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

Venkata Manem,Harald Paganetti,Clemens Grassberger

doi:10.3390/cancers9090119

Venkata Manem, Harald Paganetti + Show 1 more

Open Access

https://doi.org/10.3390/cancers9090119

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Journal: Cancers	Publication Date: Sep 6, 2017
Citations: 5	License type: CC BY 4.0

Affiliation: Massachusetts General Hospital, Harvard University

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.

Highlights

One of the success stories in the treatment of cancer in the past decades is the improvement in survival rates for childhood cancers: 5-year overall survival for all childhood cancers combined has increased from 58% in the late 1970s to 83% in the 2000s [1]
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
Our aim in this study is to develop a biologically motivated mathematical formalism to estimate the secondary cancer risks for lung, breast and thyroid tissue stemming from combined chemo-radiation treatments, and estimate the corresponding relative risks

Summary

Introduction

One of the success stories in the treatment of cancer in the past decades is the improvement in survival rates for childhood cancers: 5-year overall survival for all childhood cancers combined has increased from 58% in the late 1970s to 83% in the 2000s [1]. Late toxicities remain a major concern in childhood cancer survivors. Several case control and epidemiological studies have suggested one of the causes of mortality in childhood cancer survivors are secondary neoplasms [2,3,4,5]. The two modes of treatments, radiation therapy as well as chemotherapy, can induce secondary cancer [10,11,12,13,14,15,16,17]. The first evidence of radiation-induced malignancies came from the atomic bomb survivor studies [10]. The impact of various radiotherapy techniques such as three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT) or proton therapy on secondary cancer induction is discussed in [11,12,13]

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