{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:30:30Z","timestamp":1787020230594,"version":"build-2736575974"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100019229","name":"ViewRay, Inc.","doi-asserted-by":"crossref","award":["Provided funding to the institution"],"award-info":[{"award-number":["Provided funding to the institution"]}],"id":[{"id":"10.13039\/100019229","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR\u2009\u2265\u200995%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60\u00a0Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50\u00a0Gy, would lead to a\u2009&gt;\u20093 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>NCT05301283.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial status<\/jats:title>\n                    <jats:p>The trial started recruitment on March 17, 2022.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-024-12151-7","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T03:02:23Z","timestamp":1712631743000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma"],"prefix":"10.1186","volume":"24","author":[{"given":"Arash O.","family":"Naghavi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngchul","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Weygand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gage","family":"Redler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin J.","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Coucoules","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Taylor","family":"Michael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren E.","family":"Gloria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn M.","family":"Bui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evita B.","family":"Henderson-Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin D.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo J.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Feygelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Eschrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob G.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Torres-Roca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kujtim","family":"Latifi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nainesh","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Costello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"issue":"1","key":"12151_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.radonc.2015.12.002","volume":"119","author":"RL Haas","year":"2016","unstructured":"Haas RL, Miah AB, LePechoux C, et al. Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies. Radiother Oncol Apr. 2016;119(1):14\u201321. https:\/\/doi.org\/10.1016\/j.radonc.2015.12.002","journal-title":"Radiother Oncol Apr"},{"key":"12151_CR2","doi-asserted-by":"publisher","unstructured":"Siegel RL, Miller KD, Jemal A, Cancer statistics. 2015. CA Cancer J Clin. 2015;65(1):5\u201329. https:\/\/doi.org\/10.3322\/caac.21254","DOI":"10.3322\/caac.21254"},{"key":"12151_CR3","doi-asserted-by":"crossref","unstructured":"Farhidzadeh H, Chaudhury B, Scott JG, et al. Signal intensity analysis of ecological defined habitat in soft tissue sarcomas to predict metastasis development. SPIE; 2016:7.","DOI":"10.1117\/12.2216961"},{"key":"12151_CR4","doi-asserted-by":"crossref","unstructured":"Farhidzadeh H, Chaudhury B, Zhou M, et al. Prediction of treatment outcome in soft tissue sarcoma based on radiologically defined habitats. SPIE; 2015:5.","DOI":"10.1117\/12.2082324"},{"issue":"7","key":"12151_CR5","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1002\/cncr.10425","volume":"1","author":"I Shmulevich","year":"2002","unstructured":"Shmulevich I, Hunt K, El-Naggar A, et al. Tumor specific gene expression profiles in human leiomyosarcoma: an evaluation of intratumor heterogeneity. Cancer Apr. 2002;1(7):2069\u201375.","journal-title":"Cancer Apr"},{"issue":"8","key":"12151_CR6","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1016\/S1470-2045(19)30326-2","volume":"20","author":"S Bonvalot","year":"2019","unstructured":"Bonvalot S, Rutkowski PL, Thariat J, et al. NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2\u20133, randomised, controlled