Skip to main content
SpringerLink
Log in

Oligometastatic Disease: Basic Aspects and Clinical Results in NSCLC

  • Chapter
  • First Online:
Advances in Radiation Oncology in Lung Cancer

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

  • 323 Accesses

Abstract

Oligometastatic disease (OMD) represents a unique subset of metastatic disease that is limited in extent, with a generally accepted definition being metastatic disease confined to one or a few sites. Such limited metastatic disease can be amenable to resection or ablative doses of radiation. OMD treated with stereotactic ablative radiotherapy (SABR)/stereotactic body therapy (SBRT) has been shown to be associated with a survival advantage in prospective randomized phase II clinical studies, including studies specific to patients with non-small cell lung cancer. Currently, there are ongoing phase III studies around the world validating the initial findings in these studies. There are limitations to our understanding of OMD. For example, there are no validated molecular biomarkers to stratify the patients who would benefit most from SBRT/SABR. Furthermore, the definition of the oligometastatic state is limited by the currently available imaging modalities’ ability to identify sites of metastatic disease. With new advances on the horizon in imaging and molecular markers, the study of OMD is burgeoning. Future endeavors to further sub-stratify oligometastatic state, and possible expansion of the definition for more patients to benefit from the survival advantage, are also on the horizon.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ashworth A, Rodrigues G, Boldt G, Palma D (2013) Is there an oligometastatic state in non-small cell lung cancer? A systematic review of the literature. Lung Cancer 82(2):197–203. https://doi.org/10.1016/j.lungcan.2013.07.026. Epub 2013 Aug 20

    Article  Google Scholar 

  • Ashworth AB, Senan S, Palma DA, Riquet M, Ahn YC, Ricardi U, Congedo MT, Gomez DR, Wright GM, Melloni G, Milano MT, Sole CV, De Pas TM, Carter DL, Warner AJ, Rodrigues GB (2014) An individual patient data meta-analysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer 15(5):346–355. https://doi.org/10.1016/j.cllc.2014.04.003. Epub 2014 May 15

    Article  Google Scholar 

  • Aujla KS, Katz AW, Singh DP, Okunieff P, Milano MT (2019) Hypofractionated stereotactic radiotherapy for non-breast or prostate cancer oligometastases: a tail of survival beyond 10 years. Front Oncol 9:111. https://doi.org/10.3389/fonc.2019.00111

    Article  Google Scholar 

  • Bauml JM, Mick R, Ciunci C, Aggarwal C, Davis C, Evans T, Deshpande C, Miller L, Patel P, Alley E, Knepley C, Mutale F, Cohen RB, Langer CJ (2019) Pembrolizumab after completion of locally ablative therapy for oligometastatic non-small cell lung cancer: a phase 2 trial. JAMA Oncol 5(9):1283–1290. https://doi.org/10.1001/jamaoncol.2019.1449. Epub ahead of print

    Article  Google Scholar 

  • Bergsma DP, Salama JK, Singh DP, Chmura SJ, Milano MT (2015) The evolving role of radiotherapy in treatment of oligometastatic NSCLC. Expert Rev Anticancer Ther 15(12):1459–1471. https://doi.org/10.1586/14737140.2015.1105745. Epub 2015 Nov 4

    Article  Google Scholar 

  • Bergsma DP, Salama JK, Singh DP, Chmura SJ, Milano MT (2017) Radiotherapy for oligometastatic lung cancer. Front Oncol 7:210. https://doi.org/10.3389/fonc.2017.00210

    Article  Google Scholar 

  • Brooks ED, Chang JY (2019) Time to abandon single-site irradiation for inducing abscopal effects. Nat Rev Clin Oncol 16(2):123–135. https://doi.org/10.1038/s41571-018-0119-7

    Article  Google Scholar 

  • Chalkidou A, Macmillan T, Grzeda MT, Peacock J, Summers J, Eddy S, Coker B, Patrick H, Powell H, Berry L, Webster G, Ostler P, Dickinson PD, Hatton MQ, Henry A, Keevil S, Hawkins MA, Slevin N, van As N (2021) Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study. Lancet Oncol 22(1):98–106. https://doi.org/10.1016/S1470-2045(20)30537-4

    Article  Google Scholar 

  • Cheruvu P, Metcalfe SK, Metcalfe J, Chen Y, Okunieff P, Milano MT (2011) Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer. Radiat Oncol 6:80. https://doi.org/10.1186/1748-717X-6-80

