Weekly measurement of HMGB1 during neoadjuvant chemoradiotherapy in rectal cancer patients: correlations with MRI response and ctDNA
References
- Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, et al. NCCN guidelines insights: Rectal cancer, Version 6.2020. J Natl Compr Canc Netw 2020; 18: 806-15. doi: 10.6004/jʼnccn.2020.0032
- Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 2012; 30: 1926-33. doi: 10.1200/JCO.2011.40.1836
- Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22: 702-15. doi: 10.1016/S1470-2045(21)00079-6
- Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22: 29-42. doi: 10.1016/S1470-2045(20)30555-6
- Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol 2022; 40: 2546-56. doi: 10.1200/JCO.22.00032
- Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010; 11: 835-44. doi: 10.1016/S1470-2045(10)70172-8
- Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, et al. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 2003; 22: 5551-60. doi: 10.1093/emboj/cdg516
- Kwak MS, Kim HS, Lee B, Kim YH, Son M, Shin JS. Immunological significance of HMGB1 post-translational modification and redox biology. Front Immunol 2020; 11: 1189. doi: 10.1038/s12276-022-00736-w
- Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med 2022; 54: 91-102. doi: 10.1038/s12276-022-00736-w
- Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology 2014; 3: e955691. doi: 10.4161/21624011.2014.955691
- Liao Y, Liu S, Fu S, Wu J. HMGB1 in radiotherapy: a two headed signal regulating tumor radiosensitivity and immunity. Onco Targets Ther 2020; 13: 6859-71. doi: 10.2147/OTT.S253772
- Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 2007; 13: 1050-9. doi: 10.1038/nm1622
- Chung HW, Lim JB, Jang S, Lee KJ, Park KH, Song SY. Serum high mobility group box-1 is a powerful diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma. Cancer Sci 2012; 103: 1714-21. doi: 10.1111/j.1349-7006.2012.02358.x
- Qiu G, Li Y, Liu Z, Wang M, Ge J, Bai X. Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous cell carcinoma. Med Oncol 2014; 31: 316. doi: 10.1007/s12032-014-0316-x
- Tabata C, Shibata E, Tabata R, Kanemura S, Mikami K, Nogi Y, et al. Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma. BMC Cancer 2013; 13: 205. doi: 10.1186/1471-2407-13-205
- Holz A, Paul B, Zapf A, Pantel K, Joosse SA. Circulating tumor DNA as prognostic marker in patients with metastatic colorectal cancer undergoing systemic therapy: a systematic review and meta-analysis. Cancer Treat Rev 2025; 139: 102999. doi: 10.1016/j.ctrv.2025.102999
- Bartolomucci A, Nobrega M, Ferrier T, Dickinson K, Kaorey N, Nadeau A, et al. Circulating tumor DNA to monitor treatment response in solid tumors and advance precision oncology. NPJ Precis Oncol 2025; 9: 84. doi: 10.1038/s41698-025-00876-y
- Henriksen TV, Demuth C, Frydendahl A, Nors J, Nesic M, Rasmussen MH, et al. Unraveling the potential clinical utility of circulating tumor DNA detection in colorectal cancer-evaluation in a nationwide Danish cohort. Ann Oncol 2024; 35: 229-39. doi: 10.1016/j.annonc.2023.11.009
- Clasen K, Gani C, Schuetz L, Clasen S, Ballin N, Bonzheim I, et al. Dynamics of cell-free tumor DNA correlate with early MRI response during chemoradiotherapy in rectal cancer. Radiat Oncol 2024; 19: 153. doi: 10.1186/s13014-024-02540-4
- Clasen K, Ballin N, Schutz L, Bonzheim I, Kelemen O, Orth M, et al. Tumor sequencing before and after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: Genetic tumor characterization and clinical outcome. Clin Transl Radiat Oncol 2025; 50: 100894. doi: 10.1016/j.ctro.2024.100894
- Clasen K, Welz S, Faltin H, Zips D, Eckert F. Dynamics of HMBG1 (High Mobility Group Box 1) during radiochemotherapy correlate with outcome of HNSCC patients. Strahlenther Onkol 2022; 198: 194-200. doi: 10.1007/s00066-021-01860-8
- Suzuki Y, Mimura K, Yoshimoto Y, Watanabe M, Ohkubo Y, Izawa S, et al. Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res 2012; 72: 3967-76. doi: 10.1158/0008-5472.CAN-12-0851
- Zandarashvili L, Sahu D, Lee K, Lee YS, Singh P, Rajarathnam K, et al. Realtime kinetics of high-mobility group box 1 (HMGB1) oxidation in extracellular fluids studied by in situ protein NMR spectroscopy. J Biol Chem 2013; 288: 11621-7. doi: 10.1074/jbc.M113.449942
- Chung HW, Lee SG, Kim H, Hong DJ, Chung JB, Stroncek D, et al. Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer. J Transl Med 2009; 7: 38. doi: 10.1186/1479-5876-7-38
- Liikanen I, Koski A, Merisalo-Soikkeli M, Hemminki O, Oksanen M, Kairemo K, et al. Serum HMGB1 is a predictive and prognostic biomarker for oncolytic immunotherapy. Oncoimmunology 2015; 4: e989771. doi: 10.4161/2162402X.2014.989771
- Masuda K, Ono A, Aikata H, Kawaoka T, Nelson Hayes C, Teraoka Y, et al. Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy. J Gastroenterol 2018; 53: 107-18. doi: 10.1007/s00535-017-1348-8
Language: English
Page range: 294 - 300
Submitted on: Feb 24, 2026
Accepted on: May 7, 2026
Published on: Jun 26, 2026
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Keywords:
Related subjects:
© 2026 Franziska Eckert, Vlatko Potkrajcic, Stephan Clasen, Elgin Hoffmann, Julian Taugner, Olga Seibel-Kelemen, Christopher Schroeder, Maximilian Niyazi, Kerstin Clasen, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.