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Cited by 27Radiation Therapy and DosimetryAdvanced Radiotherapy TechniquesEffects of Radiation Exposure

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Workshop Report for Cancer Research: Defining the Shades of Gy: Utilizing the Biological Consequences of Radiotherapy in the Development of New Treatment Approaches—Meeting Viewpoint

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Ahmed, Mansoor M., Coleman, C. Norman, Mendonca, Marc, Bentzen, Soren, Vikram, Bhadrasain, Seltzer, Stephen M., Goodhead, Dudley, Obcemea, Ceferino, Mohan, Radhe, Prise, Kevin M., Capala, Jacek, Citrin, Deborah, Kao, Gary, Aryankalayil, Molykutty, Eke, Iris, Buchsbaum, Jeffrey C., Prasanna, Pataje G.S., Liu, Fei-Fei, Le, Quynh-Thu, Teicher, Beverly, Kirsch, David G., Smart, DeeDee, Tepper, Joel, Formenti, Silvia, Haas-Kogan, Daphne, Raben, David, Mitchell, James·2018·Cancer Research
DOI 10.1158/0008-5472.can-17-3760PMC PMC6825324
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Abstract

The ability to physically target radiotherapy using image-guidance is continually improving with photons and particle therapy that include protons and heavier ions such as carbon. The unit of dose deposited is the gray (Gy); however, particle therapies produce different patterns of ionizations, and there is evidence that the biological effects of radiation depend on dose size, schedule, and type of radiation. This National Cancer Institute (NCI)–sponsored workshop addressed the potential of using radiation-induced biological perturbations in addition to physical dose, Gy, as a transformational approach to quantifying radiation.New directions included: Controversies to: Current challenges in: Altogether, these approaches can facilitate the incorporation of radiation technology and biology into treatment strategies for personalized medicine, including molecular and immune-targeted therapies.The National Cancer Institute's Radiation Research Program hosted the workshop “Shades of Gy (gray): Biological Consequences of Radiation Therapy” on September 11–12, 2017 (agenda; https://dctd.cancer.gov/NewsEvents/biological_consequences_of_radiation_therapy_workshop_agenda.pdf). The focus is a novel concept of defining radiation dose both in energy deposition (Gy) and biologically meaningful perturbations in the tumor and normal tissue. This is intended to broaden the application of radiotherapy in precision medicine. The workshop's long-term goal is to build from a combination of well-known reliable models, new cancer biology, and clinical experience to develop new paradigms for clinical cancer care.Norman Coleman (NCI) opened the workshop stressing the potential use of radiation as a drug with radiation dose described in appropriate units similar to drug therapy such as pharmacokinetics and pharmacodynamics. This requires returning to fundamental processes including the mechanism(s) of radiation damage, biophysics, stress and adaptive responses, and tumor microenvironment effects under the umbrella of “Accurate, Precision Radiation Medicine.” The importance of physical dose remains paramount. Emphasizing ambiguous terminology in use is that the unit “gray” used in biodosimetry is actually a biological change (a “biodose”) and not the physical dose. The new paradigm for biological dose in addition to physical dose uses modern molecular endpoints that can improve cancer care.Several challenging issues on current radiation “Dose-Effect Models” were discussed in Session I. Soren Bentzen (University of Maryland, Baltimore, MD) stressed the importance of a normalized dose-response gradient that would allow the tumor control probability/normal tissue complication probability percentage versus total radiation dose when given as 1.8 Gy per fraction to be predicted for radiation plus chemotherapy or immunotherapy and all three treatments combined. He suggested the use of the linear quadratic (LQ) EQD2α/β to predict actual clinical outcome in patients with head and neck squamous cell cancer and to compare the LQ model with treatment biomarkers ranging from biological to imaging markers that can provide integral effects of dose and time for tumor and normal tissue. This approach could provide lead time for changes in treatment, thereby improving both cancer treatment outcomes and quality of life. Dr. Martin Brown (Stanford University, Stanford, CA) supported the use of the LQ model and pointed out key exceptions to their use, such as the role of the tumor stroma and tumor vasculature in determining tumor radiation sensitivity, for which the endpoint TCD50 (dose to control 50% of the murine tumors irradiated) should be adopted. He asserted that radiosensitivity of tumors is only relevant to tumor control if the radiation-damaged vasculature is restored by bone marrow–derived cells (1). Blocking the SDF-1/CXCR4 pathway would block the bone marrow–derived cell's recruitment and increase tumor control, with the added benefit of protecting normal tissues. Philip Lambin (Maastricht University, Maastricht, the Netherlands) discussed that the LQ models should be revisited to understand whether low or high α/β-ratio tumors can be explained with modern molecular biological endpoints, and he also suggested to study whether a tumor is slowly or rapidly proliferating. He proposed that to help predict treatment response and overall survival, quantitative imaging radiomics (with three-dimensional dose delivery and four-dimensional radiomics) would enable the measure of proliferation signatures and other tumor parameters that would help link classical α/β concepts with relevant biology such as DNA repair, proliferation, and reoxygenation.That basic biophysics provides a great deal of information on radiation effects and also supports the need for biological assessment to enhance physical dose was discussed in Session II. The track structure patterns of ionization and excitation from various radiation particle types and their secondary charged pa

