Evidence map›Paper›PMID 31836957›Full record

ArticleJournal of neuro-oncology2020

The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study.

Filipe Martins, Luis Schiappacasse, Marc Levivier, Constantin Tuleasca, Michel A Cuendet, Veronica Aedo-Lopez, Bianca Gautron Moura, Krisztian Homicsko, Adrienne Bettini, Gregoire Berthod and 4 more

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Article in Journal of neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Filipe MartinsCentre Hospitalier Universitaire Vaudois (CHUV), Hematology Service and Central Laboratory, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland. filipe.martins@epfl.ch.ORCID http://orcid.org/0000-0002-3096-8907
Luis SchiappacasseCentre Hospitalier Universitaire Vaudois (CHUV), Radio-Oncology Service, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-7621-1662
Marc LevivierCentre Hospitalier Universitaire Vaudois (CHUV), Neurosurgery Service and Gamma Knife Center, Clinical Neurosciences Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Constantin TuleascaCentre Hospitalier Universitaire Vaudois (CHUV), Neurosurgery Service and Gamma Knife Center, Clinical Neurosciences Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Michel A CuendetCentre Hospitalier Universitaire Vaudois (CHUV), Precision Oncology Center, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-0754-3425
Veronica Aedo-LopezCentre Hospitalier Universitaire Vaudois (CHUV), Oncology Service, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Bianca Gautron MouraCentre Hospitalier Universitaire Vaudois (CHUV), Oncology Service, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Krisztian HomicskoCentre Hospitalier Universitaire Vaudois (CHUV), Oncology Service, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Adrienne BettiniFribourg Cantonal Hospital (HFR), Internal Medicine Department, Oncology Service, CH-1708, Fribourg, Switzerland.
Gregoire BerthodCentre Hospitalier Universitaire Vaudois (CHUV), Oncology Service, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Camille L GérardCentre Hospitalier Universitaire Vaudois (CHUV), Precision Oncology Center, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Alexandre WickyCentre Hospitalier Universitaire Vaudois (CHUV), Precision Oncology Center, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Jean BourhisCentre Hospitalier Universitaire Vaudois (CHUV), Radio-Oncology Service, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland. jean.bourhis@chuv.ch.
Olivier MichielinCentre Hospitalier Universitaire Vaudois (CHUV), Oncology Service, Precision Oncology Center, Oncology Department, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland. olivier.michielin@chuv.ch.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEvidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients' and disease characteristics as predictors of OS in patients treated with SRS.

methodsWe identified patients with BM from cutaneous or unknown primary origin melanoma treated with SRS between 2011 and 2018.

resultsWe included 84 patients. The median OS was 12 months (95% CI 9-20 months). The median follow-up was 30 months (95% CI 28-49). Twenty-eight patients with newly diagnosed BM initiated anti-PD-1 +/-CTLA-4 therapy (n = 18), ipilimumab monotherapy (n = 10) or BRAF+/- MEK inhibitors (n = 11), during the 9 weeks before or after SRS. Patients who received anti-PD-1 +/-CTLA-4 mAb showed an improved survival in comparison to ipilimumab monotherapy (OS 24 vs. 7.5 months; HR 0.32, 95% 0.12-0.83, p = 0.02) and BRAF +/-MEK inhibitors (OS 24 vs. 7 months, respectively; HR 0.11, 95% 0.04-0.34, p = 0.0001). This benefit remained significant when compared to the subgroup of patients treated with dual BRAF/MEK inhibition (BMi) (n = 5). In a multivariate Cox regression analysis an age > 65, synchronous BM, > 2 metastatic sites, > 4 BM, and an ECOG > 1 were correlated with poorer prognosis. A treatment with anti-PD-1+/-CTLA-4 mAbs within 9 weeks of SRS was associated with better outcomes. The presence of serum lactate dehydrogenase (LDH) levels ≥ 2xULN at BM diagnosis was associated with lower OS (HR 1.60, 95% CI 1.03-2.50; p = 0.04).

conclusionsThe concurrent administration of anti-PD-1+/-CTLA-4 mAbs with SRS was associated with improved survival in melanoma patients with newly diagnosed BM. In addition to CNS tumor burden, the extension of systemic disease retains its prognostic value in patients treated with SRS. Elevated serum LDH levels are predictors of poor outcome in these patients.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBrain NeoplasmsCombined Modality TherapyFemaleFollow-Up StudiesHumansImmunotherapyIpilimumabMaleMelanomaMiddle AgedMolecular Targeted TherapyPrognosisAntineoplastic Agents, ImmunologicalIpilimumabProtein Kinase InhibitorsBRAFCTLA-4CyberKnifeGamma knifeImmune-checkpoint inhibitorsImmunotherapyMEKPD-1PD-L1Stereotactic radiation surgery

Identifiers

PMID31836957

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.