Table Info

Table 1.

Overview of studies included in the systematic review for melanoma primaries

Author, year	Study type	Patients	SRT	Systemic therapy	Non-target response	Criteria
Postow et al. [22], 2012	Case report	39*, F	28.5 Gy/3 fx to a paraspinal mass	Ipilimumab during and after (maintenance dosage) RT	PR at and SD at 10 months FUP of R hila N and splenic mtxs	Temporal with serum changes
Grimaldi et al. [23], 2014	Retrospective monocentric	3/4 (75%)	20–24 Gy SRS	PD under ipilimumab	PR on cutaneous/liver/lung mtxs	PD under IT
Schoenfeld et al. [24], 2015	Case series	NR	18–24 Gy SRS	Ipilimumab	11/15 istancies	All “index” lesions changes
Ribeiro Gomes et al. [25], 2016	Retrospective monocentric	1/3 (33%)	SBRT to lung and vertebra	Anti PD-1 monotherapy started 30 weeks before	AE after 6 weeks with 8 months survival after IT	Regression outside RT field
Kropp et al. [26], 2016	Retrospective monocentric	0/16 (0%)	30–36 Gy/5–6 fx	PD under ipilimumab	Within 3–6 months of IT	Temporal, excluding delayed IT effect
Sperduto et al. [27], 2017	Case report	37*, F	20–24 Gy SRS to 3 BMs 25 Gy/5 fx SBRT to a pelvic mass (previous 64 Gy to neck and scalp)	Cytokine + CHT 9 months prior to brain and soft tissue mtxs; 6 months CHT after RT. No systemic treatment for 10 yrs	10 yrs systemic progression-free	Long time progression-free
Roger et al. [28], 2018	Prospective monocentric	15/25 (60%)	26 Gy/3–5 fx	Anti-PD-1 monotherapy	Rates of CR, PR, SD, PD of 20%, 19%, 12% and 40%	Temporal
Gutkin et al. [29], 2018	Case report	57*, M	54 Gy/3 fx liver SBRT (previous adj 50 Gy in 20 fx to the L posterior arm)	Concomitant ipilimumab (2 cycles before, 2 after)	6.5 yrs systemic progression-free	Long time progression-free
Moran et al. [30], 2019	Case report	71*, M	50 Gy/5 fx to L pulmonary mtxs	Concomitant nivolumab	13 months after, PR of in the chest and CR in the abdomen-pelvis. 41 months progression-free	Any response outside RT field
Sundahl et al. [31], 2019	Prospective monocentric	0/20 (0%)	24 Gy/3 fx to the largest lesion	Nivolumab	No substantial AE but response-analyzing ctDNA of a subset of patients only after SBRT	Response outside RT field > nivolumab alone
Galli et al. [32], 2019	Retrospective monocentric	0/36 (0%)	20–24 Gy SRS	Pembrolizumab/Nivolumab	None	Response outside RT field
Funck-Brentano et al. [33] 2020	Prospective monocentric	8/26 (31%)	Various	Failing anti PD-1 monotherapy	35% of patients	Response outside RT field
Le Rhun et al. [34], 2020	Retrospective monocentric	0/52 (0%)	-	32 IT/20 non-IT	None	No concomitant systemic treatment/SRT + IT > IT alone
Watanabe et al. [35], 2020	Case series	72*, F	45 Gy/3 fx to 3 liver mtxs	Anti PD-1 (nivolumab started 4 weeks before, continued for 2 cycles after)	2 months after combined treatment, PR of liver mtxs and also of a muscle lesion in the upper L leg, and a lesion in the L groin. 4.5 yrs PF	Regression outside RT field
Watanabe et al. [35], 2020	Case series	79*, M	45 Gy/3 fx to 2 liver mtxs; 2nd 60 Gy/8 fx to N mtx; 3rd 60/7.7 Gy lung SBRT	Pembrolizumab (started 4 weeks before the 1st SBRT, continued after and then discontinued before the 3rd SBRT, and resumed after)	1 months after the 1st SBRT, SD of non-irradiated liver mtxs, then CR; 1 month after the 2nd SBRT, CR of non-irradiated lung and liver mtxs	Serum immunological changes probably induced by RT (higher Ki67+, PD-1, CD8+ T cells)
Saiag et al. [36], 2022	Retrospective monocentric	64/206 (31.5%)	20–26 Gy/2–5 fx	Anti PD-1 monotherapy or ipilimumab + nivolumab	31.5% of patients	Regression outside RT field
Sumodhee et al. [37], 2022	Retrospective monocentric	1/17 (6%)	Various	Anti-PD-1 or anti-CTLA-4	Almost CR of all target and non-targeted lesions	Regression outside RT field
Trommer et al. [38], 2022	Retrospective monocentric	3/65 (5%)	SRS NOS	Anti-PD-1 monotherapy	AE more frequently with concurrent RT-IT with longer OS rates	Regression outside RT field
Cerbon et al. [39], 2023	Case report	68*, M	50 Gy/5 fx to liver mtxs	Concomitant nivolumab-relatlimab discontinued 2 months after RT. Previous nivolumab and ipilimumab twice	CR on all other liver and lumbar spine mtxs	IT discontinuation

