Top

Published in:

Open Access 01-12-2020 | NSCLC | Review

Oligometastasis and local ablation in the era of systemic targeted and immunotherapy

Authors: Rosario Mazzola, Barbara Alicja Jereczek-Fossa, Davide Franceschini, Slavisa Tubin, Andrea Riccardo Filippi, Maria Tolia, Andrea Lancia, Giuseppe Minniti, Stefanie Corradini, Stefano Arcangeli, Marta Scorsetti, Filippo Alongi

Published in: Radiation Oncology | Issue 1/2020

Abstract

Background

During these last years, new agents have dramatically improved the survival of the metastatic patients. Oligometastases represent a continuous field of interest in which the integration of metastases-directed therapy and drugs could further improve the oncologic outcomes.

Herein a narrative review is performed regarding the main rationale in combining immunotherapy and target therapies with SBRT looking at the available clinical data in case of oligometastatic NSCLC, Melanoma and Kidney cancer.

Material and method

Narrative Review regarding retrospective and prospective studies published between January 2009 to November 2019 with at least 20 patients analyzed.

Results

Concerning the combination between SBRT and Immunotherapy, the correct sequence of remains uncertain, and seems to be drug-dependent. The optimal patients’ selection is crucial to expect substantial benefits to SBRT/Immunotherapy combination and, among several factors. A potential field of interest is represented by the so-called oligoprogressed disease, in which SBRT could improve the long-term efficacy of the existing target therapy.

Conclusions

A low tumor burden seems to be the most relevant, thus making the oligometastatic disease represent the ideal setting for the use of combination therapies with immunological drugs.

Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13(1):8–10. https://doi.org/10.1200/JCO.1995.13.1.8.CrossRefPubMed

Alongi F, Arcangeli S, Filippi AR, Ricardi U, Scorsetti M. Review and uses of stereotactic body radiation therapy for oligometastases. Oncologist. 2012;17(8):1100–7. https://doi.org/10.1634/theoncologist.2012-0092.CrossRefPubMedPubMedCentral

Mazzola R, Corradini S, Gregucci F, Figlia V, Fiorentino A, Alongi F. Role of radiosurgery/stereotactic radiotherapy in Oligometastatic disease: brain Oligometastases. Front Oncol. 2019;9:206. https://doi.org/10.3389/fonc.2019.00206.CrossRefPubMedPubMedCentral

Alongi F, Mazzola R, Figlia V, Guckenberger M. Stereotactic body radiotherapy for lung oligometastases: literature review according to PICO criteria. Tumori. 2018;104(3):148–56. https://doi.org/10.1177/0300891618766820.CrossRefPubMed

Mazzola R, Fersino S, Ferrera G, Targher G, Figlia V, Triggiani L, et al. Stereotactic body radiotherapy for lung oligometastases impacts on systemic treatment-free survival: a cohort study. Med Oncol. 2018;35(9):121. https://doi.org/10.1007/s12032-018-1190-8.CrossRefPubMed

Zeng J, Baik C, Bhatia S, Mayr N, Rengan R. Combination of stereotactic ablative body radiation with targeted therapies. Lancet Oncol. 2014;15:e426–34. https://doi.org/10.1016/S1470-2045(14)70026-9.CrossRefPubMed

Park HJ, Griffin RJ, Hui S, Levitt SH, Song CW. Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Rad Res. 2012;177:311–27. https://doi.org/10.1667/rr2773.1.CrossRef

Hellevik T, Martinez-Zubiaurre I. Radiotherapy and the tumor stroma: the importance of dose and fractionation. Front Oncol. 2014;4:1. https://doi.org/10.3389/fonc.2014.00001.CrossRefPubMedPubMedCentral

Andisheh B, Edgren M, Belkic D, Mavroidis P, Brahme A, Lind BK. A comparative analysis of radiobiological models for cell surviving fractions at high doses. Technol Cancer Res Treat. 2013;12:183–92. https://doi.org/10.7785/tcrt.2012.500306.CrossRefPubMed

10.

Weichselbaum RR, Liang H, Deng L, Fu YX. Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol. 2017;14:365–79. https://doi.org/10.1038/nrclinonc.2016.211.CrossRefPubMed

11.

