Medical Radiology and Radiation Safety. 2026. Vol. 71. № 2

DOI:10.33266/1024-6177-2026-71-2-122-128

A.A. Sazhina, A.N. Bashkov, Yu.D. Udalov, E.I. Matkevich, S.V. Lischuk

Reccurent Papillary Necrosis of the Right Kidney in the Setting of Drud-Induced Nephritis:
a Case Report on Radiologic Diagnosis

A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

Contact person: A.A. Sazhina, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

Purpose: To present a histologically verified clinical case of renal papillary necrosis that developed as a complication of drug-induced nephritis and was accompanied by secondary obstructive suppurative destructive pyelonephritis, with an emphasis on the diagnostic capabilities of radiological imaging.

Material and methods: А clinical case of a female patient with acute suppurative destructive pyelonephritis complicated by papillary necrosis, who was hospitalized in our clinic in January–February 2018.

Results: This case highlights the diagnostic value of CT in detecting papillary necrosis and determining the extent of renal involvement, which is crucial for treatment planning. Notably, papillary necrosis developed in the absence of classical risk factors such as diabetes mellitus or long-term analgesic abuse, underlining the significance of infectious-obstructive mechanisms.

Conclusion: This case illustrates a rare and complex course of drug-induced nephritis complicated by the development of renal papillary necrosis and secondary obstructive suppurative destructive pyelonephritis. Contrast-enhanced multislice computed tomography proved to be the most informative imaging modality, revealing calicopyeloectasia, filling defects, and characteristic signs of papillary necrosis, whereas MRI was less informative due to the absence of collecting system dilatation. Renal papillary necrosis should be considered as a potential cause of gross hematuria, particularly in patients with a history of prolonged analgesic use, as early recognition of this condition may prevent severe infectious and destructive complications. This case emphasizes the importance of an integrated diagnostic approach combining clinical, laboratory, radiological, and histopathological findings to ensure accurate diagnosis and optimal management strategy.

Keywords: renal papillary necrosis, acute suppurative destructive pyelonephritis, computed tomography (CT), multislice CT (MSCT), case report, nephrectomy, clinical case

For citation: Sazhina AA, Bashkov AN, Udalov YuD, Matkevich EI, Lischuk SV. Reccurent Papillary Necrosis of the Right Kidney in the Setting of Drud-Induced Nephritis: a Case Report on Radiologic Diagnosis. Medical Radiology and Radiation Safety. 2026;71(2):122–128. DOI:10.33266/1024-6177-2026-71-2-122-128

References

1. Friedrich N. Über Necrosis of nirenpapillen bei Hydronephrosis. The Virchow Arch 1877;69:308-12. http://dx.doi.org/10.1007/BF02326121.
2. Froboese K. Über sequestrierende Marknekrosen der Nieren bei Diabetes Severity. Upper Dtsh Ges Pathol. 1937;30:431-43.
3. Hunter GB. Die Papillennekrosen der Niere bei Diabetes.. 1937;84:1695. 
4. Mandel EE. Necrosis of the medulla of the kidneys. Am J Med. 1952;13:322-7. http://dx.doi.org/10.1016/0002-9343(52)90286-6.
5. Tublin, T. et al «Radiological Diagnostics. Organs of the Urinary System» (translated from English). Moscow: Panfilov Publishing House, 2018. 608 p.: ill. ISBN 978-5-91839-098-6.
6. Strokova L. A. The case of ultrasound diagnosis of necrotizing papillitis // Nephrology 2005. №1. URL: https://cyberleninka.ru/article/n/sluchay-ultrazvukovoy-diagnostiki-nekroticheskogo-papillita.
7. Timofeeva L.A., Bukova A.V., Aleshina T.N. Comprehensive radiological diagnostics in urology. Cheboksary: Publishing House of the Chuvash University, 2013. – 96 p. 
8. Gaudji GR, Bida M, Conradie M, Damane BP, Bester MJ. Renal Papillary Necrosis (RPN) in an African Population: Disease Patterns, Relevant Pathways, and Management. Biomedicines. 2022 Dec 29;11(1):93. doi: 10.3390/biomedicines11010093. PMID: 36672600; PMCID: PMC9855351.
9. Renal Papillary Necrosis: Review and Comparison of Findings at Multi–Detector Row CT and Intravenous Urography Dae Chul Jung, Seung Hyup Kim, Sung Il Jung, Sung Il Hwang, Sun Ho Kim Author AffiliationsPublished Online:Nov 1 2006https://doi.org/10.1148/rg.266065039.
10. Pan HH, Luo YJ, Zhu QG, Ye LF. Renal papillary necrosis with urinary tract obstruction: A case report. World J Clin Cases. 2022 Jun 6;10(16):5400-5405. doi: 10.12998/wjcc.v10.i16.5400. PMID: 35812662; PMCID: PMC9210877.
11. Tallai B, Gulistan TG, Alrayashi MNAB, Al Mughalles SAA, Kamkoum HM, Ebrahim MAA, Abdelkarim MAA, Salah MA. A Rare Presentation of Renal Papillary Necrosis iт a COVID-19-Positive Patient. Case Rep Urol. 2021 Jan 11;2021:6611861. doi: 10.1155/2021/6611861. PMID: 33489409; PMCID: PMC7805526.
12. Renal Papillary Necrosis Associated with Multiple Risk Factors: A Case Report Amin Mirsani, Raheleh Baradaran  and Abbas Sadeghian https://doi.org/10.5812/numonthly-127074
13. Sutariya HC, Pandya VK. Renal Papillary Necrosis: Role of Radiology. J Clin Diagn Res. 2016 Jan;10(1):TD10-2. doi: 10.7860/JCDR/2016/15092.7091. Epub 2016 Jan 1. PMID: 26894147; PMCID: PMC4740675.
14. Pinto DS, George A, Hoisala RV. MR urogram findings and diffusion restriction in the renal papilla and calyx in papillary necrosis – a new finding: preliminary report. BJR Case Rep. 2017 Feb 7;3(2):20150476. doi: 10.1259/bjrcr.20150476. PMID: 30363219; PMCID: PMC6159245.
15. Schroeder, J., Thacker, P.G. & Purves, T.J. Magnetic resonance urography of renal papillary necrosis. Pediatr Radiol 44, 491–493 (2014). https://doi.org/10.1007/s00247-014-2883-6.
16. Geller SA, de Campos FPF. Renal papillary necrosis. Autops Case Rep. 2013 Dec 31;3(4):69-71. doi: 10.4322/acr.2013.042. PMID: 28584810; PMCID: PMC5453664.

 PDF (RUS) Full-text article (in Russian)

Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.02.2026. Accepted for publication: 25.03.2026.

Medical Radiology and Radiation Safety. 2026. Vol. 71. № 2

DOI:10.33266/1024-6177-2026-71-2-135-146

E.S. Lyubaeva, T.A. Astrelina, I.V. Kobzeva, Yu.D. Udalov

Features of the Effect of Radiation Therapy on the Body in Patients with Breast Cancer (Literature Review)

A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

Contact person: E.S. Lyubaeva, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

The article presents a literature review describing the features of the effect of radiation therapy on the body in patients with breast cancer. Presented are the current results of studies with an assessment of skin reactions, cellular immunity, inflammatory reaction after radiation therapy in patients with breast cancer.

Keywords: radiation therapy, breast cancer, skin reactions, cellular immunity, inflammatory reaction

For citation: Lyubaeva ES, Astrelina TA, Kobzeva IV, Udalov YuD. Features of the Effect of Radiation Therapy on the Body in Patients with Breast Cancer (Literature Review). Medical Radiology and Radiation Safety. 2026;71(2):135–146. DOI:10.33266/1024-6177-2026-71-2-135-146