* Age at time of SRT. NR: not reported; fx: fraction(s); SRS: stereotactic radiosurgery; SBRT: stereotactic body radiotherapy; BMs: brain metastases; L: left; mtxs: metastases; mtx: metastasis; NOS: not otherwise specified; RT: radiation treatment; PD: progression disease; CHT: chemotherapy; IT: immunotherapy; SD: stable disease; FUP: follow-up; PR: partial response; AE: abscopal effect; yrs: years; CR: complete response; PF: progression free; SRT: stereotactic radiation techniques; R: right; F: female; M: male; OS: overall survival; N: node/nodal; adj: adjuvant

Declarations

Author contributions

AB: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. M Caroprese: Conceptualization, Investigation, Writing—original draft. CF: Conceptualization, Investigation, Writing—original draft. EC: Investigation, Writing—original draft. CAG: Investigation, Writing—review & editing. CO: Investigation, Writing—original draft. SC: Investigation, Writing—original draft. AF: Investigation, Writing—original draft, Writing—review & editing. M Conson: Validation, Writing—review & editing, Supervision. RP: Conceptualization, Investigation, Validation, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Datasets are available on request.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Pacelli R, Caroprese M, Palma G, Oliviero C, Clemente S, Cella L, et al. Technological evolution of radiation treatment: Implications for clinical applications. Semin Oncol. 2019;46:193–201. [DOI] [PubMed]

Martin A, Gaya A. Stereotactic body radiotherapy: a review. Clin Oncol (R Coll Radiol). 2010;22:157–72. [DOI] [PubMed]

Barillaro A, Caroprese M, Cella L, Viggiano A, Buccelli F, Daponte C, et al. Stereotactic Radiation Therapy for Brain Metastases: Factors Affecting Outcomes and Radiation Necrosis. Cancers (Basel). 2023;15:2094. [DOI] [PubMed] [PMC]

Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174:7516–23. [DOI] [PubMed]

Chioccola E, Caroprese M, Goodyear CA, Barillaro A, Oliviero C, Clemente S, et al. Metastasis-Directed Stereotactic Body Radiotherapy in Prostate Cancer Patients Treated with Systemic Therapy and Undergoing Oligoprogression: Report on 11 Consecutive Cases. Radiation. 2024;4:115–24. [DOI]

Shibamoto Y, Otsuka S, Iwata H, Sugie C, Ogino H, Tomita N. Radiobiological evaluation of the radiation dose as used in high-precision radiotherapy: effect of prolonged delivery time and applicability of the linear-quadratic model. J Radiat Res. 2012;53:1–9. [DOI]

Hlavata Z, Solinas C, De Silva P, Porcu M, Saba L, Willard-Gallo K, et al. The Abscopal Effect in the Era of Cancer Immunotherapy: a Spontaneous Synergism Boosting Anti-tumor Immunity? Target Oncol. 2018;13:113–23. [DOI] [PubMed]

Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004;58:862–70. [DOI] [PubMed]

Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009;114:589–95. [DOI] [PubMed] [PMC]

10.

Tang H, Cai L, He X, Niu Z, Huang H, Hu W, et al. Radiation-induced bystander effect and its clinical implications. Front Oncol. 2023;13:1124412. [DOI] [PubMed] [PMC]

11.

