Low predictive value of intrinsic fibroblast radiosensitivity for fibrosis development following radiotherapy for breast cancer

Russell, Nicola S.; Grummels, Annette; Hart, A.A.M.; Smolders, I. J. H.; Borger, Jacques; Bartelink, Harry; Begg, Adrian C.

doi:10.1080/095530098141915

Cited by 83 publications

(34 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is clinically relevant because large patient-to-patient variation in radiation morbidity has been documented, even after RT with a fixed dose-fractionation schedule (Tucker et al, 1992;Bentzen et al, 1993;Bentzen, 1997). The data published so far on the cellular and molecular factors underlying acute or late tissue reactions appeared to be contradictory and suggest that there is no clear-cut relationship between cellular radiosensitivity and the risk of acute or late reactions; consequently, no test has been recommended up to now for predicting the risk or the severity of late reactions in breast cancer (Burnet et al, 1992;Brock et al, 1995;Jones et al, 1995;Johansen et al, 1996;Russell et al, 1998;Kiltie et al, 1999;Barber et al, 2000;Peacock et al, 2000;Oppitz et al, 2001). To confirm our first preclinical and retrospective studies on the correlation of radiation-induced CD4 and CD8 T-lymphocyte apoptosis (RTLA) and late side effects after RT (Ozsahin et al, 1997), we assessed prospectively RTLA by the prediction of individual intrinsic radiosensitivity of 399 consenting patients treated with curative RT for miscellaneous cancers (Ozsahin et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

et al. 2004

View full text Add to dashboard Cite

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day À1 ) with concomitant RT was prescribed in 90 hormone receptorpositive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2 -57.6%) vs 66% (95% CI 49.9 -78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40 -61%) vs 80% (95% CI 67 -89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10 -31.9%), 66% (95% CI 51.1 -77.6%), and 79% (95% CI 55 -90.9%) for CD8 p16, 16 -24, and 424%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Because skin cancer is associated with UV radiation exposure, skin cancer patients were included as controls to ensure that they would not be assigned a high risk for radiation toxicity. Ethnic origins of the skin cancer patients were European (14) and Hispanic (1), and their average age was 38 years.…”

Section: Radiation-sensitive Patients and Controlsmentioning

confidence: 99%

“…Cultured skin fibroblasts from patients with acute radiation toxicity showed decreased survival after IR in some studies (13) but not others (14,15). Lymphocytes from patients with radiation toxicity showed a paradoxical decrease in IR-induced apoptosis (16).…”

mentioning

confidence: 98%

Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage

Rieger

Hong

Tusher

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

112

View full text Add to dashboard Cite

Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity. The analysis used heterogeneity-associated transformation of the data to account for a clinical outcome arising from more than one underlying cause. To compute the risk of toxicity for each patient, we applied nearest shrunken centroids, a method that identifies and cross-validates predictive genes. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of 14 patients with no false positives among 43 controls (P ‫؍‬ 2.2 ؋ 10 ؊7 ). The responses of these nine patients displayed significant heterogeneity. Of the five patients with toxicity and normal responses, two were treated with protocols that proved to be highly toxic. These results may enable physicians to predict toxicity and tailor treatment for individual patients.

show abstract

“…Considerable efforts have been made to correlate normal tissue toxicity with cellular responses to ionising radiation (IR). However, no significant relationships have yet been found between fibroblast or lymphocyte cytotoxicity and acute (Geara et al, 1993;Brock et al, 1995;Johansen et al, 1996) or late (Russell et al, 1998;Peacock et al, 2000) normal tissue reactions to IR. However, normal cell radiosensitivity in some cases may be an important factor predictive of radiation therapy response as illustrated by West et al (2001) whose results showed that blood lymphocyte radiosensitivity (SF2) is a highly significant prognostic factor for the risk of developing late radiation morbidity.…”

mentioning

confidence: 99%

Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment

Badie¹,

Dziwura²,

Raffy³

et al. 2008

Br J Cancer

View full text Add to dashboard Cite

Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (CDKN1A, GADD45A, CCNB1, and BBC3) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of BBC3, CCNB1, and GADD45A 2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for CDKN1A (Po0.002) in severe reactors compared to normal. Prediction of reaction severity of B91% of individuals sampled was achieved using this end point. Analysis of TP53 Arg72Pro and CDKN1A Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.

show abstract

Low predictive value of intrinsic fibroblast radiosensitivity for fibrosis development following radiotherapy for breast cancer

Cited by 83 publications

References 25 publications

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients

Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage

Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment

Contact Info

Product

Resources

About