References

1. Sedeta E.T., Jobre B., Avezbakiyev B. Breast cancer: Global patterns of incidence, mortality, and trends. Journal of Clinical Oncology. 2023;41;16;Suppl:10528–10528. doi: 10.1200/jco.2023.41.16_suppl.10528
2. Злокачественные новообразования в России в 2023 году (заболеваемость и смертность) / Под ред. А.Д.Каприна. М.: МНИОИ им. П.А.Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2024. 276 с. [Zlokachestvennyye Novoobrazovaniya v Rossii v 2023 Godu (Zabolevayemost’ I Smertnost’) = Malignant Neoplasms in Russia in 2023 (Incidence and Mortality). Ed. A.D. Kaprin. Moscow, Moskovskiy Nauchno-Issledovatel’skiy Onkologicheskiy Institut im. P.A. Gertsena Publ., 2024. 276 p. (In Russ.)].
3. Grubbé E.H. Priority in the Therapeutic Use of X-rays. Radiology. 1933;21;2:156-162.
4. Российское общество клинической онкологии (RUSSCO). Рак молочной железы: Клинические рекомендации. М., 2023. 112 с. [Rossiyskoye Obshchestvo Klinicheskoy Onkologii (RUSSCO). Rak Molochnoy Zhelezy = Breast Cancer. Clinical Guidelines. Moscow Publ., 2023. 112 p. (In Russ.)].
5. Offersen B.V., Boersma L.J., Kirkove C., et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage of breast cancer. Radiotherapy and Oncology. 2020;152:150–156.
6. Gradishar W.J., Moran M.S., Abraham J., et al. NCCN Guidelines® Insights: Breast Cancer. J. Natl. Compr. Canc. Netw. 2023;21;5:594–608.
7. Delaney G., Barton M., Jacob S., Jalaludin B. A model for decision making for the use of radiotherapy in breast conserving therapy. Radiotherapy and Oncology. 2005;74;2:200–206.
8. Vande Perre P., Toledano D., Corsini C., et al. Role of the general practitioner in the care of BRCA1 and BRCA2 mutation carriers: General practitioner and patient perspectives. Molecular genetics & genomic medicine. 2018;6;6:957-965.
9. Омарова Д.Ф., Зикиряходжаев А.Д., Усов Ф.Н. и др. Онкологическая безопасность онкопластических резекций у больных раком молочной железы // Вопросы онкологии. 2022. Т.68. №6. С. 752-757 [Omarova D.F., Zikiryakhodzhayev A.D., Usov F.N., et al. Oncological Safety of Oncoplastic Resections in Patients with Breast Cancer. Voprosy Onkologii = Problems in Oncology. 2022;68;6:752-757 (In Russ.)].
10. Ермощенкова М.В., Зикиряходжаев А.Д., Широких И.М. и др. Хирургическая реабилитация больных раком молочной железы на различных этапах комбинированного и комплексного лечения // Онкология. Журнал им. П.А.Герцена. 2019. Т.8. №3. С. 161-168. [Yermoshchenkova M.V., Zikiryakhodzhayev A.D., Shirokikh I.M., et al. Surgical Rehabilitation of Patients with Breast Cancer at Different Stages of Combined and Comprehensive Treatment. Onkologiya. Zhurnal im. P.A.Gertsena = P.A.Herzen Journal of Oncology. 2019;8;3:161-168 (In Russ.)].
11. Veronesi U., Saccozzi R., Del Vecchio M., et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. New England Journal of Medicine. 1981;305;1:6-11.
12. Fisher B, Bauer M., Margolese R, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. New England Journal of Medicine. 1985;312;11:665-673.
13. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer / U. Veronesi, N. Cascinelli, L. Mariani, et al. New England Journal of Medicine. 2002;347;16:1227-1232.
14. Halsted W.S. I. The Results of Radical Operations for the Cure of Carcinoma of the Breast. Ann Surg. 1907 Jul;46;1:1–19.
15. Haagensen C.D., Stout A.P. Carcinoma of the Breast. II—Criteria of Operability. Ann Surg. 1943 Dec;118;6.:1032–1051.
16. Clarke, M.; Collins, R.; Darby, S.; Davies, C.; Elphinstone, P.; Evans, V.; Godwin, J.; Gray, R.; Hicks, C.; James, S., et al. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials. Lancet 2005;366:2087–2106.
17. Nielsen, H.M.; Overgaard, M.; Grau, C.; Jensen, A.R.; Overgaard, J. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: Long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J. Clin. Oncol. 2006;24:2268–2275.
18. Taghian, A. Adjuvant Radiation Therapy for Women with Newly Diagnosed, Non-Metastatic Breast Cancer. Introduction. In UpToDate, Post TW (Ed), UpToDate, Waltham, MA, USA. URL: https://www.uptodate.com/contents/adjuvantradiation-therapy-for-women-with-newly-diagnosed-non-metastatic-breast-cancer (accessed on 22 March 2022).
19. Remick, J., Amin, N.P. Postmastectomy Breast Cancer Radiation Therapy. StatPearls; StatPearls Publishing: Treasure Island, FL, USA; Available online: https://europepmc.org/article/NBK/nbk519034 (accessed on 8 September 2023).
20. Clarke, M., Collins, R., Darby, S., Davies, C., Elphinstone, P., Evans, V., Godwin, J.,Gray, R., Hicks, C., James, S., et al. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials. Lancet. 2005;366:2087–2106.
21. Taghian, A.G., Jeong, J.H., Mamounas, E.P., Parda, D.S., Deutsch, M., Costantino, J.P.; Wolmark, N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: Results from five national surgical adjuvant breast and bowel project randomized clinical trials. J. Clin. Oncol. 2006;24:3927–3932.
22. Floyd, S.R., Buchholz, T.A., Haffty, B.G., Goldberg, S., Niemierko, A., Raad, R.A., Oswald, M.J., Sullivan, T., Strom, E.A., Powell, S.N., et al. Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger. Int. J. Radiat. Oncol. Biol. Phys. 2006;66:358–364.
23. Johnson, M.E., Handorf, E.A., Martin, J.M., Hayes, S.B. Postmastectomy radiation therapy for T3N0: A SEER analysis. Cancer. 2014;120:3569–3574.
24. Johnson, M.E., Handorf, E.A., Martin, J.M., Hayes, S.B. Postmastectomy radiation therapy for T3N0: A SEER analysis. Cancer. 2014;120:3569–3574.
25. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group); McGale, P., Taylor, C., Correa, C., Cutter, D., Duane, F., Ewertz, M., Gray, R., Mannu, G., Peto, R., et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127–2135.
26. Hansen, E., Roach, M., III (Eds.) Handbook of Evidence-Based Radiation Oncology; Berlin/Heidelberg, Germany, Springer International Publishing, 2018. ISBN 978-3-31-962642-0, 978-3-31-962641-3.
27. Tendulkar, R.D., Rehman, S., Shukla, M.E., Reddy, C.A., Moore, H., Budd, G.T., Dietz, J., Crowe, J.P., Macklis, R. Impact of postmastectomy radiation on locoregional recurrence in breast cancer patients with 1-3 positive lymph nodes treated with modern systemic therapy. Int. J. Radiat. Oncol. Biol. Phys. 2012;83:577–581.
28. Holland, R., Veling, S.H., Mravunac, M., Hendriks, J.H. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 1985;56:979–990.
29. Clarke, M., Collins, R., Darby, S., Davies, C., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Hicks, C., James, S., et al. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomized trials. Lancet. 2005;366:2087–2106.
30. Fisher, B., Anderson, S., Bryant, J., Margolese, R.G., Deutsch, M., Fisher, E.R., Jeong, J.H., Wolmark, N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N. Engl. J. Med. 2002;347:1233–1241.
31. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG); Darby, S., McGale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., Ewertz, M., et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 2011;378:1707–1716.
32. Ambrose J., Hounsfield G. Computerized transverse axial tomography. Br. J. Radiol. 1973 Feb;46;542:148-9. PMID: 4686818.
33. Bui-Mansfield L.T. Nobel prize laureates who have made significant contributions to radiology. Journal of Computer Assisted Tomography. 2009;33;4:483-488.
34. Goodman L.R. The Beatles, the Nobel Prize, and CT Scanning of the Chest // Thoracic Surgery Clinics. 2010. Vol. 20. №1. P. 1-7
35. Abe O., Abe R., Enooto K., et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. Lancet. 2005;366;9503:2087-2106
36. Taunk N., Haffty B., Kostis J., et al. Radiation-induced heart disease: Pathologic abnormalities and putative mechanisms. Frontiers in Oncology. 2015;5;39:1-9.
37. Arsene-Henry A, Fourquet A, Kirova YM. Evolution of radiation techniques in the treatment of BC (BC) patients: From 3D conformal radiotherapy (3D CRT) to intensity-modulated RT (IMRT) using Helical Tomotherapy (HT). Radiother Oncol. 2017 Aug;124;2:333-334. doi: 10.1016/j.radonc.2017.07.002.
38. Donovan E, Bleakley N, Denholm E, Evans P, Gothard L, Hanson J, et al. Breast Technology Group. Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy. Radiother Oncol. 2007 Mar;82;3:254-64. doi: 10.1016/j.radonc.2006.12.008.
39. Pignol JP, Olivotto I, Rakovitch E, Gardner S, Sixel K, Beckham W, et al. A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol. 2008 May 1;26;13:2085-92. doi: 10.1200/JCO.2007.15.2488.
40. Barnett GC, Wilkinson JS, Moody AM, Wilson CB, Twyman N, Wishart GC, et al. Randomized controlled trial of forward-planned intensity modulated radiotherapy for early BC: interim results at 2 years. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82;2:715-23. doi: 10.1016/j.ijrobp.2010.10.068.
41. Barnett GC, Wilkinson J, Moody AM, Wilson CB, Sharma R, Klager S, et al. A randomised controlled trial of forward-planned radiotherapy (IMRT) for early breast cancer: baseline characteristics and dosimetry results. Radiother Oncol. 2009 Jul;92;1:34-41. doi: 10.1016/j.radonc.2009.03.003.
42. Mukesh MB, Qian W, Wilkinson JS, Dorling L, Barnett GC, Moody AM, et al. Patient reported outcome measures (PROMs) following forward planned field-in field IMRT: results from the Cambridge Breast IMRT trial. Radiother Oncol. 2014 May;111;2:270-5. doi: 10.1016/j.radonc.2014.02.016.
