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New directions included:

Radiation effects on the cell, tumor, and normal tissue can be exploited so that schedules beyond the conventional and still useful 2 Gy fraction can be utilized. Different radiation dose, type, and schedule (multifraction) can potentially act “as a drug,” with unique and exploitable mechanism of action. This concept pertains to radiation alone and with molecular-targeted therapy and immunotherapy.

Utilizing biomarkers of radiotherapy in precision medicine to assess both treatment efficacy and normal tissue damage, potentially including organ-specific biomarkers of tissue damage.

Controversies to:

Defining the most resistant subpopulation within a tumor, particularly at higher fractional doses. Ameliorating resistance could include targeting tumor cells and/or the vasculature.

Rethinking the target and extent of tumor volume irradiated as potential new strategies for enhancing curative benefit and avoiding normal tissue toxicity with preservation of organ function.

Current challenges in:

Defining radiation parameters for selected target induction, such as a survival pathway, tumor antigen, enhanced immune response, or change in vasculature.

Determining the duration in the change of radiation-inducible phenotype to be exploited.

Eventually modifying the treatment from the “time-honored” approaches.

Author information

Ahmed MM#1, Coleman CN#1,2, Mendonca M3, Bentzen S4, Vikram B5, Seltzer SM6, Goodhead D7, Obcemea C5, Mohan R8, Prise KM9, Capala J5, Citrin D2, Kao G10, Aryankalayil M2, Eke I2, Buchsbaum JC5, Prasanna PGS5, Liu FF11, Le QT12, Teicher B13, Kirsch DG14, Smart D2, Tepper J15, Formenti S16, Haas-Kogan D17, Raben D18, Mitchell J19.
1
Radiation Research Program, National Cancer Institute, Bethesda, Maryland. ccoleman@mail.nih.gov ahmedmm@mail.nih.gov.
2
Radiation Oncology Branch, Centre for Cancer Research, National Cancer Institute, Bethesda, Maryland.
3
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.
4
Department of Epidemiology, University of Maryland School of Medicine, Baltimore, Maryland.
5
Radiation Research Program, National Cancer Institute, Bethesda, Maryland.
6
Radiation Physics Division, NIST, Gaithersburg, Maryland.
7
Medical Research Council, Harwell, Didcot, United Kingdom.
8
Division of Radiation Oncology, Department of Radiation Physics, The University of Texas, MD Anderson Cancer Centre, Houston, Texas.
9
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom.
10
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
11
Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, Canada.
12
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
13
Development Therapeutics Program, National Cancer Institute, Bethesda, Maryland.
14
Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina.
15
Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
16
Department of Radiation Oncology, Weill Cornell Medical College, New York City, New York.
17
Department of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts.
18
Department of Radiation Oncology; University of Colorado Cancer Center, Aurora, Colorado.
19
Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland.
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Contributed equally