Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

Presented at the 50th Annual Meeting of the American Society for Radiation Oncology (ASTRO), Boston, MA, September 21-25, 2008.

• Palmira Foro, MD, PhD
, 
• Manuel Algara, MD, PhD
, 
• Joan Lozano, MD
, 
• Nuria Rodriguez, MD, PhD
, 
• Xavier Sanz, MD
, 
• Erica Torres
, 
• Joan Carles, MD, PhD
, 
• Anna Reig, MD
, 
• Ismael Membrive, MD
, 
• Jaume Quera, MD
, 
• Enric Fernandez-Velilla, MD
, 
• Oscar Pera, MD
, 
• Marti Lacruz, MD
, 
• Beatriz Bellosillo, PhD

Received 1 October 2013; received in revised form 27 December 2013; accepted 3 January 2014.

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Purpose

To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy.

Methods and Materials

214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model.

Results

The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022).

Conclusions

In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival, although larger series are needed to confirm this finding.