trial. Lancet Oncol Aug. 2019;20(8):1148\u201359. https:\/\/doi.org\/10.1016\/S1470-2045(19)30326-2","journal-title":"Lancet Oncol Aug"},{"issue":"2","key":"12151_CR7","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1148\/radiol.2512081403","volume":"251","author":"S Stacchiotti","year":"2009","unstructured":"Stacchiotti S, Collini P, Messina A, et al. High-grade soft-tissue sarcomas: tumor response assessment\u2013pilot study to assess the correlation between radiologic and pathologic response by using RECIST and Choi criteria. Radiol May. 2009;251(2):447\u201356. https:\/\/doi.org\/10.1148\/radiol.2512081403","journal-title":"Radiol May"},{"issue":"20","key":"12151_CR8","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1200\/JCO.2014.58.5828","volume":"10","author":"D Wang","year":"2015","unstructured":"Wang D, Zhang Q, Eisenberg BL, et al. Significant reduction of late toxicities in patients with extremity sarcoma treated with image-guided radiation therapy to a reduced target volume: results of radiation therapy oncology group RTOG-0630 trial. J Clin Oncol Jul. 2015;10(20):2231\u20138. https:\/\/doi.org\/10.1200\/JCO.2014.58.5828","journal-title":"J Clin Oncol Jul"},{"issue":"1","key":"12151_CR9","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1200\/JCO.1998.16.1.197","volume":"16","author":"JC Yang","year":"1998","unstructured":"Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol Jan. 1998;16(1):197\u2013203.","journal-title":"J Clin Oncol Jan"},{"issue":"1028","key":"12151_CR10","doi-asserted-by":"publisher","first-page":"20130258","DOI":"10.1259\/bjr.20130258","volume":"86","author":"V Soyfer","year":"2013","unstructured":"Soyfer V, Corn BW, Kollender Y, et al. Hypofractionated adjuvant radiation therapy of soft-tissue sarcoma achieves excellent results in elderly patients. Br J Radiol Aug. 2013;86(1028):20130258. https:\/\/doi.org\/10.1259\/bjr.20130258","journal-title":"Br J Radiol Aug"},{"issue":"10","key":"12151_CR11","doi-asserted-by":"publisher","first-page":"101165","DOI":"10.1016\/j.tranon.2021.101165","volume":"14","author":"G Yang","year":"2021","unstructured":"Yang G, Yuan Z, Ahmed K, et al. Genomic identification of sarcoma radiosensitivity and the clinical implications for radiation dose personalization. Transl Oncol Oct. 2021;14(10):101165. https:\/\/doi.org\/10.1016\/j.tranon.2021.101165","journal-title":"Transl Oncol Oct"},{"issue":"9","key":"12151_CR12","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/S1470-2045(21)00347-8","volume":"22","author":"JG Scott","year":"2021","unstructured":"Scott JG, Sedor G, Ellsworth P, et al. Pan-cancer prediction of radiotherapy benefit using genomic-adjusted radiation dose (GARD): a cohort-based pooled analysis. Lancet Oncol Sep. 2021;22(9):1221\u20139. https:\/\/doi.org\/10.1016\/S1470-2045(21)00347-8","journal-title":"Lancet Oncol Sep"},{"issue":"2","key":"12151_CR13","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S1470-2045(16)30648-9","volume":"18","author":"JG Scott","year":"2017","unstructured":"Scott JG, Berglund A, Schell MJ, et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol Feb. 2017;18(2):202\u201311. https:\/\/doi.org\/10.1016\/S1470-2045(16)30648-9","journal-title":"Lancet Oncol Feb"},{"key":"12151_CR14","doi-asserted-by":"publisher","unstructured":"Liveringhouse CL, Palm RF, Bryant JM, et al. Neoadjuvant simultaneous integrated boost radiotherapy improves clinical outcomes for retroperitoneal sarcoma: neoadjuvant simultaneous integrated boost radiotherapy for retroperitoneal sarcoma. Int J Radiat Oncol Biol Phys Mar. 2023;17. https:\/\/doi.org\/10.1016\/j.ijrobp.2023.03.037","DOI":"10.1016\/j.ijrobp.2023.03.037"},{"issue":"3","key":"12151_CR15","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1002\/gcc.20191","volume":"43","author":"P Francis","year":"2005","unstructured":"Francis P, Fernebro J, Eden P, et al. Intratumor versus intertumor heterogeneity in gene expression profiles of soft-tissue sarcomas. Genes Chromosomes Cancer Jul. 2005;43(3):302\u20138. https:\/\/doi.org\/10.1002\/gcc.20191","journal-title":"Genes Chromosomes Cancer Jul"},{"key":"12151_CR16","doi-asserted-by":"publisher","unstructured":"Henning