43. Pasquier D, Bataille B, Le Tinier F, Bennadji R, Langin H, Escande A, et al. Correlation between toxicity and dosimetric parameters for adjuvant intensity modulated radiation therapy of BC: a prospective study. Sci Rep. 2021 Feb 11;11;1:3626. doi: 10.1038/s41598-021-83159-3.
44. Elith C, Dempsey SE, Findlay N, Warren-Forward HM. An Introduction to the Intensitymodulated Radiation Therapy (IMRT) Techniques, Tomotherapy, and VMAT. J Med Imaging Radiat Sci. 2011 Mar;42;1:37-43. doi: 10.1016/j.jmir.2010.11.005.
45. Haciislamoglu E, Colak F, Canyilmaz E, Dirican B, Gurdalli S, Yilmaz AH, et al. Dosimetric comparison of leftsided whole-breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and volumetric arc therapy. Phys Med. 2015 Jun;31;4:360-7. doi: 10.1016/j.ejmp.2015.02.005.
46. Ko H, Chang JS, Moon JY, Lee WH, Shah C, Shim JSA, Ha, et al. Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided BC: A Treatment Planning Study. Front Oncol. 2021 Apr 12;11:645328. doi: 10.3389/fonc.2021.645328.
47. Lightowlers SV, Boersma LJ, Fourquet A, Kirova YM, Offersen BV, Poortmans P, et al. Preoperative breast radiation therapy: Indications and perspectives. Eur J Cancer. 2017 Sep;82:184-192. doi: 10.1016/j.ejca.2017.06.014.
48. Mu J, Xi D, Ding Y, Gu W, Li Q. Chair Heterogeneity Index: Describing the dose heterogeneity inside the tumor volume where there is a boost volume. Sci Rep. 2018 Jun 27;8;1:9763. doi: 10.1038/s41598-018-28110-9.
49. Yee C, Wang K, Asthana R, Drost L, Lam H, Lee J, et al. Radiation-induced Skin Toxicity in BC Patients: A Systematic Review of Randomized Trials. Clin BC. 2018 Oct;18;5:e825-e840. doi: 10.1016/j.clbc.2018.06.015.
50. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for BC. N Engl J Med. 2010 Feb 11;362;6:513-20. doi: 10.1056/NEJMoa0906260.
51. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardization of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013 Oct;14;11:1086-1094. doi: 10.1016/S1470-2045(13)70386-3.
52. Smith BD, Bellon JR, Blitzblau R, Freedman G, Haffty B, Hahn C, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018 May-Jun;8;3:145-152. doi: 10.1016/j.prro.2018.01.012
53. Wei J., Meng L., Hou X., et al. Radiation-induced skin reactions: mechanism and treatment. Cancer management and research. 2019;11:167-177.
54. Cox J. D. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). International journal of radiation oncology, biology, physics. 1995;31;4:1341-6.
55. Porock D. Factors influencing the severity of radiation skin and oral mucosal reactions: development of a conceptual framework. European journal of cancer care. 2002;11;1:33-43.
56. Nevens D., Duprez F., Daisne J., et al. Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology. 2017;122;2:212-216.
57. Bray F.N., Simmons B.J., Wolfson A.H., et al. Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy. Dermatology and therapy. 2016;6;2:185-206.
58. Delfino S., Brunetti B., Toto V., Persichetti P. Burn after breast reconstruction. Burns. 2008;34:873–877.
59. Bray F.N., Simmons B.J., Wolfson A.H., Nouri K. Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy. Dermatol. Ther. 2016;6:185–206.
60. Richardson, B.N., Lin, J., Buchwald, Z.S., Bai, J. Skin Microbiome and Treatment-Related Skin Toxicities in Patients with Cancer: A Mini-Review. Front. Oncol. 2022;12:924849.
61. Schuler N., Palm J., Kaiser M., Betten D., Furtwängler R., Rübe C., Graf N., Rübe C.E. DNA-Damage Foci to Detect and Characterize DNA Repair Alterations in Children Treated for Pediatric Malignancies. PLoS ONE. 2014;9:e91319.
62. Toledano A., Garaud P., Serin D., Fourquet A., Bosset J.-F., Breteau N., Body G., Azria D., Le Floch O., Calais G. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: Long-term results of the ARCOSEIN multicenter randomized study. Int. J. Radiat. Oncol. Biol. Phys. 2006;65;324–332.
63. Satzger I., Degen A., Asper H., Kapp A., Hauschild A., Gutzmer R. Serious skin toxicity with the combination of BRAF inhibitors and radiotherapy. J. Clin. Oncol. 2013;31:e220–e222.
64. Hooning M., Botma A., Aleman B., et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. Journal of the National Cancer Institute. 2007;99;5:365-375.
65. McGale P., Taylor C., Correa C., et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. The Lancet. 2014;383;9935:2127-2135.
66. Wu W., Masri A., Popovic Z., et al. Long-term survival of patients with radiation heart disease undergoing cardiac surgery: A cohort study. Circulation. 2013;127;14:1476-1484.
67. Harris E., Correa C., Hwang W., et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. Journal of Clinical Oncology. 2006;24;25:4100-4106.
68. Umberto V., Eronesi V., Atale N., et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer abstract. Background We conducted 20 years of follow-up. N Engl J Med. 2002;347;16:1227-1232.
69. Bledsoe T. J. Radiation Pneumonitis. Clinics in chest medicine. 2017;38;2:201-208.
70. Meattini I., Guenzi M., Fozza A., et al. Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with adjuvant radiotherapy for breast cancer. Breast cancer (Tokyo, Japan). 2017;24;1:52-62.
71. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021;71;3:209–249. doi: 10.3322/caac.21660.
72. Darby S.C., McGale P., Taylor C.W., Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. The Lancet. 2011;378;9804:1707–1716. doi: 10.1016/S0140-6736(11)61629-2.
73. Bentzen, S.M. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues / S.M. Bentzen, L.S. Constine, J.O. Deasy, A. Eisbruch, A. Jackson, L.B. Marks, R.K. Ten Haken, E.D. Yorke. International Journal of Radiation Oncology, Biology, Physics. 2010;76;3Suppl:S3–S9. doi: 10.1016/j.ijrobp.2009.09.040.
74. Mantovani, A. Cancer-related inflammation / A. Mantovani, P. Allavena, A. Sica, F. Balkwill. Nature. 2008;454;7203:436–444. doi: 10.1038/nature07205.
75. Citrin, D.E. Radiation modifiers / D.E. Citrin, D.G. Mitchell, J.B. Mitchell. Hematology/Oncology Clinics of North America. 2019;33;6:1041–1055. doi: 10.1016/j.hoc.2019.08.005.
76. Proctor, M.J. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study / M.J. Proctor, D.S. Morrison, D. Talwar, D.C. McMillan. British Journal of Cancer. 2011;104;4:726–734. doi: 10.1038/sj.bjc.6606087.
77. Hanahan, D. Hallmarks of Cancer: New Dimensions. Cancer Discovery. 2022;12;1:31–46. doi: 10.1158/2159-8290.CD-21-1059.
78. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144;5:646–674. doi: 10.1016/j.cell.2011.02.013.
79. Greten FR, Grivennikov SI. Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity. 2019;51;1:27–41. doi: 10.1016/j.immuni.2019.06.025.
80. Hibino S, Kawazoe T, Kasahara H, et al. Inflammation induced tumorigenesis and metastasis. Int J Mol Sci. 2021;22;11:5421. doi: 10.3390/ijms22115421.
81. Brenner DR, Scherer D, Muir K, et al. A review of the application of inflammatory biomarkers in epidemiologic cancer research. Cancer Epidemiol Biomarkers Prev. 2014;23;9:1729–1751. doi: 10.1158/1055-9965.EPI-14-0064.
82. Guner A, Kim H-I. Biomarkers for evaluating the inflammation status in patients with cancer. J Gastric Cancer. 2019;19;3:254–277. doi: 10.5230/jgc.2019.19.e29.
83. Maharjan CK, Mo J, Wang L, et al. Natural and synthetic estrogens in chronic inflammation and breast cancer. Cancers (Basel). 2021;14;1:206. doi: 10.3390/cancers14010206.
84. Danforth DN. The role of chronic inflammation in the development of breast cancer. Cancers (Basel). 2021;13;15:3918. doi: 10.3390/cancers13153918.
85. Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2019;15;3:139–154. doi: 10.1038/s41574-018-0126-x.
86. Hernandez C, Huebener P, Schwabe RF. Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene.2016;35;46:5931–5941. doi: 10.1038/onc.2016.104.
87. Pereira F, Ferreira A, Reis CA, et al. KRAS as a modulator of the inflammatory tumor microenvironment: Therapeutic implications. Cells. 2022;11;3:398. doi: 10.3390/cells11030398.
88. Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019;79;18:4557–4566. doi: 10.1158/0008-5472.CAN-18-3962.
89. Baram T, Rubinstein-Achiasaf L, Ben-Yaakov H, et al. Inflammation-driven breast tumor cell plasticity: Stemness/EMT, therapy resistance and dormancy. Front Oncol. 2021;10:614468. doi: 10.3389/fonc.2020.614468.
90. Morris RM, Mortimer TO, O’Neill KL. Cytokines: Can cancer get the message Cancers (Basel). 2022;14;9:2178. doi: 10.3390/cancers14092178.
91. Jones VS, Huang RY, Chen LP, et al. Cytokines in cancer drug resistance: Cues to new therapeutic strategies. Biochim Biophys Acta. 2016;1865;2:255–265. doi: 10.1016/j.bbcan.2016.03.005.
92. Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30;5:668–681. doi: 10.1016/j.ccell.2016.09.011.
93. Middleton JD, Stover DG, Hai T. Chemotherapy-exacer-bated breast cancer metastasis: A paradox explainable by dys-regulated adaptive-response. Int J Mol Sci. 2018;19;11:3333. doi: 10.3390/ijms19113333.
94. D’Alterio C, Scala S, Sozzi G, et al. Paradoxical effects of chemo-therapy on tumor relapse and metastasis promotion. Semin Cancer Biol. 2020;60:351–361. doi: 10.1016/j.semcancer.2019.08.019
