Journal of Contemporary Brachytherapy

Interventional radiation immune-boosting (iRIB). The role of concomitant interventional radiotherapy (modern brachytherapy) in immunotherapy: A hypothesis-generating systematic review

Roberta Muni 1
,
Valentina Lancellotta 2
,
Bruno Fionda 2
,
Enrico Rosa 3, 4
,
Piotr Wojcieszek 5
,
Roberto Lacovelli 6, 7
,
Monica Mangoni 8
,
Gabriella Macchia 9
,
Alessio Giuseppe Morganti 10
,
Maria Antonietta Gambacorta 2, 7
,
Roberto Iezzi 7, 11
,
Luca Tagliaferri 2, 7

  1. Department of Radiation Oncology, ASST Papa Giovanni XXIII, Bergamo, Italy

  2. Radioterapia Oncologica,
    Dipartimento di Diagnostica per Immagini e Radioterapia Oncologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

  3. UOC Fisica per le Scienze della Vita, Dipartimento di Diagnostica per Immagini e Radioterapia
    Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy,

  4. Department of Theoretical and
    Applied Sciences, eCampus University, Novedrate, Italy,

  5. Brachytherapy Department, Maria Skłodowska-Curie
    National Research Institute of Oncology Gliwice Branch, Gliwice, Poland

  6. Medical Oncology, Fondazione Policlinico Universitario
    A. Gemelli IRCCS, Rome, Italy,

  7. Università Cattolica del Sacro Cuore, Rome, Italy

  8. Radiotherapy Unit, Department of
    Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy

  9. Radiation Oncology Unit,
    Responsible Research Hospital-Campobasso and Catholic University of Sacred Heart-Rome, Rome, Italy

  10. Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna; Radiation Oncology, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy

  11. Radiologia Interventistica Avanzata, Dipartimento di Diagnostica per Immagini e Radioterapia Oncologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

