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

Author(s): William A. Hall, MD¹; Jiahe Li, MS²; Y. Nancy You, MD³; Marc J. Gollub, MD⁴; Joseph R. Grajo, MD^5,6; Mark Rosen, MD⁷; Greg dePrisco, MD⁸; Greg Yothers, PhD²; Jennifer A. Dorth, MD⁹; Osama E. Rahma, MD¹⁰; Marcia M. Russell, MD¹¹; Howard M. Gross, MD¹²; Samuel A. Jacobs, MD¹³; Bryan A. Faller, MD¹⁴; Sagila George, MD¹⁵; Tareq Al baghdadi, MD¹⁶; Michael G. Haddock, MD¹⁷; Richard Valicenti¹⁸; Theodore S. Hong, MD¹⁹; and Thomas J. George, MD^5,6

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

Dr. Maen Hussein's Thoughts

Tumor regression grade defined as the ratio between fibrosis and residual tumor, is routinely used to assess response to therapy and demonstrated to be an important predictor of patient’s outcome. In the era of TNT (total Neoadjuvant Therapy) this will help assess response to avoid surgery. It will be nice to add MRD testing in the blood as another tool.

PURPOSE

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

Author Affiliations

¹Froedtert and the Medical College of Wisconsin, Milwaukee, WI; 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

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial

There is hope for organ preservation in rectal preservation. I believe the good news is that waiting is not as harmful. Those who underwent surgery after regrowth almost had the same disease-free survival (DFS) as those who had surgery after treatment because of incomplete response. The use of CtDNA (not analyzed in the trial) may play an even a bigger role where you may not have to wait for clinical regrowth to have the surgery, but of course more trials are needed to see if this will have clinical benefit. (Is the positive or rising CtDNA enough reason to have surgery vs imaging recurrence?)
Still, this is an exciting new era that will see change in treating early-stage colorectal cancer, recall the immunotherapy results in patients who were MMR deficient.

Preoperative Treatment of Locally Advanced Rectal Cancer

Paradigm shift in rectal cancer therapy? Some may not need surgery, now some may not need radiotherapy.

Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results

Nice study showing a non-radiation approach to node-negative, earlier stage, low-lying rectal cancer, using FOLFOX/CAPEOX x 3 months followed by local excision for those with downstaging to T0/T1 disease. 79% of patients achieved organ preservation, and 2-year locoregional RFS was 90%. A good option for those who are not good candidates for radiation yet still want to avoid an APR-type surgery.

PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer

Very impressive results that may change treatment-paradigm. However, number of patients treated, and duration of follow-up are significant issues here for early adoption.