95. Круг Д., Бауман М., Буддах В. Радиотерапия рака молочной железы: современные международные стандарты // Стратегии и тактики в лучевой терапии злокачественных опухолей / Под ред. С.В.Иванова. М.: Медицинское информационное агентство, 2020. Гл. 6. С. 125–155 [Krug D., Bauman M., Buddakh V. Radiotherapy of Breast Cancer: Current International Standards. Strategii i Taktiki v Luchevoy Terapii Zlokachestvennykh Opukholey = Strategies and Tactics in Radiation Therapy of Malignant Tumors. Ed. S.V. Ivanov. Moscow, Meditsinskoye Informatsionnoye Agentstvo Publ., 2020. Ch. 6. Pp. 125-155 (In Russ.)].
96. Herskind, C. Normal tissue reactions and mechanisms / C. Herskind, J. Talbot. Radiobiology Textbook / Ed. by M. Joiner, A. van der Kogel. Springer, 2019:205–236. doi: 10.1007/978-3-319-96845-2_7.
97. Di Maggio, F.M. Portrait of inflammatory response to ionizing radiation treatment / F.M. Di Maggio, E. Minafra, G. Forte, V. Bravatà. Journal of Inflammation. 2015;12:14. doi: 10.1186/s12950-015-0058-3.
98. Lumniczky, K. Radiation-induced changes in the cytokine profile of the tumor microenvironment / K. Lumniczky, G. Sáfrány. Seminars in Cancer Biology. 2022;86;2:92–106. doi: 10.1016/j.semcancer.2021.12.010.
99. Proctor, M.J. Systemic Inflammation Predicts Cancer Survival: A Glasgow Inflammation Outcome Study. Cancer Research Frontiers. 2016;2;1:1–20. doi: 10.17980/2016.1.
100. Kumari, N. Role of interleukin-6 in cancer progression and therapeutic resistance / N. Kumari, B.S. Dwarakanath, A. Das, A.N. Bhatt. Tumor Biology. 2016;37;9:11553–11572. doi: 10.1007/s13277-016-5098-7.
101. Barcellos-Hoff, M.H. The evolution of the cancer niche during multistage carcinogenesis / M.H. Barcellos-Hoff, D. Lyden, T.C. Wang. Nature Reviews Cancer. 2013;13;7:511–518. doi: 10.1038/nrc3536.
102. Stone, H.B. Effects of radiation on normal tissue: consequences and mechanisms / H.B. Stone, C.N. Coleman, M.S. Anscher, W.H. McBride. The Lancet Oncology. 2003;4;9:529–536. doi: 10.1016/S1470-2045(03)01191-4.
103. Templeton, A.J. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis / A.J. Templeton, M.G. McNamara, B. Šeruga, F.A. Vera-Badillo, P. Aneja, A. Ocaña, R. Leibowitz-Amit, G. Sonpavde, J.J. Knox, B. Tran, I.F. Tannock, E. Amir. Journal of the National Cancer Institute. 2014;106;6:dju124. doi: 10.1093/jnci/dju124.
104. Zhang, Y. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis / Y. Zhang, L. Lv, Y. Zhang, X. Zhang, Y. Zhang, H. Wang, C. Yan, H. Li. Journal of Cellular Physiology. 2022;237;2:1321–1334. doi: 10.1002/jcp.30609.
105. Gu, L. The association of pre-treatment neutrophil to lymphocyte ratio with response to neoadjuvant chemotherapy and survival outcomes in breast cancer patients: A systematic review and meta-analysis / L. Gu, H. Ma, M. Qian, X. Zhang, L. Zhao, H. Li. Breast Cancer Research and Treatment. 2021;188;1:1–12. doi: 10.1007/s10549-021-06157-z.
106. Кудинова А.С., Губанова Т.Н., Шаповал С.А. Значение нейтрофильно-лимфоцитарного индекса в прогнозировании течения рака молочной железы // Современные проблемы науки и образования. 2020. №6. С. 95 [Kudinova A.S., Gubanova T.N., Shapoval S.A. The Importance of the Neutrophil-Lymphocyte Index in Predicting the Course of Breast Cancer Sovremennyye Problemy Nauki i Obrazovaniya = Modern Problems of Science and Education. 2020;6:95 (In Russ.)]. doi: 10.17513/spno.30285.
107. Ethier J.L, Desautels D., Templeton A., Shah P.S., Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Research. 2017;19;1:2. doi: 10.1186/s13058-016-0794-1.
108. Klinger, M.H. Platelets and inflammation. Platelets. 2021;32;3:314–322. doi: 10.1080/09537104.2020.1797321.
109. Hong, J. Prognostic value of pretreatment platelet-to-lymphocyte ratio in patients with breast cancer: a meta-analysis / J. Hong, X. Chen, W. Gao, S. Zhu, L. Wu. OncoTargets and Therapy. 2016;9:6707–6715. doi: 10.2147/OTT.S109595.
110. Chan, J.C.Y. The lymphocyte-to-monocyte ratio is a superior predictor of overall survival compared to established biomarkers in patients with metastatic breast cancer / J.C.Y. Chan, D.Y. Chan, D.A. Diakos, A. Engel, S.J. Pavlakis, A. Gill, K.A. Clarke, A. Bokey, S.J. Clarke, N. Al-Hashem. Journal of Clinical Oncology. 2015;33;15_suppl:1102. doi: 10.1200/jco.2015.33.15_suppl.1102.
111. Chen, Y. Prognostic significance of the combination of preoperative hemoglobin and lymphocyte-to-monocyte ratio in operable breast cancer patients / Y. Chen, K. Chen, X. Xiao, Y. Nie, S. Qu, J. Gong, J. Wu, H. Wu. Cancer Management and Research. 2020;12:3013–3023. doi: 10.2147/CMAR.S244764.
112. Hu, B. The systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma / B. Hu, X.R. Yang, Y. Xu, Y.F. Sun, C. Sun, W. Guo, X. Zhang, W.M. Wang, S.J. Qiu, J. Zhou, G.M. Shi. Clinical Cancer Research. 2014;20;23:6212–6222. doi: 10.1158/1078-0432.CCR-14-0442.
113. Guo, W. Systemic immune-inflammation index (SII) is useful to predict survival outcomes in patients with surgically resected non-small cell lung cancer / W. Guo, S. Lu, Y. Lu, Y. Ni, L. Shen, J. Wang, Z. Zhao, Z. Zhao, Y. Wu, J. Xia, J. Cai. Thoracic Cancer. 2021;12;2:197–206. doi: 10.1111/1759-7714.13741. 
114. Li, X. Prognostic value of the systemic immune-inflammation index in patients with breast cancer: a meta-analysis / X. Li, Y. Dai, S. Li, Z. Chen, X. Li. Cancer Cell International. 2020;20:224. doi: 10.1186/s12935-020-01308-6.
115. Allin, K.H. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer / K.H. Allin, B.G. Nordestgaard. Critical Reviews in Clinical Laboratory Sciences. 2011;48;4:155–170. doi: 10.3109/10408363.2011.599831.
116. Al Murri, A.M. Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer / A.M. Al Murri, J.M.C. Bartlett, O.E. Canney, A. Doughty, C. Wilson, D.C. McMillan. British Journal of Cancer. 2006;94;2:227–230. doi: 10.1038/sj.bjc.6602922.
117. Pierce, B.L. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients / B.L. Pierce, R. Ballard-Barbash, L. Bernstein, R.N. Baumgartner, M.L. Neuhouser, M.H. Wener, K.B. Baumgartner, F.D. Gilliland, B.E. Sorensen, A. McTiernan, C.M. Ulrich. Journal of Clinical Oncology. 2009;27;21:3437–3444. doi: 10.1200/JCO.2008.18.9068.
118. McMillan, D.C. Systemic inflammation, nutritional status and survival in patients with cancer / D.C. McMillan. Current Opinion in Clinical Nutrition and Metabolic Care. 2009;12;3:223–226. doi: 10.1097/MCO.0b013e32832a7902.
119. Chen Y, Zhong H, Zhao Y, et al. Role of platelet biomarkers in inflammatory response. Biomark Res. 2020;8:28. doi: 10.1186/s40364-020-00207-2.
120. Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33;3:127–148. doi: 10.1093/intimm/dxaa078.
121. Korkaya, H. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population / H. Korkaya, G. Kim, A. Davis, F. Malik, N.L. Henry, S. Ithimakin, A. Quraishi, N. Tawakkol, R. D’Angelo, A.K. Paulson, S. Chung, T. Luther, H. Paholak, S. Liu, K.S. Hassan, Q. Zen, K.A. Clouthier, M.S. Wicha. Molecular Cell. 2012;47;4:570–584. doi: 10.1016/j.molcel.2012.06.014.
122. Zhang, G.J. Serum levels of interleukin-6 and titers of antibodies against p53 are related to prognosis in breast cancer patients in a Chinese population / G.J. Zhang, I. Adachi. Anticancer Research. 1999;19;3B:2215–2219.
123. Todorović-Raković N, Milovanović J. Interleukin-8 in breast cancer progression. J Interferon Cytokine Res. 2013;33;10:563–570. doi: 10.1089/jir.2013.0023.
124. Yi M, Peng C, Xia B, et al. CXCL8 facilitates the survival and pacli-taxel-resistance of triple-negative breast cancers. Clin Breast Cancer. 2022;22;2:e191–e198. doi: 10.1016/j.clbc.2021.06.009.
125. Симбирцев А.С. Цитокины в патогенезе и лечении заболеваний человека. М.: Фолиант, 2018. 52 с. [Simbirtsev AS. Tsitokiny v Patogeneze i Lechenii Zabolevaniy Cheloveka = Cytokines in the Pathogenesis and Treatment of Human Diseases. Moscow, Foliant Publ., 2018. 52 p. (In Russ.)].
126. Kaur RP, Vasudeva K, Singla H, et al. Analysis of pro- and anti-inflammatory cytokine gene variants and serum cytokine levels as prognostic markers in breast cancer. J Cell Physiol. 2018 Dec;233(12):9716-9723.  doi: 10.1002/jcp.26901.  Epub 2018 Aug 4.
127. Lv Z, Liu M, Shen J, et al. Association of serum interleu-kin-10, interleukin-17A and transforming growth factor-α levels with human benign and malignant breast diseases. Exp Ther Med. 2018;15;6:5475–5480. doi: 10.3892/etm.2018.6109.
128. Paccagnella M, Abbona A, Michelotti A, et al. Circulating cytokines in metastatic breast cancer patients select different prognostic groups and patients who might benefit from treatment beyond progression. Vaccines (Basel). 2022;10;1:78. doi: 10.3390/vaccines10010078.
129. Kawaguchi K, Sakurai M, Yamamoto Y, et al. Alteration of specific cytokine expression patterns in patients with breast cancer. Sci Rep. 2019;9;1:2924. doi: 10.1038/s41598-019-39476-9.
130. Bower, J.E. Inflammation and cancer-related fatigue: Mechanisms, contributing factors, and treatment implications / J.E. Bower. Brain, Behavior, and Immunity. 2014;30:S48–S57. doi: 10.1016/j.bbi.2012.06.011.
