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Time from stereotactic radiosurgery to immunotherapy in patients with melanoma brain metastases and impact on outcome

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Abstract

Background

The role of immunotherapy for metastatic melanoma has expanded over the past decade triggering questions regarding the combination and timing of immunotherapy and radiation for brain metastases. We used the National Cancer Database (NCDB) to see if the time from radiation to immunotherapy in patients with melanoma brain metastases had an impact on survival.

Methods

We queried the NCDB from 2010 to 2015 for patients with melanoma brain metastases treated with immunotherapy and stereotactic radiosurgery (SRS). Receiver operator characteristic (ROC) curve analysis was done to determine a timepoint associated with outcome. Cox regression was used to identify predictors of survival. Propensity matching was done to account for indication bias.

Results

We identified 247 patients meeting the above criteria. The median patient age was 62 years (27–90) and the vast majority were Caucasian (99%). The median SRS dose was 22 Gy (18–24 Gy).The median time to SRS was 39 days (0–344) and the median time to immunotherapy was 56 days (6–454). The ROC analysis revealed 8 days from SRS to immunotherapy as associated with outcome. Fifty-six patients had immunotherapy prior to SRS, 30 patients had immunotherapy within 0–7 days of SRS, and the remaining 161 had immunotherapy greater than 7 days from SRS. Three year survival rates were 21%, 55%, and 35% for those timeframes, respectively (p = 0.0153). Propensity matching of the 0–7 day and > 7 day groups yielded 28 pairs and Kaplan Meier analysis showed 3 year overall survival of 55% and 35%, in favor of immunotherapy within 7 days of SRS (p = 0.0357). Multivariable Cox regression identified lack of extracranial disease, more recent year of treatment, and time from SRS to immunotherapy of 0–7 days as predictors of improved survival.

Conclusions

Immunotherapy within 7 days of SRS shows a possible association with improve outcomes in patients with brain metastases from melanoma.

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Data availability

This study was based on the NCDB registry data. The authors do not own these data and hence are not permitted to share them in the original form.

References

  1. Johnson JD, Young B (1996) Demographics of brain metastasis. Neurosurg Clin N Am 7:337–344

    Article  CAS  Google Scholar 

  2. Hong AM, Fogarty GB, Dolven-Jacobsen K, Burmeister BH, Lo SN, Haydu LE, Vardy JL, Nowak AK, Dhillon HM, Ahmed T, Shivalingam B, Long GV, Menzies AM, Hruby G, Drummond KJ, Mandel C, Middleton MR, Reisse CH, Paton EJ, Steel V, Williams NC, Scolyer RA, Morton RL, Thompson JF (2019) Adjuvant whole-brain radiation therapy compared with observation after local treatment of melanoma brain metastases: a multicenter, randomized phase III trial. J Clin Oncol 37:3132–3141. https://doi.org/10.1200/JCO.19.01414

    Article  CAS  PubMed  Google Scholar 

  3. Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol 29:134–141. https://doi.org/10.1200/JCO.2010.30.1655

    Article  PubMed  Google Scholar 

  4. Lanier CM, Hughes R, Ahmed T, LeCompte M, Masters AH, Petty WJ, Ruiz J, Triozzi P, Su J, O’Neill S, Watabe K, Cramer CK, Laxton AW, Tatter SB, Wang G, Whitlow C, Chan MD (2019) Immunotherapy is associated with improved survival and decreased neurologic death after SRS for brain metastases from lung and melanoma primaries. Neurooncol Pract 6:402–409. https://doi.org/10.1093/nop/npz004

    Article  PubMed  PubMed Central  Google Scholar 

  5. Doss LL, Memula N (1982) The radioresponsiveness of melanoma. Int J Radiat Oncol Biol Phys 8:1131–1134

    Article  CAS  Google Scholar 

  6. Espenel S, Vallard A, Rancoule C, Garcia MA, Guy JB, Chargari C, Deutsch E, Magne N (2017) Melanoma: last call for radiotherapy. Crit Rev Oncol Hematol 110:13–19. https://doi.org/10.1016/j.critrevonc.2016.12.003

