Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Mar:41:420-426.
doi: 10.1016/j.ebiom.2019.02.031. Epub 2019 Mar 1.

RILA blood biomarker as a predictor of radiation-induced sarcoma in a matched cohort study

C Mirjolet  1 , J L Merlin  2 , G Truc  1 , G Noël  3 , J Thariat  4 , J Domont  5 , P Sargos  6 , S Renard-Oldrini  7 , I Ray-Coquard  8 , X Liem  9 , C Chevreau  10 , J L Lagrange  11 , M A Mahé  12 , F Collin  13 , F Bonnetain  14 , A Bertaut  14 , P Maingon  15
Affiliations

RILA blood biomarker as a predictor of radiation-induced sarcoma in a matched cohort study

C Mirjolet et al. EBioMedicine. 2019 Mar.

Abstract

Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT).

Patients and methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry.

Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ± 16.0 Gy) and control patients (57.1 ± 15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5-55.7] and 22.3% [3.8-52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p < .0001, OR: 0.358, 95%CI [0.221-0.599].

Conclusion: RILA is a promising indicator to predict an individual risk of developing RIS. Our results should be followed up and compared with molecular and genomic testing in order to better identify patients at risk. A dedicated strategy could be developed to define and inform high-risk patients who require a specific approach for primary tumor treatment and long term follow-up.

Keywords: Apoptosis; Lymphocyte; Predictive biomarker; Radio-induced sarcoma.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flow diagram of the SARI (SArcoma Radio-Induced) study. RIS: Radiation-induced sarcoma, RILA: radiation-induced CD8 T-lymphocyte apoptosis.
Fig. 2
Fig. 2
ROC curve analysis to determine RILA cutoffs and to calculate sensitivity and specificity (all patients in A, only patients with primary breast cancer in B). RILA: radiation-induced CD8 T-lymphocyte apoptosis.
See this image and copyright information in PMC

References

    1. Lindholm C., Cavallin-Stahl E., Ceberg J., Frodin J.E., Littbrand B., Moller T.R. Radiotherapy practices in Sweden compared to the scientific evidence. Acta Oncol. 2003;42(5–6):416–429. - PubMed
    1. Brady M.S., Garfein C.F., Petrek J.A., Brennan M.F. Post-treatment sarcoma in breast cancer patients. Ann Surg Oncol. 1994;1(1):66–72. - PubMed
    1. Fraga-Guedes C., Gobbi H., Mastropasqua M.G., Botteri E., Luini A., Viale G. Primary and secondary angiosarcomas of the breast: a single institution experience. Breast Cancer Res Treat. 2012;132(3):1081–1088. - PubMed
    1. Jallali N., James S., Searle A., Ghattaura A., Hayes A., Harris P. Surgical management of radiation-induced angiosarcoma after breast conservation therapy. Am J Surg. 2012;203(2):156–161. - PubMed
    1. Kirova Y.M., Vilcoq J.R., Asselain B., Sastre-Garau X., Fourquet A. Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale single-institution review. Cancer. 2005;104(4):856–863. - PubMed

MeSH terms

Substances