MOLE RH. Whole body irradiation; radiobiology or medicine? Br J Radiol. 1953;26:234–41. [DOI] [PubMed]

12.

Wei J, Montalvo-Ortiz W, Yu L, Krasco A, Ebstein S, Cortez C, et al. Sequence of αPD-1 relative to local tumor irradiation determines the induction of abscopal antitumor immune responses. Sci Immunol. 2021;6:eabg0117. [DOI] [PubMed]

13.

Siva S, MacManus MP, Martin RF, Martin OA. Abscopal effects of radiation therapy: a clinical review for the radiobiologist. Cancer Lett. 2015;356:82–90. [DOI] [PubMed]

14.

Nikitaki Z, Mavragani IV, Laskaratou DA, Gika V, Moskvin VP, Theofilatos K, et al. Systemic mechanisms and effects of ionizing radiation: A new ‘old’ paradigm of how the bystanders and distant can become the players. Semin Cancer Biol. 2016;37–38:77–95. [DOI] [PubMed]

15.

Ohba K, Omagari K, Nakamura T, Ikuno N, Saeki S, Matsuo I, et al. Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis. Gut. 1998;43:575–7. [DOI] [PubMed] [PMC]

16.

Rekers NH, Olivo Pimentel V, Yaromina A, Lieuwes NG, Biemans R, Zegers CML, et al. The immunocytokine L19-IL2: An interplay between radiotherapy and long-lasting systemic anti-tumour immune responses. Oncoimmunology. 2018;7:e1414119. [DOI] [PubMed] [PMC]

17.

Marconi R, Strolin S, Bossi G, Strigari L. A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger? PLoS One. 2017;12:e0171559. [DOI] [PubMed] [PMC]

18.

Cella L, Monti S, Pacelli R, Palma G. Modeling frameworks for radiation induced lymphopenia: A critical review. Radiother Oncol. 2024;190:110041. [DOI] [PubMed]

19.

Tubin S. Partial tumor irradiation exploiting immunomediated effects: tumor microenvironment as a new oar. Radiother Oncol. 2019;133:S467–8.

20.

Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. [DOI] [PubMed] [PMC]

21.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. [DOI] [PubMed] [PMC]

22.

Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366:925–31. [DOI] [PubMed] [PMC]

23.

Grimaldi AM, Simeone E, Giannarelli D, Muto P, Falivene S, Borzillo V, et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunology. 2014;3:e28780. [DOI] [PubMed] [PMC]

24.

Schoenfeld JD, Mahadevan A, Floyd SR, Dyer MA, Catalano PJ, Alexander BM, et al. Ipilmumab and cranial radiation in metastatic melanoma patients: a case series and review. J Immunother Cancer. 2015;3:50. [DOI] [PubMed] [PMC]

25.

Ribeiro Gomes J, Schmerling RA, Haddad CK, Racy DJ, Ferrigno R, Gil E, et al. Analysis of the Abscopal Effect With Anti-PD1 Therapy in Patients With Metastatic Solid Tumors. J Immunother. 2016;39:367–72. [DOI] [PubMed]

26.

Kropp LM, De Los Santos JF, McKee SB, Conry RM. Radiotherapy to Control Limited Melanoma Progression Following Ipilimumab. J Immunother. 2016;39:373–8. [DOI] [PubMed] [PMC]

27.

Sperduto W, King DM, Watanabe Y, Lou E, Sperduto PW. Case Report of Extended Survival and Quality of Life in a Melanoma Patient with Multiple Brain Metastases and Review of Literature. Cureus. 2017;9:e1947. [DOI] [PubMed] [PMC]

28.

Roger A, Finet A, Boru B, Beauchet A, Mazeron JJ, Otzmeguine Y, et al. Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients. Oncoimmunology. 2018;7:e1442166. [DOI] [PubMed] [PMC]

29.

Gutkin PM, Hiniker SM, Swetter SM, Reddy SA, Knox SJ. Complete Response of Metastatic Melanoma to Local Radiation and Immunotherapy: 6.5 Year Follow-Up. Cureus. 2018;10:e3723. [DOI] [PubMed] [PMC]

30.

