Evidence map›Paper›PMID 39966261›Full record

ArticleEsophagus : official journal of the Japan Esophageal Society2025

Investigating the synergistic effects of immunochemotherapy in esophageal squamous cell carcinoma.

Jun Okui, Kengo Nagashima, Satoru Matsuda, Yasunori Sato, Hirofumi Kawakubo, Masashi Takeuchi, Kenro Hirata, Shun Yamamoto, Motoo Nomura, Takahiro Tsushima and 3 more

Abstract read
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In one paragraph

Article in Esophagus : official journal of the Japan Esophageal Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Response to Zhang and Lu.Journal of the National Cancer Institute · 2026
    Article
  2. Article
  3. Article
  4. Preoperative Low Serum Basophil Levels Predict Poor Prognosis for the Patients with Esophageal Squamous Cell Carcinoma.Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia · 2026
    Article
  5. Article
  6. 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

13 authors.

Jun Okui *Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Kengo Nagashima *Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan.
Satoru Matsuda *Department of Surgery, Keio University School of Medicine, Tokyo, Japan. s.matsuda.a8@keio.jp.ORCID 0000-0001-8441-2755
Yasunori SatoDepartment of Biostatistics, Keio University School of Medicine, Tokyo, Japan.
Hirofumi KawakuboDepartment of Surgery, Keio University School of Medicine, Tokyo, Japan.
Masashi TakeuchiDepartment of Surgery, Keio University School of Medicine, Tokyo, Japan.
Kenro HirataDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Shun YamamotoDepartment of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Motoo NomuraDepartment of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan.
Takahiro TsushimaDivision of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Hiroya TakeuchiDepartment of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Ken KatoDepartment of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Yuko KitagawaDepartment of Surgery, Keio University School of Medicine, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough combinations of immune-checkpoint inhibitors (ICI) with chemotherapy have been approved for esophageal squamous cell carcinoma (ESCC), it remains unclear whether immunochemotherapy (ICT) offers advantages over the simple addition of individual monotherapies. This study aimed to investigate whether ICT exhibits a synergistic effect in patients with advanced ESCC.

methodsReconstructed individual patient data of 3330 patients were electronically extracted from the Kaplan-Meier (KM) curves of eight randomized-controlled trials (ATTRACTION-3, CheckMate648, KEYNOTE-181, KEYNOTE-590, RATIONALE-302, RATIONALE-306, ESCORT, and ESCORT-1st). The observed progression-free survival (PFS) curve of each constituent monotherapies was used to estimate simulated PFS curves expected under a model of independent drug action. If the observed curve demonstrated significantly better PFS than the simulated curve, the combination of ICI and chemotherapy may have a synergistic effect, implying a superior outcome compared to simply adding the component monotherapy.

resultsThe 1-year, 2-year, and median PFS of the observed and simulated KM curves were 26.3% vs. 24.8%, 14.6% vs. 12.0%, and 6.9 vs. 6.4 months, respectively. The one-sample log-rank test showed no significant differences between the observed and simulated KM curves (p = 0.073).

conclusionsThe observed PFS with ICT was comparable to the simulated PFS estimated from the data for each monotherapy. Although it is unclear whether potential synergies exist for ICT, these findings suggest that the benefits of ICI and chemotherapy do not interfere with each other, thereby providing theoretical support for the efficacy of ICT.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsChemoradiotherapyEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaImmune Checkpoint InhibitorsImmunotherapyAgedFemaleHumansKaplan-Meier EstimateMaleMiddle AgedProgression-Free SurvivalRandomized Controlled Trials as TopicTreatment OutcomeImmune Checkpoint InhibitorsClinical trialsCombined modality therapyEsophageal squamous cell carcinomaImmune checkpoint inhibitorsProgression-free survival

Identifiers

PMID39966261

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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.