In vitro radiosensitivity measured in lymphocytes and fibroblasts by colony formation and comet assay: comparison with clinical acute reactions to radiotherapy in breast cancer patients

Oppitz, Ulrich; Schulte, Stephanie; Stopper, Helga; Baier, Kurt; Müller, M; Wulf, Jörn; Schakowski, Renate; Flentje, Michael

doi:10.1080/09553000210126466

Cited by 36 publications

(24 citation statements)

References 20 publications

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“…Others confirmed the lack of correlation between cellular radiosensitivity and early skin reactions (32 -34). However, a number of authors have confirmed the correlation between cellular radiosensitivity and late effects (24,25,35,36).…”

Section: Discussionmentioning

confidence: 99%

CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients

Ozşahin

Crompton

Gourgou

et al. 2005

Clinical Cancer Research

191

115

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Purpose: Predicting late effects in patients treated with radiation therapy by assessing in vitro radiation-induced CD4 and CD8 T-lymphocyte apoptosis can be useful in individualizing treatment. Experimental Design: In a prospective study, 399 curatively irradiated patients were tested using a rapid assay where fresh blood samples were in vitro irradiated with 8 Gy X-rays. Lymphocytes were collected and prepared for flow cytometric analysis. Apoptosis was assessed by associated condensation of DNA. The incidences of late toxicities were compared for CD4 and CD8 T-lymphocyte apoptoses using receiver-operating characteristic curves and cumulative incidence. Results: No association was found between early toxicity and T-lymphocyte apoptosis. Grade 2 and 3 late toxicities were observed in 31% and 7% of patients, respectively. More radiationinducedT-lymphocyte apoptosis was significantly associated with less grade 2 and 3 late toxicity (Gray's test, P < 0.0001). CD8 (area under the curve = 0.83) was more sensitive and specific than CD4. No grade 3 late toxicity was observed for patients with CD4 and CD8 values greater than 15% and 24%, respectively. The 2-year cumulative incidence for grade 2 or 3 late toxicity was 70%, 32%, and 12% for patients with absolute change in CD8 T-lymphocyte apoptosis of V16, 16 to 24, and >24, respectively.Conclusions: Radiation-induced T-lymphocyte apoptosis can significantly predict differences in late toxicity between individuals. It could be used as a rapid screen for hypersensitive patients to radiotherapy. In future dose escalation studies, patients could be selected using the apoptosis assay.

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Section: Discussionmentioning

confidence: 99%

CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients

Ozşahin

Crompton

Gourgou

et al. 2005

Clinical Cancer Research

191

115

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“…However, significant interindividual variation made the test not clinically useful. Oppitz et al (14), using comet assays of lymphocytes of 32 breast cancer patients who underwent irradiation after breast conservation, found that there was a significant correlation (p < 0.05) with acute radiation reactions. Borgmann et al (15), studying late RT effects in 16 pair wise-matched head-and-neck cancer patients 2 to 7 years after curative therapy, found-after in vitro irradiation of lymphocytes-that there was a significant difference in chromosomal damage between patients with severe reactions and patients with mild reactions (7.2 AE 0.8 vs. 5.0 AE 0.3 lethal aberrations).…”

Section: Introductionmentioning

confidence: 97%

Unexpectedly Severe Acute Radiotherapy Side Effects Are Associated With Single Nucleotide Polymorphisms of the Melanocortin-1 Receptor

Fogarty

Muddle

Sprung

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

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“…There was only one study reporting on a positive correlation between individual sensitivity and the extent of acute reaction (Oppitz et al 2001). This result, however, was not confirmed in a recent paper from the same group (Oppitz et al 2002). Almost all these studies were performed with breast cancer patients and the individual sensitivity was generally determined with fibroblasts using the colony assay.…”

Section: Introductionmentioning

confidence: 66%

No correlation between radiosensitivity or double-strand break repair capacity of normal fibroblasts and acute normal tissue reaction after radiotherapy of breast cancer patients

El‐Awady

Mahmoud

Saleh

et al. 2005

International Journal of Radiation Biology

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The aim was to study the relationship between cellular radiosensitivity or double-strand break (dsb) repair capacity of skin fibroblasts and the extent of acute reaction after radiotherapy for breast cancer. The study was performed with 25 breast cancer patients submitted to the radiotherapy unit of the Egyptian National Cancer Institute after conserving surgery. Dermal fibroblasts, established from skin biopsies, were used to determine the cellular radiosensitivity via colony assay and the capacity of dsb repair by constant-field gel electrophoresis. Acute reactions were scored using the Radiation Therapy Oncology Group (RTOG) classification. The spectrum of acute reactions varied from grade 1 to 4, whereby most patients developed a grade 1 reaction after total doses ranging between 46 and 70 Gy. Skin fibroblasts showed a pronounced variation in both cellular radiosensitivity expressed as the mean inactivation dose (Dbar) (coefficient of variation, CV=25%) as well as in the number of residual dsb (CV=33%) with no significant correlation between these two endpoints (r2=0.20, p=0.14). Both parameters did not correlate with the extent of acute reaction of the respective patient. The data obtained indicate that the sensitivity of fibroblasts measured either by colony assay or by dsb repair capacity is not a major parameter determining the extent of acute reaction after radiotherapy of breast cancer patients.

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In vitro radiosensitivity measured in lymphocytes and fibroblasts by colony formation and comet assay: comparison with clinical acute reactions to radiotherapy in breast cancer patients

Abstract: In this cohort of patients, a significant correlation between the in vitro results of the comet assay in lymphocytes and clinical acute reactions was detected. The results of the comet assay and of fibroblast colony formation did not correlate with in vitro radiosensitivity.

Cited by 36 publications

References 20 publications

CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients

CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients

Unexpectedly Severe Acute Radiotherapy Side Effects Are Associated With Single Nucleotide Polymorphisms of the Melanocortin-1 Receptor

No correlation between radiosensitivity or double-strand break repair capacity of normal fibroblasts and acute normal tissue reaction after radiotherapy of breast cancer patients

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