Moran A, Azghadi S, Maverakis EM, Christensen S, Dyer BA. Combined Immune Checkpoint Blockade and Stereotactic Ablative Radiotherapy Can Stimulate Response to Immunotherapy in Metastatic Melanoma: A Case Report. Cureus. 2019;11:e4038. [DOI] [PubMed] [PMC]

31.

Sundahl N, Seremet T, Van Dorpe J, Neyns B, Ferdinande L, Meireson A, et al. Phase 2 Trial of Nivolumab Combined With Stereotactic Body Radiation Therapy in Patients With Metastatic or Locally Advanced Inoperable Melanoma. Int J Radiat Oncol Biol Phys. 2019;104:828–35. [DOI] [PubMed]

32.

Galli G, Cavalieri S, Di Guardo L, Cimminiello C, Nichetti F, Corti F, et al. Combination of Immunotherapy and Brain Radiotherapy in Metastatic Melanoma: A Retrospective Analysis. Oncol Res Treat. 2019;42:186–94. [DOI] [PubMed]

33.

Funck-Brentano E, Baghad B, Fort M, Aouidad I, Roger A, Beauchet A, et al. Efficacy of late concurrent hypofractionated radiotherapy in advanced melanoma patients failing anti-PD-1 monotherapy. Int J Cancer. 2020;147:1707–14. [DOI] [PubMed]

34.

Le Rhun E, Wolpert F, Fialek M, Devos P, Andratschke N, Reyns N, et al. Response assessment and outcome of combining immunotherapy and radiosurgery for brain metastasis from malignant melanoma. ESMO Open. 2020;5:e000763. [DOI] [PubMed] [PMC]

35.

Watanabe T, Firat E, Scholber J, Gaedicke S, Heinrich C, Luo R, et al. Deep abscopal response to radiotherapy and anti-PD-1 in an oligometastatic melanoma patient with unfavorable pretreatment immune signature. Cancer Immunol Immunother. 2020;69:1823–32. [DOI] [PubMed] [PMC]

36.

Saiag P, Molinier R, Roger A, Boru B, Otmezguine Y, Otz J, et al. Efficacy of Large Use of Combined Hypofractionated Radiotherapy in a Cohort of Anti-PD-1 Monotherapy-Treated Melanoma Patients. Cancers (Basel). 2022;14:4069. [DOI] [PubMed] [PMC]

37.

Sumodhee S, Guo L, Bouhlel L, Picard A, Otto J, Naghavi AO, et al. Impact of radiotherapy schedule on survival of patients treated with immune-checkpoint inhibitors for advanced melanoma and non-small cell lung cancer. Cancer Radiother. 2022;26:1045–53. [DOI] [PubMed]

38.

Trommer M, Adams A, Celik E, Fan J, Funken D, Herter JM, et al. Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups. Cancers (Basel). 2022;14:1240. [DOI] [PubMed] [PMC]

39.

Cerbon D, Moya-Brown K, Mihaylov IB, Spieler B. Abscopal effect observed in visceral and osseous metastases after liver SBRT in combination with nivolumab and relatlimab for sinonasal mucosal melanoma-a case report. Front Oncol. 2023;13:1143335. [DOI] [PubMed] [PMC]

40.

Aldakhil S, Mathieu D. Abscopal effect leading to complete disappearance of extensive meningiomatosis after gamma knife radiosurgery: Case report. Front Surg. 2022;9:908645. [DOI] [PubMed] [PMC]

41.

Choi JS, Sansoni ER, Lovin BD, Lindquist NR, Phan J, Mayo LL, et al. Abscopal Effect Following Immunotherapy and Combined Stereotactic Body Radiation Therapy in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma: A Report of Two Cases and Literature Review. Ann Otol Rhinol Laryngol. 2020;129:517–22. [DOI] [PubMed]

42.

McBride S, Sherman E, Tsai CJ, Baxi S, Aghalar J, Eng J, et al. Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2021;39:30–7. [DOI] [PubMed] [PMC]

43.

Lin J, Guo Q, Guo Z, Lu T, Chen G, Lin S, et al. Stereotactic body radiotherapy extends the clinical benefit of PD-1 inhibitors in refractory recurrent/metastatic nasopharyngeal carcinoma. Radiat Oncol. 2022;17:117. [DOI] [PubMed] [PMC]

44.