EC, Azuma C, Sotak CH, Helmer KG. Multispectral tissue characterization in a RIF-1 tumor model: monitoring the ADC and T2 responses to single-dose radiotherapy. Part II. Magn Reson Med. 2007;57(3):513\u20139. https:\/\/doi.org\/10.1002\/mrm.21178","DOI":"10.1002\/mrm.21178"},{"issue":"1","key":"12151_CR17","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1053\/SRAO0060003","volume":"6","author":"M Hockel","year":"1996","unstructured":"Hockel M, Schlenger K, Mitze M, Schaffer U, Vaupel P. Hypoxia and radiation response in human tumors. Semin Radiat Oncol Jan. 1996;6(1):3\u20139. https:\/\/doi.org\/10.1053\/SRAO0060003","journal-title":"Semin Radiat Oncol Jan"},{"issue":"6","key":"12151_CR18","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1002\/jmri.21755","volume":"29","author":"D Schnapauff","year":"2009","unstructured":"Schnapauff D, Zeile M, Niederhagen MB, et al. Diffusion-weighted echo-planar magnetic resonance imaging for the assessment of tumor cellularity in patients with soft-tissue sarcomas. J Magn Reson Imaging Jun. 2009;29(6):1355\u20139. https:\/\/doi.org\/10.1002\/jmri.21755","journal-title":"J Magn Reson Imaging Jun"},{"issue":"6","key":"12151_CR19","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1593\/tlo.12319","volume":"5","author":"R Stoyanova","year":"2012","unstructured":"Stoyanova R, Huang K, Sandler K, et al. Mapping tumor hypoxia in vivo using pattern recognition of dynamic contrast-enhanced MRI data. Transl Oncol Dec. 2012;5(6):437\u201347. https:\/\/doi.org\/10.1593\/tlo.12319","journal-title":"Transl Oncol Dec"},{"key":"12151_CR20","doi-asserted-by":"publisher","unstructured":"Cho H, Ackerstaff E, Carlin S et al. Mar. Noninvasive multimodality imaging of the tumor microenvironment: registered dynamic magnetic resonance imaging and positron emission tomography studies of a preclinical tumor model of tumor hypoxia. Neoplasia. 2009;11(3):247\u201359, 2p following 259. https:\/\/doi.org\/10.1593\/neo.81360","DOI":"10.1593\/neo.81360"},{"issue":"1","key":"12151_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ijrobp.2005.04.049","volume":"1","author":"J Varlotto","year":"2005","unstructured":"Varlotto J, Stevenson MA. Anemia, tumor hypoxemia, and the cancer patient. Int J Radiat Oncol Biol Phys Sep. 2005;1(1):25\u201336. https:\/\/doi.org\/10.1016\/j.ijrobp.2005.04.049","journal-title":"Int J Radiat Oncol Biol Phys Sep"},{"issue":"5","key":"12151_CR22","first-page":"941","volume":"01","author":"DM Brizel","year":"1996","unstructured":"Brizel DM, Scully SP, Harrelson JM, et al. Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res Mar. 1996;01(5):941\u20133.","journal-title":"Cancer Res Mar"},{"key":"12151_CR23","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3233\/BD-2007-26105","volume":"26","author":"N Chaudary","year":"2006","unstructured":"Chaudary N, Hill RP. Hypoxia and metastasis in breast cancer. Breast Dis. 2006;26:55\u201364.","journal-title":"Breast Dis"},{"issue":"13","key":"12151_CR24","doi-asserted-by":"publisher","first-page":"3203","DOI":"10.1200\/JCO.2001.19.13.3203","volume":"01","author":"FC Eilber","year":"2001","unstructured":"Eilber FC, Rosen G, Eckardt J, et al. Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas. J Clin Oncol Jul. 2001;01(13):3203\u20139. https:\/\/doi.org\/10.1200\/JCO.2001.19.13.3203","journal-title":"J Clin Oncol Jul"},{"issue":"9","key":"12151_CR25","first-page":"3911","volume":"32","author":"D Shah","year":"2012","unstructured":"Shah D, Borys D, Martinez SR, et al. Complete pathologic response to neoadjuvant radiotherapy is predictive of oncological outcome in patients with soft tissue sarcoma. Anticancer Res Sep. 2012;32(9):3911\u20135.","journal-title":"Anticancer Res Sep"},{"issue":"1","key":"12151_CR26","doi-asserted-by":"publisher","first-page":"101086","DOI":"10.1016\/j.adro.2022.101086","volume":"8","author":"RF Palm","year":"2023","unstructured":"Palm RF, Liveringhouse CL, Gonzalez RJ, et al. Effect of favorable pathologic response after neoadjuvant radiation therapy alone in soft-tissue sarcoma. Adv Radiat Oncol Jan-Feb. 2023;8(1):101086. https:\/\/doi.org\/10.1016\/j.adro.2022.101086","journal-title":"Adv