Total neoadjuvant therapy (TNT) is a newly established standard treatment for rectal adenocarcinoma. Current methods to communicate magnitudes of regression during TNT are subjective and imprecise. Magnetic resonance tumor regression grade (MR-TRG) is an existing, but rarely used, regression grading system. Prospective validation of MR-TRG correlation with pathologic response in patients undergoing TNT is lacking. Utility of adding diffusion-weighted imaging to MR-TRG is also unknown.

We conducted a multi-institutional prospective imaging substudy within NRG-GI002 ( identifier: NCT02921256) examining the ability of MR-based imaging to predict pathologic complete response (pCR) and correlate MR-TRG with the pathologic neoadjuvant response score (NAR). Serial MRIs were needed from 110 patients. Three radiologists independently, then collectively, reviewed each MRI for complete response (mriCR), which was tested for positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity with pCR. MR-TRG was examined for association with the pathologic NAR score. All team members were blinded to pathologic data.

A total of 121 patients from 71 institutions met criteria: 28% were female (n = 34), 84% White (n = 101), and median age was 55 (24-78 years). Kappa scores for T- and N-stage after TNT were 0.38 and 0.88, reflecting fair agreement and near-perfect agreement, respectively. Calling an mriCR resulted in a kappa score of 0.82 after chemotherapy and 0.56 after TNT reflected near-perfect agreement and moderate agreement, respectively. MR-TRG scores were associated with pCR (P < .01) and NAR (P < .0001), PPV for pCR was 40% (95% CI, 26 to 53), and NPV was 84% (95% CI, 75 to 94).

MRI alone is a poor tool to distinguish pCR in rectal adenocarcinoma undergoing TNT. However, the MR-TRG score presents a now validated method, correlated with pathologic NAR, which can objectively measure regression magnitude during TNT.

© 2023 by American Society of Clinical Oncology

  • Key Objective

  • Characterization of rectal tumor regression during total neoadjuvant therapy (TNT) is a critically important task. Currently, minimal data exist on how reliably rectal MRI can characterize regression during TNT. We prospectively validated the ability of a numerical grading scale to predict pathologic complete response (pCR) and correlate with tumor regression.

  • Knowledge Generated

  • The magnetic resonance tumor regression grade (MR-TRG) is a poor tool to predict pCR to TNT. However, MR-TRG does correlate with the magnitudes of pathologic regression during TNT. Finally, diffusion-weighted imaging improves the AUC when compared with MR-TRG alone.

  • Relevance (A.H. Ko)

  • This study highlights both the usefulness and limitations of MRI in predicting pathologic tumor response during TNT for rectal adenocarcinoma. While MR-TRG correlates with the magnitude of pathologic regression, it is not an accurate predictor of complete pathologic response.*

    *Relevance section written by JCO Associate Editor Andrew H. Ko, MD, FASCO.


Presented in part at the 2016 ASCO Annual Meeting, Chicago, IL, June 3-7, 2016; 2017 ASCO GI Symposium, San Francisco, CA, January 19-21, 2017; 2017 ASCO Annual Meeting, Chicago, IL, June 2-6, 2017; 2018 ASCO GI Symposium, San Francisco, CA, January 18-20, 2018; 2019 ASCO GI Symposium, San Francisco, CA, January 17-19, 2019; 2019 ASCO Annual Meeting, Chicago, IL, May 31-June 1, 2019; 2021 ASCO GI Symposium, virtual, January 15-17, 2021; and the 2021 American Society for Therapeutic Radiology and Oncology Annual Meeting, Chicago, IL, October 24-27, 2021.


Supported by U10CA180868, -180822; UG1-189867; U24-196067; 5U24CA180803; BIQSPF grant; AbbVie; and Merck.



The study Protocol (online only) and informed consent form will be made available. Individual participant data that underlie the results reported in this article, after deidentification, will be available within 1 year after publication and will be accessible through the NCTN Data Archive. Data will be available to researchers who wish to analyze the data in secondary studies to enhance the public health benefit of the original work. Requirements may include (but not be limited to) a research plan, a Data Use Agreement (DUA), and legally binding signatures. (,Data%20Use%20Agreement%20%28DUA%29%20containing%20auto-...%20More%20).