Endo M, Fukuda Y, Okada K, Ogawa K, Nakamura M, Takahashi S, et al. Abscopal Effect after Stereotactic Body Radiotherapy with Nivolumab for Lung Metastasis of Head and Neck Cancer: A Case Report. Case Rep Oncol. 2023;16:1345–52. [DOI] [PubMed] [PMC]

45.

Ito M, Abe S, Adachi S, Oshima Y, Takeuchi A, Ohashi W, et al. Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects. Jpn J Radiol. 2024;42:424–34. [DOI] [PubMed] [PMC]

46.

Kim JS, Chang AR. Abscopal effect in metastatic breast cancer treated with stereotactic body radiotherapy in the absence of immunotherapy. Front Oncol. 2023;13:1243053. [DOI] [PubMed] [PMC]

47.

Xu C, Sun J, Zhang W, Yuan Z, Wang J. The safety and efficacy of Cyberknife® for thymic malignancy. Cancer Radiother. 2021;25:119–25. [DOI] [PubMed]

48.

Siva S, Callahan J, MacManus MP, Martin O, Hicks RJ, Ball DL. Abscopal Effects after Conventional and Stereotactic Lung Irradiation of Non–Small-Cell Lung Cancer. J Thorac Oncol. 2013;8:e71–2.

49.

Cong Y, Shen G, Wu S, Hao R. Abscopal regression following SABR for non-small-cell-lung cancer: A case report. Cancer Biol Ther. 2017;18:1–3. [DOI] [PubMed] [PMC]

50.

Britschgi C, Riesterer O, Burger IA, Guckenberger M, Curioni-Fontecedro A. Report of an abscopal effect induced by stereotactic body radiotherapy and nivolumab in a patient with metastatic non-small cell lung cancer. Radiat Oncol. 2018;13:102. [DOI] [PubMed] [PMC]

51.

Hamilton AJ, Seid J, Verdecchia K, Chuba P. Abscopal Effect after Radiosurgery for Solitary Brain Metastasis from Non-small Cell Lung Cancer. Cureus. 2018;10:e3777. [DOI] [PubMed] [PMC]

52.

Tubin S, Khan MK, Salerno G, Mourad WF, Yan W, Jeremic B. Mono-institutional phase 2 study of innovative Stereotactic Body RadioTherapy targeting Partial Tumor HYpoxic (SBRT-PATHY) clonogenic cells in unresectable bulky non-small cell lung cancer: profound non-targeted effects by sparing peri-tumoral immune microenvironment. Radiat Oncol. 2019;14:212. [DOI]

53.

Lin X, Lu T, Xie Z, Qin Y, Liu M, Xie X, et al. Extracranial abscopal effect induced by combining immunotherapy with brain radiotherapy in a patient with lung adenocarcinoma: A case report and literature review. Thorac Cancer. 2019;10:1272–5. [DOI]

54.

Chen D, Menon H, Verma V, Guo C, Ramapriyan R, Barsoumian H, et al. Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials. J Immunother Cancer. 2020;8:e000492. [DOI] [PubMed] [PMC]

55.

Kareff SA, Lischalk JW, Krochmal R, Kim C. Abscopal effect in pulmonary carcinoid tumor following ablative stereotactic body radiation therapy: a case report. J Med Case Rep. 2020;14:177. [DOI] [PubMed] [PMC]

56.

Ye H, Pang H, Shi X, Ren P, Huang S, Yu H, et al. Nivolumab and Hypofractionated Radiotherapy in Patients With Advanced Lung Cancer: ABSCOPAL-1 Clinical Trial. Front Oncol. 2021;11:657024. [DOI]

57.

Wang P, Yin T, Zhao K, Yu J, Teng F. Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer. J Cancer Res Clin Oncol. 2022;148:1253–61. [DOI] [PubMed] [PMC]

58.

Huang YS, Li Z, Xiao ZF, Li D, Liu WY. Case report: Radiotherapy plus pneumococcal conjugate vaccine stimulates abscopal immune response in a patient with ALK+ NSCLC. Front Immunol. 2022;13:950252. [DOI]

59.

Chino F, Pollis KE, Choi S, Salama JK, Palta M. Stereotactic Body Radiation Therapy-Induced Abscopal Effect on Hepatocellular Carcinoma After Treatment for Lung Cancer: A Case Report. Hepatology. 2018;68:1653–5. [DOI] [PubMed]

60.

