Acute Toxicity of Radiochemotherapy in Rectal Cancer Patients: A Risk Particularly for Carriers of the TGFB1 Pro25 variant

作者：Schirmer Markus Anton; Mergler Caroline Patricia Nadine; Rave Fraenk Margret; Herrmann Markus Karl; Hennies Steffen; Gaedcke Jochen; Conradi Lena Christin; Jo Peter; Beis**arth Tim; Hess Clemens Friedrich; Becker Heinz; Ghadimi Michael; Brockmoeller Juergen; Christiansen Hans; Wolff Hendrik Andreas^*

来源：International Journal of Radiation Oncology, Biology, Physics, 2012, 83(1): 149-157.

DOI：10.1016/j.ijrobp.2011.05.063

• Acute toxicity
• Polymorphism
• Radiochemotherapy
• Rectal cancer
• TGFB1

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.

• 出版日期2012-5-1