Saint David’s, United Kingdom
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Pirie A.,University of Cambridge | Guo Q.,University of Cambridge | Kraft P.,Harvard University | Canisius S.,Netherlands Cancer Institute | And 163 more authors.
Breast Cancer Research | Year: 2015

Introduction: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. Methods: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. Results: Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. Conclusions: Although no variants reached genome-wide significance (P <5 x 10-8), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels. © 2015 Pirie et al.


Verhaart R.F.,Erasmus MCCancer Institute | Rijnen Z.,Erasmus MCCancer Institute | Fortunati V.,Erasmus University Rotterdam | Verduijn G.M.,Erasmus MCCancer Institute | And 3 more authors.
Strahlentherapie und Onkologie | Year: 2014

Background and purpose: Hyperthermia treatment planning (HTP) is used in the head and neck region (H&N) for pretreatment optimization, decision making, and real-time HTP-guided adaptive application of hyperthermia. In current clinical practice, HTP is based on power-absorption predictions, but thermal dose–effect relationships advocate its extension to temperature predictions. Exploitation of temperature simulations requires region- and temperature-specific thermal tissue properties due to the strong thermoregulatory response of H&N tissues. The purpose of our work was to develop a technique for patient group-specific optimization of thermal tissue properties based on invasively measured temperatures, and to evaluate the accuracy achievable.Patients and methods: Data from 17 treated patients were used to optimize the perfusion and thermal conductivity values for the Pennes bioheat equation-based thermal model. A leave-one-out approach was applied to accurately assess the difference between measured and simulated temperature (∆T). The improvement in ∆T for optimized thermal property values was assessed by comparison with the ∆T for values from the literature, i.e., baseline and under thermal stress.Results: The optimized perfusion and conductivity values of tumor, muscle, and fat led to an improvement in simulation accuracy (∆T: 2.1 ± 1.2 °C) compared with the accuracy for baseline (∆T: 12.7 ± 11.1 °C) or thermal stress (∆T: 4.4 ± 3.5 °C) property values.Conclusion: The presented technique leads to patient group-specific temperature property values that effectively improve simulation accuracy for the challenging H&N region, thereby making simulations an elegant addition to invasive measurements. The rigorous leave-one-out assessment indicates that improvements in accuracy are required to rely only on temperature-based HTP in the clinic. © 2014, Springer-Verlag Berlin Heidelberg.


PubMed | Erasmus MCCancer Institute
Type: Journal Article | Journal: Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] | Year: 2015

Hyperthermia treatment planning (HTP) is used in the head and neck region (H&N) for pretreatment optimization, decision making, and real-time HTP-guided adaptive application of hyperthermia. In current clinical practice, HTP is based on power-absorption predictions, but thermal dose-effect relationships advocate its extension to temperature predictions. Exploitation of temperature simulations requires region- and temperature-specific thermal tissue properties due to the strong thermoregulatory response of H&N tissues. The purpose of our work was to develop a technique for patient group-specific optimization of thermal tissue properties based on invasively measured temperatures, and to evaluate the accuracy achievable.Data from 17 treated patients were used to optimize the perfusion and thermal conductivity values for the Pennes bioheat equation-based thermal model. A leave-one-out approach was applied to accurately assess the difference between measured and simulated temperature (T). The improvement in T for optimized thermal property values was assessed by comparison with the T for values from the literature, i.e., baseline and under thermal stress.The optimized perfusion and conductivity values of tumor, muscle, and fat led to an improvement in simulation accuracy (T: 2.11.2C) compared with the accuracy for baseline (T: 12.711.1C) or thermal stress (T: 4.43.5C) property values.The presented technique leads to patient group-specific temperature property values that effectively improve simulation accuracy for the challenging H&N region, thereby making simulations an elegant addition to invasive measurements. The rigorous leave-one-out assessment indicates that improvements in accuracy are required to rely only on temperature-based HTP in the clinic.

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