131. Коренков В.И., Ожогин А.А. Молекулярные механизмы радиационно-индуцированного фиброза: роль трансформирующего ростового фактора бета // Радиационная биология. Радиоэкология. 2018. Т.58. №6. С. 579–587 [Korenkov V.I., Ozhogin A.A. Molecular Mechanisms of Radiation-Induced Fibrosis: the Role of Transforming Growth Factor Beta. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 2018;58;6:579–587 (In Russ.)]. doi: 10.1134/S0869803118060058.
132. Liu, J. Prognostic value of inflammatory scores in patients with breast cancer: a real-world study / J. Liu, Y. Chen, X. Ling, L. Chen, Y. Wang, J. Wang. Annals of Translational Medicine. 2021;9;17:1389. doi: 10.21037/atm-21-3821.
133. 133            Bottai, G. An immune inflammation score predicts prognosis of patients with operable breast cancer: results from a multicenter study / G. Bottai, C. Truffi, M. Corsi, F. Santarpia, F. Bianchi, M. Marrazzo, M. Di Benedetto, S. Morganti, M. Vingiani, L. Bonini, F. Sottotetti, M. Callari, F. Riva, P. Verderio, M. Sandri, L. Bascialla, M. Battuello, M. Generali, M. Campanile, L. Despini, P. Veronesi, V. Galimberti, M. Tagliabue, T. Triulzi. OncoImmunology. 2021;10;1:1852795. doi: 10.1080/2162402X.2020.1852795.
134. Zhong, S. The role of anti-inflammatory drugs in colorectal cancer / S. Zhong, L. Chen, X. Zhang, D. Yu, J. Tang, J. Zhao. Annual Review of Pharmacology and Toxicology. 2023;63:449–472. doi: 10.1146/annurev-pharmtox-051921-023206.
135. McBride, W.H. Radiation and the microenvironment - tumorigenesis and therapy / W.H. McBride, C.S. Chiang, J.L. Olson, C.C. Wang, J.H. Hong, F. Pajonk, G.J. Dougherty, K.S. Iwamoto, M. Pervan, Y.P. Liao. Nature Reviews Cancer. 2004;4;11:860–867. doi: 10.1038/nrc1475.
136. Lumniczky, K. Radiation-induced changes in the cytokine profile of the tumor microenvironment / K. Lumniczky, G. Sáfrány. Seminars in Cancer Biology. 2022;86;2:92–106. doi: 10.1016/j.semcancer.2021.12.010.
137. Galli, F. Relevance of Immune Cell and Tumor Microenvironment Imaging in the New Era of Immunotherapy / F. Galli, A. Aguilera, A. Esposito, R. C. Delgado, A. L. Malvi, M. I. Ferrer, C. L. Rossi, F. D. Lorenzo. Journal of Experimental & Clinical Cancer Research. 2020;39;1:89. doi: 10.1186/s13046-020-01586-y.
138. Demaria, S. Role of Local Radiation Therapy in Cancer Immunotherapy / S. Demaria, M. L. Formenti. JAMA Oncology. 2015;1;9:1325–1332. doi: 10.1001/jamaoncol.2015.2756.
139. Formenti, S.C. Radiotherapy effects on anti-tumor immunity: implications for cancer treatment / S.C. Formenti, S. Demaria. Frontiers in Oncology. 2013;3:128. doi: 10.3389/fonc.2013.00128.
140. Yovino, S. The etiology of Treatment-Related Lymphopenia in Patients with Malignant Gliomas: Modeling Radiation Dose to Circulating Lymphocytes Explains Clinical Observations and Suggests Methods of Modifying the Impact of Radiation on Immune Cells / S. Yovino, R. Grossman. Cancer Investigation. 2013;31;2:140–144. doi: 10.3109/07357907.2012.762780.
141. Dancey, J. Radiation-induced apoptosis in human lymphocytes: potential as a biological dosimeter / J. Dancey, E. Depledge, A. Norman, K. Childs, R. Savage. Health Physics. 1996;71;5:685–691. doi: 10.1097/00004032-199611000-00011.
142. Golden, E.B. An Abscopal Response to Radiation and Ipilimumab in a Patient with Metastatic Non–Small Cell Lung Cancer / E.B. Golden, S. Demaria, P.B. Schiff, A. Chachoua, S.C. Formenti. Cancer Immunology Research. 2013;1;6:365–372. doi: 10.1158/2326-6066.CIR-13-0115.
143. Galluzzi, L. Immunogenic cell death in cancer and infectious disease / L. Galluzzi, A. Buqué, O. Kepp, L. Zitvogel, G. Kroemer. Nature Reviews Immunology. 2017;17;2:97–111. doi: 10.1038/nri.2016.107.
144. Vanpouille-Box, C. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity / C. Vanpouille-Box, J.M. Diamond, K.A. Pilones, J. Zavadil, S.C. Formenti, M. Barcellos-Hoff, S. Demaria. Nature Communications. 2017;8;1:15618. doi: 10.1038/ncomms15618.
145. Deng, L. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice / L. Deng, H. Liang, M. Xu, X. Yang, B. Burnette, A. Arina, X.-D. Li, H. Mauceri, M. Beckett, T. Darga, X. Huang, T.F. Gajewski, Z.J. Chen, Y.-X. Fu, R.R. Weichselbaum. Journal of Clinical Investigation. 2014;124;2:687–695. doi: 10.1172/JCI67313.
146. Gropper, A.B. Culturing CTLs under Hypoxic Conditions Enhances Their Cytolysis and Improves Their Anti-tumor Function / A.B. Gropper, R. Shapira, R. Dahan, T. Meir, N. Karako-Lampert, K. Hershkovitz, A. Elboim, O. Mandelboim. Cell Reports. 2017;18;4:920–931. doi: 10.1016/j.celrep.2016.12.078.
147. Reits, E.A. Radiation modulates the peptide repertoireenhances MHC class I expression, and induces successful antitumor immunotherapy / E.A. Reits, J.W. Hodge, C.A. Herberts, T.A. Groothuis, M. Chakraborty, E.K. Wansley, K. Camphausen, R.M. Luiten, A.H. de Ru, J. Neijssen, A. Griekspoor, J. Mesman, F.A. Vyth-Dreese, T. van Hall, B. Ossendorp, J.J. Neefjes, J.P. Schlom, H.M. Pinedo. Journal of Experimental Medicine. 2006;203;5:1259–1271. doi: 10.1084/jem.20052494.
148. Lhuillier, C. Radiotherapy-exposed CD8+ and CD4+ neoantigens enhance tumor control / C. Lhuillier, N. Rudqvist, T. Yamazaki, T. Zhang, M. Charpentier, J. Galluzzi, S. Dephoure, R. Clancy-Thompson, P. Lussier, J. P. G. Vanpouille-Box, S. Demaria, S.C. Formenti, J. N. Kochenderfer, E. Stanchina, E. R. Fearon, E. A. Grimm, S. W. Lowe, R. D. Schreiber, S. A. Chow, K. S. Campbell, N. P. Restifo, S. C. Formenti. Journal of Clinical Investigation. 2021;131;5:e138740. doi: 10.1172/JCI138740.
149. Cho, O. Radiation-related Lymphopenia as a New Prognostic Factor in Limited-stage Small Cell Lung Cancer / O. Cho, M. Chun, Y.-Y. Oh, M.H. Guak, Y.L. Noh. Tumori Journal. 2016;102;5:496–502. doi: 10.5301/tj.5000469.
150. Tang, C. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes / C. Tang, M.S. Liao, D.E. Gomez, C.L. Lee, C. Lin, X.R. Zhu, R. Mohan, J.Y. Chang. International Journal of Radiation Oncology, Biology, Physics. 2014;89;5:1084–1091. doi: 10.1016/j.ijrobp.2014.04.025.
151. Grossman, S.A. Immunosuppression in Patients with High-Grade Gliomas Treated with Radiation and Temozolomide / S.A. Grossman, J. Ye, G. Lesser, A. Sloan, H. Carraway, S. Desideri, S. Piantadosi. Clinical Cancer Research. 2011;17;16:5473–5480. doi: 10.1158/1078-0432.CCR-11-0774.
152. Смирнова Л.Е., Поддубная И.В., Гарин А.М. Динамика показателей клеточного иммунитета у больных раком молочной железы после комбинированного лечения // Российский биотерапевтический журнал. 2019. Т.18. №4. С. 44–50 [Smirnova L.Ye., Poddubnaya I.V., Garin A.M. Dynamics of Cellular Immunity Parameters in Breast Cancer Patients after Combination Treatment. Rossiyskiy Bioterapevticheskiy Zhurnal = Russian Journal of Biotherapy. 2019;18;4:44–50 (In Russ.)]. doi: 10.17650/1726-9784-2019-18-4-44-50.
153. Campian, J.L. Severe treatment-related lymphopenia in patients with newly diagnosed rectal cancer / J.L. Campian, M. Sarai, X. Ye, M. Marur, S.A. Grossman. Cancer Medicine. 2014;3;6:1505–1511. doi: 10.1002/cam4.321.
154. Schaue, D. T-cell responses to survivin in cancer patients undergoing radiation therapy / D. Schaue, W.H. McBride. Clinical Cancer Research. 2005;11;14:5204–5211. doi: 10.1158/1078-0432.CCR-05-0098.
155. Kachikwu, E.L. Radiation enhances regulatory T cell representation / E.L. Kachikwu, K.S. Iwamoto, Y.-P. Liao, J.-J. Wang, F. DeMarco, P. Agazaryan, T.G. Economou, J.S. Nelson, W.H. McBride. International Journal of Radiation Oncology, Biology, Physics. 2011;81;4:1128–1135. doi: 10.1016/j.ijrobp.2010.09.034.
156. Petit, T. Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer / T. Petit, M. Haegele, P. Fargeot, J. Ghnassia, J. Vogel, J. Bey. Breast Cancer Research. 2001;3;3:157–163. doi: 10.1186/bcr290.
157. Lissoni, P. Effects of radiotherapy on the lymphocyte subpopulations and lymphokine-activated killer cell activity in cancer patients / P. Lissoni, F. Rovelli, F. Brivio, A. Ardizzoia, M. Cazzaniga, G. Tancini. Tumori Journal. 1990;76;5:464–467. doi: 10.1177/030089169007600510.
158. Potter, R. In vivo parameters influencing the fate of T-cell receptor (TCR)-transduced T cells after locoregional adoptive transfer for cancer therapy / R. Potter, K. Schuler, J. Geiselhart, K. Losch, M. Wiesinger, L. Edinger, U. Gückel, A. Mackensen, R. Handgretinger, U. M. Lauer. Cancer Immunology, Immunotherapy. 2001;50;4:200–210. doi: 10.1007/s002620100190.
159. Qu, Y. Gamma-ray resistance of regulatory CD4+CD25+Foxp3+ T cells in mice / Y. Qu, J. Zhang, G. Wu, H. Zhang, J. Wang, P. Zhang, X. Liu, F. Du, X. Cao, Z. Liu. Radiation Research. 2010;173;2:148–157. doi: 10.1667/RR1989.1.
160. Balmanoukian, A. The association between treatment-related lymphopenia and survival in newly diagnosed patients with resected adenocarcinoma of the pancreas / A. Balmanoukian, X. Ye, K. Herman, E. Laheru, S.A. Grossman. Cancer Investigation. 2012;30;8: 571–576. doi: 10.3109/07357907.2012.700987.
161. Lee, Y. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment / Y. Lee, S.L. Auh, Y. Wang, B. Burnette, Y. Wang, Y. Meng, M. Beckett, R. Sharma, R. Chin, T. Tu, M.J. Weichselbaum, R.R. Fu. Blood. 2009;114;3:589–595. doi: 10.1182/blood-2009-02-206870.
162. Weichselbaum, R.R. Radiotherapy and immunotherapy: a beneficial liaison? / R.R. Weichselbaum, H. Liang, L. Deng, Y.-X. Fu. Nature Reviews Clinical Oncology. 2017;14;6:365–379. doi: 10.1038/nrclinonc.2016.211.