Nakabori T, Ikawa T, Kozumi K, Urabe M, Kai Y, Takada R, et al. Abscopal effect in a patient with advanced hepatocellular carcinoma upon resuming bevacizumab in combination with atezolizumab after radiotherapy. Clin J Gastroenterol. 2024;17:1053–7. [DOI] [PubMed]

61.

Zhao X, Kang J, Zhao R. Abscopal effect of radiation on lymph node metastasis in esophageal carcinoma: A case report and literature review. Oncol Lett. 2018;16:3555–60. [DOI] [PubMed] [PMC]

62.

Hai T, Liu J, Lai J, Zhou L. A good response to anti-PD-1 monoclonal antibody plus SBRT in a patient with PD-L1-negative recurrent advanced esophageal cancer: a long-term follow-up case report of a possible abscopal effect. Front Oncol. 2024;14:1369035. [PubMed] [PMC]

63.

Kim JO, Kim CA. Abscopal Resolution of a Hepatic Metastasis in a Patient with Metastatic Cholangiocarcinoma Following Radical Stereotactic Body Radiotherapy to a Synchronous Early Stage Non-small Cell Lung Cancer. Cureus. 2019;11:e4082. [DOI] [PubMed] [PMC]

64.

Liu X, Yao J, Song L, Zhang S, Huang T, Li Y. Local and abscopal responses in advanced intrahepatic cholangiocarcinoma with low TMB, MSS, pMMR and negative PD-L1 expression following combined therapy of SBRT with PD-1 blockade. J Immunother Cancer. 2019;7:204. [DOI]

65.

Ishiyama H, Teh BS, Ren H, Chiang S, Tann A, Blanco AI, et al. Spontaneous regression of thoracic metastases while progression of brain metastases after stereotactic radiosurgery and stereotactic body radiotherapy for metastatic renal cell carcinoma: abscopal effect prevented by the blood- brain barrier? Clin Genitourin Cancer. 2012;10:196–8. [DOI]

66.

Xie G, Gu D, Zhang L, Chen S, Wu D. A rapid and systemic complete response to stereotactic body radiation therapy and pembrolizumab in a patient with metastatic renal cell carcinoma. Cancer Biol Ther. 2017;18:547–51. [DOI]

67.

LaPlant Q, Deselm C, Lockney NA, Hsieh J, Yamada Y. Potential abscopal response to dual checkpoint blockade in RCC after reirradiation using dose- painting SBRT. Pract Radiat Oncol. 2017;7:396–9. [DOI]

68.

Dengina N, Mitin T, Gamayunov S, Safina S, Kreinina Y, Tsimafeyeu I. Stereotactic body radiation therapy in combination with systemic therapy for metastatic renal cell carcinoma: a prospective multicentre study. ESMO Open. 2019;4:e000535. [DOI] [PubMed] [PMC]

69.

Margulis V, Freifeld Y, Pop LM, Manna S, Kapur P, Pedrosa I, et al. Neoadjuvant SABR for Renal Cell Carcinoma Inferior Vena Cava Tumor Thrombus-Safety Lead-in Results of a Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2021;110:1135–42. [DOI]

70.

Zhang X, Zhang Y, Liu Y, Yang Y, Dong P, He L, et al. Stereotactic body radiotherapy-induced abscopal effect twice after pembrolizumab failure in hereditary leiomyomatosis and renal cell carcinoma: a case report with genetic and immunologic analysis. Transl Androl Urol. 2021;10:4304–12. [PubMed] [PMC]

71.

Feinaj A, Fox E, Sinibaldi V, Kleinberg L, Ged Y. Abscopal effect following checkpoint inhibitor therapy and localized radiotherapy for metastatic clear cell renal cell carcinoma: A case report. Urol Case Rep. 2024;56:102824. [DOI] [PubMed] [PMC]

72.

Kono S, Hashimoto Y, Shirai Y, Kunihiro Y, Ohmatsu K, Kawanishi M, et al. A long-term survival case of bladder cancer with distant metastases: abscopal effect of brain metastases after stereotactic radiotherapy with immune checkpoint blockade therapy to lung metastases. Int Cancer Conf J. 2023;12:205–9. [DOI]

73.

