Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

Mohamad, Osama; Sishc, Brock J.; Saha, Janapriya; Pompoš, A.; Rahimi, Asal; Story, Michael D.; Davis, Anthony J.; Kim, D. W.Nathan

doi:10.3390/cancers9060066

Cited by 143 publications

(146 citation statements)

References 199 publications

(210 reference statements)

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“…The subsequent processing of potentially lethal DSBs into chromosome aberrations is a major mechanisms of action underlying the reproductive cell death of tumor cells as well as cells in at-risk organs and tissues in radiation therapy. Corrections for LET-dependent spatial variations in particle RBE, especially near the distal edge of a spread-out Bragg peak, are essential in carbon ion radiation therapy [71][72][73]. A peak RBE DSB value of 2.6 to 3.4 for high-LET carbon ions, as illustrated in Figure 3, is generally consistent with the RBE for fast neutron [74] and carbon ion [71] therapy clinical end points.…”

Section: Discussionmentioning

confidence: 52%

“…Corrections for LET-dependent spatial variations in particle RBE, especially near the distal edge of a spread-out Bragg peak, are essential in carbon ion radiation therapy [71][72][73]. A peak RBE DSB value of 2.6 to 3.4 for high-LET carbon ions, as illustrated in Figure 3, is generally consistent with the RBE for fast neutron [74] and carbon ion [71] therapy clinical end points. Detailed Monte Carlo modeling of the University of Washington's clinical neutron therapy system [75,76], which is based on 50.5 MeV protons incident on a beryllium target, gives, for example, an RBE DSB of 2.8 6 0.1 (Stewart et al [3]).…”

Section: Discussionmentioning

confidence: 52%

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Induction of DNA Damage by Light Ions Relative to 60Co γ-rays

Stewart

2018

International Journal of Particle Therapy

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The specific types and numbers of clusters of DNA lesions, including both DNA doublestrand breaks (DSBs) and non-DSB clusters, are widely considered 1 of the most important initiating events underlying the relative biological effectiveness (RBE) of the light ions of interest in the treatment of cancer related to megavoltage x-rays and 60 Co crays. This review summarizes the categorization of DNA damage, reviews the underlying mechanisms of action by ionizing radiation, and quantifies the general trends in DSB and non-DSB cluster formation by light ions under normoxic and anoxic conditions, as predicted by Monte Carlo simulations that reflect the accumulated evidence from decades of research on radiation damage to DNA. The significance of the absolute and relative numbers of clusters and the local complexity of DSB and non-DSB clusters are discussed in relation to the formation of chromosome aberrations and the loss of cell reproductive capacity. Clinical implications of the dependence of DSB induction on ionization density is reviewed with an eye towards increasing the therapeutic ratio of proton and carbon ion therapy through the explicit optimization of RBE-weighted dose.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 52%

Induction of DNA Damage by Light Ions Relative to 60Co γ-rays

Stewart

2018

International Journal of Particle Therapy

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“…With carbon ion therapy (for review, see [96]), the toxicities in bone and soft tissue sarcomas decreased compared with conventional radiotherapy [97]. However, skin reactions can be substantial [98][99][100][101].…”

Section: Tumor Control and Normal Tissue Tolerance In Hadrontherapymentioning

confidence: 99%

Hadrontherapy Interactions in Molecular and Cellular Biology

Thariat

Valable

Laurent

et al. 2019

IJMS

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The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues. Sensitive organs near the tumor that is to be treated can be affected by direct irradiation or experience nontargeted reactions, leading to early or late effects that disrupt the quality of life of patients. For several decades, new modalities of irradiation that involve accelerated particles have been available, such as proton therapy and carbon therapy, raising the possibility of specifically targeting the tumor volume. The goal of this review is to examine the up-to-date radiobiological and clinical aspects of hadrontherapy, a discipline that is maturing, with promising applications. We first describe the physical and biological advantages of particles and their application in cancer treatment. The contribution of the microenvironment and surrounding healthy tissues to tumor radioresistance is then discussed, in relation to imaging and accurate visualization of potentially resistant hypoxic areas using dedicated markers, to identify patients and tumors that could benefit from hadrontherapy over conventional irradiation. Finally, we consider combined treatment strategies to improve the particle therapy of radioresistant cancers.

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“…Due to unwillingness or inoperability because of difficult tumor sites, radiotherapy like stereotactic body radiation (SBRT) is considered alternative standard therapy. Recently, carbon-ion radiotherapy (Cion RT) has emerged as an alternative therapeutic option and is currently practiced in a few centers of the world [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…However, still recurrences or metastases are not so rare. Prognostic studies and accordingly treatment planning are required to prevent disease progression [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of semi-quantitative FDG-PET parameters in stage I non-small cell lung cancer treated with carbon-ion radiotherapy

Shrestha

Higuchi

Shirai

et al. 2019

Eur J Nucl Med Mol Imaging

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Purpose Prognostic significance of volumetric 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computer tomography (PET/CT) parameters in carbon-ion radiotherapy (C-ion RT) treated stage I non-small cell lung cancer, and need of histology-wise separate cutoff values for risk stratification were assessed. Methods Thirty-nine patients (29 men and 10 women, 71.9 ± 8.3 years) who underwent FDG PET/CT examinations before Cion RT were retrospectively evaluated. FDG-PET parameters: standardized uptake values (SUVmax, SUVpeak, and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinicopathological variables were assessed for prognosis using Cox proportional hazards regression analysis. Mann-Whitney test compared medians of significant parameters between adenocarcinoma (AC) and squamous cell carcinoma (SCC), and Kaplan-Meier curves were plotted for median-based low-and high-risk groups. Results Median follow-up period was 44.8 months. 1/2/3-year overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 94.

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Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

Cited by 143 publications

References 199 publications

Induction of DNA Damage by Light Ions Relative to 60Co γ-rays

Induction of DNA Damage by Light Ions Relative to 60Co γ-rays

Hadrontherapy Interactions in Molecular and Cellular Biology

Prognostic significance of semi-quantitative FDG-PET parameters in stage I non-small cell lung cancer treated with carbon-ion radiotherapy

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