Evidence map›Paper›PMID 40183423›Full record

ArticleHistopathology2025

The tumour-stroma ratio as predictive aid towards a biopsy-based treatment strategy in rectal carcinoma.

Meaghan Polack, Gabi W van Pelt, Davita H van den Heuvel, Elma Meershoek Klein-Kranenbarg, Annet G H Roodvoets, Hein Putter, Augustinus S L P Crobach, Iris D Nagtegaal, Koen C M J Peeters, Rob A E M Tollenaar and 2 more

Registry-linked trialAbstract readMulticenter Study
In one paragraph

Article in Histopathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01558921 (Randomized Multicentre Phase III Study of Short Course Radiation Therapy Followed by Prolonged Pre-operative Chemotherapy and Surgery in Primary High Risk Rectal Cancer Compared to Standard Chemoradiotherapy and Surgery and Optional Adjuvant Chemotherapy.), which is not on this 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.

NCT01558921 phase3active not recruitingnot on this map

Randomized Multicentre Phase III Study of Short Course Radiation Therapy Followed by Prolonged Pre-operative Chemotherapy and Surgery in Primary High Risk Rectal Cancer Compared to Standard Chemoradiotherapy and Surgery and Optional Adjuvant Chemotherapy.

TypeinterventionalSponsorUniversity Medical Center GroningenRan2011 to 2026Enrolled920ConditionsRectal CancerArmsM1 scheme, standard long course chemoradiotherapy
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. 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

12 authors.

Meaghan PolackDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0001-7980-7533
Gabi W van PeltDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0003-1449-7348
Davita H van den HeuvelDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Elma Meershoek Klein-KranenbargClinical Research Center, Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-1750-2221
Annet G H RoodvoetsClinical Research Center, Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-0412-1075
Hein PutterDepartment of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0001-5395-1422
Augustinus S L P CrobachDepartment of Pathology, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-1289-4406
Iris D NagtegaalDepartment of Pathology, Radboudumc, Nijmegen, the Netherlands.ORCID https://orcid.org/0000-0003-0887-4127
Koen C M J PeetersDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-9332-1334
Rob A E M TollenaarDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-6831-6082
J Han J M van KriekenDepartment of Pathology, Radboudumc, Nijmegen, the Netherlands.ORCID https://orcid.org/0000-0002-8105-0450
Wilma E MeskerDepartment of Surgery, Leiden University Medical Center, Leiden, the Netherlands.ORCID https://orcid.org/0000-0001-5533-4778

Funding

Bollenstreekfonds, Hillegom, the Netherlands
6 · The paper itself

Abstract

aimsTumour-stroma ratio (TSR) scores of biopsy material in rectal carcinoma (RC) could aid a biomarker-based, upfront and personalised treatment strategy selection for RC patients. In a large retrospective, multicentre cohort, we aimed to validate the predictive value of biopsy-scored TSR on neoadjuvant therapy response, and secondarily, disease-free and overall survival (DFS, OS). METHODS AND

resultsScanned haematoxylin and eosin-stained RC biopsy slides were collected from Leiden University Medical Center (N = 116) and from the clinical PROCTOR-SCRIPT (N = 142) and RAPIDO (N = 271) trials. TSR was scored per protocol and categorised as stroma-low (≤ 50%) or stroma-high (> 50%). Major response was defined as tumour regression grade (TRG) 1 + 2 by Mandard, including pathological complete response. Ultimately, a large and varied cohort with 373 RC patients was established. Locally advanced RC was more often stroma-high (P < 0.001). We subsequently observed significantly lower major response rates in the stroma-high RC after a neoadjuvant treatment approach (hazard ratio = 0.63, 95% confidence interval = 0.41-0.99; P = 0.044). Despite correction for well-known risk factors in Cox hazard regression analysis, such as (y)pTNM substages or residual tumour status, the TSR had no singular significant influence on DFS nor OS in multivariate analysis (P = 0.438; P = 0.934, respectively).

conclusionsBiopsy-scored TSR can predict neoadjuvant therapy efficacy, as RC patients with stroma-high biopsies show less major response. However, patient survival is multifactorial, although response is an important predictor, influenced by TSR. Scoring TSR on RC biopsy material is a reliable histological parameter, implementation of which in treatment guidelines could improve upfront selection for a watch-and-wait strategy.

Indexed as

Rectal NeoplasmsStromal CellsAdultAgedAged, 80 and overBiopsyDisease-Free SurvivalFemaleHumansMaleMiddle AgedNeoadjuvant TherapyPrognosisRetrospective Studiesneoadjuvant treatmentpredictionrectal cancertumour microenvironmenttumour regression gradetumour responsetumour–stroma ratio

Identifiers

PMID40183423
PMCPMC12129608

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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.