163. Dovedi, S.J. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade / S.J. Dovedi, A.L. Adlard, G. Lipowska-Bhalla, C. McKenna, S. Jones, E.J. Cheadle, I.F. Stratford, M. Poon, R. Morrow, V. Stewart, C. Crowther, H. Wykosky, L.A. Emens, P. Hersey, M.J. Glennie, A. Patin, R.W. Wilkinson, R. Illidge. Cancer Research. 2014;74;19:5458–5468. doi: 10.1158/0008-5472.CAN-14-1258.
164. Schaue, D. Regulatory T cells in radiotherapeutic responses / D. Schaue, W.H. McBride. Frontiers in Oncology. 2012;2;Art. 90. doi: 10.3389/fonc.2012.00090.
165. Sakaguchi, S. Regulatory T Cells and Human Disease / S. Sakaguchi, K. Wing, Y. Onishi, P. Prieto-Martin, T. Yamaguchi. Annual Review of Immunology. 2020;38:541–566. doi: 10.1146/annurev-immunol-042718-041717.
166. Klug, F. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy / F. Klug, H. Prakash, P.E. Huber, T. Seibel, N. Bender, N. Halama, C. Pfirschke, R.H. Voss, C. Timke, L. Umansky, K. Klapproth, K. Schakel, S. Garbi, D. Jäger, J. Weitz, H. Schmitz-Winnenthal, G.J. Hammerling, P. Beckhove. Cancer Cell. 2013;24;5:589–602. doi: 10.1016/j.ccr.2013.09.014.
167. Shiao, S.L. TH2-Polarized CD4+ T Cells and Macrophages Limit Efficacy of Radiotherapy / S.L. Shiao, S. Ruffell, D. DeNardo, B.M. Faddegon, C.C. Park, L.M. Coussens. Cancer Immunology Research. 2015;3;5:518–525. doi: 10.1158/2326-6066.CIR-14-0232.
168. Sakaguchi, S. FOXP3+ regulatory T cells in the human immune system / S. Sakaguchi, M. Miyara, C. Costantino, D. Hafler. Nature Reviews Immunology. 2010;10;7:490–500. doi: 10.1038/nri2785.
169. Vitale, M. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor / M. Vitale, C. Bottino, S. Sivori, L. Sanseverino, R. Castriconi, E. Marcenaro, R. Augugliaro, L. Moretta, A. Moretta. Blood. 2005;106;2:566–571. doi: 10.1182/blood-2004-10-4035.
170. Krijgsman, D. Natural Killer Cells in Clinical Development as Non-Engineered, Engineered, and Combination Therapies / D. Krijgsman, P. Hokland, P.J.K. Kuppen. Journal of Hematology & Oncology. 2022;15;1;Art. 164. doi: 10.1186/s13045-022-01382-5.
171. Kopp, H.G. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy / H.G. Kopp, S.T. Placke, H.R. Salih. Blood. 2009;114;3:589–595. doi: 10.1182/blood-2009-01-201368. (Об NK при РМЖ см. след.)
172. Gasser, S. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor / S. Gasser, S. Orsulic, E.J. Brown, D.H. Raulet. Nature. 2005;436;7054:1186–1190. doi: 10.1038/nature03884.
173. Janssen, E.M. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes / E.M. Janssen, E.E. Lemmens, T. Wolfe, U. Christen, M.G. von Herrath, S.P. Schoenberger. Nature. 2003;421;6925:852–856. doi: 10.1038/nature01441.
174. Merrick, A.  Immunosuppressive effects of radiation on human dendritic cells: reduced IL-12 production on activation and impairment of naïve T-cell priming / A. Merrick, J. Errington, K. Jones, K. O’Donnell, K. Self, K. Harrington, R. Pandha, L. Vile, P. Selby, R. Prestwich, A. Melcher. British Journal of Cancer. 2005;92;8:1450–1458. doi: 10.1038/sj.bjc.6602518.
175. Moeller, B.J. Radiation Activates HIF-1 to Regulate Vascular Radiosensitivity in Tumors: Role of Reoxygenation, Free Radicals, and Stress Granules / B.J. Moeller, Y. Cao, C.Y. Li, M.W. Dewhirst. Cancer Cell. 2004;5;5:429–441. doi: 10.1016/S1535-6108(04)00115-1.
176. Wild, A.T. Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients with Unresectable Pancreatic Cancer / A.T. Wild, J.M. Herman, K.S. Dholakia, T.R. Moningi, Y. Lu, T.M. Rosati, S.A. Pawlik, E.K. Fishman, R.H. Hruban, E.J. Wolfgang, L. Zheng, D. Laheru, E.G. Weiss, M.G. Goggins, J.L. Cameron, C.L. Wolfgang, J. Tran. International Journal of Radiation Oncology, Biology, Physics. 2016;94;3:571–579. doi: 10.1016/j.ijrobp.2015.11.026.
177. Bates, G.J. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse / G.J. Bates, S.B. Fox, C. Han, R.D. Leek, J.F. Garcia, A.L. Harris, A.H. Banham. Journal of Clinical Oncology. 2006;24;34:5373–5380. doi: 10.1200/JCO.2006.05.9584.
178. Denkert, C. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer / C. Denkert, G. von Minckwitz, S.D. Darb-Esfahani, B. Lederer, B.M. Heppner, K.E. Weber, J. Budczies, J. Huober, F. Klauschen, J.U. Blohmer, S. Loibl, M. Schmitt, W.D. Schmitt, K.S. Tesch, P.A. Fasching, K. Engels, C. Schneeweiss, A. Hartmann, W. Dietel, K. Engels, C. Schneeweiss, A. Hartmann, W. Dietel, K. Engels, C. Schneeweiss, A. Hartmann, W. Dietel. Journal of Clinical Oncology. 2010;28;1:105–113. doi: 10.1200/JCO.2009.23.7370.
179. 179..          Twyman-Saint Victor, C. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer / C. Twyman-Saint Victor, A.J. Rech, A. Maity, R. Rengan, K.E. Pauken, E. Stelekati, J.L. Benci, B. Xu, H. Dada, P.M. Odorizzi, R.S. Herati, K.D. Mansfield, D. Patsch, R.K. Amaravadi, L.M. Schuchter, H. Ishwaran, R. Mick, D.A. Pryma, X. Xu, M.D. Feldman, T.C. Gangadhar, S.M. Hahn, E.J. Wherry, R.H. Vonderheide, A.J. Minn. Nature. 2015;520;7547:373–377. doi: 10.1038/nature14292.
180. Theelen, W.S.M.E. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non–Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial / W.S.M.E. Theelen, H.M.U. Peulen, F. Lalezari, V. van der Noort, J.F. de Vries, J.G. Aerts, M.A. Dumoulin, I. Bahce, M. Niemeijer, C. De Langen, E.F. Smit, H.J.M. Groen, E. E. Schuurbiers, J. P. J. van der Heijden, E. H. F. M. van der Heijden, C. H. van den Heuvel, C. M. L. Herder, G. J. M. Herder, C. R. C. Riedl, M. H. F. M. van der Heijden, C. H. van den Heuvel, C. M. L. Herder, G. J. M. Herder, C. R. C. Riedl, M. H. F. M. van der Heijden, C. H. van den Heuvel, C. M. L. Herder, G. J. M. Herder, C. R. C. Riedl. JAMA Oncology. 2019;5;9:1276–1282. doi: 10.1001/jamaoncol.2019.1478.
181. Huang, A.C. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response / A.C. Huang, M.A. Postow, R.J. Orlowski, R. Mick, B. Bengsch, S. Manne, W. Xu, S. Harmon, J.R. Giles, B. Wenz, M. Adamow, D. Kuk, K.S. Panageas, C. Carrera, P. Wong, F. Quagliarello, B. Wubbenhorst, K. D’Andrea, K.L. Pauken, R.C. Herati, R.P. Staupe, J.M. Schenkel, S. McGettigan, S. Kothari, S.M. George, R.H. Vonderheide, R.K. Amaravadi, G.C. Karakousis, L.M. Schuchter, X. Xu, K.L. Nathanson, J.D. Wolchok, E.J. Wherry, T.C. Gangadhar. Nature. 2017;545;7652:60–65. doi: 10.1038/nature22079.
182. Martin, M. Late normal tissue sequelae from radiation therapy for carcinoma of the tonsil: patterns of fractionation study of radiobiology / M. Martin, F. Lefaix, S. Delanian. International Journal of Radiation Oncology, Biology, Physics. 2000;48;3:737–744. doi: 10.1016/S0360-3016(00)00685-4.
183. Demaria, S. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated / S. Demaria, B. Ng, M.L. Devitt, J.S. Babb, N. Kawashima, L. Liebes, S.C. Formenti. International Journal of Radiation Oncology, Biology, Physics. 2004;58;3:862–870. doi: 10.1016/j.ijrobp.2003.09.012.
184. De Wolf, K. The potential of hypofractionated radiation therapy to improve the therapeutic ratio in breast cancer / K. De Wolf, P. Ost. Breast Care. 2013;8;1:33–38. doi: 10.1159/000346826.
185. Deutsch, E. Stereotactic ablative radiation therapy for oligometastatic cancer: a new standard of care or a fad? / E. Deutsch, J. Soria, D. Planchard, J. Bahleda, C. Le Péchoux, A. Dunant, F. André, P. Besse. The Lancet Oncology. 2013;14;6:e229–e238. doi: 10.1016/S1470-2045(13)70001-8.
186. Ghiringhelli, F. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients / F. Ghiringhelli, C. Menard, P.E. Puig, S. Ladoire, S. Roux, F. Martin, E. Solary, A. Le Cesne, L. Zitvogel, C. Chauffert. Cancer Immunology, Immunotherapy. 2007;56;5:641–648. doi: 10.1007/s00262-006-0225-8.
187. Kirkwood, J.M. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684 / J.M. Kirkwood, M.H. Strawderman, M.S. Ernstoff, T.J. Smith, E.C. Borden, R.H. Blum. Journal of Clinical Oncology. 1996;14;1:7–17. doi: 10.1200/JCO.1996.14.1.7.
188. Балдуева С.А., Липатова А.В. Роль фактора некроза опухоли-альфа в онкогенезе // Онкология. Журнал им. П.А. Герцена. 2018. Т.7. №3. С. 45-53 [Balduyeva S.A., Lipatova A.V. The Role of Tumor Necrosis Factor-Alpha in Oncogenesis. Onkologiya. Zhurnal im. P.A. Gertsena = P.A. Herzen Journal of Oncology. 2018;7;3:45-53 (In Russ.)]. doi: 10.17116/onkolog20187345-53.
189. Wilson AG, Symons JA, McDowell TL, et al. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997;94;7:3195-3199. doi: 10.1073/pnas.94.7.3195.
190. Козлов В.А. Цитокины: регуляция иммунного ответа при патологии // Медицинская иммунология. 2003. Т.5. №5-6. С. 465-478 [Kozlov V.A. Cytokines: Regulation of the Immune Response in Pathology. Meditsinskaya Immunologiya = Medical Immunology. 2003;5;5-6:465-478 (In Russ.)].
191. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71;3:209-249. doi: 10.3322/caac.21660.
192. Balkwill F. TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev. 2006;25;3:409-416.doi: 10.1007/s10555-006-9005-3.
193. Sethi G, Sung B, Aggarwal BB. TNF: a master switch for inflammation to cancer. Front Biosci. 2008;13:5094-5107. doi: 10.2741/3066.
194. Leek RD, Landers RJ, Harris AL, Lewis CE. Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J. Cancer. 1999 Feb;79;5-6:991-5. doi: 10.1038/sj.bjc.6690158.

