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Sawyer M.B.,Cross Cancer Institute | Sawyer M.B.,University of Alberta | Sawyer M.B.,11560 University Avenue Northwest | Pituskin E.,Cross Cancer Institute | And 29 more authors.
Clinical Breast Cancer | Year: 2016

Background Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in single nucleotide polymorphisms (SNPs). We studied whether the -161 C > T germline SNP in UGT2B7 was related to epirubicin metabolism and whether differences exist in the toxicity and efficacy of epirubicin-based chemotherapy among patients who were TT homozygotes, CT heterozygotes, and CC homozygotes. Patients and Methods A total of 132 women with non-metastatic breast cancer receiving FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) were prospectively enrolled. Toxicity was assessed in cycle 1 using the National Cancer Institute Common Toxicity Criteria, version 2.0. Results The sequence at -161 was studied in 132 subjects; 37 were TT homozygotes, 63 were CT heterozygotes, 26 were CC homozygotes, and 6 could not be genotyped. The CC genotype patients had decreased epirubicin clearance (median, 103.3 L/hr) compared with the CT/TT genotype patients (median, 134.0 L/hr; P =.002). The CC homozygous patients had an increased risk of grade 3 to 4 leukopenia compared with the TT homozygotes or heterozygotes (P =.038 and P =.032, respectively). TT homozygotes or heterozygotes had an increased risk of early recurrence (P =.039; χ2 test). Conclusion The results of the present prospective pharmacogenetic study suggest that the UGT2B7 -161 C > T SNP correlate with drug metabolism, toxicity, and efficacy in patients receiving epirubicin chemotherapy. Further studies of this UGT2B7 SNP as a predictor of epirubicin toxicity and efficacy are warranted. © 2016 Elsevier Inc.

St. Aubin J.,11560 University Avenue Northwest | Keyvanloo A.,11560 University Avenue Northwest | Vassiliev O.,Tom Baker Cancer Center | Fallone B.G.,11560 University Avenue Northwest
Medical Physics | Year: 2015

Purpose: Accurate radiotherapy dose calculation algorithms are essential to any successful radiotherapy program, considering the high level of dose conformity and modulation in many of todays treatment plans. As technology continues to progress, such as is the case with novel MRI-guided radiotherapy systems, the necessity for dose calculation algorithms to accurately predict delivered dose in increasingly challenging scenarios is vital. To this end, a novel deterministic solution has been developed to the first order linear Boltzmann transport equation which accurately calculates x-ray based radiotherapy doses in the presence of magnetic fields. Methods: The deterministic formalism discussed here with the inclusion of magnetic fields is outlined mathematically using a discrete ordinates angular discretization in an attempt to leverage existing deterministic codes. It is compared against the EGSnrc Monte Carlo code, utilizing the emf-macros addition which calculates the effects of electromagnetic fields. This comparison is performed in an inhomogeneous phantom that was designed to present a challenging calculation for deterministic calculations in 0, 0.6, and 3 T magnetic fields oriented parallel and perpendicular to the radiation beam. The accuracy of the formalism discussed here against Monte Carlo was evaluated with a gamma comparison using a standard 2%/2 mm and a more stringent 1%/1 mm criterion for a standard reference 10±10 cm2 field as well as a smaller 2±2 cm2 field. Results: Greater than 99.8% (94.8%) of all points analyzed passed a 2%/2 mm (1%/1 mm) gamma criterion for all magnetic field strengths and orientations investigated. All dosimetric changes resulting from the inclusion of magnetic fields were accurately calculated using the deterministic formalism. However, despite the algorithms high degree of accuracy, it is noticed that this formalism was not unconditionally stable using a discrete ordinate angular discretization. Conclusions: The feasibility of including magnetic field effects in a deterministic solution to the first order linear Boltzmann transport equation is shown. The results show a high degree of accuracy when compared against Monte Carlo calculations in all magnetic field strengths and orientations tested. © 2015 American Association of Physicists in Medicine.

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