available in a subset of patients. Between December 2009 and September 2012, 7344 NSCLC specimens were tested. An EML4-ALK+ transcript was detected in 200 cases (2.7%), including 109 V1 (54.5%), 20 V2 (10.0%), 68 V3 (34.0%), and three V5a (1.5%) variants. Median age was 54.5 years (range, 23-89), and 104 patients (52.0%) were women. The great majority (n=188, 94.0%) of EML4-ALK+ NSCLC tumors had adenocarcinoma histology. ALK expression level varied significantly among different EML4-ALK+ variants and individual tumors. Only one case each of concurrent EGFR or KRAS mutation was detected. The median thymidylate synthase RNA level from 85 EML4-ALK+ cancers was significantly lower compared with that of EML4-ALK-negative lung adenocarcinomas (2.02 versus 3.29, respectively, p<0.001). This panel of variant-specific, quantitative RT-PCR assays detects common EML4-ALK+ variants as well as ALK gene expression level in archival formalin-fixed paraffin-embedded NSCLC specimens. These RT-PCR assays may be useful as an adjunct to the standard fluorescence in situ hybridization assay to better understand biologic variability and response patterns to anaplastic lymphoma kinase inhibitors.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2014; 9(1):18-25. · 4.55 Impact Factor
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    ABSTRACT: Background Previous work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications. Methods ADNI subjects diagnosed with amnestic MCI (n = 138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion. Results Four clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD. Conclusions Subjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 01/2014; · 14.48 Impact Factor
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    ABSTRACT: Motivation Diseases that progress slowly are often studied by observing cohorts at different stages of disease for short periods of time. The Alzheimer's Disease Neuroimaging Initiative (ADNI) follows elders with various degrees of cognitive impairment, from normal to impaired. The study includes a rich panel of novel cognitive tests, biomarkers, and brain images collected every 6 months for as long as 6 years. The relative timing of the observations with respect to disease pathology is unknown. We propose a general semiparametric model and iterative estimation procedure to estimate simultaneously the pathological timing and long-term growth curves. The resulting estimates of long-term progression are fine-tuned using cognitive trajectories derived from the long-term “Personnes Agées Quid” study. Results We demonstrate with simulations that the method can recover long-term disease trends from short-term observations. The method also estimates temporal ordering of individuals with respect to disease pathology, providing subject-specific prognostic estimates of the time until onset of symptoms. When the method is applied to ADNI data, the estimated growth curves are in general agreement with prevailing theories of the Alzheimer's disease cascade. Other data sets with common outcome measures can be combined using the proposed algorithm. Availability Software to fit the model and reproduce results with the statistical software R is available as the grace package. ADNI data can be downloaded from the Laboratory of NeuroImaging.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 01/2014; · 14.48 Impact Factor
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    ABSTRACT: Generalized linear mixed models were used to examine longitudinal trajectories of everyday functional limitations by diagnostic stability/progression. Older adults (N = 384) were followed an average 3.6 years; participants were grouped by diagnosis at study baseline and last follow-up (normal cognition, Mild Cognitive Impairment, or dementia at each time point). At study baseline there were clear group differences; most notably among participants initially characterized as cognitively normal, those who developed Mild Cognitive Impairment or dementia over follow-up already demonstrated greater functional impairment compared with those who remained cognitively normal. Change in functional impairment progressed slowly in the early disease groups, but showed an accelerated worsening in those converting to dementia. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
    Psychology and Aging 12/2013; 28(4):1070-5. · 2.73 Impact Factor
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    ABSTRACT: A fundamental controversy is whether cognitive decline with advancing age can be entirely explained by decreased processing speed, or whether specific neural changes can elicit cognitive decline, independent of slowing. These hypotheses are anchored by studies of healthy older individuals where age is presumed the sole influence. Unfortunately, advancing age is also associated with asymptomatic brain white matter injury. We hypothesized that differences in white matter injury extent, manifest by MRI white matter hyperintensities (WMH), mediate differences in visual attentional control in healthy aging, beyond processing speed differences. We tested young and cognitively healthy older adults on search tasks indexing speed and attentional control. Increasing age was associated with generally slowed performance. WMH was also associated with slowed search times independent of processing speed differences. Consistent with evidence attributing reduced network connectivity to WMH, these results conclusively demonstrate that clinically silent white matter injury contributes to slower search performance indicative of compromised cognitive control, independent of generalized slowing of processing speed.