    Article  PubMed  Google Scholar 

  7. Fertil B, Malaise EP (1985) Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves. Int J Radiat Oncol Biol Phys 11:1699–1707

    Article  CAS  Google Scholar 

  8. Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316:401–409. https://doi.org/10.1001/jama.2016.9839

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gabani P, Fischer-Valuck BW, Johanns TM, Hernandez-Aya LF, Keller JW, Rich KM, Kim AH, Dunn GP, Robinson CG, Chicoine MR, Huang J, Abraham CD (2018) Stereotactic radiosurgery and immunotherapy in melanoma brain metastases: patterns of care and treatment outcomes. Radiother Oncol 128:266–273. https://doi.org/10.1016/j.radonc.2018.06.017

    Article  PubMed  Google Scholar 

  10. Minniti G, Anzellini D, Reverberi C, Cappellini GCA, Marchetti L, Bianciardi F, Bozzao A, Osti M, Gentile PC, Esposito V (2019) Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity. J Immunother Cancer 7:102. https://doi.org/10.1186/s40425-019-0588-y

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kalbasi A, June CH, Haas N, Vapiwala N (2013) Radiation and immunotherapy: a synergistic combination. J Clin Investig 123:2756–2763. https://doi.org/10.1172/JCI69219

    Article  CAS  PubMed  Google Scholar 

  12. Tang C, Wang X, Soh H, Seyedin S, Cortez MA, Krishnan S, Massarelli E, Hong D, Naing A, Diab A, Gomez D, Ye H, Heymach J, Komaki R, Allison JP, Sharma P, Welsh JW (2014) Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Cancer Immunol Res 2:831–838. https://doi.org/10.1158/2326-6066.CIR-14-0069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, Inghirami G, Coleman CN, Formenti SC, Demaria S (2017) DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 8:15618. https://doi.org/10.1038/ncomms15618

    Article  PubMed  PubMed Central  Google Scholar 

  14. White RJ, Abel S, Horne ZD, Lee J, Edington H, Greenberg L, Younes H, Hilton C, Wegner RE (2020) Melanoma brain metastases: is it time to eliminate radiotherapy? J Neurooncol. https://doi.org/10.1007/s11060-020-03485-w

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rahman R, Cortes A, Niemierko A, Oh KS, Flaherty KT, Lawrence DP, Sullivan RJ, Shih HA (2018) The impact of timing of immunotherapy with cranial irradiation in melanoma patients with brain metastases: intracranial progression, survival and toxicity. J Neurooncol 138:299–306. https://doi.org/10.1007/s11060-018-2795-7

    Article  PubMed  Google Scholar 

  16. Cohen-Inbar O, Shih HH, Xu Z, Schlesinger D, Sheehan JP (2017) The effect of timing of stereotactic radiosurgery treatment of melanoma brain metastases treated with ipilimumab. J Neurosurg 127:1007–1014. https://doi.org/10.3171/2016.9.JNS161585

    Article  PubMed  Google Scholar 

  17. Wegner REAS, White RJ, Finely G, Monga D, Colonias A, Verma V (2019) Time from stereotactic radiotherapy to immunotherapy is a predictor for outcome in stage IV non-small cell lung cancer. J Immunol Sci 3:7

    Article  Google Scholar 

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REW: Project conception and design, statistical analysis, manuscript preparation; SA: Statistical analysis, manuscript editing; RSD: Manuscript Editing; GUM: Manuscript editing; JS: Manuscript Editing, final approval.

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Correspondence to Rodney E. Wegner.

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Wegner, R.E., Abel, S., D’Amico, R.S. et al. Time from stereotactic radiosurgery to immunotherapy in patients with melanoma brain metastases and impact on outcome. J Neurooncol 152, 79–87 (2021). https://doi.org/10.1007/s11060-020-03663-w

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  • DOI: https://doi.org/10.1007/s11060-020-03663-w

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