Advances in Radiation Therapy. Группа авторов
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89van den Heuvel MM, et al: NHS-IL2 combined with radiotherapy: preclinical rationale and phase Ib trial results in metastatic non-small cell lung cancer following first-line chemotherapy. J Transl Med 2015;13:32.
90Schilbach K, et al: Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation. Oncoimmunology 2015;4:e1014760.
91Paoloni M, et al: Defining the pharmacodynamic profile and therapeutic index of NHS-IL12 immunocytokine in dogs with malignant melanoma. PLoS One 2015;10:e0129954.
92Eckert F, et al: Enhanced binding of necrosis-targeting immunocytokine NHS-IL12 after local tumour irradiation in murine xenograft models. Cancer Immunol Immunother 2016;65:1003–1013.
93Kang J, Demaria S, Formenti S: Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer 2016;4:51.
94Kulzer L, et al: Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells. J Immunotoxicol 2014;11:328–336.
95Gandhi SJ, et al: Awakening the immune system with radiation: optimal dose and fractionation. Cancer Lett 2015;368:185–190.
96Golden EB, et al: An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res 2013;1:365–372.
97Eckert F, Jelas I, Oehme M, Huber SM, Sonntag K, Welker C, Gillies SD, Strittmatter W, Zips D, Handgretinger R, Schilbach K: Tumor-targeted IL-12 combined with local irradiation leads to systemic tumor control via abscopal effects in vivo. Oncoimmunology 2017;6:e1323161.
Franziska Eckert, MD
Department of Radiation Oncology, Eberhard Karls University of Tübingen
Hoppe-Seyler-Strasse 3
DE–2076 Tübingen (Germany)
E-Mail [email protected]
Guckenberger M, Combs SE, Zips D (eds): Advances in Radiotherapy.
Prog Tumor Res. Basel, Karger, 2018, vol 44, pp 11–24 (DOI: 10.1159/000486985)
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Imageable Biomarkers for Radiotherapy Response
W. Woliner-van der Weg · P.N. Span · P.M. Braam · J. Bussink
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
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Abstract
Ideally, each patient with a malignancy who is eligible for radiation therapy should receive the most tumoricidal form of this this treatment with the lowest possible risk of toxicity. To overcome radiotherapy resistance, some patients would benefit from a more aggressive approach. This could be treatment intensification, for example by acceleration of the treatment to prevent the negative effects of accelerated tumor cell proliferation, or by boosting certain areas to specifically address intrinsic radioresistance, or a combination of radiotherapy with, for example, a hypoxic cell sensitizer or chemotherapy to reduce the radiotherapy resistance caused by hypoxia. For some patients, one of these approaches can be beneficial but for others could lead to unacceptable side effects. Therefore, it is highly desirable to make the selection upfront. The use of imageable biomarkers could be the key to a more patient-tailored treatment. Different biomarkers for hypoxia and proliferation that could be valuable for radiotherapy are discussed here, including their mechanism, the imaging procedure, quantification, and the value of the results.
© 2018 S. Karger AG, Basel
In recent decades, technological developments in treatment planning and image-guided radiotherapy have led to increased precision of radiation treatments. To make the next big step, a more patient-customized treatment is anticipated, with radiation doses as high as needed for a tumoricidal effect, and as low as possible to minimize the risk of healthy tissue toxicity. To achieve this goal, the biological effectiveness can be improved for instance by treatment acceleration, i.e., reducing the overall treatment time, or by combining radiotherapy with a radiosensitizer. Selecting the most appropriate treatment for a patient requires knowledge about the potential effect of different types of treatment on an individual level. Individual biological information, obtained by the imaging of biomarkers, could be the key to move from population-based to patient-tailored treatments [1].
There is no clear definition of “biomarkers,” but, in general, the term means “objective, quantifiable characteristics of a biological process that can be measured accurately and is reproducible” [2]. We use the term biomarker for quantifiable biological characteristics that can predict treatment efficacy, and, although a broad range of biomarkers can be included, e.g., patient weight, or pulmonary function, we confine ourselves to noninvasively imageable biomarkers that give an indication with respect to the biology of the tumor microenvironment.
In contrast to biopsies and characteristics derived from blood samples, imaging provides 3-dimensional (3D) information about tumor characteristics. At the cost of a relatively low resolution – that is relative to the microscopic or even molecular level at which resistance takes place – information is obtained for the whole tumor. In general, imaging can be performed repetitively and, apart from the additional radiation burden or administration of contrast fluid or radioactive compounds, it is noninvasive. Another advantage of imaging is its already defined role in diagnosis and patient management [1].
Since the early 1980s, when computed tomography (CT) imaging became widely used, tumor size has been the best-known imaging biomarker. Volumetric measurements also remain the basis for the evaluation of tumor response according to the RECIST-criteria. However, size is a biomarker reflecting the final part of a biological response, i.e., for a size reduction tumor cells must have died and been removed from the tissue. Thus, it is a “late” marker, delaying evaluation up to 12 weeks following radiotherapy since the principle of cell kill resulting from radiotherapy is predominantly caused by mitotic catastrophe. Receptor expression, proliferation, metabolism, vascularization, diffusion, and perfusion change can be detected earlier than a difference in size [3] (Fig. 1 a, b). Therefore, molecular and functional