Combining precision radiotherapy with molecular targeting and immunomodulatory agents: a guideline by the American Society for Radiation Oncology

Bristow, Robert G.; Alexander, Brian M.; Baumann, Michaël; Bratman, Scott V.; Brown, J. Martin; Camphausen, Kevin; Choyke, Peter L.; Citrin, Deborah E.; Contessa, Joseph N.; Dicker, Adam P.; Kirsch, David G.; Krause, Mechthild; Le, Quynh Thu; Milosevic, Michael; Morris, Zachary S.; Sarkaria, Jann N.; Sondel, Paul M.; Tran, Phuoc T.; Wilson, George D.; Willers, Henning; Wong, Rebecca; Harari, Paul M.

doi:10.1016/s1470-2045(18)30096-2

Cited by 101 publications

(80 citation statements)

References 87 publications

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“…One example of such therapy is the use of epidermal growth factor receptor (EGFR) inhibitors for HNSCC. Other potential target pathways include PI3K/AKT/mTOR, VEGF, and cell‐cycle checkpoints . The current study indicates different responses in the above pathways to PRT vs XRT, thereby providing information that may be valuable for optimizing combinations of targeted therapies with PRT or XRT to improve HNSCC treatment outcomes.…”

Section: Discussionmentioning

confidence: 72%

Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy

et al. 2019

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Background: Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear. Methods: Proteomics analyses of protein expression profiles by reverse-phase protein arrays were done for two human papillomavirus [HPV]-negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested.Results: Compared with PRT, XRT tended to induce lower expression of DNA damage repair-and cell cycle arrest-related proteins and higher expression of cell survival-and proliferation-related proteins. Conclusions: Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT. K E Y W O R D Shead & neck cancer, photon radiotherapy, proton radiotherapy, radiation-induced molecular changes, reverse-phase protein array (RPPA)Portions of this work were presented in poster form at the annual Global Academic Programs

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Section: Discussionmentioning

confidence: 72%

Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy

et al. 2019

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“…This also extends to predictive insights into the response of tumors to other therapeutic agents that may be administered in combination with radiotherapy. Although molecular diagnostic tools are making their way into clinical practice in other settings, the lack of equivalent molecular indicators in the field of radiobiology has impeded translation in this domain (Baumann et al, 2016;Bibault et al, 2013;Bristow et al, 2018) .…”

Section: Discussionmentioning

confidence: 99%

“…However, despite decades of research there remain no clinically utilized radiosensitivity biomarkers that have been discovered from cell culture radiogenomic studies. There are many reasons for this, including the need for clonogenic assays when measuring intrinsic radiosensitivity in vitro (Puck and Marcus, 1956) , which are cumbersome and are not amenable to large screens or radiogenomic studies (Bristow et al, 2018;Yard et al, 2015) . Furthermore, radiosensitivity varies with dose in a complex and highly individual manner, rendering measurements at multiple dose-levels a necessity.…”

Section: Introductionmentioning

confidence: 99%

Modeling cellular response in large-scale radiogenomic databases to advance precision radiotherapy

Manem¹,

Lambie²,

Смирнов³

et al. 2018

Preprint

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Radiotherapy is integral to the care of a majority of cancer patients. Despite differences in tumor responses to radiation (radioresponse), dose prescriptions are not currently tailored to individual patients. Recent large-scale cancer cell line databases hold the promise of unravelling the complex molecular arrangements underlying cellular response to radiation, which is critical to novel predictive biomarker discovery. Here, we present RadioGx, a computational platform for integrative analyses of radioresponse using radiogenomic databases. We first used RadioGx to investigate the robustness of radioresponse assays and indicators. We then combined radioresponse and genome-wide molecular data with established radiobiological models to predict molecular pathways that are relevant for individual tissue types and conditions. We also applied RadioGx to pharmacogenomic data to identify several classes of drugs whose effects correlate with radioresponse. RadioGx provides a unique computational toolbox to advance preclinical research for radiation oncology and precision medicine.

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“…Precision radiotherapy is the associated field that may receive immediate benefits from the availability of imaging-integrated diagnostic tools useful for therapy selection and response assessment (37). Method standardization is a requirement for applications across multiple centers and in prospective clinical trials so to establish the essential role of novel imaging biomarkers.…”

Section: Precision In Radiomicsmentioning

confidence: 99%

Role of Complex Networks for Integrating Medical Images and Radiomic Features of Intracranial Ependymoma Patients in Response to Proton Radiotherapy

et al. 2020

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Human cancers exhibit phenotypic diversity that medical imaging can precisely and non-invasively detect. Multiple factors underlying innovations and progresses in the medical imaging field exert diagnostic and therapeutic impacts. The emerging field of radiomics has shown unprecedented ability to use imaging information in guiding clinical decisions. To achieve clinical assessment that exploits radiomic knowledge sources, integration between diverse data types is required. A current gap is the accuracy with which radiomics aligns with clinical endpoints. We propose a novel methodological approach that synergizes data volumes (images), tissue-contextualized information breadth, and network-driven resolution depth. Following the Precision Medicine paradigm, disease monitoring and prognostic assessment are tackled at the individual level by examining medical images acquired from two patients affected by intracranial ependymoma (with and without relapse). The challenge of spatially characterizing intratumor heterogeneity is tackled by a network approach that presents two main advantages: (a) Increased detection in the image domain power from high spatial resolution, (b) Superior accuracy in generating hypotheses underlying clinical decisions.

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Combining precision radiotherapy with molecular targeting and immunomodulatory agents: a guideline by the American Society for Radiation Oncology

Cited by 101 publications

References 87 publications

Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy

Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy

Modeling cellular response in large-scale radiogenomic databases to advance precision radiotherapy

Role of Complex Networks for Integrating Medical Images and Radiomic Features of Intracranial Ependymoma Patients in Response to Proton Radiotherapy

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