Higa J, Wilenius K, Savino S, Larsen C, Scholz M, Vogelzang N. Real World Experience With Pembrolizumab in Recurrent or Advanced Prostate Cancer. Clin Genitourin Cancer. 2020;18:e397–401. [DOI] [PubMed]

74.

Welsh JW, Tang C, de Groot P, Naing A, Hess KR, Heymach JV, et al. Phase II Trial of Ipilimumab with Stereotactic Radiation Therapy for Metastatic Disease: Outcomes, Toxicities, and Low-Dose Radiation-Related Abscopal Responses. Cancer Immunol Res. 2019;7:1903–9. [DOI] [PubMed] [PMC]

75.

Menon H, Chen D, Ramapriyan R, Verma V, Barsoumian HB, Cushman TR, et al. Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy. J Immunother Cancer. 2019;7:237. [DOI] [PubMed] [PMC]

76.

Tubin S, Popper HH, Brcic L. Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects. Radiat Oncol. 2019;14:21. [DOI]

77.

Woody S, Hegde A, Arastu H, Peach MS, Sharma N, Walker P, et al. Survival Is Worse in Patients Completing Immunotherapy Prior to SBRT/SRS Compared to Those Receiving It Concurrently or After. Front Oncol. 2022;12:785350. [DOI] [PubMed] [PMC]

78.

Damen PJJ, Suijkerbuijk KPM, VAN Lindert ASR, Eppinga WSC, El Sharouni SY, Verhoeff JJC. Long-term Local Control and Overall Survival After Radiotherapy in Oligoprogressive Patients During Treatment With Checkpoint Inhibitors. Anticancer Res. 2022;42:4795–804. [DOI] [PubMed]

79.

Zagardo V, Martorana E, Harikar M, Pergolizzi S, Ferini G. Effectiveness of radiotherapy in delaying treatment changes in primary or secondary immunorefractory oligoprogressive patients: preliminary results from a single-center study. Discov Oncol. 2024;15:531. [DOI] [PubMed] [PMC]

80.

Chang JY, Xu X, Shroff GS, Comeaux NI, Li W, Rodon Ahnert J, et al. Phase I/II study of BMS-986156 with ipilimumab or nivolumab with or without stereotactic ablative radiotherapy in patients with advanced solid malignancies. J Immunother Cancer. 2024;12:e009975. [DOI] [PubMed] [PMC]

81.

Zafra J, Onieva JL, Oliver J, Garrido-Barros M, González-Hernández A, Martínez-Gálvez B, et al. Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer. Int J Mol Sci. 2024;25:4533. [DOI]

82.

Mizumatsu S, Nomura R. Highly Radiosensitive Diffuse Large B-cell Lymphoma of the Skull Treated With Low-Dose CyberKnife Radiotherapy: A Case Report. Cureus. 2023;15:e51227. [DOI] [PubMed] [PMC]

83.

Feng L, Ye T, Zhang J, Yuan S, Chen Y, Chen J. Stereotactic body radiotherapy for lung metastases in a patient with giant cell tumor of bone: a case report and literature review. Ann Transl Med. 2022;10:156. [DOI] [PubMed] [PMC]

84.

Callaghan CM, Seyedin SN, Mohiuddin IH, Hawkes KL, Petronek MS, Anderson CM, et al. The Effect of Concurrent Stereotactic Body Radiation and Anti-PD-1 Therapy for Recurrent Metastatic Sarcoma. Radiat Res. 2020;194:124–32. [DOI]

85.

Bhatia A, Burtness B. Treating Head and Neck Cancer in the Age of Immunotherapy: A 2023 Update. Drugs. 2023;83:217–48. [DOI] [PubMed]

86.

Ganti A, Raman A, Shay A, Kuhar HN, Auger SR, Patel T, et al. Treatment modalities in sinonasal mucosal melanoma: A national cancer database analysis. Laryngoscope. 2020;130:275–82. [DOI] [PubMed]

87.

Leven C, Padelli M, Carré JL, Bellissant E, Misery L. Immune Checkpoint Inhibitors in Melanoma: A Review of Pharmacokinetics and Exposure-Response Relationships. Clin Pharmacokinet. 2019;58:1393–405. [DOI] [PubMed]

88.

