ES21.02 Biological Disease Characterization of OMD

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Tabled 1Variation in the characterization of OMDTrialOMD characteristicsOMD timingIyengar et al (2017)· ≤6 sites of extracranial disease (including primary) · ≤3 sites in liver or lung ·Up to 2 contiguous vertebral metastases considered a single siteAfter first-line therapy and without progressionGomez et al (2016)· ≤3 metastatic sites · Any N1-3 thoracic nodes considered a single site · Satellite lesions counted as separate sitesAfter first-line therapy and without progressionParikh et al (2014)· ≤5 metastatic sitesAfter first-line therapy and without progressionCheruvu et al (2011)· ≤8 metastatic sitesAt time of initial stagingKhan et al (2006)· 1-2 metastatic sites · Definitive (surgery and/or chemoradiation) treatment of thoracic diseaseAfter treatment of thoracic disease Open table in a new tab Recent years have seen a marked increase in interest in the concept of oligometastatic disease (OMD) in non-small cell lung cancer (NSCLC). Lacking a precise and consistent definition, OMD is generally considered to represent a relatively favorable clinical state, with more indolent biology, a limited number of disease sites, and potential for prolonged periods of disease control. Discussions of oligometastatic NSCLC area inexorably linked with management considerations, specifically the use of local therapies such as surgery and radiation therapy. There are numerous clinical and biological rationales to support such approaches: (1) disease progression most commonly occurs in original sites of gross disease1; (2) metastatic sites may propagate secondary metastases (parallel progression model)2; (3) solid tumors are composed of faster growing (sensitive) and slower growing (resistant) cell populations (Norton-Simon hypothesis)3; (4) resistance depends on spontaneous mutations and therefore increases with time (Goldie-Coldman hypothesis).4 Nevertheless, several questions regarding the characterization and optimal management of OMD remain (Table 1). Up to how many sites of disease constitute an oligometastatic state? Does a “site” of disease comprise a single lesion or neighboring tumors? Does the anatomic site matter? For instance, brain metastases have historically been considered a more favorable location for definitive treatment of OMD, and their emergence may reflect pharmacokinetic failure rather than molecular evolution.5,6 Additionally, there are likely meaningful clinical differences between OMD states depending on whether they are defined at diagnosis (de novo), after initial exposure to systemic therapy (induced), recurrence, or progression. OMD may also have a distinct biologic phenotype. The metastatic cascade includes loss of cellular adhesion, increased motility, primary tumor invasiveness, entry into and survival in the circulation, and entry into and colonization of distant organs.7 Tumor dormancy, regulated in part by interferon signaling, may impact the number, location, and timing of metastases.8 Expression of genes that positively regulate the cell cycle may determine whether cancer growth occurs as polymetastasis versus oligometastasis. Ideally, ongoing and future clinical trials will collect biospecimens for discovery and validation of OMD biomarkers, thereby enabling the identification of cases most likely to benefit from OMD treatment paradigms. 1. Rusthoven KE, Hammerman SF, Kavanagh BD, Birtwhistle MJ, Stares M, Camidge DR. Is there a role for consolidative stereotactic body radiation therapy following first-line systemic therapy for metastatic lung cancer? A patterns-of-failure analysis. Acta Oncol 2009;48:578-83. 2. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer 2009;9:302-12. 3. Norton L, Simon R. Tumor size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep 1977;61:1307-17. 4. Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63:1727-33. 5. Hu C, Chang EL, Hassenbusch SJ, 3rd, et al. Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis. Cancer 2006;106:1998-2004. 6. Grommes C, Oxnard GR, Kris MG, et al. "Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 2011;13:1364-9. 7. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006;127:679-95. 8. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nature reviews Immunology 2006;6:836-48. stereotactic radiation therapy, Oligometastatic, Non-Small Cell Lung Cancer