 PDF (RUS) Full-text article (in Russian)

Conflict of interest. The authors declare no conflict of interest.

Compliance with ethical standards. The study was approved by the Bioethics Committee at the section of the Academic Council of the A.I. Burnazyan Federal Medical Biophysical Center (extract No. 112 dated 22.11.2023).

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.01.2026. Accepted for publication: 25.02.2026.

Medical Radiology and Radiation Safety. 2026. Vol. 71. № 2

DOI:10.33266/1024-6177-2026-71-2-129-134

I.V. Sycheva¹, S.A. Ivanov^{1, 2}, A.D. Kaprin^{2, 3, 4}

Treatment of Total Necrosis of the Vagina with Vulvar Necrosis (Grade Iv) after Chemoradiotherapy of Cervical Cancer

¹ A.F. Tsyb Medical Radiological Research Centre, Obninsk, Russia

² P. Lumumba Рeoples Friendship University of Russia, Moscow, Russia

³ National Medical Research Radiological Centre, Obninsk, Russia

⁴ P.A. Hertsen Moscow Oncology Research Institute, Moscow, Russia

Contact person: I.V. Sycheva, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Relevance: Radiation therapy (RT) is widely used for the treatment of cervical cancer, however, a number of patients develop radiation complications of nearby organs with the development of late radiation cystitis, urethritis, proctitis and late radiation epithelitis of the vagina and vulva, which worsen the quality of life. There are very few scientific publications in Russia and abroad on late radiation ulcerative necrotic epithelitis of the vagina and vulva, with a small number of clinical cases. There are still no uniform standards for the treatment of this disease worldwide. Often, patients after RT have a combination of late radiation injuries (RI) to the pelvic organs (vagina and vulva, rectum, bladder). 

Purpose: To demonstrate the successful comprehensive conservative treatment of late radiation ulcerative necrotic epithelitis of the vagina and vulva (total ulceration and necrosis of the vagina with vulvar necrosis, grade IV toxicity according to the RTOG/EORTC classification). Remission was obtained after 11 months and persists to the present (6 years). There were no complications in the treatment of necrosis. This disease developed after complex treatment with type IIA1 breast cancer (pT₂a₁N₀M₀). CRT + Wertheim’s operation in 2012. EBRT TFD 30 Gy. Metastasis to the lower third of the vagina in 2017. CRT. TFD: BT 30 Gy and EBRT 18 Gy. Conservative therapy during the treatment of necrosis was performed every 3 months, then for late radiation proctitis, grade II cystitis ‒ every six months. In January 2023, metastasis to the left inguinal lymph node was detected, and surgery was performed: left-sided inguinal lymphadenectomy, crossectomy for thrombosis of the large saphenous vein on the left. 9 lymph nodes were removed, 1 of which has metastasis of squamous cell carcinoma. Next, the patient received 6 cycles of polychemotherapy (carboplatin + paclitaxel) on the background of anticoagulants. The patient is currently in remission of RI in our department. 

Conclusion: Total necrosis of the vagina is a rare disease, the description of which is extremely rare in the literature. It is necessary to raise awareness about late-stage RI, further study of this pathology and new approaches in the treatment of this category of patients. In this clinical case, he was successfully treated and received remission for 6 years without complications. Pronounced late local RI are not a guarantee of the absence of recurrence or progression of the underlying cancer in the future. 

Keywords: cervical cancer, radiation therapy, radiation complications, radiation ulcerative-necrotic epithelitis of the vagina and vulva, radiation proctitis, radiation cystitis

For citation: Sycheva IV, Ivanov SA, Kaprin AD. Treatment of Total Necrosis of the Vagina with Vulvar Necrosis (Grade Iv) after Chemoradiotherapy of Cervical Cancer. Medical Radiology and Radiation Safety. 2026;71(2):129–134. DOI:10.33266/1024-6177-2026-71-2-129-134

References

1. International Agency for Research on Cancer (IARC) (In Russ.). URL: https://gco.iarc.fr/today/en/dataviz/bars? (Date of Access 27/06/2025).
2. Kaprin A.D., Starinskiy V.V., Shakhzadova A.O. Zlokachestvennyye Novoobrazovaniya v Rossii v 2023 godu (Zabolevayemost’ i Smertnost’) = Malignant Neoplasms in Russia in 2023 (Incidence and Mortality). Moscow, MNIOI im. P.A.Gertsena − Filial NMITS Radiologii Minzdrava Rossii Publ., 2024. 276 p. (In Russ.).
3. Dunayeva Ye.A., Boyko A.V., Demidova L.V., et al. Conservative Methods of Prevention and Treatment of Radiation Injuries in Patients with Malignant Neoplasms of the Female Genital Organs. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost’ = Medical Radiology and Radiation Safety. 2015;60;5:59–73 (In Russ.).
4. Stolyarova I.V., Vinokurov V.A. Problems of Patients after Treatment of Cervical Cancer (Prevention and Treatment of Post-Radiation Complications). Prakticheskaya Onkologiya = Practical Oncology. 2002;3:220–227 (In Russ.).
5. Jia A.Y., Viswanathan A.N. Vaginal Necrosis: A Rare Late Toxicity after Radiation Therapy. Gynecol Oncol. 2021 Feb;160;2:602-609. Doi: 10.1016/j.ygyno.2020.11.025.
6. Fawaz Z.S., Barkati M., Beauchemin M.C., Sauthier P., Gauthier P., Nguyen T.V. Cervical Necrosis after Chemoradiation for Cervical Cancer: Case Series and Literature Review. Radiat Oncol. 2013 Sep 23;8:220. Doi: 10.1186/1748-717X-8-220.
7. Delishaj D., Barcellini A., D’Amico R., Ursino S,. Pasqualetti F., Fumagalli I.C., Soatti C.P. Vaginal Toxicity after High-Dose-Rate Endovaginal Brachytherapy: 20 Years of Results. J Contemp Brachytherapy. 2018 Dec;10;6:559-566. Doi: 10.5114/jcb.2018.79713. Epub 2018 Dec 28. PMID: 30662479; PMCID: PMC6335557.
8. Kazakova S.N., Teterina T.A., Apolikhina I.A., Ishchuk M.P. An Integrated Approach to the Rehabilitation of Women with Post-Radiation Complications after Endometrial Cancer (a Clinical Case). Doktor.Ru = Doctor.Ru. 2021;20;6:97–101 (In Russ.). Doi: 10.31550/1727-2378-2021-20-6-97-101.
9. Semirdzhanyants E.G., Petrovskiy A.V., Fanshteyn I.A., et al. Surgical Rehabilitation of Patients with Post-Radiation Rectovaginal Fistulas in Cervical Cancer. Koloproktologiya = Coloproctology. 2013;46;4:13–17 (In Russ.).
10. Topchiy T.B., Sycheva I.V., Rukhadze G.O., et al. Luchevyye Proktity = Radiation Proctitis. A Handbook for Physicians. Moscow, Prima Print Publ., 2019. 36 p. (In Russ.).
11. Sycheva I.V., Kaprin A.D., Pasov V.V., S.A. Ivanov S.A. Treatment of Late Radiation Injuries after Brachytherapy and Combined Radiation Therapy for Prostate Cancer. Voprosy Urologii i Andrologii = Urology and Andrology. 2014;3;3:15-20 (In Russ).
12. Kirwan J.M., Symonds P., Green J.A., Tierney J., Collingwood M., Williams C.J. A Systematic Review of Acute and Late Toxicity of Concomitant Chemoradiation for Cervical Cancer. Radiother Oncol. 2003 Sep;68;3:217-26. Doi: 10.1016/s0167-8140(03)00197-x.
13. Güth U., Ella W.A., Olaitan A., Hadwin R.J., Arora R., McCormack M. Total Vaginal Necrosis: a Representative Example of Underreporting Severe Late Toxic Reaction after Concomitant Chemoradiation for Cervical Cancer. Int J Gynecol Cancer. 2010;20;1:54-60. Doi: 10.1111/IGC.0b013e3181c4a63f.
14. Sycheva I.V., Severskaya N.V., Ivanov S.A., Kaprin A.D. Combined Treatment of Late  Grade  III Radiation  Proctitis  with  the  Use  of  Formalin of Reduced Concentration. Voprosy  Onkologii  =  Problems  in  Oncology. 2025; 71(5): 1102-1110.  (In Russian). doi: 10.37469/0507-3758-2025-71-5-OF-2462.
15. Kirchheiner K., Fidarova E., Nout R.A., et al. Radiationinduced Morphological Changes in the Vagina. Strahlenther. Onkol. 2012;188;11:1010–7. Doi: 10.1007/ s00066-012-0222-0.
16. Arakaki Y., Shimoji Y., Nakasone T., Taira Y., Nakamoto T., Kudaka W., Mekaru K., Aoki Y. Hyperbaric Oxygen Therapy for Suburethral Vaginal Mucosal Necrosis after Interstitial Irradiation for Recurrent Cervical Cancer. Case Rep Obstet Gynecol. 2021 Sep 9;2021:1737975. Doi: 10.1155/2021/1737975.
17. Sycheva I.V., Kaprin A.D., Ivanov S.A. Combination of Late Radiation Injuries of the Pelvic Organs in a Patient after Chemoradiation Therapy for Stage IIB Cervical Cancer cT2bN0M0 and their Treatment (a Clinical Example). Voprosy Onkologii = Problems in Oncology. 2022;68;1:90-105 (In Russ.). Doi: 10.37469/0507-3758-2022-68-1-99-105.
18. Sycheva I.V. Optimizatsiya Lecheniya Pozdnego Radiatsionnogo Proktita Posle Gormonoluchevogo Lecheniya Raka Predstatel’noy Zhelezy = Optimization of the Treatment of Late Radiation Proctitis after Hormonal Radiation Therapy for Prostate Cancer. Doctor’s Thesis (Med.). Moscow Publ., 2024. 167 p. (In Russ.).
19. Sycheva I.V. Luchevyye Povrezhdeniya Organov Malogo Taza u Onkoginekologicheskikh Bol’nykh i ikh Lecheniye = Radiation Injuries of the Pelvic Organs in Gynecologic Oncology Patients and their Treatment: Certificate of Database Registration RU 2020620609. Russian Federation; Applicant. National Medical Research Center of Radiology of the Ministry of Health of the Russian Federation. Priority date 03/20/2020. URL: https://elibrary.ru/item.asp?id=42711276.
20. Boyko I., Pasov V., Sycheva I., Kurpesheva A. Radiation Injuries in Patients with Prostate Cancer after Interstitial Radiation Therapy with Sealed I-125-Sources and Concurrent Radiation Therapy. Annals of Oncology. 2010;21;8:33.

 PDF (RUS) Full-text article (in Russian)

Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.01.2026. Accepted for publication: 25.02.2026.

