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Oxaliplatin-induced neuropathy after total neoadjuvant therapy for rectal cancer: dose-response relationship and impact on quality of life : cancer therapy and prevention

Oxaliplatin-based regimens are increasingly used in total neoadjuvant therapy (TNT) for locally advanced rectal cancer, frequently causing dose-limiting chemotherapy-induced peripheral neuropathy (CIPN), whose extent and impact on health-related quality of life (HrQoL) remain insufficiently characte...

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Main Authors: Wurschi, Georg (Author) , Hinz, Andreas (Author) , Schneider, Melanie (Author) , Becker, Jan-Niklas (Author) , Frerker, Bernd (Author) , Vorbach, Samuel M. (Author) , Ehret, Felix (Author) , Diefenhardt, Markus (Author) , Schunn, Fabian (Author) , von Gruben, Maria-Elena (Author) , Büttner, Marcel (Author) , Hoffmann, Elgin (Author) , Rühle, Alexander (Author) , Beier, Josephine (Author) , Ferdinandus, Simone (Author) , Trommer, Maike (Author) , Sahin, Ezgi Ceren (Author) , Hlouschek, Julian (Author) , Aninditha, Kynann (Author) , von Ohlen, Daphne Schepers (Author) , Kaufmann, Justus (Author) , Depardon, Alina (Author) , Ha, Hai Minh (Author) , Kessler, Christopher (Author) , Cieślak, Adrianna (Author) , Trommer, Simon (Author) , Fabian, Alexander (Author) , Rißner, Florian (Author) , Römer, Maximilian (Author) , Pietschmann, Klaus (Author)
Format: Article (Journal)
Language:English
Published: 2026
In: International journal of cancer
Year: 2026, Pages: 1-12
ISSN:1097-0215
DOI:10.1002/ijc.70396
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.70396
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.70396
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Author Notes:Georg W. Wurschi, Andreas Hinz, Melanie Schneider, Jan-Niklas Becker, Bernd Frerker, Samuel M. Vorbach, Felix Ehret, Markus Diefenhardt, Fabian Schunn, Maria-Elena von Gruben, Marcel Büttner, Elgin Hoffmann, Alexander Rühle, Josephine Beier, Simone Ferdinandus, Maike Trommer, Ezgi Ceren Sahin, Julian Hlouschek, Kynann Aninditha, Daphne Schepers von Ohlen, Justus Kaufmann, Alina Depardon, Hai Minh Ha, Christopher Kessler, Adrianna Cieslak, Simon Trommer, Alexander Fabian, Florian Rißner, Maximilian Römer, Klaus Pietschmann
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Summary:Oxaliplatin-based regimens are increasingly used in total neoadjuvant therapy (TNT) for locally advanced rectal cancer, frequently causing dose-limiting chemotherapy-induced peripheral neuropathy (CIPN), whose extent and impact on health-related quality of life (HrQoL) remain insufficiently characterized. The optimal duration and intensity of chemotherapy within TNT for tumor response and toxicity remain unclear. This retrospective multicenter study (DRKS00033000) assessed the dose-response relationship of CIPN with cumulative oxaliplatin dose (cOXAd) and its impact on HrQoL. A total of 227 patients (164 men) with a median age of 63 (Q1-Q3: 54-68) years, who underwent oxaliplatin-based TNT between 2015 and 2024, were analyzed. HrQoL was assessed cross-sectionally during follow-up using the EORTC QLQ-C30 and QLQ-CIPN20 questionnaires. Multivariable logistic regression was applied to evaluate the relationship between cOXAd and CIPN grade ≥2, and known-group comparisons examined differences in HrQoL scores. At follow-up, 61 patients (26.9%) experienced CIPN grade ≥2 after a median cOXAd of 758.8 mg/m2. Higher cOXAd was associated with an increased likelihood of CIPN grade ≥2 (adjusted OR 1.004, 95% CI: 1.002-1.007), corresponding to a 7.8% higher probability per additional FOLFOX cycle (+85 mg/m2 cOXAd). Patients with CIPN grade ≥2 reported lower mean QLQ-C30 Global Health Scores and Summary Scores (−13.0 and −12.4 points; Cohen's d = −0.59 and −0.68) and higher QLQ-CIPN20 Summary Scores (+23.9 points; Cohen's d = 1.65) compared to those without CIPN. These findings indicate that CIPN is a common dose-dependent toxicity of oxaliplatin-based TNT, associated with considerably reduced HrQoL and markedly increased neuropathy-related symptom burden at follow-up.
Item Description:Erstmals online veröffentlicht: 18. Februar 2026
Gesehen am 17.03.2026
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.70396

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