    Neuropsychologia 10/2013; · 3.48 Impact Factor
  • The British journal of radiology 10/2013; · 2.11 Impact Factor
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    ABSTRACT: Background Despite advances in targeted therapies, there is an ongoing need to develop new and effective cytotoxic drug combinations in non-small cell lung cancer (NSCLC). Based on preclinical demonstration of additive cytotoxicity, we evaluated the safety and efficacy of combining pemetrexed and nanoparticle albumin bound (nab) paclitaxel with a focus on NSCLC for phase II expansion. Methods A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Three dose levels were tested: pemetrexed 500 mg/m(2) day 1 and nab-paclitaxel day 1 at 180, 220, & 260 mg/m(2) every 21 days. Phase II eligibility included advanced NSCLC, ≤2 line prior therapy, PS 0-1, adequate organ function. Primary endpoint for further study was response rate (RR) ≥ 25 %. Results Planned dose escalation was completed without reaching the MTD. The RP2D was pemetrexed 500 mg/m(2) and nab-paclitaxel 260 mg/m(2). The phase II portion accrued 37 pts before early closure due to increasing first-line pemetrexed/platinum doublet use in non-squamous NSCLC. In 31 assessable phase II patients there were 5 partial responses, 12 stable disease, 14 progressive disease. The median overall survival was 8.8 months; progressive disease 4.4 months and disease control 15.6 months. Conclusions Pemetrexed 500 mg/m(2) day 1 with nab-paclitaxel 260 mg/m(2) was feasible and well tolerated. The phase II component demonstrated activity in second/third-line therapy of advanced NSCLC; response rate 14 % and disease control rate 46 %. Treatment practice patterns of advanced NSCLC have evolved; further trials of this regimen are not planned.
    Investigational New Drugs 09/2013; · 3.50 Impact Factor
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    ABSTRACT: Blood analytes are critical for evaluating the general health of cetacean populations, so it is important to understand the intrinsic variability of hematology and serum chemistry values. Previous studies have reported data for follow-up periods of several years in managed and wild populations, but studies over long periods of time (> 20 yr) have not been reported. The study objective was to identify the influences of partitioning characteristics on hematology and serum chemistry analytes of apparently healthy managed beluga (Delphinapterus leucas). Blood values from 31 managed belugas, at three facilities, collected over 22 yr, were assessed for seasonal variation and aging trends, and evaluated for biologic variation among and within individuals. Linear mixed effects models assessed the relationship between the analytes and sex, age, season, facility location, ambient air temperature, and photoperiod. Sex differences in analytes and associations with increasing age were observed. Seasonal variation was observed for hemoglobin, hematocrit, mean corpuscular volume, monocytes, alkaline phosphatase, total bilirubin, cholesterol, and triglycerides. Facilities were associated with larger effects on analyte values compared to other covariates, whereas age, sex, and ambient temperature had smaller effects compared to facility and season. Present findings provide important baseline information for future health monitoring efforts. Interpretation of blood analytes and animal health in managed and wild populations over time is aided by having available typical levels for the species and reference intervals for the degree to which individual animals vary from the species average and from their own baseline levels during long-term monitoring.
