Evidence map›Paper›PMID 40546050›Full record

ArticleInternational journal of cancer2025

Fragility Index analysis for robustness of evidence in Randomized Controlled Trials in National Comprehensive Cancer Network (NCCN) guidelines for rectal cancer.

Nir Horesh, Justin Dourado, Peter Rogers, Pauline Aeschbacher, Zoe Garoufalia, Rachel Gefen, Ebram Salama, Sameh Hany Emile, Steven D Wexner

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Nir HoreshEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.
Justin DouradoEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.
Peter RogersEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.
Pauline AeschbacherDepartment of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Zoe GaroufaliaEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.
Rachel GefenEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.
Ebram SalamaEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.
Sameh Hany EmileEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.
Steven D WexnerEllen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida, USA.ORCID 0000-0001-8046-5753

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Robustness of evidence from randomized controlled trials (RCTs) is crucial for guiding clinical decisions in rectal cancer. We evaluated the reliability of RCTs cited by the National Comprehensive Cancer Network (NCCN) guidelines for rectal cancer using the Fragility Index (FI) that quantifies the stability of trial outcomes. RCTs referenced in the latest NCCN guidelines for rectal cancer were reviewed. Data from eligible trials were extracted. FI was calculated to assess the robustness of evidence across different treatment modalities. Sixty-seven RCTs (published: 1987-2022) involving 16,990 patients were analyzed. Most studies (58.2%) were conducted in Europe. Common treatment areas included metastatic liver disease (28.9%) and neoadjuvant chemotherapy (14.9%). Primary outcomes were disease-free survival and overall survival (OS) in 15 studies each (22.4%), local recurrence rates in 6 (9%), and tumor response in 5 (7.5%). The median FI was 9 (interquartile range [IQR] 2-20). Studies on surgical interventions had the highest median FI (21 [IQR 7-27]) followed by studies on neoadjuvant radiotherapy (19 [IQR 14-25]). Neoadjuvant immunotherapy studies had the lowest median FI of 0, indicating less robust evidence. Notably, surgical intervention studies showed the largest gap between FI and patients lost to follow-up (21 vs. 13.5), while neoadjuvant immunotherapy studies showed more patients lost to follow-up than the median FI (0 vs. 5), highlighting the need for stronger evidence. In conclusion, evidence supporting most treatments for rectal cancer in the NCCN guidelines is robust, although neoadjuvant immunotherapy requires further scrutiny due to its low FI. FI offers a nuanced perspective on the reliability of trial outcomes.

Indexed as

Practice Guidelines as TopicRandomized Controlled Trials as TopicRectal NeoplasmsDisease-Free SurvivalHumansNeoadjuvant TherapyNeoplasm Recurrence, Localimmunotherapyrectal cancersurgerysurvival

Identifiers

PMID40546050
PMCPMC12407045

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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.