Oligometastatic Non-Small Cell Lung Cancer: A Practical Review of Prospective Trials

Atallah Baydoun, VeAnn L Lee, Tithi Biswas, Atallah Baydoun, VeAnn L Lee, Tithi Biswas

Abstract

Oligometastatic non-small cell lung cancer (NSCLC) is an intermediate state between localized and widely metastatic NSCLC, where systemic therapy in combination with aggressive local therapy when feasible can yield a favorable outcome. While different societies have adopted different definitions for oligometastatic NSCLC, the feasibility of curative intent treatment remains a major determinant of the oligometastatic state. The management involves a multidisciplinary approach to identify such patients with oligometastatic stage, including the presence of symptomatic or potentially symptomatic brain metastasis, the presence of targetable mutations, and programmed death-ligand (PD-L1) expression. Treatment requires a personalized approach with the use of novel systemic agents such as tyrosine kinase inhibitors and immune checkpoint inhibitors with or without chemotherapy, and addition of local ablative therapy via surgery or stereotactic radiation therapy when appropriate.

Keywords: NSCLC; SBRT; oligometastatis; oligoprogression.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart for articles and trials inclusion for the current review article. (NSCLC: non-small cell lung cancer, EGFR: epidermal growth factor receptor).
Figure 2
Figure 2
Historical Landmarks in Oligometastatic NSCLC. (NSCLC: Non-small cell lung cancer; ICI: Immune checkpoint inhibitors; TKI: Tyrosine kinase inhibitors; EGFR: Epidermal growth factor receptor).
Figure 3
Figure 3
Flowchart for the suggested initial approach in patients presenting with metastatic (NSCLC: non-small cell lung cancer; EORTC-LG: the European Organization Research and Treatment of Cancer: Lung Cancer Group; NCCN: National Comprehensive Cancer Network; PD-L1: programmed death-ligand; EGFR: epidermal growth factor receptor).

References

    1. Planchard D., Popat S., Kerr K., Novello S., Smit E.F., Faivre-Finn C., Mok T.S., Reck M., Van Schil P.E., Hellmann M.D., et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2018;29:iv192–iv237. doi: 10.1093/annonc/mdy275.
    1. No H.J., Raja N., Von Eyben R., Das M., Roy M., Myall N., Neal J., Wakelee H., Chin A., Diehn M., et al. Characterization of Metastatic Non-Small Cell Lung Cancer and Oligometastatic Incidence in an Era of Changing Treatment Paradigms. Int. J. Radiat. Oncol. Biol. Phys. 2022;114:603–610. doi: 10.1016/j.ijrobp.2022.04.050.
    1. Mentink J.F., Paats M.S., Dumoulin D.W., Cornelissen R., Elbers J.B.W., Maat A., von der Thusen J.H., Dingemans A.C. Defining oligometastatic non-small cell lung cancer: Concept versus biology, a literature review. Transl. Lung Cancer Res. 2021;10:3329–3338. doi: 10.21037/tlcr-21-265.
    1. Iyengar P., Wardak Z., Gerber D.E., Tumati V., Ahn C., Hughes R.S., Dowell J.E., Cheedella N., Nedzi L., Westover K.D., et al. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018;4:e173501. doi: 10.1001/jamaoncol.2017.3501.
    1. Gomez D.R., Blumenschein G.R., Lee J.J., Hernandez M., Ye R., Camidge D.R., Doebele R.C., Skoulidis F., Gaspar L.E., Gibbons D.L., et al. 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. 2016;17:1672–1682. doi: 10.1016/S1470-2045(16)30532-0.
    1. Wang X., Bai Y.F., Zeng M. First-Line Tyrosine Kinase Inhibitor with or Without Aggressive Upfront Local Radiation Therapy in Patients with EGFRm Oligometastatic Non-Small-Cell Lung Cancer: Interim Results of a Randomized Phase III, Open-Label Clinical Trial (SINDAS) (NCT02893332) Int. J. Radiat. Oncol. Biol. Phys. 2020;108:e81. doi: 10.1016/j.ijrobp.2020.07.1169.
    1. Remon J., Menis J., Levy A., De Ruysscher D.K.M., Hendriks L.E.L. How to optimize the incorporation of immunotherapy in trials for oligometastatic non-small cell lung cancer: A narrative review. Transl. Lung Cancer Res. 2021;10:3486–3502. doi: 10.21037/tlcr-20-1065.