Medical Radiology and Radiation Safety. 2026. Vol. 71. № 2

DOI:10.33266/1024-6177-2026-71-2-147-152

Zh.Zh. Smirnova, D.Yu. Bobrov, A.A. Zavialov

Predicting Gamma Passing Rate for Patient Specific Quality Assurance Using Machine and Deep Learning: A Review of Methodological Approaches

A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

Contact person: Zh.Zh. Smirnova, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

Introduction: In radiation therapy using advanced techniques such as intensity modulated radiation therapy (IMRT) and volumetric‐arc radiation therapy (VMAT), patient specific quality assurance (QA) should be performed before treatment. The measured and planned dose distributions are commonly quantified by means of a gamma analysis (Gamma Passing Rate, GPR). However, patient‐specific QA procedures are requiring significant time and effort by the physicists. Various ML and DL models have shown promising prediction accuracy and a high potential as time‐efficient virtual QA tool.

Purpose: In this paper, we review the ML and DL based models that were developed for patient specific IMRT and VMAT QA GPR predictions, as well as to identify perspective directions for future research in the field of virtual QA.

Conclusion: The prediction of Gamma Passing Rates (GPR) using Machine Learning (ML) and Deep Learning (DL) is a rapidly evolving and highly promising field. This review demonstrates the evolution of methodological approaches, from the analysis of individual plan complexity metrics to the application of ensemble regression models, and further to sophisticated deep learning architectures. Research confirms that these predictive models can accurately identify plans at risk of verification failure, paving the way for a risk-based approach and a significant reduction in routine measurements. Key challenges for broader clinical integration remain, including ensuring model interpretability, overcoming class imbalance in datasets, improving model generalizability, and their integration into clinical workflows. Successfully addressing these challenges will enable the creation of intelligent decision-support systems capable of enhancing the efficiency, safety, and standardization of radiotherapy.

Keywords: radiotherapy, PSQA, GPR, gamma analysis, prediction, Machine Learning, Deep Learning, virtual QA

For citation: Smirnova ZhZh, Bobrov DYu, Zavialov AA. Predicting Gamma Passing Rate for Patient Specific Quality Assurance Using Machine and Deep Learning: A Review of Methodological Approaches. Medical Radiology and Radiation Safety. 2026;71(2):147–152. (In Russian). DOI:10.33266/1024-6177-2026-71-2-147-152

References

1. Otto K. Volumetric Modulated Arc Therapy: IMRT in a Single Gantry Arc. Med Phys. 2008 Jan;35;1:310-7. Doi: 10.1118/1.2818738.
2. Miften M., Olch A., Mihailidis D., Moran J., Pawlicki T., Molineu A., Li H., Wijesooriya K., Shi J., Xia P., Papanikolaou N., A Low D. Tolerance Limits and Methodologies for IMRT Measurement-Based Verification QA: Recommendations of AAPM Task Group No. 218. Med Phys. 2018 Apr; 45;4:e53-e83. Doi: 10.1002/mp.12810.
3. Olch A.J. Dosimetric Performance of an Enhanced Dose Range Radiographic Film for Intensity‐Modulated Radiation Therapy Quality Assurance. Med Phys. 2002 Sep;29;9:2159-68. Doi: 10.1118/1.1500398.
4. Wouter van Elmpt, McDermott L., Nijsten S., Wendling M., Lambin P., Mijnheer B. A Literature Review of Electronic Portal Imaging for Radiotherapy Dosimetry. Radiother Oncol. 2008 Sep;88;3:289-309. Doi: 10.1016/j.radonc.2008.07.008.
5. Low D.A., Harms W.B., Mutic S., Purdy J.A. A Technique for the Quantitative Evaluation of Dose Distributions. Med Phys. 1998 May;25;5:656-61. Doi: 10.1118/1.598248.
6. Depuydt T., Van Esch A., Pierre Huyskens D. A Quantitative Evaluation of IMRT Dose Distributions: Refinement and Clinical Assessment of the Gamma Evaluation. Radiother Oncol. 2002 Mar;62;3:309-19. Doi: 10.1016/s0167-8140(01)00497-2.
7. Ford E.C., Terezakis S., Souranis A., Harris K., Gay H., Mutic S. Quality Control Quantification (QCQ): a Tool to Measure the Value of Quality Control Checks in Radiation Oncology. Int J Radiat Oncol Biol Phys. 2012 Nov 1;84;3:e263-9. Doi: 10.1016/j.ijrobp.2012.04.036.
8. Chan M.F., Witztum A., Valdes G. Integration of AI and Machine Learning in Radiotherapy QA. Front Artif Intell. 2020 Sep 29:3:577620. Doi: 10.3389/frai.2020.577620.
9. Valdes G., Chan M.F., Boh Lim Seng, Scheuermann R., O Deasy J., D Solberg T. IMRT QA Using Machine Learning: a Multi-Institutional Validation. J Appl Clin Med Phys. 2017 Sep;18;5:279-284. Doi: 10.1002/acm2.12161.
10. Международное агентство по атомной энергии. Искусственный интеллект в медицинской физике. Функции, обязанности, образование и подготовка медицинских физиков клинической квалификации: Серия учебных курсов №83. Вена: МАГАТЭ, 2025. 54 с. [Mezhdunarodnoye Agentstvo po Atomnoy Energii. Iskusstvennyy Intellekt v Meditsinskoy Fizike. Funktsii, Obyazannosti, Obrazovaniye i Podgotovka Meditsinskikh Fizikov Klinicheskoy Kvalifikatsii = Artificial Intelligence in Medical Physics. Roles, Responsibilities, Education, and Training of Clinically Qualified Medical Physicists. Training Course Series No. 83. Vienna, IAEA Publ., 2025. 54 p. (In Russ.)].
11. Younge K.C., Roberts D., Janes L.A., Anderson C., Moran J.M., Matuszak M.M. Predicting Deliverability of Volumetric-Modulated arc Therapy (VMAT) Plans Using Aperture Complexity Analysis. J Appl Clin Med Phys. 2016 Jul 8;17;4:124-31. Doi: 10.1120/jacmp.v17i4.6241.
12. McNiven A.L., Sharpe M.B., Purdie T.G. A New Metric for Assessing IMRT Modulation Complexity and Plan Deliverability. Med Phys. 2010 Feb;37;2:505-15. Doi: 10.1118/1.3276775.
13. Park J.M., Park S.-Y., Kim H. Modulation Index for VMAT Considering both Mechanical and Dose Calculation Uncertainties. Physics in Medicine & Biology. 2015;60;18:7101–7125. Doi: 10.1088/0031-9155/60/18/7101.
14. Park J.M., Wu H.G., Kim J.H., Carlson J.N., Kim K. The Effect of MLC Speed and Acceleration on the Plan Delivery Accuracy of VMAT. Br J Radiol. 2015 May; 88;1049:20140698. Doi: 10.1259/bjr.20140698.
15. Nyflot M.J., Thammasorn P., Wootton L.S., Ford E.C., Chaovalitwongse W.A. Deep Learning for Patient-Specific Quality Assurance: Identifying Errors in Radiotherapy Delivery by Radiomic Analysis of Gamma Images with Convolutional Neural Networks. Med Phys. 2019 Feb;46;2:456-464. Doi: 10.1002/mp.13338.
16. Hideaki Hirashima, Tomohiro Ono, Mitsuhiro Nakamura, Yuki Miyabe, Nobutaka Mukumoto, Hiraku Iramina, Takashi Mizowaki. Improvement of Prediction and Classification Performance for Gamma Passing Rate by Using Plan Complexity and Dosiomics Features. Radiother Oncol. 2020 Dec:153:250-257. Doi: 10.1016/j.radonc.2020.07.031.
17. Valdes G., Scheuermann R., Hung C.Y., Olszanski A., Bellerive M., Solberg T.D. A Mathematical Framework for Virtual IMRT QA Using Machine Learning. Med Phys. 2016 Jul;43;7:4323. Doi: 10.1118/1.4953835.
18. Jiaqi Li, Le Wang, Xile Zhang, Lu Liu, Jun Li, Maria F Chan, Jing Sui, Ruijie Yang. Machine Learning for Patient-Specific Quality Assurance of VMAT: Prediction and Classification Accuracy. Int J Radiat Oncol Biol Phys. 2019 Nov 15;105;4:893-902. Doi: 10.1016/j.ijrobp.2019.07.049.
19. Bin S., Zhang J., Shen L., Zhang Jand Wang Q. Study of the Prediction of Gamma Passing Rate in Dosimetric Verification of Intensity-Modulated Radiotherapy Using Machine Learning Models Based on Plan Complexity. Front Oncol. 2023 Jul;21;13:1094927. Doi: 10.3389/fonc.2023.1094927.
20. Sangutid Thongsawad, Somyot Srisatit , Todsaporn Fuangrod. Predicting Gamma Evaluation Results of Patient-Specific Head and Neck Volumetric-Modulated Arc Therapy Quality Assurance Based on Multileaf Collimator Patterns and Fluence Map Features: a Feasibility Study. J Appl Clin Med Phys. 2022 Jul;23;7:e13622. Doi: 10.1002/acm2.13622.
21. Shane McCarthy, Brent Harrison, Damodar Pokhrel. A Predictive Quality Assurance Model for Patient-Specific Gamma Passing Rate of Hyperarc-Based Stereotactic Radiotherapy and Radiosurgery of Brain Metastases. J Appl Clin Med Phys. 2025 Sep; 26;9:e70225. Doi: 10.1002/acm2.70225.
22. Tomohiro Kajikawa, Noriyuki Kadoya, Kengo Ito, Yoshiki Takayama, Takahito Chiba, Seiji Tomori, Hikaru Nemoto, Suguru Dobashi, Ken Takeda, Keiichi Jingu. A Convolutional Neural Network Approach for IMRT Dose Distribution Prediction in Prostate Cancer Patients. J Radiat Res. 2019 Oct 23;60;5:685-693. Doi: 10.1093/jrr/rrz051.
23. Haibo He, Yang Bai, Edwardo A. Garcia, Shutao Li. ADASYN: Adaptive Synthetic Sampling Approach for Imbalanced Learning In. IEEE International Joint Conference on Neural Networks. 2008:1322-1328. Doi: 10.1109/IJCNN.2008.4633969.
24. Chawla N.V., et al. SMOTE: Synthetic Minority Over-Sampling Technique. Journal of Artificial Intelligence Research. 2002;16;1:321-357. Doi: 10.1613/jair.953.
25. Alexander F I Osman, Nabil M Maalej. Applications of Machine and Deep Learning to Patient‐Specific IMRT/VMAT Quality Assurance. Appl Clin Med Phys. 2021 Aug 3;22;9:20–36. Doi: 10.1002/acm2.13375.

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Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.01.2026. Accepted for publication: 25.02.2026.