Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • This trial evaluated the predictive

    2018-11-13

    This trial evaluated the predictive impact of an individual radiosensitivity biomarker in accordance with the methodology published by the REMARK international committee (Altman et al., 2012). Before the current trial, we and others presented promising results of correlation between RILA and late side-effects but only in retrospective manner or in a prospective single center study (Azria et al., 2010; Foro et al., 2014; Ozsahin et al., 2005; Schnarr et al., 2009). Here, the level of evidence of RILA was highly improved and allowed a rapid implementation of the RILA assay in daily practice. The main findings of this trial confirmed that a biological assay by itself will not be sufficient to predict the risk of late effects. To predict if a patient is at risk or not of developing severe effects after curative intent RT, many factors have to be added to the biological determinant, namely systemic treatments and tobacco smoking. In addition, RILA taken as a continuous variable is strongly predictive of late fibrosis and reinforces the usefulness of this test in multifactorial support systems integrating clinical, physical and biological factors to decide the optimal treatment strategy (Lambin et al., 2013). In the current study, adjuvant hormonotherapy but not chemotherapy was found to be an independent factor of late fibrosis. We and others identified that risk in previous cohorts but mainly with tamoxifen (Azria et al., 2010; Azria et al., 2004; Bentzen et al., 1996; Johansen et al., 2007) and probably through synergistic RGDfK of profibrotic cytokines such as transforming growth factor β (Canney and Dean, 1990). New chemotherapy regimens including taxanes seem to reduce the risk compared to the CMF protocol (cyclophosphamide, methotrexate, and 5-FU) (Johansen et al., 2007). Tobacco smoking was also a potential factor that may increase the risk of late fibrosis by 60% but with only a statistical trend. Nevertheless, we are still convinced that this factor has to be considered in a multifactorial model as it alters recovery after RT and/or surgery and impairs cosmetic outcome in case of breast reconstruction (Kern et al., 2015). The absence of correlation between RILA and acute toxicities in the multifactorial analysis is in concordance with our preliminary trial (Ozsahin et al., 2005). More than 60% of late fibrosis appeared 6months after the end of RT, suggesting that mechanisms other than DNA repair are represented by the RILA assay. Correlation between cellular radiosensitivity and early skin reactions is highly controversial (Begg et al., 1993; Johansen et al., 1996) and could not explain by itself the late reactions observed clinically in tissues. In lymphocytes from 26 patients with locally advanced breast carcinoma, an inverse correlation was found between initial damage to DNA and RILA (Pinar et al., 2010). It is still unknown why the lymphocyte and particularly the CD8 subtype present this property to be the mirror of healthy tissues. Ongoing works within RGDfK a European consortium (West et al., 2014) are trying to identify if some genetic polymorphisms (Azria et al., 2008; Seibold et al., 2015) may explain the incorrect healing of the irradiated tissue. Recently, we started the BIORISE project to evaluate the underlying mechanisms using a proteomics approach (Lacombe et al., 2013). Interesting preliminary results show protein overexpression and significant ROS production in lymphocytes of patients with radiation-induced severe late effects and low RILA (manuscript in preparation). Research to understand how lymphocytes can predict late RT-toxicity has now been launched in Montpellier. Breast is of course not the only site for which RILA is useful. In our first clinical trial (Ozsahin et al., 2005), many tumor sites were included and RILA predicted late rectal, bladder, or cervical toxicities after RT. It was then confirmed by others in prostate (Foro et al., 2014), head and neck (Bordon et al., 2010), and cervix (Bordon et al., 2011). PHRC trial 2 (NCT00893035) dedicated to prostate is now closed to recruitment and will be presented with longer follow-up. The mechanism underlying the predictive property of RILA seems to be ubiquitous whatever the irradiated site.