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Accepted for/Published in: JMIR Research Protocols

Date Submitted: Jan 23, 2019
Open Peer Review Period: Jan 28, 2019 - Feb 11, 2019
Date Accepted: May 14, 2019
(closed for review but you can still tweet)

The final, peer-reviewed published version of this preprint can be found here:

Uniform Noting for International Application of the Tumor-Stroma Ratio as an Easy Diagnostic Tool: Protocol for a Multicenter Prospective Cohort Study

Smit M, van Pelt G, Roodvoets A, Meershoek-Klein Kranenbarg E, Putter H, Tollenaar R, van Krieken JH, Mesker W

Uniform Noting for International Application of the Tumor-Stroma Ratio as an Easy Diagnostic Tool: Protocol for a Multicenter Prospective Cohort Study

JMIR Res Protoc 2019;8(6):e13464

DOI: 10.2196/13464

PMID: 31199317

PMCID: 6595942

Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

Uniform Noting for International Application of the Tumor-Stroma Ratio as an Easy Diagnostic Tool: Protocol for a Multicenter Prospective Cohort Study

  • Marloes Smit; 
  • Gabi van Pelt; 
  • Annet Roodvoets; 
  • Elma Meershoek-Klein Kranenbarg; 
  • Hein Putter; 
  • Rob Tollenaar; 
  • J Han van Krieken; 
  • Wilma Mesker

Background:

Colon cancer treatment is dependent on the stage at diagnosis. The current Tumor-Node-Metastasis (TNM) staging for the selection of patients for adjuvant chemotherapy needs additional prognostic and predictive biomarkers. Better decision making for chemotherapy will result in reducing over- and undertreatment. We developed a new, easy-to-apply, practice-changing method to select colon cancer patients for adjuvant chemotherapy: the tumor-stroma ratio (TSR). The TSR distinguishes within stage II-III patients who will likely benefit from adjuvant chemotherapy and those who will not.

Objective:

The aim of the study was to add, in addition to the TNM classification, the TSR to current routine pathology evaluation. Pathologists will be instructed for scoring the TSR in combination with a quality assessment program. An international multicenter study will validate the parameter prospectively.

Methods:

The study is designed for future implementation of the TSR to the current TNM guidelines, using routinely Haematoxylin- and Eosin-stained tumor tissue sections. In part 1 of the study, an electronic learning (e-learning) module with a quality assessment program using the European Society of Pathology framework will be developed. This module will be used to assess the reliability and reproducibility of the TSR, conducted by national and international pathologists. Part 2 will involve the validation of the TSR in a prospective cohort of colon cancer p-stage II-III patients in a multicenter setting. In total, 1500 patients will be included.

Results:

The results of part 1 will be expected in the first half of 2019. For part 2, the inclusion of patients in the prospective study, which started at the end of 2018, will take 3 years with an additional follow-up after another 3 years.

Conclusions:

The main endpoints of this study are as follows: in part 1, trained (international) pathologists who are able to reliably score the TSR, resulting in low intra- and interobserver variation; in part 2, confirmation of significant survival differences for patients with a stroma-high tumor versus patients with a stroma-low tumor. On the basis of these findings, a modification in current treatment guidelines will be suggested.

ClinicalTrial:

Netherlands Trial Register NTR7270; https://www.trialregister.nl/trial/7072

International Registered Report:

DERR1-10.2196/13464


 Citation

Please cite as:

Smit M, van Pelt G, Roodvoets A, Meershoek-Klein Kranenbarg E, Putter H, Tollenaar R, van Krieken JH, Mesker W

Uniform Noting for International Application of the Tumor-Stroma Ratio as an Easy Diagnostic Tool: Protocol for a Multicenter Prospective Cohort Study

JMIR Res Protoc 2019;8(6):e13464

DOI: 10.2196/13464

PMID: 31199317

PMCID: 6595942

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