    Journal of Zoo and Wildlife Medicine 06/2013; 44(2):376-88. · 0.43 Impact Factor
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    ABSTRACT: The challenges of balancing a career and family life disproportionately affect women in academic health sciences and medicine, contributing to their slower career advancement and/or their attrition from academia. In this article, the authors first describe their experiences at the University of California, Davis, School of Medicine developing and implementing an innovative accelerator intervention designed to promote faculty work-life balance by improving knowledge, awareness, and access to comprehensive flexible career policies. They then summarize the results of two faculty surveys-one conducted before the implementation of their intervention and the second conducted one year into their three-year intervention-designed to assess faculty's use and intention to use the flexible career policies, their awareness of available options, barriers to their use of the policies, and their career satisfaction. The authors found that the intervention significantly increased awareness of the policies and attendance at related educational activities, improved attitudes toward the policies, and decreased perceived barriers to use. These results, however, were most pronounced for female faculty and faculty under the age of 50. The authors next discuss areas for future research on faculty use of flexible career policies and offer recommendations for other institutions of higher education-not just those in academic medicine-interested in implementing a similar intervention. They conclude that having flexible career policies alone is not enough to stem the attrition of female faculty. Such policies must be fully integrated into an institution's culture such that faculty are both aware of them and willing to use them.
    Academic medicine: journal of the Association of American Medical Colleges 04/2013; · 2.34 Impact Factor
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    ABSTRACT: Fecal pathogens are transported from a variety of sources in multi-use ecosystems such as upper Cook Inlet (CI), Alaska, which includes the state's urban center and is highly utilized by humans and animals. This study used a novel water quality testing approach to evaluate the presence and host sources of potential fecal pathogens in surface waters and sediments from aquatic ecosystems in upper CI. Matched water and sediment samples, along with effluent from a municipal wastewater treatment facility, were screened for Salmonella spp., Vibrio spp., Cryptosporidium spp., Giardia spp., and noroviruses. Additionally, Bacteroidales spp. for microbial source tracking, and the fecal indicator bacteria Enterococcus spp. as well as fecal coliforms were evaluated. Overall, Giardia and Vibrio were the most frequently detected potential pathogens, followed by Cryptosporidium and norovirus, while Salmonella was not detected. Sample month, matrix type, and recent precipitation were found to be significant environmental factors for protozoa or host-associated Bacteroidales marker detection, whereas location and water temperature were not. The relative contribution of host-associated markers to total fecal marker concentration was estimated using a Monte Carlo method, with the greatest relative contribution to the Bacteroidales marker concentration coming from human sources, while the remainder of the universal fecal host source signal was uncharacterized by available host-associated assays, consistent with wildlife fecal sources. These findings show how fecal indicator and pathogen monitoring, along with identifying contributing host sources, can provide evidence of coastal pathogen pollution and guidance as to whether to target human and/or animal sources for management.
    Environmental science. Processes & impacts. 04/2013;
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    ABSTRACT: The use of brass mesh as a bolus is relatively uncommon in postmastectomy chest wall radiation therapy (PMRT). This study aimed to characterize the skin dose effects of using 2-mm fine brass mesh as an alternative to the traditional tissue-equivalent bolus during chest wall PMRT. Data were collected from patients who received PMRT using brass mesh at the University of California Davis Department of Radiation Oncology between January 2008 and June 2011. Several patient characteristics including age, body habitus, and ethnicity were analyzed along with several disease and treatment characteristics to determine whether or not they had an impact on the skin reaction observed during radiation treatment. Additionally, in vivo surface dose measurements were obtained for 16 of the 48 patients (33%). Forty-eight female patients aged 28-83 received PMRT using brass mesh. As expected, the severity of skin toxicity increased with subsequent doses of radiation with all patients beginning treatment with no skin reaction (National Cancer Institute scores [NCIS] = 0) and the majority of patients completing treatment with either faint to moderate erythema (n = 19, 40%, NCIS = 1) or moderate to brisk erythema (n = 23, 48%, NCIS = 2). In vivo dosimetry analysis revealed surface doses between 81% and 122% of the prescribed dose, with an average of 99% of the prescribed radiation dose and standard deviation of 10% being delivered. For postmastectomy chest wall radiation therapy, brass mesh is an effective alternative to tissue-equivalent bolus. The brass mesh achieved moderate erythema in the majority of patients at the end of treatment and the surface dose was validated using in vivo dosimetry.
    Practical radiation oncology. 04/2013; 3(2):e45-53.
