In vitro cellular radiosensitivity in relationship to late normal tissue reactions in breast cancer patients: a multi-endpoint case-control study

Vandevoorde, Charlot; Depuydt, Julie; Veldeman, Liv; Neve, Wilfried De; Sebastià, Natividad; Wieme, Greet; Baert, Annelot; Langhe, Sofie De; Philippé, Jan; Thierens, Hubert; Vral, Anne

doi:10.1080/09553002.2016.1230238

Cited by 22 publications

(18 citation statements)

References 73 publications

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“…For instance, the last published study compared four assays in a recent small cohort ( n = 12). Even though this study was very small, RILA still performed best ( 39 ).…”

Section: Radio-induced Toxicity Biomarkers Eramentioning

confidence: 86%

Personalizing Breast Cancer Irradiation Using Biology: From Bench to the Accelerator

et al. 2018

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While adjuvant treatments of early breast cancers (BCs) had significantly improved patients’ overall survival, some of them will still develop locoregional relapses and/or severe late radio-induced toxicities. Here, we propose to review how to personalize locoregional treatment by identifying patients at high and low risk of locoregional relapse, patients at risk of late radio-induced side effects. We will, therefore, discuss how to enhance BC radiosensitivity. Finally, we will address how personalized radiotherapy could be implemented in prospective clinical trials.

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“…For instance, the last published study compared four assays in a recent small cohort ( n = 12). Even though this study was very small, RILA still performed best ( 39 ).…”

Section: Radio-induced Toxicity Biomarkers Eramentioning

confidence: 86%

Personalizing Breast Cancer Irradiation Using Biology: From Bench to the Accelerator

et al. 2018

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“…Cultures were irradiated after 72 hours using a 6MV photon beam produced by an Elekta Precise linear accelerator (LINAC), operating at a nominal dose rate of 6 Gy/min. Doses of 0.05 and 0.5 Gy were used as low dose irradiation is routinely used in in vitro cellular radiosensitivity assays [12, 14, 15]. In order to achieve a uniform irradiation of flasks, a 30 × 35 cm 2 field was used and the flasks were positioned 10 cm deep in a water equivalent phantom 90 cm from the source.…”

Section: Methodsmentioning

confidence: 99%

“…Summary of band changes and associated tentative assignments between spectra from lymphocytes from grade 0-1 and grade 2+ patients [41][42][43][44] Band (cm −1 ) Although the flow cytometry γH2AX assay used here is not as sensitive as assays based on manual or automated foci scoring by microscopy, positive correlations between γH2AX fluorescence and late normal tissue toxicity have been found using both microscopy [14,15] and flow cytometry assays [13].…”

Section: T a B L Ementioning

confidence: 99%

“…In contrast, other studies have found no such correlations [11,12]. Using the γH2AX assay, residual DNA damage has been shown to correlate with late normal tissue response [13][14][15], although other studies have not shown such a clear relationship [11,[16][17][18]. The radiation-induced lymphocyte apoptosis assay (RILA) has shown good evidence of an inverse correlation between RILA and radiation toxicity [15,[19][20][21][22] but again other studies did not show a clear correlation [11,18].…”

Section: Introductionmentioning

confidence: 99%

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Raman spectroscopy of lymphocytes for the identification of prostate cancer patients with late radiation toxicity following radiotherapy

Cullen

Bryant

Maguire

et al. 2020

Transl Biophotonics

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The success of radiotherapy in tumour control depends on the total dose given. However, the tolerance of the normal tissues surrounding the tumour limits this dose. It is not known why some patients develop radiation toxicity and, currently, it is not possible to predict before treatment which patients will experience adverse effects. Thus, there is an unmet clinical need for a new test to identify patients at risk of radiation toxicity. Here, we report a new approach based on Raman spectroscopy. Blood samples were collected from 42 patients who had undergone radiotherapy for prostate cancer and had shown either severe or no/minimal late radiation toxicity in follow up. Radiation response was assessed following in vitro irradiation using Raman spectroscopy in addition to the G2 chromosomal radiosensitivity assay and the γH2AX DNA damage assay. A partial least squares discriminant analysis model was developed to classify patients using known radiation toxicity scores. A sensitivity of 95%, specificity of 92% and overall accuracy of 93% was achieved. In the future, this technology may have potential to lead to individualized patient radiotherapy by identifying which patients are at risk of radiation toxicity.

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“…The formation of dicentrics, translocations, and interstitial deletions, also results in the formation of micronuclei [5]. It has been well established that micronuclei can be utilized as a marker of radiation damage and radiation sensitivity [6,7,8,9]. …”

Section: Introductionmentioning

confidence: 99%

DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions

Cartwright

Haskins

et al. 2018

IJMS

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It has been well established that hypoxia significantly increases both cellular and tumor resistance to ionizing radiation. Hypoxia associated radiation resistance has been known for some time but there has been limited success in sensitizing cells to radiation under hypoxic conditions. These studies show that, when irradiated with low linear energy transfer (LET) gamma-rays, poly (ADP-ribose), polymerase (PARP), Fanconi Anemia (FANC), and mutant Chinese Hamster Ovary (CHO) cells respond similarly to the non-homologous end joining (NHEJ) and the homologous recombination (HR) repair mutant CHO cells. Comparable results were observed in cells exposed to 13 keV/μm carbon ions. However, when irradiated with higher LET spread out Bragg peak (SOBP) carbon ions, we observed a decrease in the oxygen enhancement ratio (OER) in all the DNA of repair mutant cell lines. Interestingly, PARP mutant cells were observed as having the largest decrease in OER. Finally, these studies show a significant increase in the relative biological effectiveness (RBE) of high LET SOBP carbon and iron ions in HR and PARP mutants. There was also an increase in the RBE of NHEJ mutants when irradiated to SOBP carbon and iron ions. However, this increase was lower than in other mutant cell lines. These findings indicate that high LET radiation produces unique types of DNA damage under hypoxic conditions and PARP and HR repair pathways play a role in repairing this damage.

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In vitro cellular radiosensitivity in relationship to late normal tissue reactions in breast cancer patients: a multi-endpoint case-control study

Cited by 22 publications

References 73 publications

Personalizing Breast Cancer Irradiation Using Biology: From Bench to the Accelerator

Personalizing Breast Cancer Irradiation Using Biology: From Bench to the Accelerator

Raman spectroscopy of lymphocytes for the identification of prostate cancer patients with late radiation toxicity following radiotherapy

DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions

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