1. Acute toxicity of radiochemotherapy in rectal cancer patients: a risk particularly for carriers of the TGFB1 Pro25 variant.
- Author
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Schirmer MA, Mergler CP, Rave-Fränk M, Herrmann MK, Hennies S, Gaedcke J, Conradi LC, Jo P, Beissbarth T, Hess CF, Becker H, Ghadimi M, Brockmöller J, Christiansen H, and Wolff HA
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemoradiotherapy methods, Cohort Studies, Cystitis pathology, Dermatitis pathology, Enteritis pathology, Female, Fluorouracil therapeutic use, Humans, Intestine, Small radiation effects, Male, Middle Aged, Neoadjuvant Therapy adverse effects, Neoadjuvant Therapy methods, Neoplasm Staging, Organoplatinum Compounds administration & dosage, Organoplatinum Compounds adverse effects, Organs at Risk radiation effects, Proctitis pathology, Pyridines administration & dosage, Pyridines adverse effects, Radiation Injuries complications, Radiation Injuries pathology, Radiotherapy Dosage, Rectal Neoplasms pathology, Regression Analysis, Urinary Bladder radiation effects, Chemoradiotherapy adverse effects, Polymorphism, Single Nucleotide genetics, Quality of Life, Radiation Injuries genetics, Rectal Neoplasms genetics, Rectal Neoplasms therapy, Transforming Growth Factor beta1 genetics
- Abstract
Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions., Methods and Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade ≥2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped., Results: In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT., Conclusion: The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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