Emens LA. Breast Cancer Immunotherapy: Facts and Hopes. Clin Cancer Res. 2018;24:511–20. [DOI] [PubMed] [PMC]

89.

Zhong S, Cui Y, Liu Q, Chen S. CAR-T cell therapy for lung cancer: a promising but challenging future. J Thorac Dis. 2020;12:4516–21. [DOI] [PubMed] [PMC]

90.

Takamori S, Toyokawa G, Takada K, Shoji F, Okamoto T, Maehara Y. Combination Therapy of Radiotherapy and Anti-PD-1/PD-L1 Treatment in Non-Small-cell Lung Cancer: A Mini-review. Clin Lung Cancer. 2018;19:12–6. [DOI] [PubMed]

91.

Yamane H, Isozaki H, Takeyama M, Ochi N, Kudo K, Honda Y, et al. Programmed cell death protein 1 and programmed death-ligand 1 are expressed on the surface of some small-cell lung cancer lines. Am J Cancer Res. 2015;5:1553–7. [PubMed] [PMC]

92.

Sellars MC, Wu CJ, Fritsch EF. Cancer vaccines: Building a bridge over troubled waters. Cell. 2022;185:2770–88. [DOI] [PubMed] [PMC]

93.

Doi T, Piha-Paul SA, Jalal SI, Mai-Dang H, Yuan S, Koshiji M, et al. Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma: Preliminary results from KEYNOTE-028. J Clin Oncol. 2015;33:S4010. [DOI]

94.

Kojima T, Hara H, Yamaguchi K, Hironaka S, Iwasa S, Kato K, et al. Phase II study of nivolumab (ONO-4538/BMS-936558) in patients with esophageal cancer: Preliminary report of overall survival. J Clin Oncol. 2016;34:TPS175. [DOI]

95.

Antwi SO, Mousa OY, Patel T. Racial, ethnic, and age disparities in incidence and survival of intrahepatic cholangiocarcinoma in the United States; 1995-2014. Ann Hepatol. 2018;17:274–85.

96.

Sharabi AB, Nirschl CJ, Kochel CM, Nirschl TR, Francica BJ, Velarde E, et al. Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen. Cancer Immunol Res. 2015;3:345–55. [DOI] [PubMed] [PMC]

97.

Amini A, Altoos B, Bourlon MT, Bedrick E, Bhatia S, Kessler ER, et al. Local control rates of metastatic renal cell carcinoma (RCC) to the bone using stereotactic body radiation therapy: Is RCC truly radioresistant? Pract Radiat Oncol. 2015;5:e589–96. [DOI] [PubMed] [PMC]

98.

Ranck MC, Golden DW, Corbin KS, Hasselle MD, Liauw SL, Stadler WM, et al. Stereotactic body radiotherapy for the treatment of oligometastatic renal cell carcinoma. Am J Clin Oncol. 2013;36:589–95. [DOI] [PubMed]

99.

Graff JN, Alumkal JJ, Drake CG, Thomas GV, Redmond WL, Farhad M, et al. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016;7:52810–7. [DOI] [PubMed] [PMC]

100.

De Bono JS, Goh JCH, Ojamaa K, Rodriguez JMP, Drake CG, Hoimes CJ, et al. KEYNOTE-199: Pembrolizumab (pembro) for docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2018;36:5007. [DOI]

101.

Mendenhall WM, Zlotecki RA, Scarborough MT, Gibbs CP, Mendenhall NP. Giant cell tumor of bone. Am J Clin Oncol. 2006;29:96–9. [DOI] [PubMed]

102.

Farhood B, Najafi M, Mortezaee K. CD8⁺cytotoxic T lymphocytes in cancer immunotherapy: A review. J Cell Physiol. 2019;234:8509–21. [DOI] [PubMed]

103.

Tang C, Wang X, Soh H, Seyedin S, Cortez MA, Krishnan S, et al. Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Cancer Immunol Res. 2014;2:831–8. [DOI] [PubMed] [PMC]

104.

Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–7. [DOI] [PubMed] [PMC]

105.

Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat Rev Clin Oncol. 2016;13:516–24. [DOI] [PubMed] [PMC]