Radiat Oncol Jan-Feb"},{"issue":"6","key":"12151_CR27","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1007\/s00330-004-2237-0","volume":"14","author":"H Einarsdottir","year":"2004","unstructured":"Einarsdottir H, Karlsson M, Wejde J, Bauer HC. Diffusion-weighted MRI of soft tissue tumours. Eur Radiol Jun. 2004;14(6):959\u201363. https:\/\/doi.org\/10.1007\/s00330-004-2237-0","journal-title":"Eur Radiol Jun"},{"issue":"4","key":"12151_CR28","doi-asserted-by":"publisher","first-page":"308","DOI":"10.18383\/j.tom.2016.00202","volume":"2","author":"W Huang","year":"2016","unstructured":"Huang W, Beckett BR, Tudorica A, et al. Evaluation of soft tissue sarcoma response to preoperative chemoradiotherapy using dynamic contrast-enhanced magnetic resonance imaging. Tomography Dec. 2016;2(4):308\u201316. https:\/\/doi.org\/10.18383\/j.tom.2016.00202","journal-title":"Tomography Dec"},{"issue":"11","key":"12151_CR29","doi-asserted-by":"publisher","first-page":"e4000","DOI":"10.1002\/nbm.4000","volume":"31","author":"S Xing","year":"2018","unstructured":"Xing S, Freeman CR, Jung S, Turcotte R, Levesque IR. Probabilistic classification of tumour habitats in soft tissue sarcoma. NMR Biomed Nov. 2018;31(11):e4000. https:\/\/doi.org\/10.1002\/nbm.4000","journal-title":"NMR Biomed Nov"},{"issue":"4","key":"12151_CR30","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/ncponc1073","volume":"5","author":"DM Patterson","year":"2008","unstructured":"Patterson DM, Padhani AR, Collins DJ. Technology insight: water diffusion MRI\u2013a potential new biomarker of response to cancer therapy. Nat Clin Pract Oncol Apr. 2008;5(4):220\u201333. https:\/\/doi.org\/10.1038\/ncponc1073","journal-title":"Nat Clin Pract Oncol Apr"},{"issue":"6","key":"12151_CR31","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1088\/0031-9155\/56\/6\/006","volume":"21","author":"L Alic","year":"2011","unstructured":"Alic L, van Vliet M, van Dijke CF, Eggermont AM, Veenland JF, Niessen WJ. Heterogeneity in DCE-MRI parametric maps: a biomarker for treatment response? Phys Med Biol Mar. 2011;21(6):1601\u201316. https:\/\/doi.org\/10.1088\/0031-9155\/56\/6\/006","journal-title":"Phys Med Biol Mar"},{"issue":"3","key":"12151_CR32","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1148\/radiol.2015142463","volume":"278","author":"T Soldatos","year":"2016","unstructured":"Soldatos T, Ahlawat S, Montgomery E, Chalian M, Jacobs MA, Fayad LM. Multiparametric assessment of treatment response in high-grade soft-tissue sarcomas with anatomic and functional MR imaging sequences. Radiol Mar. 2016;278(3):831\u201340. https:\/\/doi.org\/10.1148\/radiol.2015142463","journal-title":"Radiol Mar"},{"key":"12151_CR33","unstructured":"Gatenby RA, Gillies RJ, Raghavan M. Prediction of treatment outcome in soft tissue sarcoma based on radiologically defined habitats. Presented at: medical imaging 2015: Computer-Aided Diagnosis; 2015; Orlando, FL."},{"key":"12151_CR34","doi-asserted-by":"publisher","unstructured":"Henning EC, Azuma C, Sotak CH, Helmer KG. Multispectral quantification of tissue types in a RIF-1 tumor model with histological validation. Part I. Magn Reson Med. 2007;57(3):501\u201312. https:\/\/doi.org\/10.1002\/mrm.21161","DOI":"10.1002\/mrm.21161"},{"key":"12151_CR35","volume-title":"Co-registration of MRI and histological habitats in pre-clinical tumor models","author":"BV Jardim-Perassi","year":"2018","unstructured":"Jardim-Perassi BV, Huang S, Dominguez-Viqueira W, et al. Co-registration of MRI and histological habitats in pre-clinical tumor models. presented at: ISMRM; 2018. Paris, France."