Evidence map›Paper›PMID 42608608›Full record

ArticleJournal of neuro-oncology2026

Exclusion of patients with brain metastases from early-phase systemic therapy trials: a cross-sectional analysis of eligibility criteria.

Cody Zatzman, Italo Fernandes, Isabella Kojundzic, Natasha D'Souza, Evan Cescon, Eva Zhang, Meghna Katyal, Farideh Tavangar, Martin Smoragiewicz, Mary-Jane Lim-Fat and 2 more

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Article in Journal of neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Cody ZatzmanFaculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Italo FernandesDivision of Medical Oncology and Hematology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
Isabella KojundzicFaculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Natasha D'SouzaDepartment of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
Evan CesconDepartment of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
Eva ZhangDepartment of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
Meghna KatyalDepartment of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
Farideh TavangarLawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada.
Martin SmoragiewiczDivision of Medical Oncology and Hematology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
Mary-Jane Lim-FatDepartment of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
Arjun SahgalDepartment of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
Katarzyna J JerzakDepartment of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada. katarzyna.jerzak@sunnybrook.ca.ORCID http://orcid.org/0000-0002-3995-0308

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposePatients with brain metastases (BrM) are frequently excluded from early-phase clinical trials, limiting evaluation of central nervous system (CNS) efficacy of novel therapies. We aimed to determine the proportion of phase I systemic therapy trials for patients with metastatic solid tumours that permit enrolment of patients with BrM and to characterise BrM-specific eligibility criteria.

methodsClinicalTrials.gov was searched in July 2024 for phase I systemic therapy trials for patients with advanced solid tumours and publicly available protocols. Trial characteristics and BrM eligibility criteria were independently abstracted by paired reviewers, with third-reviewer adjudication.

resultsOf 3,210 studies screened, 873 with protocols were analysed. Patients with BrM were eligible with stipulations in 70.3%, excluded in 13.2%, and unspecified in 16.5% of phase I trials. Genitourinary trials excluded patients with BrM more frequently than trials for other tumour types (26.4%). Among trials permitting enrolment of patients with BrM (n = 614), patients with active, unstable, and/or progressing BrM (84.0%), those with previously untreated (75.9%) and/or symptomatic (58.5%) BrM were excluded. Corticosteroid use and antiseizure medication use were completely prohibited in 19.4% and 9.4% of these trials, respectively. The proportion of trials permitting enrolment of patients with BrM varied without a consistent temporal trend (66.2% in 2010-2014, 72.8% in 2015-2019, and 67.6% from 2020 onwards). Trials combining immunotherapy and targeted therapy most frequently permitted enrolment (85.1%) of patients with BrM, whereas cytotoxic chemotherapy trials were least permissive (40.9%).

conclusionInclusion of patients with BrM in phase I trials remains variable, with the greatest permissiveness observed in trials combining immunotherapy and targeted therapy. However, restrictive eligibility criteria for active and/or symptomatic BrM remain common.

Indexed as

Brain NeoplasmsClinical Trials, Phase I as TopicEligibility DeterminationPatient SelectionCross-Sectional StudiesHumansBrain metastasesClinical trial accessEligibility criteriaMetastatic solid tumoursPatient selectionPhase I clinical trials

Identifiers

PMID42608608

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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.