    1. Schanne D.H., Heitmann J., Guckenberger M., Andratschke N.H.J. Evolution of treatment strategies for oligometastatic NSCLC patients—A systematic review of the literature. Cancer Treat. Rev. 2019;80:101892. doi: 10.1016/j.ctrv.2019.101892.
    1. Congedo M.T., Cesario A., Lococo F., De Waure C., Apolone G., Meacci E., Cavuto S., Granone P. Surgery for oligometastatic non-small cell lung cancer: Long-term results from a single center experience. J. Thorac. Cardiovasc. Surg. 2012;144:444–452. doi: 10.1016/j.jtcvs.2012.05.051.
    1. De Ruysscher D., Wanders R., van Baardwijk A., Dingemans A.M., Reymen B., Houben R., Bootsma G., Pitz C., van Eijsden L., Geraedts W., et al. 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. 2012;7:1547–1555. doi: 10.1097/JTO.0b013e318262caf6.
    1. Adler I. Primary Malignant Growths of the Lungs and Bronchi: A Pathological and Clinical Study. Longmans, Green; New York, NY, USA: 1912.
    1. Hellman S., Weichselbaum R.R. Oligometastases. J. Clin. Oncol. 1995;13:8–10. doi: 10.1200/JCO.1995.13.1.8.
    1. Treasure T. Oligometastatic cancer: An entity, a useful concept, or a therapeutic opportunity? J. R. Soc. Med. 2012;105:242–246. doi: 10.1258/jrsm.2011.110279.
    1. Downey R.J., Ng K.K. The management of non-small-cell lung cancer with oligometastases. Chest Surg. Clin. N. Am. 2001;11:121–132. doi: 10.1016/j.thorsurg.2014.07.003.
    1. Szturz P., Vermorken J.B. Oligometastatic Cancer: Key Concepts and Research Opportunities for 2021 and Beyond. Cancers. 2021;13:2518. doi: 10.3390/cancers13112518.
    1. Ouyang W., Yu J., Nuerjiang S., Li Z., Wang D., Wang X., Zhang J., Xie C. Stereotactic body radiotherapy improves the survival of patients with oligometastatic non-small cell lung cancer. Cancer Med. 2019;8:4605–4614. doi: 10.1002/cam4.2366.
    1. Ashworth A.B., Senan S., Palma D.A., Riquet M., Ahn Y.C., Ricardi U., Congedo M.T., Gomez D.R., Wright G.M., Melloni G., et al. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin. Lung Cancer. 2014;15:346–355. doi: 10.1016/j.cllc.2014.04.003.
    1. Lievens Y., Guckenberger M., Gomez D., Hoyer M., Iyengar P., Kindts I., Mendez Romero A., Nevens D., Palma D., Park C., et al. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiother. Oncol. 2020;148:157–166. doi: 10.1016/j.radonc.2020.04.003.
    1. Levy A., Hendriks L.E., Berghmans T., Faivre-Finn C., GiajLevra M., GiajLevra N., Hasan B., Pochesci A., Girard N., Greillier L., et al. EORTC Lung Cancer Group survey on the definition of NSCLC synchronous oligometastatic disease. Eur. J. Cancer. 2019;122:109–114. doi: 10.1016/j.ejca.2019.09.012.
    1. Dingemans A.C., Hendriks L.E.L., Berghmans T., Levy A., Hasan B., Faivre-Finn C., Giaj-Levra M., Giaj-Levra N., Girard N., Greillier L., et al. Definition of Synchronous Oligometastatic Non-Small Cell Lung Cancer-A Consensus Report. J. Thorac. Oncol. 2019;14:2109–2119. doi: 10.1016/j.jtho.2019.07.025.
    1. Detterbeck F.C., Boffa D.J., Kim A.W., Tanoue L.T. The eighth edition lung cancer stage classification. Chest. 2017;151:193–203. doi: 10.1016/j.chest.2016.10.010.
    1. Belluomini L., Dodi A., Caldart A., Kadrija D., Sposito M., Casali M., Sartori G., Ferrara M.G., Avancini A., Bria E. A narrative review on tumor microenvironment in oligometastatic and oligoprogressive non-small cell lung cancer: A lot remains to be done. Transl. Lung Cancer Res. 2021;10:3369. doi: 10.21037/tlcr-20-1134.