    Article  Google Scholar 

  • Chiang AC, MassaguĂ© J (2008) Molecular basis of metastasis. N Engl J Med 359(26):2814–2823. https://doi.org/10.1056/NEJMra0805239

    Article  Google Scholar 

  • Collen C, Christian N, Schallier D, Meysman M, Duchateau M, Storme G, De Ridder M (2014) Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. Ann Oncol 25(10):1954–1959. https://doi.org/10.1093/annonc/mdu370. Epub 2014 Aug 11

    Article  Google Scholar 

  • De Ruysscher D, Wanders R, van Baardwijk A, Dingemans AM, Reymen B, Houben R, Bootsma G, Pitz C, van Eijsden L, Geraedts W, Baumert BG, Lambin P (2012) Radical treatment of non-small-cell lung cancer patients with synchronous oligometastases: long-term results of a prospective phase II trial (Nct01282450). J Thorac Oncol 7(10):1547–1555. https://doi.org/10.1097/JTO.0b013e318262caf6

    Article  Google Scholar 

  • Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One 4(9):e7181. https://doi.org/10.1371/journal.pone.0007181

    Article  Google Scholar 

  • Elson-Schwab I, Lorentzen A, Marshall CJ (2010) MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion. PLoS One 5(10):e13176. https://doi.org/10.1371/journal.pone.0013176

    Article  Google Scholar 

  • Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV (2016) Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol 17(12):1672–1682. https://doi.org/10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24

    Article  Google Scholar 

  • Gomez DR, Tang C, Zhang J, Blumenschein GR Jr, Hernandez M, Lee JJ, Ye R, Palma DA, Louie AV, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Welsh JW, Gibbons DL, Karam JA, Kavanagh BD, Tsao AS, Sepesi B, Swisher SG, Heymach JV (2019) Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol 37(18):1558–1565. https://doi.org/10.1200/JCO.19.00201. Epub 2019 May 8

    Article  Google Scholar 

  • Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10(5):593–601. https://doi.org/10.1038/ncb1722. Epub 2008 Mar 30

    Article  Google Scholar 

  • Guckenberger M, Lievens Y, Bouma AB, Collette L, Dekker A, deSouza NM, Dingemans AC, Fournier B, Hurkmans C, Lecouvet FE, Meattini I, MĂ©ndez Romero A, Ricardi U, Russell NS, Schanne DH, Scorsetti M, Tombal B, Verellen D, Verfaillie C, Ost P (2020) Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol 21(1):e18–e28. https://doi.org/10.1016/S1470-2045(19)30718-1

    Article  Google Scholar 

  • Gupta GP, MassaguĂ© J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695. https://doi.org/10.1016/j.cell.2006.11.001

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD (2018) Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol 4(1):e173501. https://doi.org/10.1001/jamaoncol.2017.3501. Epub 2018 Jan 11

    Article  Google Scholar 

  • Kumar A, Straka C, Courtney PT, Vitzthum L, Riviere P, Murphy JD (2021) Cost-Effectiveness Analysis of Stereotactic Ablative Radiation Therapy in Patients With Oligometastatic Cancer. Int J Radiat Oncol Biol Phys. 109(5):1185–1194. https://doi.org/10.1016/j.ijrobp.2020.09.045. Epub 2020 Sep 28. PMID: 33002541.

  • Lee P, Loo BW Jr, Biswas T, Ding GX, El Naqa IM, Jackson A, Kong FM, LaCouture T, Miften M, Solberg T, Tome WA, Tai A, Yorke E, Li XA (2021) Local control after stereotactic body radiation therapy for stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys 110(1):160–171

    Article  Google Scholar 

  • Lehrer EJ, Singh R, Wang M, Chinchilli VM, Trifiletti DM, Ost P, Siva S, Meng MB, Tchelebi L, Zaorsky NG (2021) Safety and survival rates associated with ablative stereotactic radiotherapy for patients with oligometastatic cancer: a systematic review and meta-analysis. JAMA Oncol 7(1):92–106. https://doi.org/10.1001/jamaoncol.2020.6146

    Article  Google Scholar 

  • Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH (2001) Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 7(5):630–636. https://doi.org/10.3748/wjg.v7.i5.630

    Article  Google Scholar 

  • Li J, Xu W, Kong F, Sun X, Zuo X (2013) Meta-analysis: accuracy of 18FDG PET-CT for distant metastasis staging in lung cancer patients. Surg Oncol 22(3):151–155. https://doi.org/10.1016/j.suronc.2013.04.001. Epub 2013 May 9