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    ABSTRACT: Previous work examining Alzheimer's Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey's Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
    Psychology and Aging 03/2013; 28(1):191-201. · 2.73 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate how demographic variables relate to cognitive change and address whether cross-sectional demographic effects on cognitive tests are mirrored in differences in longitudinal trajectories of cognitive decline. We hypothesized that race and ethnicity, education, and language of test administration would relate to cross-sectional status and that the rate of cognitive decline would differ among African Americans, Hispanics, and Caucasians, across levels of educational attainment, and according to linguistic background. Participants were 404 educationally, ethnically, and cognitively diverse older adults enrolled in an ongoing longitudinal study of cognition. Mixed-effects regression analysis was used to measure baseline status and longitudinal change in episodic memory, executive functioning, and semantic memory. Results showed that ethnicity and education were strongly associated with baseline scores, but were, at most, weakly associated with change in cognition over time after accounting for confounding variables. There was evidence that the episodic-memory scores of Spanish-speaking Hispanic participants with limited education underestimated their true abilities in the initial evaluation, which may reflect lack of familiarity with the testing environment. These results-consistent with other reports in the literature-suggest that cross-sectional effects of demographic variables on cognitive-test scores result from differences in life experiences that directly influence test performance and do not indicate greater disease effects on cognition in minorities and those with limited education. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
    Psychology and Aging 02/2013; · 2.73 Impact Factor
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    ABSTRACT: Quantitative Image Analysis (QIA) of digitized whole slide images for morphometric parameters and immunohistochemistry of breast cancer antigens was used to evaluate the technical reproducibility, biological variability, and intratumoral heterogeneity in three transplantable mouse mammary tumor models of human breast cancer. The relative preservation of structure and immunogenicity of the three mouse models and three human breast cancers was also compared when fixed with representatives of four distinct classes of fixatives. The three mouse mammary tumor cell models were an ER+/PR+ model (SSM2), a Her2+ model (NDL), and a triple negative model (MET1). The four breast cancer antigens were ER, PR, Her2, and Ki67. The fixatives included examples of (1) strong cross-linkers, (2) weak cross-linkers, (3) coagulants, and (4) combination fixatives. Each parameter was quantitatively analyzed using modified Aperio Technologies ImageScope algorithms. Careful pre-analytical adjustments to the algorithms were required to provide accurate results. The QIA permitted rigorous statistical analysis of results and grading by rank order. The analyses suggested excellent technical reproducibility and confirmed biological heterogeneity within each tumor. The strong cross-linker fixatives, such as formalin, consistently ranked higher than weak cross-linker, coagulant and combination fixatives in both the morphometric and immunohistochemical parameters.Laboratory Investigation advance online publication, 11 February 2013; doi:10.1038/labinvest.2013.10.
    Laboratory Investigation 02/2013; · 3.96 Impact Factor
  • Megan E. Daly, Laurel A. Beckett, Allen M. Chen
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    ABSTRACT: Purpose Uncertainty exists regarding the optimal surveillance imaging strategy following stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC), particularly with respect to timing. We sought to determine how routine use of early (< 6 months) posttreatment imaging affects subsequent management. Methods and materials The records of all patients treated with SBRT between January 2007 and January 2013 for early-stage NSCLC were reviewed. Eligible patients underwent ≥ 1 early (defined as within 6 months following SBRT) surveillance imaging study. Radiographic findings and subsequent diagnostic or therapeutic interventions were identified. Proportions and exact 95% confidence intervals (CI) with early posttreatment surveillance findings and altered treatment were calculated, and cases were examined descriptively. Results Sixty-two patients with 67 lung tumors underwent 92 early surveillance imaging studies (86 computed tomographic [CT] and 6 positron emission/CT) at a median of 2.1 months (range, 0.1-5.9 months). New lung nodules were identified in 8 patients (13%), leading to a diagnosis of metastatic disease treated with systemic therapy in 2 patients and biopsy proven solitary lung recurrence in 2 patients, both treated successfully with local therapy. Tumor growth meeting Response Evaluation Criteria in Solid Tumors (RECIST) criteria was identified in 1 patient, who was followed with subsequent radiographic regression. In aggregate, the treatment of 4 patients (6.5%, 95% CI 1.7%-15.2%) was altered by early imaging; 2 (3.2%, 95% CI 0.4%-10.8%) with a potentially curative intervention. No predictors for utility of early surveillance were identified. Conclusions Imaging within 6 months following SBRT for early-stage NSCLC resulted in a definitive intervention in approximately 3% of patients. In the era of cost-effective health care, a first scan at 6 months posttreatment may be adequate for most patients. Larger scale prospective studies are needed to address the optimal surveillance regimen following SBRT and to identify patients who may benefit from more aggressive surveillance regimens.