    1. Amini A., Verma V., Simone C.B., 2nd, Chetty I.J., Chun S.G., Donington J., Edelman M.J., Higgins K.A., Kestin L.L., Movsas B., et al. American Radium Society Appropriate Use Criteria for Radiation Therapy in Oligometastatic or Oligoprogressive Non-Small Cell Lung Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2022;112:361–375. doi: 10.1016/j.ijrobp.2021.09.022.
    1. Laurie S., Banerji S., Blais N., Brule S., Cheema P., Cheung P., Daaboul N., Hao D., Hirsh V., Juergens R. Canadian consensus: Oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer. Curr. Oncol. 2019;26:81–93. doi: 10.3747/co.26.4116.
    1. Collen C., Christian N., Schallier D., Meysman M., Duchateau M., Storme G., De Ridder M. Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. Ann. Oncol. 2014;25:1954–1959. doi: 10.1093/annonc/mdu370.
    1. Petty W.J., Urbanic J.J., Ahmed T., Hughes R., Levine B., Rusthoven K., Papagikos M., Ruiz J.R., Lally B.E., Chan M., et al. Long-Term Outcomes of a Phase 2 Trial of Chemotherapy with Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2018;102:527–535. doi: 10.1016/j.ijrobp.2018.06.400.
    1. Arrieta O., Barron F., Maldonado F., Cabrera L., Corona-Cruz J.F., Blake M., Ramirez-Tirado L.A., Zatarain-Barron Z.L., Cardona A.F., Garcia O., et al. Radical consolidative treatment provides a clinical benefit and long-term survival in patients with synchronous oligometastatic non-small cell lung cancer: A phase II study. Lung Cancer. 2019;130:67–75. doi: 10.1016/j.lungcan.2019.02.006.
    1. Gomez D.R., Tang C., Zhang J., Blumenschein G.R., Jr., Hernandez M., Lee J.J., Ye R., Palma D.A., Louie A.V., Camidge D.R. 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. 2019;37:1558. doi: 10.1200/JCO.19.00201.
    1. Palma D.A., Olson R., Harrow S., Gaede S., Louie A.V., Haasbeek C., Mulroy L., Lock M., Rodrigues G.B., Yaremko B.P. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: Long-term results of the SABR-COMET phase II randomized trial. J. Clin. Oncol. 2020;38:2830. doi: 10.1200/JCO.20.00818.
    1. Bauml J.M., Mick R., Ciunci C., Aggarwal C., Davis C., Evans T., Deshpande C., Miller L., Patel P., Alley E., et al. Pembrolizumab After Completion of Locally Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer: A Phase 2 Trial. JAMA Oncol. 2019;5:1283–1290. doi: 10.1001/jamaoncol.2019.1449.
    1. Theelen W., Peulen H.M.U., Lalezari F., van der Noort V., de Vries J.F., Aerts J., Dumoulin D.W., Bahce I., Niemeijer A.N., de Langen A.J., 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. doi: 10.1001/jamaoncol.2019.1478.
    1. Chen Y., Wang Y., Yang Z., Hu M., Lu J., Zhang Y., Qian F., Zhang B., Wang S., Wang K., et al. Local consolidative therapy for synchronous oligometastatic non-small cell lung cancer treated with first-line pembrolizumab: A retrospective observational study. Thorac. Cancer. 2022;13:732–741. doi: 10.1111/1759-7714.14312.
    1. Xu Q., Zhou F., Liu H., Jiang T., Li X., Xu Y., Zhou C. 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;13:1383–1392. doi: 10.1016/j.jtho.2018.05.019.
    1. Wang X.S., Bai Y.F., Verma V., Yu R.L., Tian W., Ao R., Deng Y., Xia J.L., Zhu X.Q., Liu H., et al. Randomized Trial of First-Line Tyrosine Kinase Inhibitor with or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated NSCLC. J. Natl. Cancer Inst. 2022 doi: 10.1093/jnci/djac015.
    1. Ostrava U.H. Consolidation Conventional Radiotherapy + Stereotactic Body Radiotherapy at 3 Months after First-Line Chemotherapy in Stage IV Oligometastatic Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2021 Available online: .
    1. University of Wisconsin-Madison AstraZeneca: Phase Ib Study of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Non-Small Lung Cancer (NSCLC) With Dual Immune Checkpoint Inhibition. [(accessed on 15 August 2022)];2018 Available online: .