    Article  Google Scholar 

  • Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, MĂ©ndez Romero A, Nevens D, Palma D, Park C, Ricardi U, Scorsetti M, Yu J, Woodward WA (2020) Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus document. Radiother Oncol 148:157–166. https://doi.org/10.1016/j.radonc.2020.04.003. Epub 2020 Apr 22

    Article  Google Scholar 

  • Lussier YA, Xing HR, Salama JK, Khodarev NN, Huang Y, Zhang Q, Khan SA, Yang X, Hasselle MD, Darga TE, Malik R, Fan H, Perakis S, Filippo M, Corbin K, Lee Y, Posner MC, Chmura SJ, Hellman S, Weichselbaum RR (2011) MicroRNA expression characterizes oligometastasis(es). PLoS One 6(12):e28650. https://doi.org/10.1371/journal.pone.0028650. Epub 2011 Dec 13

    Article  Google Scholar 

  • Lussier YA, Khodarev NN, Regan K, Corbin K, Li H, Ganai S, Khan SA, Gnerlich JL, Darga TE, Fan H, Karpenko O, Paty PB, Posner MC, Chmura SJ, Hellman S, Ferguson MK, Weichselbaum RR (2012) Oligo- and polymetastatic progression in lung metastasis(es) patients is associated with specific microRNAs. PLoS One 7(12):e50141. https://doi.org/10.1371/journal.pone.0050141. Epub 2012 Dec 10. Erratum in: PLoS One. 2013;8(6). https://doi.org/10.1371/annotation/2489ae5e-3650-4897-8df6-3e974ca585c4. Gnerlich, Jennifer [corrected to Gnerlich, Jennifer L]

    Article  Google Scholar 

  • Madsen PH, Holdgaard PC, Christensen JB, Hoilund-Carlsen PF (2016) Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer. Eur J Nucl Med Mol Imaging 43:2084–2097

    Article  Google Scholar 

  • Milano MT, Constine LS, Okunieff P (2008) Normal tissue toxicity after small field hypofractionated stereotactic body radiation. Radiat Oncol 3:36. https://doi.org/10.1186/1748-717X-3-36

    Article  Google Scholar 

  • Milano MT, Biswas T, Simone CB II, Lo SS (2021) Oligometastases: history of a hypothesis. Ann Palliat Med 10(5):5923–5930

    Article  Google Scholar 

  • Nguyen DX, MassaguĂ© J (2007) Genetic determinants of cancer metastasis. Nat Rev Genet 8(5):341–352. https://doi.org/10.1038/nrg2101

    Article  Google Scholar 

  • Palma DA, Louie AV, Rodrigues GB (2015) New strategies in stereotactic radiotherapy for oligometastases. Clin Cancer Res 21(23):5198–5204. https://doi.org/10.1158/1078-0432.CCR-15-0822

    Article  Google Scholar 

  • Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Griffioen G, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Bauman GS, Warner A, Senan S (2019) Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 393(10185):2051–2058. https://doi.org/10.1016/S0140-6736(18)32487-5. Epub 2019 Apr 11. PMID: 30982687.

  • Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Schlijper R, Bauman GS, Laba J, Qu XM, Warner A, Senan S (2020) Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 38(25):2830–2838. https://doi.org/10.1200/JCO.20.00818. Epub 2020 Jun 2. PMID: 32484754; PMCID: PMC7460150

  • Peters LJ, Milas L, Fletcher GH (1983) The role of radiation therapy in the curative treatment of metastatic disease. Symp Fundam Cancer Res 36:411–420

    Google Scholar 

  • Pitroda SP, Weichselbaum RR (2019) Integrated molecular and clinical staging defines the spectrum of metastatic cancer. Nat Rev Clin Oncol 16(9):581–588. https://doi.org/10.1038/s41571-019-0220-6

    Article  Google Scholar 

  • Pitroda SP, Chmura SJ, Weichselbaum RR (2019) Integration of radiotherapy and immunotherapy for treatment of oligometastases. Lancet Oncol 20(8):e434–e442. https://doi.org/10.1016/S1470-2045(19)30157-3. Epub 2019 Jul 29

    Article  Google Scholar 

  • Qu XM, Chen Y, Zaric GS, Senan S, Olson RA, Harrow S, John-Baptiste A, Gaede S, Mulroy LA, Schellenberg D, Senthi S, Swaminath A, Kopek N, Liu M, Warner A, Rodrigues GB, Palma DA, Louie AV (2021) Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of the SABR-COMET Randomized Trial. Int J Radiat Oncol Biol Phys. 109(5):1176–1184. https://doi.org/10.1016/j.ijrobp.2020.12.001. Epub 2020 Dec 10. PMID: 33309977.

