Prospective Correlation of Magnetic Resonance Tumor Regression Grade With Pathologic Outcomes in Total Neoadjuvant Therapy for Rectal Adenocarcinoma
2The University of Pittsburgh, Pittsburgh, PA
3University of Texas MD Anderson Cancer Center, Houston, TX
4Memorial Sloan Kettering Cancer Center, New York, NY
5University of Florida, Gainesville, FL
6University of Florida Health Cancer Center, Gainesville, FL
7Imaging and Radiation Oncology Core (IROC) Group, and the University of Pennsylvania, Philadelphia, PA
8Baylor Scott and White Health Baylor University Medical Center at Dallas, Dallas, TX
9University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH
10Dana-Farber/Harvard Cancer Institute, Boston, MA
11Department of Surgery, David Geffen School of Medicine at UCLA, and VA Greater Los Angeles Healthcare System, Los Angeles, CA
12Dayton Clinical Oncology Program, Dayton, OH
13NSABP Foundation, Pittsburgh, PA
14Missouri Baptist Medical Center/Heartland NCORP, St Louis, MO
15Stephenson Cancer Center University of Oklahoma Health Sciences Center, Oklahoma City, OK
16Trinity Health Ann Arbor Hospital, Michigan Cancer Research Consortium (NCORP), Ann Arbor, MI
17Mayo Clinic, Rochester, MN
18University of California Davis Comprehensive Cancer Center/UC Davis School of Med/UC Davis Health, Sacramento, CA
19Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
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 (ClinicalTrials.gov 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).
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.
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. (https://nctn-data-archive.nci.nih.gov/about-us#:~:text=%20To%20request%20data%2C%20the%20following%20are%20required%3A,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
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 www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
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
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: https://openpaymentsdata.cms.gov/physician/127090
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: https://openpaymentsdata.cms.gov/physician/321938
No other potential conflicts of interest were reported.