Evidence map›Paper›PMID 41748622›Full record

Trial reportNature communications2026

Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial.

Jian L Campian, Son B Le, Ashley Ghiaseddin, Omar H Butt, Harshit Manektalia, Dongjiang Chen, Yifei Xu, Jingxia Liu, Maryam Rahman, Nathan Thai and 11 more

Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled TrialClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02311582 (A Phase I/II Study Testing the Safety, Toxicities, and Efficacy of MK-3475 in Combination With MRI-guided Laser Ablation in Recurrent Malignant Gliomas), which is not on this map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 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.

NCT02311582 phase1 / phase2completednot on this map

A Phase I/II Study Testing the Safety, Toxicities, and Efficacy of MK-3475 in Combination With MRI-guided Laser Ablation in Recurrent Malignant Gliomas

TypeinterventionalSponsorWashington University School of MedicineRan2015 to 2024Enrolled55ConditionsMalignant GliomaArmsMK-3475, MRI-guided laser ablation
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Laser interstitial thermal therapy in pediatric neurosurgery: a prospective nationwide study on indications, safety, and early outcomes.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Article
  3. Review
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

21 authors.

Jian L Campian *Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Son B Le *Division of Neuro-Oncology, Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Ashley Ghiaseddin *Department of Neurosurgery, University of Florida College of Medicine, Gainesville, FL, USA.ORCID 0000-0001-5599-4610
Omar H Butt *Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Harshit Manektalia *Division of Neuro-Oncology, Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Dongjiang ChenDivision of Neuro-Oncology, Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0003-4611-3898
Yifei XuDivision of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St Louis, St. Louis, MO, USA.
Jingxia LiuDivision of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St Louis, St. Louis, MO, USA.ORCID 0000-0002-9434-7907
Maryam RahmanDepartment of Neurosurgery, University of Florida College of Medicine, Gainesville, FL, USA.
Nathan ThaiDivision of Neuro-Oncology, Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
William A LeidigThe Brain Tumor Center, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA.
Tanner JohannsDivision of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
George AnsstasDivision of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.ORCID 0000-0002-7178-8777
Alice Y ZhouDivision of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Sangami PugazenthiThe Brain Tumor Center, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA.ORCID 0000-0002-5179-5232
Gavin P DunnDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jiayi HuangThe Brain Tumor Center, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA.ORCID 0000-0002-5153-506X
Milan G ChhedaDivision of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. mchheda@wustl.edu.ORCID 0000-0001-8282-9098
Albert H KimThe Brain Tumor Center, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA. alberthkim@wustl.edu.ORCID 0000-0002-1751-8493
Eric C LeuthardtThe Brain Tumor Center, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA. leuthardte@wustl.edu.ORCID 0000-0003-4154-3135
David D TranDivision of Neuro-Oncology, Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. david.tran@med.usc.edu.ORCID 0000-0002-2380-8921

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immune checkpoint inhibitors (ICIs) show minimal efficacy in recurrent high-grade astrocytoma (rHGA). Laser interstitial thermal therapy (LITT), a minimally invasive cytoreductive approach, may prime rHGA for ICI response. A phase 1/randomized phase 2b trial (ClinicalTrials.gov: NCT02311582 ) was designed to test pembrolizumab in combination with LITT in patients with rHGA. Nine patients were enrolled in the phase I dose-escalation lead-in study. No dose-limiting toxicities were observed and 200 mg of pembrolizumab every three weeks was determined as the recommended phase 2 dose. The phase 2b study was initially designed to randomize (up to 45) patients 1:1 to either LITT followed by pembrolizumab (LITT + PEM) or non-LITT surgery followed by pembrolizumab (NLS + PEM). Phase 2's primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), safety, and immune signature. After 21 patients, based on an independent Data and Safety Monitoring Committee request of unscheduled interim review of accumulating efficacy data, randomization stopped as benefit from NLS + PEM appeared limited, and the subsequent 24 patients received LITT + PEM. The pre-specified study endpoints were achieved. Among 39 per-protocol patients, LITT + PEM (n = 33) improved median OS (11.8 versus 5.2 months) and 18-month survival (42% versus 0%) compared to NLS + PEM (n = 6) (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06-0.49; P = 0.0002). Median PFS was longer in LITT + PEM (4.5 versus 1.6 months; HR 0.21; 95% CI, 0.08-0.56; P = 0.0006). In an intent-to-treat sensitivity analysis (n = 21), OS (HR 0.29; 95% CI, 0.10-0.88) and PFS (HR 0.30; 95% CI, 0.10-0.87) again favored LITT + PEM (n = 13). Treatment was well tolerated. LITT activated non-classical monocytes, and pembrolizumab unleashed CD8⁺ T cell proliferation, clonal expansion, and coordinated memory T-cell responses. Overall, LITT + PEM is safe and may overcome rHGA immunosuppression to generate antitumor immunity.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAstrocytomaBrain NeoplasmsLaser TherapyNeoplasm Recurrence, LocalAdultAgedCombined Modality TherapyFemaleHumansMaleMiddle AgedProgression-Free SurvivalTreatment OutcomeAntibodies, Monoclonal, HumanizedAntineoplastic Agents, Immunologicalpembrolizumab

Identifiers

PMID41748622
PMCPMC12946167

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Registered trials

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.