  • Rubin P (1968) Comment: Are metastases curable? JAMA 204(7):612–613

    Article  Google Scholar 

  • Rubin P, Green J (1968) Solitary metastases. C. C. Thomas, Springfield, IL

    Google Scholar 

  • SABR-COMET 3: Olson R, Mathews L, Liu M, Schellenberg D, Mou B, Berrang T, Harrow S, Correa RJM, Bhat V, Pai H, Mohamed I, Miller S, Schneiders F, Laba J, Wilke D, Senthi S, Louie AV, Swaminath A, Chalmers A, Gaede S, Warner A, de Gruijl TD, Allan A, Palma DA (2020) Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial. BMC Cancer. 20(1):380. https://doi.org/10.1186/s12885-020-06876-4. PMID: 32370765; PMCID: PMC7201684.

  • SABR COMET 10: Palma DA, Olson R, Harrow S, Correa RJM, Schneiders F, Haasbeek CJA, Rodrigues GB, Lock M, Yaremko BP, Bauman GS, Ahmad B, Schellenberg D, Liu M, Gaede S, Laba J, Mulroy L, Senthi S, Louie AV, Swaminath A, Chalmers A, Warner A, Slotman BJ, de Gruijl TD, Allan A, Senan S (2019) Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 19(1):816. https://doi.org/10.1186/s12885-019-5977-6. PMID: 31426760; PMCID: PMC6699121.

  • Salama JK, Milano MT (2014) Radical irradiation of extracranial oligometastases. J Clin Oncol 32(26):2902–2912. https://doi.org/10.1200/JCO.2014.55.9567. Epub 2014 Aug 11

    Article  Google Scholar 

  • Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331(6024):1565–1570. https://doi.org/10.1126/science.1203486

    Article  Google Scholar 

  • Shindo-Okada N, Takeuchi K, Nagamachi Y (2001) Establishment of cell lines with high- and low-metastatic potential from PC-14 human lung adenocarcinoma. Jpn J Cancer Res 92(2):174–183. https://doi.org/10.1111/j.1349-7006.2001.tb01080.x

    Article  Google Scholar 

  • Sutera P, Clump DA, Kalash R, D’Ambrosio D, Mihai A, Wang H, Petro DP, Burton SA, Heron DE (2019) Initial results of a multicenter phase 2 trial of stereotactic ablative radiation therapy for oligometastatic cancer. Int J Radiat Oncol Biol Phys 103(1):116–122. https://doi.org/10.1016/j.ijrobp.2018.08.027. Epub 2018 Aug 25

    Article  Google Scholar 

  • Tönnies S, Tönnies M, Kollmeier J, Bauer TT, Förster GJ, Kaiser D, Wernecke KD, Pfannschmidt J (2016) Impact of preoperative 18F-FDG PET/CT on survival of resected mono-metastatic non-small cell lung cancer. Lung Cancer 93:28–34. https://doi.org/10.1016/j.lungcan.2015.12.008. Epub 2015 Dec 30

    Article  Google Scholar 

  • Weichselbaum RR, Liang H, Deng L, Fu YX (2017) Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol 14(6):365–379. https://doi.org/10.1038/nrclinonc.2016.211. Epub 2017 Jan 17

    Article  Google Scholar 

  • Wong AC, Watson SP, Pitroda SP, Son CH, Das LC, Stack ME, Uppal A, Oshima G, Khodarev NN, Salama JK, Weichselbaum RR, Chmura SJ (2016) Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT). Cancer 122(14):2242–2250. https://doi.org/10.1002/cncr.30058. Epub 2016 May 20

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Rochester, Rochester, NY, USA

    Gukan Sakthivel, Deepinder P. Singh, Haoming Qiu & Michael T. Milano

Authors
  1. Gukan Sakthivel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deepinder P. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haoming Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael T. Milano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael T. Milano .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Kragujevac, Kragujevac, Serbia

    Branislav Jeremić

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sakthivel, G., Singh, D.P., Qiu, H., Milano, M.T. (2022). Oligometastatic Disease: Basic Aspects and Clinical Results in NSCLC. In: Jeremić, B. (eds) Advances in Radiation Oncology in Lung Cancer. Medical Radiology(). Springer, Cham. https://doi.org/10.1007/174_2022_344

Download citation

  • DOI: https://doi.org/10.1007/174_2022_344

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-34846-4

  • Online ISBN: 978-3-031-34847-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation