Evidence map›Paper›PMID 42084869›Full record

SynthesisJAMA network open2026

Time-of-Day Immunotherapy Administration and Outcomes in Advanced Cancers: A Systematic Review and Meta-Analysis.

Shota Inoue, Ichiro Tsuboi, Marcin Miszczyk, Keiichiro Miyajima, Navid Roessler, Ahmed R Alfarhan, Satoshi Katayama, Pierre I Karakiewicz, Motoo Araki, Shahrokh F Shariat

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in JAMA network open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  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

10 authors.

Shota InoueDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Ichiro TsuboiDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Marcin MiszczykDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Keiichiro MiyajimaDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Navid RoesslerDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Ahmed R AlfarhanDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Satoshi KatayamaDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Pierre I KarakiewiczCancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.
Motoo ArakiDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shahrokh F ShariatDepartment of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Circadian rhythms affect immunity, which could affect the effectiveness of immune checkpoint inhibitor (ICI). Whether the time of ICI administration is associated with clinical outcomes in advanced cancers remains unclear. Objective: To evaluate the association between time of day of ICI administration and oncologic outcomes in patients with advanced solid tumors. Data Sources: MEDLINE (via PubMed), Embase, and Web of Science Core Collection were searched in February 2026 to identify eligible studies. Study Selection: Randomized clinical trials and prospective or retrospective cohort studies were included that compared early vs late time-of-day ICI administration and reported overall survival (OS) and progression-free survival (PFS). Data Extraction and Synthesis: This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Two authors independently extracted data and assessed risk of bias. Random effects meta-analyses with inverse-variance method were performed. Main Outcomes and Measures: The primary outcomes were OS and PFS. These outcomes were reported as hazard ratios (HRs) with 95% CIs for early vs late ICI administration. Results: Of the 7892 records screened, 29 studies with 6129 patients were included. Among these studies, 1 was a randomized clinical trial in non-small cell lung cancer (NSCLC; 210 patients), 1 was a prospective cohort study in head and neck squamous cell carcinoma (62 patients), and 27 were retrospective cohort studies (5857 patients) across NSCLC, melanoma, gastric cancer, head and neck squamous cell carcinoma, renal cell carcinoma (RCC), esophageal cancer, small cell lung cancer, urothelial carcinoma, biliary tract cancer, hepatocellular carcinoma, and other cancers. Earlier ICI administration was associated with increased OS (HR, 0.60; 95% CI, 0.51-0.70) and PFS (HR, 0.62; 95% CI, 0.54-0.71). Subset analyses by cancer type confirmed significantly increased OS and PFS in NSCLC (OS: HR, 0.58 [95% CI, 0.46-0.74]; PFS: HR, 0.60 [95% CI, 0.46-0.76]), gastric cancer (OS: HR, 0.61 [95% CI, 0.49-0.77]; PFS: HR, 0.62 [95% CI, 0.43-0.89]), RCC (OS: HR, 0.60 [95% CI, 0.40-0.90]; PFS: HR, 0.70 [95% CI, 0.50-0.98]), small cell lung cancer (OS: HR, 0.37 [95% CI, 0.26-0.53]; PFS: HR, 0.48 [95% CI, 0.36-0.65]), and biliary tract cancer (OS: HR, 0.62 [95% CI, 0.41-0.93]; PFS: HR, 0.55 [95% CI, 0.38-0.79]). Conclusions and Relevance: In this systematic review and meta-analysis of studies including patients with advanced cancers, early immunotherapy administration was associated with improved outcomes. These findings suggest that treatment timing may have clinical relevance and warrant prospective evaluation to establish standardized timing strategies across cancer settings.

Indexed as

Immune Checkpoint InhibitorsImmunotherapyNeoplasmsHumansTime FactorsTreatment OutcomeImmune Checkpoint Inhibitors

Identifiers

PMID42084869
PMCPMC13147196

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.