Remaining chromosomal and immunological changes years after prostate cancer brachy- and teletherapy
PO-2239
Abstract
Remaining chromosomal and immunological changes years after prostate cancer brachy- and teletherapy
Authors: Zsolt Juranyi1, Zsuzsa S. Kocsis1, Katalin Lumniczky2, Katalin Balázs2, Péter Ágoston3, Gyöngyi Farkas1, Gyöngyvér O. Sándor1, Gábor Székely1, Tibor Major3, Csilla Pesznyák3, Gábor Stelczer3, Kliton Jorgo3, László Gesztesi3, Csaba Polgár3, Géza Sáfrány2
1National Institute of Oncology, Centre of Radiotherapy, Department of Radiobiology and Diagnostic Onco-Cytogenetics, Budapest, Hungary; 2National Center for Public Health, Dept. of Radiobiology and Radiation Hygiene, Unit of Radiation Medicine, Budapest, Hungary; 3National Institute of Oncology, Centre of Radiotherapy, Budapest, Hungary
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Purpose or Objective
There is of increasing importance of knowledge of effect of radiotherapy on immune cells due to the advancement of immunotherapies and its combination with conventional therapies.
Material and Methods
We recruited prostate cancer patients; 65 Cyberknife therapy (5 x 7.5-8), 55 conventional LINAC teletherapy (28 x 2.5 Gy v. 39 x 2 Gy), 52 high dose rate brachytherapy (HDR, 1 x 19/21 Gy), 69 low dose rate brachytherapy (LDR, 1 x 145 Gy) patients and the median follow up were 36, 48, 48, 60 months, respectively. We performed chromosomal aberration measurements and flow cytometric analysis of the frequency of Treg and NK subsets of immune cells. We compared the side effects between the groups and evaluated the connection between clinical and biological variables.
Results
The local relapse free survival at 48 months was 95.5 ± 2.5%; 100%; 97.3 ± 2.7 and 93.1 ± 4.7 after LDR, conventional LINAC, cyberknife and HDR therapy, respectively. There were 43.3%; 33.3%; 33.3% and 18.4% late genitourinary ≥G2 side effects for LDR, conventional LINAC, cyberknife, HDR therapy, respectively. We observed grade 2 late gastrointestinal side effects only after cyberknife (6.7%) and conventional teletherapy (7.2%) and no grade 3 side effects. The dicentrics+rings frequency (/100 cells) at three months after radiotherapy was 5.4 ± 0.6 for cyberknife; 9.1 ± 1.2 for conventional LINAC therapy, 1.1 ± 0.2 for HDR and 2.1 ± 0.2 for LDR therapy. After 12 months, the aberration frequency decreased, but in case LDR and conventional teletherapy, at 48th month, total aberration frequency was still significantly different from baseline. Total aberration frequency baselines were: Cyberknife 4.5 ± 0.5, HDR 3.8 ± 0.6, seed 3.0 ± 0.3, teletherapy 4.1 ± 0.4. Furthermore, we found that chromosome aberrations shortly after radiotherapy correlated significantly with cumulative late side effects. For example, chromatid breaks measured 6 months after LDR therapy, correlated with late genitourinary side effects (r= 0.31, p=0.010). We found that in case of higher radiation induced lymphocyte apoptosis (RILA) value there was less risk of late genitourinary toxicities (p=0.035). We observed long term changes due to radiotherapy in case of LDR patients: For example, CTLA4+ protein saturation (measured by mean fluorescence intensity) on CD4+, Foxp3+ (Treg) cells increased after radiotherapy and it was still significantly different after 36 months from the healthy average.
Conclusion
We showed that radiotherapy causes damage in the chromosomes of lymphocytes and it changes their immunological properties and distribution of their subpopulations even on a time scale of 3-5 years.