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  • br after completing definitive RT These findings are reflected


    after completing definitive RT. These findings are reflected in various guidelines, which currently recommend against the use of 18FDG-PET/CT for routine surveillance imaging after curative-intent interventions in NSCLC.
    Approximately 15% to 30% of stage III NSCLC patients will have intracranial relapses after definitive therapy.21,22 An analysis of 422 stage III NSCLC patients enrolled onto 4 prospective protocols of combined modality therapy demonstrated that approximately 60% of intracranial relapses occur within 6 months of treatment.23 Further-more, a study of 455 NSCLC patients of differing stages found the rate of symptomatic BODIPY 505/515 metastases was < 10% over a period of 16 months.24 Intracranial relapses were the most common site of DR in our study (30%) and were mostly identified by symptomatic presen-tation, despite 81% of patients undergoing pretreatment assessment by MRI. Because the majority of patients underwent pretreatment evaluation of the brain, our higher rate of symptomatic brain metastases is likely a reflection of aggressive biology and not profound un-derestimates of the pretreatment intracranial tumor burden.
    This study found that most relapses happen within the first year of completing definitive CRT, and just over half of these are identified after symptomatic presentation. Although we found that symptomatic relapses correlated with worse OS, a more intensive surveillance regimen within the first 6 months of completing treatment may help identify more asymptomatic relapses. This would be advantageous because it may provide an opportunity to initiate salvage therapy sooner, possibly in patients with better PS and with a lower burden of disease. Of note, adjuvant therapy with durvalumab after CRT is now the standard of care in stage III disease and has been proven to increase the time to progression.25 Thus, before symptomatic recurrence, administration of durvalu-mab may improve OS when the disease burden is lower or via the synergistic interactions between RT and immunotherapies.26
    We provide what to our knowledge is the first evidence to sup-port the recently changed NCCN guidelines recommending post-surveillance imaging and examination at 3 to 6 months after definitive treatment. Of note, however, our findings suggest that somewhat more frequent follow-up than this is probably preferable, because patients with asymptomatic recurrences detected on imag-ing fared better in our cohort. These findings also raise the question of whether periodic repeat brain imaging might be of benefit in the asymptomatic patient. Optimally, our findings should be validated in a prospective randomized controlled trial or (more realistically) a larger retrospective analysis of pooled patients from multiple in-stitutions to better define an optimal posttreatment surveillance interval after curative-intent CRT.
    Clinical Practice Points
    The optimal surveillance frequency after definitive CRT for stage III NSCLC patients is unknown.
    Most relapses after definitive CRT for stage III NSCLC happen within 1 year of completing treatment.
    Symptomatic relapses result in worse OS compared to asymp-tomatic relapses identified by surveillance imaging.
    More aggressive surveillance imaging may improve outcomes by identifying asymptomatic relapses that are amenable to earlier salvage therapy.
    The authors have stated that they have BODIPY 505/515 no conflict of interest.
    3. Didkowska J, Wojciechowska U, Manczuk M, Lobaszewski J. Lung cancer epidemiology: contemporary and future challenges worldwide. Ann Transl Med 2016; 4:150.
    4. Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III nonesmall cell lung cancer. World J Clin Oncol 2017; 8:1-20.
    5. Baker S, Dahele M, Lagerwaard FJ, Senan S. A critical review of recent developments in radiotherapy for nonesmall cell lung cancer. Radiat Oncol 2016; 11:115.
    6. Bradley JD, Paulus R, Komaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB nonesmall-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 2015; 16:187-99.