},{"issue":"5","key":"12151_CR36","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1016\/j.ijrobp.2004.08.036","volume":"01","author":"LM White","year":"2005","unstructured":"White LM, Wunder JS, Bell RS, et al. Histologic assessment of peritumoral edema in soft tissue sarcoma. Int J Radiat Oncol Biol Phys Apr. 2005;01(5):1439\u201345. https:\/\/doi.org\/10.1016\/j.ijrobp.2004.08.036","journal-title":"Int J Radiat Oncol Biol Phys Apr"},{"key":"12151_CR37","doi-asserted-by":"publisher","unstructured":"Wang D, Harris J, Kraybill WG, et al. Pathologic complete response and clinical outcomes in patients with localized soft tissue sarcoma treated with neoadjuvant chemoradiotherapy or radiotherapy: the NRG\/RTOG 9514 and 0630 nonrandomized clinical trials. JAMA Oncol Mar. 2023;30. https:\/\/doi.org\/10.1001\/jamaoncol.2023.0042","DOI":"10.1001\/jamaoncol.2023.0042"},{"issue":"5","key":"12151_CR38","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1080\/09553008914551731","volume":"56","author":"RR Weichselbaum","year":"1989","unstructured":"Weichselbaum RR, Rotmensch J, Ahmed-Swan S, Beckett MA. Radiobiological characterization of 53 human tumor cell lines. Int J Radiat Biol Nov. 1989;56(5):553\u201360. https:\/\/doi.org\/10.1080\/09553008914551731","journal-title":"Int J Radiat Biol Nov"},{"issue":"2","key":"12151_CR39","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/0360-3016(90)90539-v","volume":"19","author":"RR Weichselbaum","year":"1990","unstructured":"Weichselbaum RR, Beckett MA, Vijayakumar S, et al. Radiobiological characterization of head and neck and sarcoma cells derived from patients prior to radiotherapy. Int J Radiat Oncol Biol Phys Aug. 1990;19(2):313\u20139. https:\/\/doi.org\/10.1016\/0360-3016(90)90539-v","journal-title":"Int J Radiat Oncol Biol Phys Aug"},{"issue":"14","key":"12151_CR40","doi-asserted-by":"publisher","first-page":"4897","DOI":"10.1088\/0031-9155\/58\/14\/4897","volume":"21","author":"J Jeong","year":"2013","unstructured":"Jeong J, Shoghi KI, Deasy JO. Modelling the interplay between hypoxia and proliferation in radiotherapy tumour response. Phys Med Biol Jul. 2013;21(14):4897\u2013919. https:\/\/doi.org\/10.1088\/0031-9155\/58\/14\/4897","journal-title":"Phys Med Biol Jul"},{"issue":"11","key":"12151_CR41","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1007\/s00330-003-1957-x","volume":"13","author":"K Scheffler","year":"2003","unstructured":"Scheffler K, Lehnhardt S. Principles and applications of balanced SSFP techniques. Eur Radiol Nov. 2003;13(11):2409\u201318. https:\/\/doi.org\/10.1007\/s00330-003-1957-x","journal-title":"Eur Radiol Nov"},{"issue":"7","key":"12151_CR42","doi-asserted-by":"publisher","first-page":"815","DOI":"10.6004\/jnccn.2022.0035","volume":"20","author":"M von Mehren","year":"2022","unstructured":"von Mehren M, Kane JM, Agulnik M, et al. Soft tissue sarcoma, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw Jul. 2022;20(7):815\u201333. https:\/\/doi.org\/10.6004\/jnccn.2022.0035","journal-title":"J Natl Compr Canc Netw Jul"},{"issue":"6","key":"12151_CR43","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/nbt1306","volume":"25","author":"E Segal","year":"2007","unstructured":"Segal E, Sirlin CB, Ooi C, et al. Decoding global gene expression programs in liver cancer by noninvasive imaging. Nat Biotechnol Jun. 2007;25(6):675\u201380. https:\/\/doi.org\/10.1038\/nbt1306","journal-title":"Nat Biotechnol Jun"},{"issue":"19","key":"12151_CR44","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1056\/NEJMoa1801993","volume":"10","author":"V Kasivisvanathan","year":"2018","unstructured":"Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-Targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;10(19):1767\u201377. https:\/\/doi.org\/10.1056\/NEJMoa1801993","journal-title":"N Engl J Med"},{"issue":"33","key":"12151_CR45","doi-asserted-by":"publisher","first-page":"53362","DOI":"10.18632\/oncotarget.10523","volume":"16","author":"R Stoyanova","year":"2016","unstructured":"Stoyanova R, Pollack A, Takhar M, et al. Association of multiparametric MRI quantitative imaging features with prostate cancer gene expression in MRI-targeted prostate biopsies. Oncotarget Aug. 2016;16(33):53362\u201376. https:\/\/doi.org\/10.18632\/oncotarget.10523","journal-title":"Oncotarget Aug"},{"issue":"7","key":"12151_CR46","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1200\/JCO.19.01162","volume":"1","author":"JD Bradley","year":"2020","unstructured":"Bradley JD, Hu C, Komaki RR, et al. Long-term results of NRG oncology rtog 0617: standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable stage III non-small-cell lung cancer. J Clin Oncol Mar. 2020;1(7):706\u201314. https:\/\/doi.org\/10.1200\/JCO.19.01162","journal-title":"J