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Cancers 2017, 9(9), 119; doi:10.3390/cancers9090119

Predicting Organ-Specific Risk Interactions between Radiation and Chemotherapy in Secondary Cancer Survivors

Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
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Author to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Received: 6 July 2017 / Revised: 29 August 2017 / Accepted: 4 September 2017 / Published: 6 September 2017
(This article belongs to the Special Issue Radiation-Induced Carcinogenesis)
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Abstract

Several studies have shown that pediatric patients have an increased risk of developing a secondary malignancy several decades after treatment with radiotherapy and chemotherapy. In this work, we use a biologically motivated mathematical formalism to estimate the relative risks of breast, lung and thyroid cancers in childhood cancer survivors due to concurrent therapy regimen. This model specifically includes possible organ-specific interaction between radiotherapy and chemotherapy. The model predicts relative risks for developing secondary cancers after chemotherapy in breast, lung and thyroid tissues, and compared with the epidemiological data. For a concurrent therapy protocol, our model predicted relative risks of 3.2, 9.3, 4.5 as compared to the clinical data, i.e., 1.4, 8.0, 2.3 for secondary breast, lung and thyroid cancer risks, respectively. The extracted chemotherapy mutation induction rates for breast, lung and thyroid are 10−9, 0.5 × 10−6, 0.9 × 10−7 respectively. We found that there exists no synergistic interaction between radiation and chemotherapy for neither mutation induction nor cell kill in lung tissue, but there is an interaction in cell kill for the breast and thyroid organs. These findings help understand the risks of current clinical protocols and might provide rational guidance to develop future multi-modality treatment protocols to minimize secondary cancer risks. View Full-Text
Keywords: secondary malignancies; relative risks; chemotherapy-radiotherapy interaction; synergy secondary malignancies; relative risks; chemotherapy-radiotherapy interaction; synergy
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Manem, V.S.; Grassberger, C.; Paganetti, H. Predicting Organ-Specific Risk Interactions between Radiation and Chemotherapy in Secondary Cancer Survivors. Cancers 2017, 9, 119.

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