Local control outcomes for combination of stereotactic radiosurgery and immunotherapy for non-small cell lung cancer brain metastases.
Brain metastasis
Immunotherapy
Lung cancer
Overall survival
Stereotactic radiosurgery
Journal
Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
28
11
2021
accepted:
20
01
2022
pubmed:
16
2
2022
medline:
7
4
2022
entrez:
15
2
2022
Statut:
ppublish
Résumé
Previous series have demonstrated CNS activity for immune checkpoint inhibitors, yet no prior data exists regarding whether this activity can improve outcomes of stereotactic radiosurgery. In this single institution retrospective series, the clinical outcomes of 80 consecutive lung cancer patients treated with concurrent immune checkpoint inhibitors and stereotactic radiosurgery were compared to 235 in the historical control cohort in which patients were treated prior to immune checkpoint inhibition being standard upfront therapy. Overall survival was estimated using the Kaplan Meier method. Cumulative incidence of local progression was estimated using a competing risk model. Median overall survival time was improved in patients receiving upfront immunotherapy compared to the historical control group (40 months vs 8 months, p < 0.001). Factors affected overall survival include concurrent immunotherapy (HR 0.23, p < 0.0001) and KPS (HR 0.97, p = 0.0001). Cumulative incidence of local failure in the historical control group was 10% at 1 year, compared to 1.1% at 1 year in the concurrent immunotherapy group (p = 0.025). Factors affected local control included use of concurrent immunotherapy (HR 0.09, p = 0.012), and lowest margin dose delivered to a metastasis (HR 0.8, p = 0.0018). Local control and overall survival were both improved in patients receiving concurrent immune checkpoint inhibitors with radiosurgery compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent use of immunotherapy with SRS.
Sections du résumé
BACKGROUND
BACKGROUND
Previous series have demonstrated CNS activity for immune checkpoint inhibitors, yet no prior data exists regarding whether this activity can improve outcomes of stereotactic radiosurgery.
METHODS
METHODS
In this single institution retrospective series, the clinical outcomes of 80 consecutive lung cancer patients treated with concurrent immune checkpoint inhibitors and stereotactic radiosurgery were compared to 235 in the historical control cohort in which patients were treated prior to immune checkpoint inhibition being standard upfront therapy. Overall survival was estimated using the Kaplan Meier method. Cumulative incidence of local progression was estimated using a competing risk model.
RESULTS
RESULTS
Median overall survival time was improved in patients receiving upfront immunotherapy compared to the historical control group (40 months vs 8 months, p < 0.001). Factors affected overall survival include concurrent immunotherapy (HR 0.23, p < 0.0001) and KPS (HR 0.97, p = 0.0001). Cumulative incidence of local failure in the historical control group was 10% at 1 year, compared to 1.1% at 1 year in the concurrent immunotherapy group (p = 0.025). Factors affected local control included use of concurrent immunotherapy (HR 0.09, p = 0.012), and lowest margin dose delivered to a metastasis (HR 0.8, p = 0.0018).
CONCLUSION
CONCLUSIONS
Local control and overall survival were both improved in patients receiving concurrent immune checkpoint inhibitors with radiosurgery compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent use of immunotherapy with SRS.
Identifiants
pubmed: 35166988
doi: 10.1007/s11060-022-03951-7
pii: 10.1007/s11060-022-03951-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101-107Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Haslam A, Gill J, Prasad V (2020) Estimation of the percentage of US patients with cancer who are eligible for immune checkpoint inhibitor drugs. JAMA Netw Open 3:e200423
doi: 10.1001/jamanetworkopen.2020.0423
Kann BH, Park HS, Johnson SB et al (2017) Radiosurgery for brain metastases: changing practice patterns and disparities in the United States. J Natl Compr Cancer Netw 15:1494–1502
doi: 10.6004/jnccn.2017.7003
Ellis TL, Neal MT, Chan MD (2012) The role of surgery, radiosurgery and whole brain radiation therapy in the management of patients with metastatic brain tumors. Int J Surg Oncol 2012:952345
pubmed: 22312545
Haughton ME, Chan MD, Watabe K et al (2016) Treatment of brain metastases of lung cancer in the era of precision medicine. Front Biosci 8:219–232
doi: 10.2741/e763
Gandhi L, Rodríguez-Abreu D, Gadgeel S et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378:2078–2092
doi: 10.1056/NEJMoa1801005
Lanier CM, Hughes R, Ahmed T et al (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
