Oncotarget

Research Papers:

Absence of correlation between radiationinduced CD8 Tlymphocyte apoptosis and sequelae in patients with prostate cancer accidentally overexposed to radiation

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Oncotarget. 2018; 9:32680-32689. https://doi.org/10.18632/oncotarget.26001

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Guillaume Vogin1,2,*, Jean-Louis Merlin3,4,5,*, Alexandra Rousseau6, Didier Peiffert4, Alexandre Harlé1,2,3, Marie Husson3, Labib El Hajj4, Mihai Levitchi4, Tabassome Simon6 and Jean-Marc Simon7

1Institut de Cancérologie de Lorraine, Département de Radiothérapie, 54500 Vandœuvre-lès-Nancy, France

2UMR 7365 CNRS-Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France

3Université de Lorraine, Faculté de Pharmacie, 54000 Nancy, France

4CNRS UMR 7039 CRAN Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France

5Institut de Cancérologie de Lorraine, Service de Biopathologie, 54500 Vandœuvre-lès-Nancy, France

6APHP, Unité de Recherche Clinique de l'Est Parisien (URC-Est), Hôpital Saint Antoine, 75012 Paris, France

7APHP, Hôpital Universitaire de la Pitié Salpêtrière, Service de Radiothérapie, 75013 Paris, France

*These authors have contributed equally to this work

Correspondence to:

Guillaume Vogin, email: [email protected]

Keywords: late radiation-induced toxicity; radiation-induced lymphocyte apoptosis; prostate cancer; Epinal adverse event; individual radiation sensitivity

Received: June 23, 2018     Accepted: August 04, 2018     Published: August 24, 2018

ABSTRACT

Purpose: 454 patients with prostate adenocarcinoma were accidentally overexposed to radiation in Epinal hospital, France, between August 1999 and January 2007. We aimed toevaluate whether radiation-induced CD4 or CD8 T-lymphocyte apoptosis (RILA) correlates with the severity of radiation toxicity.

Methods: Between 2007 and 2013, all patients who received more than 108% of the prescribed radiation dose, after correction of the treatment plan, were convened, and blood was sampled at 6-months follow-up. Maximal Digestive toxicity (MDT) and maximal urinary toxicity (MUT) were graded using the Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 scale. RILA was assessed using flow cytometry.

Results: 245 patients were included in our study. After a median follow-up of 4.8 years, the MDT and MUT reached grade 3-4 in 37 patients and 56 patients, respectively. Patients with prostatectomy exhibited a statistically higher grade of MUT compared with those treated with definitive radiotherapy (p=0.03). The median RILA values were 11.8% and 15.3% for CD4 and CD8 T-lymphocytes, respectively. We found no significant correlation between CD4 or CD8 RILA and either MDT or MUT.

Conclusion: RILA does not correlate with the inter-individual variation in MDT or MUT in the largest cohort of patients overexposed to radiation. The magnitude of the overdosage probably overrides biological predictors of toxicity, including individual radiosensitivity.