Conception and design: William A. Hall, Marc J. Gollub, Joseph R. Grajo, Mark Rosen, Greg dePrisco, Greg Yothers, Marcia M. Russell, Samuel A. Jacobs, Richard Valicenti, Theodore S. Hong, Thomas J. George

Administrative support: Greg Yothers, Richard Valicenti

Provision of study materials or patients: Howard M. Gross, Bryan A. Faller, Tareq Al baghdadi, Richard Valicenti

Collection and assembly of data: Y. Nancy You, Marc J. Gollub, Joseph R. Grajo, Mark Rosen, Greg dePrisco, Greg Yothers, Howard M. Gross, Bryan A. Faller, Tareq Al baghdadi, Richard Valicenti

Data analysis and interpretation: Jiahe Li, Marc J. Gollub, Joseph R. Grajo, Greg dePrisco, Greg Yothers, Jennifer A. Dorth, Osama E. Rahma, Marcia M. Russell, Samuel A. Jacobs, Bryan A. Faller, Tareq Al baghdadi, Michael G. Haddock, Richard Valicenti, Theodore S. Hong, Thomas J. George

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

Prospective Correlation of Magnetic Resonance Tumor Regression Grade With Pathologic Outcomes in Total Neoadjuvant Therapy for Rectal Adenocarcinoma

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to or

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

William A. Hall

Consulting or Advisory Role: Aktis Oncology

Research Funding: Elekta (Inst)

Travel, Accommodations, Expenses: Elekta (Inst)

Marc J. Gollub

Stock and Other Ownership Interests: Pfizer

Greg Yothers

Employment: Mountainview Pediatrics

Consulting or Advisory Role: Orbus Therapeutics

Jennifer A. Dorth

Travel, Accommodations, Expenses: Varian Medical Systems

Osama E. Rahma

Employment: Outcomes4me, AstraZeneca/MedImmune

Leadership: Outcomes4me, AstraZeneca/MedImmune

Stock and Other Ownership Interests: Outcomes4Me, AstraZeneca/MedImmune

Honoraria: Merck, Clinical Care Options, MI Bioresearch, PRMA Consulting, Leerink, Alaunus Global

Consulting or Advisory Role: Celgene, Alcimed, Gfk, Merck, Five Prime Therapeutics, Putnam Associates, Defined Health, PureTech, Leerink, Genentech, Imvax, GlaxoSmithKline, Maverick Therapeutics, Bayer, Sobi

Research Funding: Amgen (Inst), Merck

Patents, Royalties, Other Intellectual Property: Pending patent (DFCI 2386.010) (Inst), PD-1/PD-L1 (Inst)

Travel, Accommodations, Expenses: Merck, Clinical Care Options, PureTech, PRMA Consulting, Genentech

Marcia M. Russell

Honoraria: Healthgrades, American College of Surgeons

Samuel A. Jacobs

Employment: Exact Sciences

Consulting or Advisory Role: Exact Sciences

Bryan A. Faller

Consulting or Advisory Role: LEK

Travel, Accommodations, Expenses: Genentech, Novartis, EB SQUIBB, Celgene, Boehringer Ingelheim, Eisai, AstraZeneca, Lilly, Amgen, Merck, Takeda

Open Payments Link:

Sagila George

Research Funding: Natera (Inst)

Travel, Accommodations, Expenses: Caris Life Sciences

Tareq Al baghdadi

Stock and Other Ownership Interests: Bristol Myers Squibb, Epizyme, HERON

Honoraria: Cardinal Health

Consulting or Advisory Role: Bristol Myers Squibb, Kite, a Gilead company, Lilly, AstraZeneca

Theodore S. Hong

Stock and Other Ownership Interests: PanTher Therapeutics

Consulting or Advisory Role: Merck, Synthetic Biologics, Novocure, Syndax, Boston Scientific

Research Funding: Taiho Pharmaceutical (Inst), AstraZeneca (Inst), IntraOp (Inst), Tesaro (Inst), Bristol Myers Squibb (Inst), Ipsen (Inst)

Thomas J. George

Consulting or Advisory Role: Tempus, BillionToOne, Pfizer/Array

Research Funding: Bristol Myers Squibb (Inst), Merck (Inst), AstraZeneca/MedImmune (Inst), Lilly (Inst), Bayer (Inst), Incyte (Inst), Ipsen (Inst), Seagen (Inst), Genentech (Inst), Astellas Pharma (Inst), BioMed Valley Discoveries (Inst), GlaxoSmithKline (Inst), Amgen (Inst), OncoC4 (Inst), BillionToOne (Inst), Jounce Therapeutics (Inst), Elicio Therapeutics (Inst)

Open Payments Link:

No other potential conflicts of interest were reported.


No companion articles


DOI: 10.1200/JCO.22.02525 Journal of Clinical Oncology 41, no. 29 (October 10, 2023) 4643-4651.

Published online July 21, 2023.

PMID: 37478389

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