Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

Journal Article · Sat Mar 01 04:00:00 EST 2014 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2013.11.218· OSTI ID:22416471

Mumbrekar, Kamalesh Dattaram ^[1]; Fernandes, Donald Jerard ^[2]; Goutham, Hassan Venkatesh ^[1]; Sharan, Krishna ^[2]; Vadhiraja, Bejadi Manjunath ^[3]; Satyamoorthy, Kapaettu ^[4]

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1. Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India)
2. Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India)
3. Manipal Hospital, Bangalore, Karnataka (India)
4. Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India)

Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

• OSTI ID: 22416471
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 88; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
DNA REPAIR
IN VITRO
LYMPHOCYTES
MAMMARY GLANDS
NEOPLASMS
PATIENTS
RADIATION DOSES
RADIOSENSITIVITY
RADIOTHERAPY
SKIN
STANDARD OF LIVING
STRAND BREAKS
TOXICITY
X RADIATION