    1. Esslingen K. Prospective Trial of Induction Immunotherapy in Locally Advanced or Oligometastatic NSCLC Without a Primary Curative Option. [(accessed on 15 August 2022)];2017 Available online: .
    1. Hospital TMUS Sintilimab after Stereotactic Ablation Brachytherapy for Refractory Oligometastatic Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2020 Available online: .
    1. OMEGA, Local Ablative Therapy in Oligometastatic NSCLC (OMEGA) [(accessed on 15 August 2022)];2019 Available online: .
    1. Tata Memorial Hospital Local Consolidative Radiation Therapy Plus TKI Versus TKI Alone in Driver Mutated OM-NSCLC. [(accessed on 15 August 2022)];2019 Available online: .
    1. Sichuan Cancer Hospital and Research Institute. Mianyang Central Hospital. Cancer Hospital of Guizhou Province. The Optimal Intervention Time of Radiotherapy for Oligometastatic Stage IV Non-Small Cell Lung Cancer (NSCLC) [(accessed on 15 August 2022)];2014 Available online: .
    1. Wu Jieping Medical Foundation. Shanghai Chest Hospital. Shanghai Pulmonary Hospital, Shanghai, China The Value of Radiotherapy in the Oligometastatic Non-Squamous Non-Small Cell Lung Cancer with Clinical Benefits from Erlotinib as Second-Line Treatment. [(accessed on 15 August 2022)];2012 Available online: .
    1. Tata Memorial Hospital Standard Maintenance Therapy (SMT) vs. Local Consolidative Radiation Therapy and SMT in OM-NSCLC. [(accessed on 15 August 2022)];2020 Available online: .
    1. Shanghai Chest Hospital Phase II Trial of SBRT Compared with Conventional Radiotherapy for Oligometastatic Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2016 Available online: .
    1. University College, London, Cancer Research UK Stereotactic Ablative Radiotherapy for Oligometastatic Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2016 Available online: .
    1. Nanfang Hospital, Southern Medical University Local Non-Salvage Radiotherapy for Synchronous Oligometastatic Non-Small-Cell Lung Cancer. [(accessed on 15 August 2022)];2017 Available online: .
    1. Yonsei University The Safety and Efficacy of First-Line Lazertinib and Locally Ablative Radiotherapy in Patients with Synchronous Oligo-Metastatic EGFR-mutant Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2021 Available online: .
    1. Shandong Cancer Hospital and Institute Chemotherapy Combination with Local Radiotherapy and rhGM-CSF for Oligometastatic Stage IV NSCLC Patients. [(accessed on 15 August 2022)];2018 Available online: .
    1. M.D. Anderson Cancer Center, National Cancer Institute (NCI) Surgery and/or Radiation Therapy or Standard Therapy and/or Clinical Observation in Treating Patients with Previously Treated Stage IV Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2012 Available online: .
    1. ETOP IBCSG Partners Foundation, AstraZeneca AstraZeneca: Immunotherapy, Chemotherapy, Radiotherapy and Surgery for Synchronous Oligo-Metastatic NSCLC. [(accessed on 15 August 2022)];2019 Available online: .
    1. Institut Claudius Regaud A Trial Evaluating Stereotactic Radiotherapy Plus Durvalumab Continuation for Patients with NSCLC Metachronous Oligometastatic Disease Under Durvalumab Consolidation Following Chemoradiation. [(accessed on 15 August 2022)];2021 Available online: .
    1. Chia Tai Tianqing Pharmaceutical Group Co. L. A Study of TQB2450 Injection Combined with Stereotactic Body Radiation Therapy (SBRT) in Subjects with Advanced Oligometastatic Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2020 Available online: .
    1. ETOP IBCSG Partners Foundation, AstraZeneca AstraZeneca: Osimertinib and Locally Ablative Radiotherapy in Patients with Synchronous Oligo-Metastatic EGFR Mutant NSCLC (STEREO) [(accessed on 15 August 2022)];2021 Available online: .
    1. Zhejiang Cancer Hospital Durvalumab Combined with Chemotherapy and Stereotactic Body Radiotherapy (SBRT) in Patients with Oligometastatic Non-Small Cell Lung Cancer (NSCLC) [(accessed on 15 August 2022)];2020 Available online: .
    1. Instituto Nacional de Cancerologia de Mexico: Radical Treatment of Synchronous Oligometastatic Non-Small Cell Lung Carcinoma. [(accessed on 15 August 2022)];2015 Available online: .