Ngwa W, Irabor OC, Schoenfeld JD, Hesser J, Demaria S, Formenti SC. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018;18:313–22. https://doi.org/10.1038/nrc.2018.6.CrossRefPubMedPubMedCentral

12.

Buchwald ZS, Wynne J, Nasti TH, Zhu S, Mourad WF, Yan W, et al. Radiation, immune checkpoint blockade and the Abscopal effect: a critical review on timing. Dose and Fractionation. Front Oncol. 2018;8:612. https://doi.org/10.3389/fonc.2018.CrossRefPubMed

13.

Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, et al. Radiation and dual checkpoint blockade activate nonredundant immune mechanisms in cancer. Nature. 2015;520:373–7. https://doi.org/10.1038/nature14292.CrossRefPubMed

14.

Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74:5458–68. https://doi.org/10.1158/0008-5472.CAN-14-1258.CrossRefPubMed

15.

Chen L, Douglass J, Kleinberg L, Ye X, Marciscano AE, Forde PM, et al. Concurrent immune checkpoint inhibitors and stereotactic radiosurgery for brain metastases in non-small cell lung Cancer, melanoma, and renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2018;100(4):916–25. https://doi.org/10.1016/j.ijrobp.2017.11.041.CrossRefPubMed

16.

Verma V, Cushman TR, Selek U, Tang C, Welsh JW. Safety of combined immunotherapy and thoracic radiation therapy: analysis of 3 single-institutional phase I/II trials. Int J Radiat Oncol Biol Phys. 2018;101(5):1141–8. https://doi.org/10.1016/j.ijrobp.2018.04.054.CrossRefPubMed

17.

Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, 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. https://doi.org/10.1001/jamaoncol.2019.1478.

18.

Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, 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(17):5379–88. https://doi.org/10.1158/1078-0432.CCR-09-0265.CrossRefPubMedPubMedCentral

19.

Bauml JM, Mick R, Ciunci C, Aggarwal C, Davis C, Evans T, et al. Pembrolizumab after completion of locally ablative therapy for Oligometastatic non-small cell lung Cancer: a phase 2 trial. JAMA Oncol. 2019. https://doi.org/10.1001/jamaoncol.2019.

20.

Lesueur P, Escande A, Thariat J, Vauléon E, Monnet I, Cortot A, et al. Safety of combined PD-1 pathway inhibition and radiation therapy for non-small-cell lung cancer: a multicentric retrospective study from the GFPC. Cancer Med. 2018;7(11):5505–13. https://doi.org/10.1002/cam4.1825.CrossRefPubMedPubMedCentral

21.

Schapira E, Hubbeling H, Yeap BY, Mehan WA Jr, Shaw AT, Oh K, et al. Improved overall survival and Locoregional disease control with concurrent PD-1 pathway inhibitors and stereotactic radiosurgery for lung Cancer patients with brain metastases. Int J Radiat Oncol Biol Phys. 2018;101(3):624–9. https://doi.org/10.1016/j.ijrobp.2018.02.175.CrossRefPubMed

22.

Hubbeling HG, Schapira EF, Horick NK, Goodwin KEH, Lin JJ, Oh KS, et al. Safety of combined PD-1 pathway inhibition and intracranial radiation therapy in non-small cell lung Cancer. J Thorac Oncol. 2018;13(4):550–8. https://doi.org/10.1016/j.jtho.2018.01.012.CrossRefPubMed

23.

Iyengar P, Kavanagh BD, Wardak Z, Smith I, Ahn C, Gerber DE, et al. Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer. J Clin Oncol. 2014;32:3824–30. https://doi.org/10.1200/JCO.2014.56.7412.CrossRefPubMed

24.

Qiu B, Liang Y, Li QW, Liu G, Wang F, Chen Z, et al. Local therapy for Oligoprogressive disease in patients with advanced stage non-small-cell lung Cancer harboring epidermal growth factor receptor mutation. Clin Lung Cancer. 2017;18(6):e369–73. https://doi.org/10.1016/j.cllc.2017.04.002.CrossRefPubMed

25.

Borghetti P, Bonù ML, Giubbolini R, Levra NG, Mazzola R, Perna M, et al. Concomitant radiotherapy and TKI in metastatic EGFR- or ALK-mutated non-small cell lung cancer: a multicentric analysis on behalf of AIRO lung cancer study group. Radiol Med. 2019;124(7):662–70. https://doi.org/10.1007/s11547-019-00999-w.CrossRefPubMed

26.

Rossi S, Finocchiaro G, Noia VD, Bonomi M, Cerchiaro E, Rose F, et al. Survival outcome of tyrosine kinase inhibitors beyond progression in association to radiotherapy in oligoprogressive EGFR-mutant non-small-cell lung cancer. Future Oncol. 2019;15(33):3775–82. https://doi.org/10.2217/fon-2019-0349.CrossRefPubMed

27.

Xu Q, Zhou F, Liu H, Jiang T, Li X, Xu Y, et al. Consolidative local ablative therapy improves the survival of patients with synchronous oligometastatic NSCLC harboring EGFR activating mutation treated with first-line EGFR-TKIs. J Thorac Oncol. 2018;13(9):1383–92. https://doi.org/10.1016/j.jtho.2018.05.019.CrossRefPubMed

28.

Kroeze SG, Fritz C, Hoyer M, Lo SS, Ricardi U, Sahgal A, et al. Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev. 2017;53:25–37. https://doi.org/10.1016/j.ctrv.2016.11.013.CrossRefPubMed

29.

Weickhardt AJ, Scheier B, Burke JM, Gan G, Lu X, Bunn PA Jr, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012;7(12):1807–14. https://doi.org/10.1097/JTO.0b013e3182745948.CrossRefPubMedPubMedCentral

30.

Weiss J, Kavanagh B, Deal A, Villaruz L, Stevenson J, Camidge R, et al. Phase II study of stereotactic radiosurgery for the treatment of patients with oligoprogression on erlotinib. Cancer Treat Res Commun. 2019;19:100126. https://doi.org/10.1016/j.ctarc.2019.100126.CrossRefPubMed

31.

Chan OSH, Lam KC, Li J, et al. ATOM: A Phase II Study to Assess Efficacy of Preemptive Local Ablative Therapy to Residual Oligometastases After EGFR TKI. J Thorac Oncol. 2018;13(10):S336. https://doi.org/10.1016/j.jtho.2018.08.270.CrossRef

32.

Qin R, Olson A, Singh B, Thomas S, Wolf S, Bhavsar NA, et al. Safety and efficacy of radiation therapy in advanced melanoma patients treated with Ipilimumab. Int J Radiat Oncol Biol Phys. 2016;96(1):72–7. https://doi.org/10.1016/j.ijrobp.2016.04.017.CrossRefPubMed

33.

Diao K, Bian SX, Routman DM, Yu C, Ye JC, Wagle NA, et al. Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity. J Neuro-Oncol. 2018;139(2):421–9. https://doi.org/10.1007/s11060-018-2880-y.CrossRef

34.

Anderson ES, Postow MA, Wolchok JD, Young RJ, Ballangrud Å, Chan TA, et al. Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. J Immunother Cancer. 2017;5(1):76. https://doi.org/10.1186/s40425-017-0282-x.CrossRefPubMedPubMedCentral

35.

Gabani P, Robinson CG, Ansstas G, Johanns TM, Huang J. Use of extracranial radiation therapy in metastatic melanoma patients receiving immunotherapy. Radiother Oncol. 2018;127(2):310–7. https://doi.org/10.1016/j.radonc.2018.02.022.CrossRefPubMed

36.

Stera S, Balermpas P, Blanck O, Wolff R, Wurster S, Baumann R, et al. Stereotactic radiosurgery combined with immune checkpoint inhibitors or kinase inhibitors for patients with multiple brain metastases of malignant melanoma. Melanoma Res. 2019;29(2):187–95. https://doi.org/10.1097/CMR.0000000000000542.CrossRefPubMed

37.

Liniker E, Menzies AM, Kong BY, Cooper A, Ramanujam S, Lo S, et al. Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma. Oncoimmunology. 2016;5(9):e1214788. https://doi.org/10.1080/2162402X.2016.1214788.CrossRefPubMedPubMedCentral

38.

