Evidence map›Paper›PMID 40668314›Full record

ArticleJournal of neuro-oncology2025

Distinct size and spatial distribution patterns of ALK-inhibitor-naïve versus ALK-inhibitor exposed ALK-positive NSCLC brain metastases.

Tia Cheunkarndee, Zsombor Ritter, Max Saint-Germain, Paola Ghanem, Kristen A Marrone, Joseph C Murray, Josephine L Feliciano, Christine L Hann, Jordina Rincon Torroella, Solmaz Sahebjam and 8 more

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. Article
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

18 authors.

Tia CheunkarndeeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zsombor RitterSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Max Saint-GermainSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Paola GhanemSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kristen A MarroneSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joseph C MurraySidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Josephine L FelicianoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christine L HannSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jordina Rincon TorroellaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Solmaz SahebjamSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Susan C ScottSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David S EttingerSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Valsamo AnagnostouSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Patrick M FordeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Julie R BrahmerSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Benjamin P LevySidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Vincent K LamSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David O KamsonSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. dkamson1@jhmi.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeNon-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase rearrangement (ALK+) has a high affinity to form brain metastases (BMs). The cumulative incidence of BMs in ALK + lung cancer is over 50%, despite highly effective ALK tyrosine kinase inhibitors (TKIs) with CNS activity. Pharmacokinetic (PK) data from other CNS-active lung cancer TKIs have raised the possibility of a PK-driven effect on BMs formation and response. This study aims to compare the size and distribution of ALK + NSCLC BMs at diagnosis in a TKI-naïve and TKI-exposed cohort.

methodsWe retrospectively reviewed brain MRIs from the date of initial BMs detection for patients diagnosed with ALK + NSCLC at Johns Hopkins between 2007 and 2022. Demographic and clinical information were collected by chart review. Each tumor was marked in a standard space brain model in the corresponding anatomic location represented by a sphere of corresponding diameter. The data for patients who were TKI-naïve, had current or prior treatment with crizotinib, or had current or prior treatment with second-generation TKIs at the time of BMs diagnosis were then analyzed separately to compare the size and localization of BMs between the groups.

results405 BMs were identified in 48 patients, of which 30 patients TKI-naïve, 11 were crizotinib-treated, and 7 were second-generation TKI-treated. TKI-naïve BMs were significantly larger in diameter than both crizotinib-treated and second-generation TKI-treated BMs (mean diameter 8.78 ± 6.0 mm vs. 6.0 ± 7.2 mm, p < 0.001, and 5.6 ± 3.2 mm, p = 0.003, respectively). Patients in the crizotinib-treated group also had significantly more BMs exclusively in the white matter compared to the other two groups (OR = 1.9 [CI 95%: 1.17-2.99], p = 0.008 and 3.3 [CI 95% 1.52-7.25], p = 0.002, respectively).

conclusionOur data highlight differences in size and distribution among TKI-naïve, crizotinib-treated, and second-generation TKI-treated BMs in ALK + NSCLC. These findings suggest that suboptimal drug CNS distribution in the white matter may underlie brain progression of ALK + NSCLC despite TKI therapy and raise the possibility of a spatially-mediated resistance mechanism.

Indexed as

Anaplastic Lymphoma KinaseBrain NeoplasmsCarcinoma, Non-Small-Cell LungLung NeoplasmsProtein Kinase InhibitorsAdultAgedCrizotinibFemaleFollow-Up StudiesHumansMagnetic Resonance ImagingMaleMiddle AgedRetrospective StudiesALK protein, humanAnaplastic Lymphoma KinaseCrizotinibProtein Kinase InhibitorsALKBrain metastasesLung cancerNSCLCTargeted therapyTKI

Identifiers

PMID40668314

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.