Evidence map›Paper›PMID 33986126›Full record

ArticleJournal for immunotherapy of cancer2021

Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study.

Nikolaus B Wagner, Max M Lenders, Kathrin Kühl, Lydia Reinhardt, Fiona André, Milena Dudda, Natalie Ring, Chiara Ebel, Ramon Stäger, Caroline Zellweger and 29 more

Open access · goldAbstract readMulticenter StudyValidation Study
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 20% of its field
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

7 citing papers in PubMed, 15 citations in OpenAlex.

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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

39 authors at 16 institutions in 3 countries.

Nikolaus B WagnerDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany nikolaus.wagner@gmx.de.ORCID 0000-0003-4708-2886
Max M LendersDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Kathrin KühlDepartment of Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany.
Lydia ReinhardtDepartment of Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany.
Fiona AndréDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
Milena DuddaDepartment of Dermatology, University Medical Center Mainz, Mainz, Germany.
Natalie RingDepartment of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
Chiara EbelDepartment of Dermatology, Allergy, and Venereology, University of Lubeck, Lubeck, Germany.
Ramon StägerDepartment of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Caroline ZellwegerInstitute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.
Roland LangDepartment of Dermatology and Allergology, Paracelsus Medical University Salzburg, Salzburg, Austria.
Michael PaarInstitute of Radiology, Paracelsus Medical University Salzburg, Salzburg, Austria.
Philipp GussekDepartment of Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, Germany.
Georg RichtigOtto Loewi Research Center, Pharmacology Section, Medical University of Graz, Graz, Austria.
Suzan H StürmerDepartment of Dermatology, Ludwig Maximilians University of Munich, Munich, Germany.
Susanne KimeswengerDepartment of Dermatology, Johannes Kepler University Linz, Linz, Austria.
Angela OellingerDepartment of Dermatology, Johannes Kepler University Linz, Linz, Austria.
Andrea ForschnerDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.ORCID 0000-0002-6185-4945
Ulrike LeiterDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Benjamin WeideDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Maximilian GassenmaierDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Amadeus SchraagDepartment of Trauma Surgery, Technical University of Munich, Munich, Germany.
Bernhard KlumppDepartment for Diagnostic and Interventional Radiology, Eberhard Karls University Tübingen, Tubingen, Germany.
Wolfram HoetzeneckerDepartment of Dermatology, Johannes Kepler University Linz, Linz, Austria.
Carola BerkingDepartment of Dermatology, Ludwig Maximilians University of Munich, Munich, Germany.
Erika RichtigDepartment of Dermatology, Medical University of Graz, Graz, Austria.
Mirjana ZiemerDepartment of Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, Germany.
Johanna ManganaDepartment of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Patrick TerheydenDepartment of Dermatology, Allergy, and Venereology, University of Lubeck, Lubeck, Germany.ORCID 0000-0002-5894-1677
Carmen LoquaiDepartment of Dermatology, University Medical Center Mainz, Mainz, Germany.
Van Anh NguyenDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
Christoffer GebhardtDepartment of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0001-7090-9584
Friedegund MeierDepartment of Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany.
Stefan DiemDepartment of Oncology and Hematology, Kantonsspital St Gallen, Sankt Gallen, Switzerland.
Antonio CozzioDepartment of Dermatology and Allergology, Kantonsspital St Gallen, Sankt Gallen, Switzerland.
Lukas FlatzDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Martin RöckenDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Claus GarbeDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Thomas K EigentlerDepartment of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
University of Tübingen · DEKantonsspital St. Gallen · CHJohannes Gutenberg University Mainz · DEJohannes Kepler University of Linz · ATNational Center for Tumor Diseases · DEUniversity Hospital of Zurich · CHInnsbruck Medical University · ATMedical University of Graz · ATParacelsus Medical University · ATUniversity Hospital Leipzig · DEUniversity of Lübeck · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DELudwig-Maximilians-Universität München · DERems-Murr-Klinikum · DETechnical University of Munich · DEUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCheckpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.

methodsMGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB-IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR.

resultsPretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, p<0.0001), in the confirmation cohort (HR 3.62, 95% CI 2.19 to 5.98, p<0.0001) and in the independent validation cohort (HR 2.57, 95% CI 1.56 to 4.25, p=0.00023). Prior lines of systemic treatment did not influence the significance of MGR. Importantly, the prognostic impact of MGR was independent of total tumor burden, diameter of the largest metastasis, number of prior lines of systemic treatment, LDH, as well as liver and brain metastasis (discovery and confirmation cohorts: both p<0.0001). Superiority of MGR compared with these variables was confirmed in the independent multicenter validation cohort (HR 2.92, 95% CI 1.62 to 5.26, p=0.00036).

conclusionsHigh pretreatment MGR is an independent strong prognostic biomarker associated with unfavorable survival of melanoma patients receiving anti-PD-1 antibodies. Further investigations are warranted to assess the predictive impact of MGR in distinct systemic therapeutic regimens.

Indexed as

Cell ProliferationTomography, X-Ray ComputedAntibodies, Monoclonal, HumanizedEuropeFemaleHumansImmune Checkpoint InhibitorsMaleMelanomaMiddle AgedNeoplasm StagingNivolumabPredictive Value of TestsProgrammed Cell Death 1 ReceptorReproducibility of ResultsRetrospective StudiesAntibodies, Monoclonal, HumanizedImmune Checkpoint InhibitorsNivolumabPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptorbiomarkersimmunotherapymelanomatumor

Identifiers

PMID33986126
PMCPMC8126291
OpenAlexW3163441327

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