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  • There is limited understanding of track structure patterns of ionization and excitation resulting from various radiation types and secondary charged particles in complex biologic media, particularly at the end of their range where energy transfer is most pronounced.

    “The de fi ciencies start with limited understanding of track structure patterns of ionization and excitation resulting from various radiation types and the secondary charged particles in complex biologic media, particularly at the end of their range, where the energy transfer is most pronounced ( 108 ).”

    From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [108]

    The REPORT says track-structure patterns in complex biological media are unclear for various radiation particles and their secondary charged particles. It places the greatest energy transfer at low incident energies, however, rather than explicitly at the end of the particles’ range. (LLM, conf=0.85)

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Authors
Ahmed, M. M., Coleman, C. N., Mendonca, M., Bentzen, S., Vikram, B., Seltzer, S. M., Goodhead, D., Obcemea, C., Mohan, R., Prise, K. M., Capala, J., Citrin, D., Kao, G., Aryankalayil, M., Eke, I., Buchsbaum, J. C., Prasanna, P. G. S., Liu, F.-F., Le, Q.-T., Teicher, B., Kirsch, D. G., Smart, D., Tepper, J., Formenti, S., Haas-Kogan, D., Raben, D., & Mitchell, J.
Affiliations
  • National Cancer Institute (US)
  • Indiana University Indianapolis (US)
  • 4Department of Epidemiology, University of Maryland School of Medicine, Baltimore, Maryland.
  • National Institute of Standards and Technology (US)
  • Medical Research Council (GB)
  • The University of Texas MD Anderson Cancer Center (US)
  • Queen's University Belfast (GB)
  • University of Pennsylvania (US)
  • University of Toronto (CA)
  • Stanford Medicine (US)
  • Duke University (US)
  • 2Radiation Oncology Branch, Centre for Cancer Research, National Cancer Institute, Bethesda, Maryland.
  • University of North Carolina at Chapel Hill (US)
  • Weill Cornell Medicine (US)
  • Harvard University (US)
  • University of Colorado Cancer Center (US)
Corresponding author
  • Ahmed, Mansoor M.
  • Coleman, C. Norman
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2018-04-30
Volume
78
Issue
9
Pages
2166-2170
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-17-3760
PMC
PMC6825324
OpenAlex
W2802492698
Cited by
27
References
9
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 1
FWCI
2.83
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Purdue University Indianapolis (Indiana University) (submittedVersion)
Funders
  • National Institutes of Health (Z99 CA999999)
  • National Cancer Institute (Z01BC010850)
Topics
  • Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
  • Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
radiotherapy, radiation dose, biological dose, biological dosimetry, particle therapy, proton therapy, carbon ion radiotherapy, dose-response modeling, tumor control probability, normal tissue complication probability, radiation-induced DNA damage, adaptive radiation response, tumor microenvironment, radiation-induced immune response, molecular endpoints, image-guided radiotherapy, precision oncology
MeSH terms
Humans, Neoplasms, Radiotherapy, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted

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