J Contemp Brachytherapy 2026

DOI: https://doi.org/10.5114/jcb.2026.164592
Data publikacji online: 2026/09/18
Article file
Interventional radiation.pdf
  1. Hodi FS, O’Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723.
  2. Topalian SL, Hodi FS, Brahmer JR et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443-2454.
  3. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science 2018; 359: 1350-1355.
  4. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017; 168: 707-723.
  5. Galluzzi L, Humeau J, Buqué A et al. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol 2020; 17: 725-741.
  6. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 2013; 105: 256-265.
  7. Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer immunotherapy. JAMA Oncol 2015; 1: 1325-1332.
  8. Sharabi AB, Lim M, DeWeese TL, Drake CG. Radiation and checkpoint blockade immunotherapy: radiosensitization and potential mechanisms of synergy. Lancet Oncol 2015; 16: e498-e509.
  9. Kang J, Demaria S, Formenti SC. Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer 2016; 4: 51.
  10. Dewan MZ, Galloway AE, Kawashima N et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 2009; 15: 5379-5388.
  11. Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys 2012; 83: 1306-1310.
  12. Golden EB, Frances D, Pellicciotta I et al. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology 2014; 3: e28518.
  13. Wang L, Lynch C, Pitroda SP et al. Radiotherapy and immunology. J Exp Med 2024; 221: e20232101.
  14. Liu S, Wang W, Hu S et al. Radiotherapy remodels the tumor microenvironment for enhancing immunotherapeutic sensitivity. Cell Death Dis 2023; 14: 679.
  15. Vanpouille-Box C, Formenti SC, Demaria S. Toward precision radiotherapy for use with immune checkpoint blockers. Clin Cancer Res 2018; 24: 259-265.
  16. Serre R, Benzekry S, Padovani L et al. Mathematical modeling of cancer immunotherapy and its synergy with radiotherapy. Cancer Res 2016; 76: 4931-4940.
  17. Serre R, Gabro A, Andraud M et al. Brachytherapy: Perspectives for combined treatments with immunotherapy. Clin Transl Radiat Oncol 2025; 52: 100924.
  18. Patel RB, Baniel CC, Sriramaneni RN et al. Combining brachytherapy and immunotherapy to achieve in situ tumor vaccination: A review of cooperative mechanisms and clinical opportunities. Brachytherapy 2018; 17: 995-1003.
  19. Rodriguez-Ruiz ME, Rodriguez I, Garasa S et al. Abscopal effects of radiotherapy are enhanced by combined immunostimulatory mAbs and are dependent on CD8 T cells and crosspriming. Cancer Res 2016; 76: 5994-6005.
  20. Reynders K, Illidge T, Siva S et al. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev 2015; 41: 503-510.
  21. Chargari C, Deutsch E, Blanchard P et al. Brachytherapy: An overview for clinicians. CA Cancer J Clin 2019; 69: 386-401.
  22. Major T, Fröhlich G, Agoston P et al. The value of brachytherapy in the age of advanced external beam radiotherapy: a review of the literature in terms of dosimetry. Strahlenther Onkol 2022; 198: 93-109.
  23. McGovern MK, Witt E, Rhodes AC et al. Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia. J Biomed Mater Res A 2024; 112: 931-940.
  24. Barker CA, Postow MA. Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int J Radiat Oncol Biol Phys 2014; 88: 986-997.
  25. Marciscano AE, Ghasemzadeh A, Nirschl TR et al. Elective nodal irradiation attenuates the combinatorial efficacy of radiation and immunotherapy. Clin Cancer Res 2018; 24: 5058-5071.
  26. Lambin P, Lieverse RIY, Eckert F et al. Lymphocyte-sparing radiotherapy: the rationale for protecting lymphocyte-rich organs when combining radiotherapy with immunotherapy. Semin Radiat Oncol 2020; 30: 187-193.
  27. Yovino S, Kleinberg L, Grossman SA et al. 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. Cancer Invest 2013; 31: 140-144.
  28. Liu J, Liu C, Yue J. Radiotherapy and the gut microbiome: facts and fiction. Radiat Oncol 2021; 16: 9.
  29. Luke JJ, Lemons JM, Karrison TG et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy. J Clin Oncol 2018; 36: 1611-1618.
  30. Tang C, Wang X, Soh H et al. Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Cancer Immunol Res 2014; 2: 831-838.
  31. Ngwa W, Irabor OC, Schoenfeld JD et al. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer 2018; 18: 313-322.
  32. Page MJ, McKenzie JE, Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 29: 372:n71.
  33. Munker S, Roessler D, Öcal O et al. Concomitant irradiation to checkpoint inhibitor therapy of hepatocellular carcinoma patients: a systematic retrospective, single-center analysis. Oncol Res Treat 2023; 46: 466-475.
  34. Schwarzlmueller S, Corradini S, Seidensticker M et al. High-dose rate brachytherapy combined with PD-1 blockade as a treatment for metastatic adrenocortical carcinoma – a single center case series. Horm Metab Res 2024; 56: 30-37.
  35. Tao X, Liang L, Xu J et al. Efficacy and safety of immune checkpoint inhibitors combined with iodine-125 seed implantation in driver gene-negative non-small cell lung cancer: a retrospective cohort study. J Thorac Dis 2025; 17: 278-288.
  36. Chyrek AJ, Galus L, Mackiewicz J et al. Harnessing the synergy of contact brachytherapy and immune checkpoint inhibitors in advanced melanoma: first reported case series. Rep Pract Oncol Radiother 2025; 30: 773-780.
  37. Suzuki G, Masui K, Yamazaki H et al. Abscopal effect of high-dose-rate brachytherapy on pelvic bone metastases from renal cell carcinoma: a case report. J Contemp Brachytherapy 2019; 11: 458-461.
  38. Appalanaido GK, Ahmad MZ, Shukor SA et al. Pathological complete response with immunotherapy and brachytherapy to 15 metastatic liver lesions in a single patient. Hepat Oncol 2022; 9: HEP44.
  39. Yuan M, Wang L, Xiao Y et al. Iodine-125 seed brachytherapy combined with pembrolizumab for advanced non-small-cell lung cancer after failure of first-line chemotherapy: A report of two cases and literature review. J Contemp Brachytherapy 2023; 15: 81-88.
  40. Yang M, You Y, Wang X, Dong W. I-125 seeds brachytherapy combined with immunotherapy for MET amplification in non-small cell lung cancer from clinical application to related lncRNA mechanism explore: a case report. Front Cell Dev Biol 2023; 11: 1176083.
  41. Ouyang SR, Bao XZ, Li YP et al. Combined use of radioactive 125I seeds and PD-1 inhibitor provides sustained clinical benefit in an elderly patient with advanced non-small cell lung cancer: a case report. Cancer Manag Res 2026; 18: 569802.
  42. Sui A, Song H, Yu H et al. Clinical application of iodine-125 seed brachytherapy combined with anti-PD-1 antibodies in the treatment of lung cancer. Clin Ther 2020; 42: 1612-1616.
  43. Tang X, Liu Y, Chen L et al. The efficacy and safety of PD-1 inhibitors combined with 125I seed implantation in treating extra hepatic metastasis of hepatocellular carcinoma. Front Med (Lausanne) 2025; 12: 1693447.
  44. Deng X, Xiang K, He X et al. Good response of stage IV melanoma to high‑dose radiation therapy combined with immunotherapy: A case report. Oncol Lett 2024; 28: 598.
  45. Li Y, Luo J, Zhang J et al. Treatment of hepatocellular carcinoma with gluteus medius metastasis: a case report and a literature review. Front Oncol 2025; 15: 1329756.
  46. Demaria S, Formenti SC. Radiotherapy effects on anti-tumor immunity: implications for cancer treatment. Front Oncol 2013; 22: 128.
  47. Haie-Meder C, Siebert FA, Pötter R. Image guided, adaptive, accelerated, high dose brachytherapy as model for advanced small volume radiotherapy. Radiother Oncol 2011; 100: 333-343.
  48. Jiang JL, Li HZ, Ma QC et al. Synergies between radiotherapy and immunotherapy: a systematic review from mechanism to clinical application. Front Immunol 2025; 16: 1554499.
  49. Zhang Z, Liu X, Chen D, Yu J. Radiotherapy combined with immunotherapy: the dawn of cancer treatment. Signal Transduct Target Ther 2022; 7: 258.
  50. Wu J, Ni T, Deng R et al. Safety and efficacy of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for non-small cell lung cancer: A systematic review and meta-analysis. Front Immunol 2023; 14: 1065510.
  51. Antonia SJ, Villegas A, Daniel D et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 2017; 377: 1919-1929.
  52. Theelen WSME, Peulen HMU, Lalezari F et al. 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. JAMA Oncol 2019; 5: 1276-1282.
  53. Lorusso D, Xiang Y, Hasegawa K et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet 2024; 403: 1341-1350.
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