Study of the risks of radiation induced reactions in patients receiving irradiation of the pelvic organs

Background. The oncological incidence in the world and the Russian Federation of rectal cancer (RC), prostate cancer (PC) and cervical cancer (CC) over the past 10–15 years remains high, with overall incidence of the pelvic organs cancer up to 25 % of the total. Radiation therapy is included in the complex of therapeutic measures in 50–70 % of cancer patients. The main feature of radiation therapy of patients with malignant neoplasms is the effect on both tumor and healthy cells of surrounding tissues. The development of radiation damage to healthy tissues, expressed in radiation reactions (RR) and complications lead to a deterioration in the quality of life. Unfortunately, it is currently not possible to predict which of the patients will develop radiation injuries above grade 1 and at what time.

Aim. To assess the risks of RR in patients with diagnoses of RC, prostate cancer and cervical cancer who underwent radiation therapy.

Materials and methods. The study included 759 patients, including 387 CC, 175 PC, and 197 RC, who received radiation therapy from 2011 to 2019 in the medical institutions of St. Petersburg and the Leningrad region.

Results. More than 30 factors that characterized patients, tumor features and concomitant therapy options were studied. Twelve of them turned out to be significant. In order to establish the main determinants (factors) associated with the risk of radiation reactions, a discriminant analysis was carried out. A formula has been created to calculate the probability of developing RR. We conducted an additional study on changing the timing of the introduction of hydrogel compositions, in which a decrease in the frequency of radiation-induced cystitis was noted.

Conclusion. Discriminant analysis revealed predictors of RR in patients with RC, CC, and PC out of 30 factors studied. From the results of discriminant analysis, formulas for predicting the probability of developing acute RR in patients with diagnoses of RC, CC, and PC who received radiation therapy were derived. The change in the time of administration of hydrogel compositions before, during and after the end of radiation therapy contributed to a decrease in the occurrence of radiation-induced cystitis compared with the control (р <0.05).

1. The state of cancer care for the population of Russia in 2021. Ed. A.D. Kaprin, V.V. Starinskiy, A.O. Shahzadova. Moscow: P.A. Herzen Moscow State Medical Research Institute − branch of National Medical Research Center for Radiology of the Ministry of Health of Russia, 2022. 239 p. (In Russ.).

2. Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023;73(1):17–48. DOI: 10.3322/caac.21763

3. Massi M.C., Gasperoni F., Ieva F. et al. A deep learning approach validates genetic risk factors for late toxicity after prostate cancer radiotherapy in a REQUITE multi-national cohort. Front Oncol 2020;10:541281. DOI: 10.3389/fonc.2020.541281

4. Brossard C., Lefranc A.C., Pouliet A.L. et al. molecular mechanisms and key processes in interstitial, hemorrhagic and radiation cystitis. Biology (Basel). 2022;11(7):972. DOI: 10.3390/biology11070972

5. Lee S., Kerns S., Ostrer H. et al. Machine learning on a genome-wide association study to predict late genitourinary toxicity after prostate radiation therapy. Int J Radiat Oncol Biol Phys 2018;101(1):128–35. DOI: 10.1016/j.ijrobp.2018.01.054

6. Chorbińska J., Krajewski W., Zdrojowy R. Urological complications after radiation therapy-nothing ventured, nothing gained: A narrative review. Transl Cancer Res 2021;10(2):1096–118. DOI: 10.21037/tcr-20-2589

7. Widmark A., Gunnlaugsson A., Beckman L. et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 2019;394(10196):385–95. DOI: 10.1016/S0140-6736(19)31131-6

8. Choi E.P.H., Wan E.Y.F., Kwok J.Y.Y. et al. The mediating role of sleep quality in the association between nocturia and health-related quality of life. Health Qual Life Outcomes 2019;17(1):181. DOI: 10.1186/s12955-019-1251-5

9. Yang T.J., Oh J.H., Son C.H. et al. Predictors of acute gastrointestinal toxicity during pelvic chemoradiotherapy in patients with rectal cancer. Gastrointest Cancer Res 2013;6(5-6):129–36. PMID: 24312686

10. Mirjolet C., Walker P.M., Gauthier M. et al. Absolute volume of the rectum and AUC from rectal DVH between 25Gy and 50Gy predict acute gastrointestinal toxicity with IG-IMRT in prostate cancer. Radiat Oncol 2016;11(1):145. DOI: 10.1186/s13014-016-0721-8

11. Ma J.L., Hennessey D.B., Newell B.P. et al. Radiotherapy-related complications presenting to a urology department: A more common problem than previously thought? BJU Int 2018;121(Suppl. 3):28–32. DOI: 10.1111/bju.14145

12. Toia B., Seth J., Ecclestone H. et al. Outcomes of reconstructive urinary tract surgery after pelvic radiotherapy. Scand J Urol 2019;53(2-3):156–60. DOI: 10.1080/21681805.2019.1611631

13. Mallick S., Madan R., Julka P.K., Rath G.K. Radiation induced cystitis and proctitis – Prediction, assessment and management. Asian Pac J Cancer Prev 2015;16(14):5589–94. DOI: 10.7314/apjcp.2015.16.14.5589

14. Tree A.C., Ostler P., van der Voet H. et al.; PACE Trial Investigators. Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol 2022;23(10):1308–20. DOI: 10.1016/S1470-2045(22)00517-4