Clin Oncol Mar"},{"issue":"2","key":"12151_CR47","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1148\/radiology.161.2.3763909","volume":"161","author":"D Le Bihan","year":"1986","unstructured":"Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M. MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiol Nov. 1986;161(2):401\u20137. https:\/\/doi.org\/10.1148\/radiology.161.2.3763909","journal-title":"Radiol Nov"},{"issue":"3","key":"12151_CR48","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1002\/jmri.25791","volume":"47","author":"VDA Corino","year":"2018","unstructured":"Corino VDA, Montin E, Messina A, et al. Radiomic analysis of soft tissues sarcomas can distinguish intermediate from high-grade lesions. J Magn Reson Imaging Mar. 2018;47(3):829\u201340. https:\/\/doi.org\/10.1002\/jmri.25791","journal-title":"J Magn Reson Imaging Mar"},{"key":"12151_CR49","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3389\/fonc.2019.00280","volume":"9","author":"JM Winfield","year":"2019","unstructured":"Winfield JM, Miah AB, Strauss D, et al. Utility of multi-parametric quantitative magnetic resonance imaging for characterization and radiotherapy response assessment in soft-tissue sarcomas and correlation with histopathology. Front Oncol. 2019;9:280. https:\/\/doi.org\/10.3389\/fonc.2019.00280","journal-title":"Front Oncol"},{"issue":"1","key":"12151_CR50","doi-asserted-by":"publisher","first-page":"9746","DOI":"10.1038\/s41598-017-09932-5","volume":"29","author":"YC Chang","year":"2017","unstructured":"Chang YC, Ackerstaff E, Tschudi Y, et al. Delineation of tumor habitats based on dynamic contrast enhanced MRI. Sci Rep Aug. 2017;29(1):9746. https:\/\/doi.org\/10.1038\/s41598-017-09932-5","journal-title":"Sci Rep Aug"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-024-12151-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12885-024-12151-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-024-12151-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T03:02:41Z","timestamp":1712631761000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-024-12151-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,9]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["12151"],"URL":"https:\/\/doi.org\/10.1186\/s12885-024-12151-7","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,9]]},"assertion":[{"value":"25 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study is approved by the Institutional Review Board (IRB) of the H. Lee Moffitt Cancer Center and Research Institute (Moffitt IRB #21136). Subjects consent to participate after thorough discussion by signing of the IRB approved informed consent document. If any major amendments are made, subjects will be given the opportunity to re-consent after a full disclosure by the principal investigator and the clinical research coordinator.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"This manuscript does not include identifying details, images, or videos relating to an individual person.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Full disclosures include: Dr. Eschrich and Dr. Torres-Roca are co-founders, board members, and stockholders of Cvergenx, a genomics radiation informatics company. They, along with Dr. Scott, who is a stockholder, own intellectual property involved in this trial (i.e., RSI and GARD). Dr. Scott was also supported by NIH grants R37 CA244613 and 5U54CA274513-02 (Radiation Oncology Biology Integration Network), and a Research Scholar Grant from the American Cancer Society. Drs. Arash Naghavi and Stephen Rosenberg have received research grants from ViewRay, outside the scope of the submitted work. Dr. Rosenberg has also received an honorarium, served on the Lung Research Consortium Advisory Board for ViewRay, and performed consulting for Viewray, Novocure, and GE Healthcare. Drs. Vladimir Feygelman and Kujtim Latifi have received consulting fees from ViewRay. Dr. Ahmed has research funding to the institution from Eli Lilly, Gilead, and Genentech, and serves on the advisory board of Castle Biosciences. No other author has any conflict of interest to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"437"}}