    1. Lawson Health Research Institute, Academic Medical Organization of Southwestern Ontario Chest Lymph Node Sampling in Patients with Advanced Lung Cancer to be Treated with Curative-Intent Radiation Treatment. [(accessed on 15 August 2022)];2021 Available online: .
    1. Roswell Park Cancer Institute Stereotactic Body Radiation Therapy After Surgery in Treating Patients with Stage III-IV Non-Small Cell Lung Cancer. [(accessed on 15 August 2022)];2013 Available online: .
    1. Tang-Du Hospital Toripalimab in Combination with Platinum-Based Chemotherapy for Mutation-Negative Stage IV Oligometastatic NSCLC. [(accessed on 15 August 2022)];2021 Available online: .
    1. Shandong Cancer Hospital and Institute, Jiangsu HengRui Medicine Co., Ltd. A Trial of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination with Hypofraction Radiotherapy in Patients With NSCLC. [(accessed on 15 August 2022)];2018 Available online: .
    1. NRG Oncology, National Cancer Institute Maintenance Chemotherapy with or without Local Consolidative Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer. [(accessed on 15 August 2022)]; Available online: .
    1. Maastricht Radiation Oncology Concurrent and Non-Concurrent Chemo-Radiotherapy or Radiotherapy Alone for Patients with Oligo-Metastatic Stage IV Non-Small Cell Lung Cancer (NSCLC) [(accessed on 15 August 2022)];2006 Available online: .
    1. Universitaire Ziekenhuizen KU Leuven LAT for Oligoprogressive NSCLC Treated with First-Line OSImertinib. [(accessed on 15 August 2022)];2021 Available online: .
    1. Sun Yat-sen University A Study of Furmonertinib Combined with Radiotherapy for Non-small Cell Lung Cancer with Oligoprogression. [(accessed on 15 August 2022)];2021 Available online: .
    1. M.D. Anderson Cancer Center Local Consolidative Therapy and Durvalumab for Oligoprogressive and Polyprogressive Stage III NSCLC After Chemoradiation and Anti-PD-L1 Therapy. [(accessed on 15 August 2022)];2021 Available online: .
    1. Oncology Institute of Southern Switzerland. Ente Ospedaliero Cantonale, Bellinzona. Istituto Cantonale di Patologia. Clinical Trial Unit Ente Ospedaliero Cantonale Atezolizumab Plus 8 Gy Single-Fraction Radiotherapy for Advanced Oligoprogressive NSCLC. [(accessed on 15 August 2022)];2020 Available online: .
    1. Montréal ChdlUd Stereotactic Ablative Radiotherapy for Oligo-Progressive Non Small Cell Lung Cancer. [(accessed on 15 August 2022)];2021 Available online: .
    1. Center MSKC Randomized Study of Stereotactic Body Radiation Therapy (SBRT) in Patients with Oligoprogressive Metastatic Cancers of the Breast and Lung. [(accessed on 15 August 2022)];2019 Available online: .
    1. Institute of Cancer Research UK Stereotactic Body Radiotherapy for the Treatment of OPD. [(accessed on 15 August 2022)];2017 Available online: .
    1. Counago F., Luna J., Guerrero L.L., Vaquero B., Guillen-Sacoto M.C., Gonzalez-Merino T., Taboada B., Diaz V., Rubio-Viqueira B., Diaz-Gavela A.A., et al. Management of oligometastatic non-small cell lung cancer patients: Current controversies and future directions. World J. Clin. Oncol. 2019;10:318–339. doi: 10.5306/wjco.v10.i10.318.
    1. Soria J.C., Ohe Y., Vansteenkiste J., Reungwetwattana T., Chewaskulyong B., Lee K.H., Dechaphunkul A., Imamura F., Nogami N., Kurata T., et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2018;378:113–125. doi: 10.1056/NEJMoa1713137.
    1. Peters S., Camidge D.R., Shaw A.T., Gadgeel S., Ahn J.S., Kim D.-W., Ou S.-H.I., Pérol M., Dziadziuszko R., Rosell R., et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer. N. Engl. J. Med. 2017;377:829–838. doi: 10.1056/NEJMoa1704795.
    1. Brahmer J.R., Govindan R., Anders R.A., Antonia S.J., Sagorsky S., Davies M.J., Dubinett S.M., Ferris A., Gandhi L., Garon E.B., et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC) J. Immunother. Cancer. 2018;6:75. doi: 10.1186/s40425-018-0382-2.

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