Chandra RA, Wilhite TJ, Balboni TA, Alexander BM, Spektor A, Ott PA, et al. A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology. 2015;4(11):e1046028. https://doi.org/10.1080/2162402X.2015.1046028.CrossRefPubMedPubMedCentral

39.

Wolf A, Zia S, Verma R, Pavlick A, Wilson M, Golfinos JG, et al. Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases. J Neuro-Oncol. 2016;127(3):607–15. https://doi.org/10.1007/s11060-016-2072-6.CrossRef

40.

Ahmed KA, Abuodeh YA, Echevarria MI, Arrington JA, Stallworth DG, Hogue C, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy. Ann Oncol. 2016;27(12):2288–94. https://doi.org/10.1093/annonc/mdw417.CrossRefPubMed

41.

Gaudy-Marqueste C, Carron R, Delsanti C, Loundou A, Monestier S, Archier E, et al. On demand gamma-knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases. Ann Oncol. 2014;25(10):2086–91. https://doi.org/10.1093/annonc/mdu266.CrossRefPubMed

42.

Ly D, Bagshaw HP, Anker CJ, Tward JD, Grossmann KF, Jensen RL, et al. Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment. J Neurosurg. 2015;123(2):395–401. https://doi.org/10.3171/2014.9.JNS141425.CrossRefPubMed

43.

Patel KR, Chowdhary M, Switchenko JM, Kudchadkar R, Lawson DH, Cassidy RJ, et al. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res. 2016;26(4):387–94. https://doi.org/10.1097/CMR.0000000000000268.CrossRefPubMedPubMedCentral

44.

Franceschini D, Franzese C, De Rose F, Navarria P, D'Agostino GR, Comito T, et al. Role of extra cranial stereotactic body radiation therapy in the management of stage IV melanoma. Br J Radiol. 2017;90(1077):20170257. https://doi.org/10.1259/bjr.20170257.CrossRefPubMedPubMedCentral

45.

Kotecha R, Miller JA, Venur VA, Mohammadi AM, Chao ST, Suh JH, et al. Melanoma brain metastasis: the impact of stereotactic radiosurgery, BRAF mutational status, and targeted and/or immune-based therapies on treatment outcome. J Neurosurg. 2018;129(1):50–9. https://doi.org/10.3171/2017.1.JNS162797.CrossRefPubMed

46.

Hecht M, Meier F, Zimmer L, Polat B, Loquai C, Weishaupt C, et al. Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients. Br J Cancer. 2018;118(6):785–92. https://doi.org/10.1038/bjc.2017.489.CrossRefPubMedPubMedCentral

47.

Mastorakos P, Xu Z, Yu J, Hess J, Qian J, Chatrath A, et al. BRAF V600 mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases: a multicenter retrospective study. Neurosurgery. 2019;84(4):868–80. https://doi.org/10.1093/neuros/nyy203.CrossRefPubMed

48.

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(8):547–51. https://doi.org/10.1080/15384047.2017.CrossRefPubMedPubMedCentral

49.

Matsushita Y, Nakamura K, Furuse H, Ichinohe K, Miyake H, et al. Marked response to nivolumab combined with external radiation therapy for metastatic renal cell carcinoma: report of two cases. Int Cancer Conf J. 2018;8(1):29–32. https://doi.org/10.1007/s13691-018-0349-7.CrossRefPubMedPubMedCentral

50.

Cochran DC, Chan MD, Aklilu M, Lovato JF, Alphonse NK, Bourland JD, et al. The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with gamma knife surgery. J Neurosurg. 2012;116(5):978–83. https://doi.org/10.3171/2012.2.JNS111353.CrossRefPubMedPubMedCentral

51.

Verma J, Jonasch E, Allen PK, Weinberg JS, Tannir N, Chang EL, et al. The impact of tyrosine kinase inhibitors on the multimodality treatment of brain metastases from renal cell carcinoma. Am J Clin Oncol. 2013;36(6):620–4. https://doi.org/10.1097/COC.0b013e31825d59db.CrossRefPubMedPubMedCentral

52.

De Wolf K, Rottey S, Vermaelen K, Decaestecker K, Sundahl N, De Lobel L, et al. Combined high dose radiation and pazopanib in metastatic renal cell carcinoma: a phase I dose escalation trial. Radiat Oncol. 2017;12(1):157. https://doi.org/10.1186/s13014-017-0893-x.CrossRefPubMedPubMedCentral

53.

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(5):e000535. https://doi.org/10.1136/esmoopen-2019-000535.CrossRefPubMedPubMedCentral

54.

Miller JA, Balagamwala EH, Angelov L, Suh JH, Rini B, Garcia JA, et al. Spine stereotactic radiosurgery with concurrent tyrosine kinase inhibitors for metastatic renal cell carcinoma. J Neurosurg Spine. 2016;25(6):766–74. https://doi.org/10.3171/2016.4.SPINE16229.CrossRefPubMed

55.

Franzese C, Franceschini D, Di Brina L, GR DA, Navarria P, Comito T, et al. Role of stereotactic body radiation therapy for the Management of Oligometastatic Renal Cell Carcinoma. J Urol. 2019;201(1):70–5. https://doi.org/10.1016/j.juro.2018.08.049.CrossRefPubMed

56.

Alongi F, Arcangeli S, Triggiani L, Mazzola R, Buglione di mMnale E Bastia M, Fersino S, et al. Stereotactic ablative radiation therapy in renal cell carcinoma: From oligometastatic to localized disease. Crit Rev Oncol Hematol. 2017;117:48–56. https://doi.org/10.1016/j.critrevonc.2017.07.004.CrossRefPubMed

57.

Staehler M, Haseke N, Nuhn P, Tüllmann C, Karl A, Siebels M, et al. Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma. BJU Int. 2011;108(5):673–8. https://doi.org/10.1111/j.1464-410X.2010.09895.CrossRefPubMed

58.

Staehler M, Haseke N, Stadler T, Nuhn P, Roosen A, Stief CG, et al. Feasibility and effects of high-dose hypofractionated radiation therapy and simultaneous multi-kinase inhibition with sunitinib in progressive metastatic renal cell cancer. Urol Oncol. 2012;30(3):290–3. https://doi.org/10.1016/j.urolonc.2010.02.006.CrossRefPubMed

59.

Bastos DA, Molina AM, Hatzoglou V, Jia X, Velasco S, Patil S, et al. Safety and efficacy of targeted therapy for renal cell carcinoma with brain metastasis. Clin Genitourin Cancer. 2015;13(1):59–66. https://doi.org/10.1016/j.clgc.2014.06.00.CrossRefPubMed

60.

Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051–8. https://doi.org/10.1016/S0140-6736(18)32487-5.CrossRefPubMed

Title: Oligometastasis and local ablation in the era of systemic targeted and immunotherapy
Authors: Rosario Mazzola
Barbara Alicja Jereczek-Fossa
Davide Franceschini
Slavisa Tubin
Andrea Riccardo Filippi
Maria Tolia
Andrea Lancia
Giuseppe Minniti
Stefanie Corradini
Stefano Arcangeli
Marta Scorsetti
Filippo Alongi
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: NSCLC
Metastasis
Melanoma
Melanoma
NSCLC
Radiotherapy
Kidney Cancer
Kidney Cancer
Kidney Cancer
Published in: Radiation Oncology / Issue 1/2020
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/s13014-020-01544-0

2024 ASCO Annual Meeting

Springer Medicine

Oligometastasis and local ablation in the era of systemic targeted and immunotherapy

Abstract

Background

Material and method

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Material and method

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2020

Acoustic diagnosis of elastic properties of human tooth by 320 MHz scanning acoustic microscopy after radiotherapy treatment for head and neck cancer

Correction to: Effects of the Bragg peak degradation due to lung tissue in proton therapy of lung cancer patients

In regard to Cuccia et al.: impact of hydrogel peri-rectal spacer insertion on prostate gland intra-fraction motion during 1.5 T MR-guided stereotactic body radiotherapy

Squamous cell carcinoma (SCC) of the Pyriform sinus with multiple metachronous brain metastases, a case report

MRI response rate after short-course radiotherapy on rectal cancer in the elderly comorbid patient: results from a retrospective cohort study

Effect of neoadjuvant radiotherapy on survival of non-metastatic pancreatic ductal adenocarcinoma: a SEER database analysis