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      Intravoxel incoherent motion diffusion‐weighted MRI during chemoradiation therapy to characterize and monitor treatment response in human papillomavirus head and neck squamous cell carcinoma

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          Abstract

          Purpose

          Characterize and monitor treatment response in human papillomavirus (HPV) head and neck squamous cell carcinoma (HNSCC) using intra‐treatment (intra‐TX) imaging metrics derived from intravoxel incoherent motion (IVIM) diffusion‐weighted magnetic resonance imaging (DW‐MRI).

          Materials and Methods

          Thirty‐four (30 HPV positive [+] and 4 HPV negative [‐]) HNSCC patients underwent a total of 136 MRI including multi‐b value DW‐MRI (pretreatment [pre‐TX] and intra‐TX weeks 1, 2, and 3) at 3.0 Tesla. All patients were treated with chemo‐radiation therapy. Monoexponential (yielding apparent diffusion coefficient [ADC]) and bi‐exponential (yielding perfusion fraction [f], diffusion [D], and pseudo‐diffusion [D*] coefficients) fits were performed on a region of interest and voxel‐by‐voxel basis, on metastatic neck nodes. Response was assessed using RECISTv1.1. The relative percentage change in D, f, and D* between the pre‐ and intra‐TX weeks were used for hierarchical clustering. A Wilcoxon rank‐sum test was performed to assess the difference in metrics within and between the complete response (CR) and non‐CR groups.

          Results

          The delta (Δ) change in volume (V) 1wk‐0wk for the CR group differed significantly ( P = 0.016) from the non‐CR group, while not for V 2wk‐0wk and V 3wk‐0wk ( P > 0.05). The mean increase in ΔD 3wk‐0wk for the CR group was significantly higher ( P = 0.017) than the non‐CR group. ADC and D showed an increasing trend at each intra‐TX week when compared with pre‐TX in CR group ( P < 0.003). Hierarchical clustering demonstrated the existence of clusters in HPV + patients.

          Conclusion

          After appropriate validation in a larger population, these IVIM imaging metrics may be useful for individualized treatment in HNSCC patients.

          Level of Evidence: 2

          J. Magn. Reson. Imaging 2017;45:1013–1023

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          Most cited references30

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          NIH Image to ImageJ: 25 years of image analysis.

          For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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            Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis.

            To define human papillomavirus (HPV) -positive oropharyngeal cancers (OPC) suitable for treatment deintensification according to low risk of distant metastasis (DM). OPC treated with radiotherapy (RT) or chemoradiotherapy (CRT) from 2001 to 2009 were included. Outcomes were compared for HPV-positive versus HPV-negative patients. Univariate and multivariate analyses identified outcome predictors. Recursive partitioning analysis (RPA) stratified the DM risk. HPV status was ascertained in 505 (56%) of 899 consecutive OPCs. Median follow-up was 3.9 years. HPV-positive patients (n = 382), compared with HPV-negative patients (n = 123), had higher local (94% v 80%, respectively, at 3 years; P 10 reduced overall survival (HR, 1.72; 95% CI, 1.1 to 2.7; P = .03) but did not impact RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P = .65). RPA segregated HPV-positive patients into low (T1-3N0-2c; DC, 93%) and high DM risk (N3 or T4; DC, 76%) groups and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high DM risk (T3-4N3; DC, 72%) groups. The DC rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P = .02). HPV-positive T1-3N0-2c patients have a low DM risk, but N2c patients from this group have a reduced DC when treated with RT alone and seem less suited for deintensification strategies that omit chemotherapy.
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              Enhanced radiation sensitivity in HPV-positive head and neck cancer.

              Patients with human papillomavirus (HPV+)-associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV-: 0.59 vs. HPV+: 0.22; P < 0.0001), corresponding with a prolonged G2-M cell-cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%; P = 0.002). A genome-wide microarray was used to compare gene expression 24 hours following radiation between HPV+ and HPV- cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6-fold increase in TP53 (P < 0.0001). Using immortalized human tonsillar epithelial (HTE) cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC. This issue is under active investigation in a series of clinical trials attempting to de-escalate radiation (and chemotherapy) in selected patients with HPV+ HNC in light of their favorable overall survival outcome. ©2013 AACR.
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                Author and article information

                Contributors
                davea@mskcc.org
                Journal
                J Magn Reson Imaging
                J Magn Reson Imaging
                10.1002/(ISSN)1522-2586
                JMRI
                Journal of Magnetic Resonance Imaging
                John Wiley and Sons Inc. (Hoboken )
                1053-1807
                1522-2586
                11 November 2016
                April 2017
                : 45
                : 4 ( doiID: 10.1002/jmri.v45.4 )
                : 1013-1023
                Affiliations
                [ 1 ] Department of Medical PhysicsMemorial Sloan Kettering Cancer Center New York New YorkUSA
                [ 2 ] Radiation OncologyMemorial Sloan Kettering Cancer Center New York New YorkUSA
                [ 3 ] Department of Radiation OncologyJiangxi Cancer Hospital NanchangP.R. China
                [ 4 ] Department of RadiologyMemorial Sloan Kettering Cancer Center New York New YorkUSA
                [ 5 ] Department of Radiation OncologyWashington University in St. Louis St. Louis MissouriUSA
                Author notes
                [*] [* ]Address reprint requests to: A.S.‐D., Department of Medical Physics and Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065. E‐mail: davea@ 123456mskcc.org
                Article
                JMRI25523
                10.1002/jmri.25523
                5363344
                27862553
                a00a02ce-b0b7-4dae-b354-c29d32529b8d
                © 2016 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 12 August 2016
                : 07 October 2016
                Page count
                Figures: 7, Tables: 3, Pages: 11, Words: 5320
                Funding
                Funded by: MSKCC internal IMRAS grant
                Funded by: NIH/NCI Cancer Center Support Grant
                Award ID: P30 CA008748
                Categories
                Original Research
                Original Research
                Head and Neck
                Custom metadata
                2.0
                jmri25523
                April 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:23.03.2017

                Radiology & Imaging
                human papillomavirus,head and neck squamous cell carcinoma,multi b‐value diffusion‐weighted mri,intravoxel incoherent motion

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