Potential Role of Single Nucleotide Polymorphisms of XRCC1, XRCC3, and RAD51 in Predicting Acute Toxicity in Rectal Cancer Patients Treated With Preoperative Radiochemotherapy.

OBJECTIVES: To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy. METHODS: Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology. RESULTS: The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group. CONCLUSIONS: Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.

Integral dose and radiation-induced secondary malignancies: comparison between stereotactic body radiation therapy and three-dimensional conformal radiotherapy.

The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID) in stereotactic body radiation therapy (SBRT) with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT), estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/ß = 10 Gy for tumor tissue and imposing the same biological effective dose (BED) on the target (BED = 76 Gy(10)). Total NTIDs for both techniques was calculated considering α/ß = 3 Gy for healthy tissue. Excess absolute cancer risk (EAR) was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data (p ≤ 0.05). Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT (p = 0.002), secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT (p = 0.001). This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.