    Practical Radiation Oncology. 01/2013;
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    ABSTRACT: OBJECTIVES/HYPOTHESIS: To evaluate the responsiveness of human papillomavirus (HPV) -positive and HPV-negative oropharyngeal cancer to intensity-modulated radiotherapy (IMRT), using axial imaging obtained daily during the course of image-guided radiotherapy (IGRT). STUDY DESIGN: Observational cohort study with matched-pair analysis of patients irradiated for HPV-positive and HPV-negative oropharygeal cancer. METHODS AND MATERIALS: Ten patients treated by IMRT to 70 Gy for locally advanced, HPV-positive squamous cell carcinoma of the oropharynx were matched to one HPV-negative control subject by age, gender, performance status, T-category, tumor location, and the use of concurrent chemotherapy. The gross tumor volume (GTV) was delineated on daily IGRT scans obtained via kilovoltage cone-beam computed tomography (CBCT). Mathematical modeling using fitted mixed-effects repeated measure analysis was performed to quantitatively and descriptively assess the trajectory of tumor regression. RESULTS: Patients with HPV-positive tumors experienced a more rapid rate of tumor regression between day 1 of IMRT and the beginning of week 2 (-33% Δ GTV) compared to their counterparts with HPV-negative tumors (-10% Δ GTV), which was statistically significant (p<0.001). During this initial period, the average absolute change in GTV was -22.9 cc/week for HPV-positive tumors and -5.9 cc/week for HPV-negative tumors (p<0.001). After week 2 of IMRT, the rates of GTV regression were comparable between the two groups. CONCLUSIONS: HPV-positive oropharyngeal cancers exhibited an enhanced response to radiation, characterized by a dramatically more rapid initial regression than those with HPV-negative tumors. Implications for treatment de-intensification in the context of future clinical trials and the possible mechanisms underlying this increased radiosensitivity will be discussed.
    The Laryngoscope 09/2012; · 1.98 Impact Factor

Publication Stats

9k Citations
1,145.13 Total Impact Points


  • 2005–2014
    • University of California, Davis
      • Department of Public Health Sciences
      Davis, California, United States
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2013
    • BC Cancer Agency
      Vancouver, British Columbia, Canada
  • 1994–2012
    • Rush University Medical Center
      • • Department of Behavioral Sciences
      • • Alzheimer's Disease Center
      • • Department of Neurological Sciences
      Chicago, IL, United States
  • 2011
    • University of Alberta
      Edmonton, Alberta, Canada
  • 2007–2011
    • California State University, Sacramento
      Sacramento, California, United States
  • 2005–2011
    • University of California, San Francisco
      • Veterans Affairs Medical Center
      San Francisco, CA, United States
  • 2010
    • University of California, San Diego
      • Department of Neurosciences
      San Diego, CA, United States
  • 2008
    • Seoul National University
      • Institute of Health and Environment
      Seoul, Seoul, South Korea
  • 2004
    • Stanford University
      • Stanford Prevention Research Center
      Stanford, CA, United States
  • 1998–2004
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
  • 1997–2001
    • Rush Medical College
      Chicago, Illinois, United States
    • Yale University
      New Haven, Connecticut, United States
  • 1999
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 1995
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 1992
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States