pubmed: 31555455
pmcid: 6753360
LeCompte MC, Hughes RT, Farris M et al (2020) Impact of brain metastasis velocity on neurologic death for brain metastasis patients experiencing distant brain failure after initial stereotactic radiosurgery. J Neurooncol 146:285–292
doi: 10.1007/s11060-019-03368-9
McTyre E, Ayala-Peacock D, Contessa J et al (2018) Multi-institutional competing risks analysis of distant brain failure and salvage patterns after upfront radiosurgery without whole brain radiotherapy for brain metastasis. Ann Oncol 29:497–503
doi: 10.1093/annonc/mdx740
Helis CA, Hughes RT, Glenn CW et al (2020) Predictors of adverse radiation effect in brain metastasis patients treated with stereotactic radiosurgery and immune checkpoint inhibitor therapy. Int J Radiat Oncol Biol Phys 108:295–303
doi: 10.1016/j.ijrobp.2020.06.057
Tawbi HA, Forsyth PA, Algazi A et al (2018) Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med 379:722–730
doi: 10.1056/NEJMoa1805453
Goldberg SB, Schalper KA, Gettinger SN et al (2020) Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. Lancet Oncol 21:655–663
doi: 10.1016/S1470-2045(20)30111-X
Cochran DC, Chan MD, Aklilu M et al (2012) The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with gamma knife surgery. J Neurosurg 116:978–983
doi: 10.3171/2012.2.JNS111353
Johnson AG, Ruiz J, Hughes R et al (2015) Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases. Oncotarget 6:18945–18955
doi: 10.18632/oncotarget.4153
Harris S, Chan MD, Lovato JF et al (2012) Gamma knife stereotactic radiosurgery as salvage therapy after failure of whole-brain radiotherapy in patients with small-cell lung cancer. Int J Radiat Oncol Biol Phys 83:e53–e59
doi: 10.1016/j.ijrobp.2011.11.059
Hughes RT, Masters AH, McTyre ER et al (2019) Initial SRS for patients with 5 to 15 brain metastases: results of a multi-institutional experience. Int J Radiat Oncol Biol Phys 104:1091–1098
doi: 10.1016/j.ijrobp.2019.03.052
Jensen CA, Chan MD, McCoy TP et al (2011) Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis. J Neurosurg 114:1585–1591
doi: 10.3171/2010.11.JNS10939
Dohm AE, Hughes R, Wheless W et al (2018) Surgical resection and postoperative radiosurgery versus staged radiosurgery for large brain metastases. J Neurooncol 140:749–756
doi: 10.1007/s11060-018-03008-8
Shaw E, Scott C, Souhami L et al (2000) Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90–05. Int J Radiat Oncol Biol Phys 47:291–298
doi: 10.1016/S0360-3016(99)00507-6
Ayala-Peacock DN, Peiffer AM, Lucas JT et al (2014) A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy. Neuro Oncol 16:1283–1288
doi: 10.1093/neuonc/nou018
Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509
doi: 10.1080/01621459.1999.10474144
D’Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17(19):2265–2281. https://doi.org/10.1002/(sici)1097-0258(19981015)17:19%3c2265::aid-sim918%3e3.0.co;2-b
doi: 10.1002/(sici)1097-0258(19981015)17:19<2265::aid-sim918>3.0.co;2-b
pubmed: 9802183
Soike MH, Logue J, Qasem S et al (2019) CD138 plasma cells may predict brain metastasis recurrence following resection and stereotactic radiosurgery. Sci Rep 9:14385
doi: 10.1038/s41598-019-50298-7
Wolchok JD, Kluger H, Callahan MK et al (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369:122–133
doi: 10.1056/NEJMoa1302369
Kefford R, Ribas A, Hamid O et al (2014) Clinical efficacy and correlation with tumor PD-L1 expression in patients (pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475. J Clin Oncol 32:3005–3005
doi: 10.1200/jco.2014.32.15_suppl.3005
Engelhardt B, Coisne C (2011) Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle. Fluids Barriers CNS 8:4
doi: 10.1186/2045-8118-8-4
Greter M, Heppner FL, Lemos MP et al (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11:328–334
doi: 10.1038/nm1197
Wang EC, Huang AJ, Huang KE et al (2017) Leptomeningeal failure in patients with breast cancer receiving stereotactic radiosurgery for brain metastases. J Clin Neurosci 43:6–10
doi: 10.1016/j.jocn.2017.04.033
Brown PD, Ballman KV, Cerhan JH et al (2017) Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1049–1060
doi: 10.1016/S1470-2045(17)30441-2
Gabani P, Lin AJ, Barnes J et al (2019) Radiation therapy dose de-escalation compared to standard dose radiation therapy in definitive treatment of HPV-positive oropharyngeal squamous cell carcinoma. Radiother Oncol 134:81–88
doi: 10.1016/j.radonc.2019.01.016
Su J, Song Q, Qasem S et al (2020) Multi-omics analysis of brain metastasis outcomes following craniotomy. Front Oncol 10:615472
doi: 10.3389/fonc.2020.615472
Minniti G, Clarke E, Lanzetta G et al (2011) Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 6:48
doi: 10.1186/1748-717X-6-48