A nomogram that combines breast MRI-derived intra-tumoral heterogeneity (ITH) quantification with clinicopathologic factors may offer significant prognostic benefit in assessing neoadjuvant chemotherapy response in patients with breast cancer.
In a new multicenter retrospective study, recently published in Radiology, researchers trained and evaluated the capability of the nomogram to predict pathologic complete response (pCR) in a total cohort of 1,448 women (median age of 49) who had neoadjuvant chemotherapy for breast cancer.
Multivariable analysis revealed the ITH score (with an odds ratio of 0.12) was an independent predictor of pCR for neoadjuvant chemotherapy.
In three external validation cohorts, the study authors found the nomogram incorporating ITH quantification and clinicopathologic variables had an average sensitivity of 85 percent and an average negative predictive value (NPV) of 93 percent for predicting pCR. The nomogram also offered 10-15 percent higher area under the receiver operating characteristic curves (AUCs) in the external validation cohorts (79 to 82 percent) in comparison to a clinicopathologic model (67 to 71 percent), according to the researchers.
“There is currently no noninvasive and convenient method to accurately predict pathologic complete response (pCR) to neoadjuvant chemotherapy in patients with breast cancer. … This model demonstrated good performance across three external validation sets, yielding area under the receiver operating characteristic curve values ranging from (79 to 82 percent),” wrote lead study author Yao Huang, M.D., who is affiliated with the Department of Radiology at the Chongqing University Cancer Hospital and the Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer in Chongqing, China, and colleagues.
Emphasizing the association of nonogram scores with tumor proliferation and aggressive disease, the researchers found that patients with lower nonogram scores had a fourfold higher likelihood of poorer recurrence-free survival.
Three Key Takeaways
1. Noninvasive prognostic tool. The MRI-based nomogram combining intra-tumoral heterogeneity (ITH) and clinicopathologic factors demonstrated high accuracy (AUC 79 to 82 percent) in predicting pathologic complete response (pCR) to neoadjuvant chemotherapy in breast cancer patients, outperforming clinicopathologic models alone.
2. High predictive value in external validation. The nomogram achieved strong predictive performance across three external validation cohorts with an average 85 percent sensitivity and an average 93 percent negative predictive value (NPV), making it potentially valuable for treatment planning.
3. Prognostic significance of ITH. Lower nomogram scores, reflecting greater ITH, were associated with a fourfold higher risk of poorer recurrence-free survival, highlighting its role in stratifying patients based on tumor aggressiveness.
Noting the uneven distribution of diverse cell populations within a tumor that can occur with the rise of ITH, the researchers said previous research focusing on intratumoral kinetic properties to characterize spatial heterogeneity were often flawed because they didn’t examine tumor subregion distribution.
“In this study, the ITH score was calculated using an unsupervised clustering algorithm, which does not require a large sample size. This method quantitatively assesses ITH by integrating local tumor features with global pixel distribution patterns,” pointed out Huang and colleagues.
(Editor’s note: For related content, see “Imaging-Based Treatment Modifications Only Used in 15 Percent of Neoadjuvant Systemic Therapy Trials for Breast Cancer,” “Breast MRI and Ultrasound Findings Linked to Elevated Risk of Axillary Residual Disease After Neoadjuvant Therapy” and “Surveillance Breast MRI Associated with Lower Risks of Advanced Second Breast Cancers.”)
In regard to study limitations, the authors noted the retrospective nature of the research and the small survival and genomics cohorts. They conceded that manual tumor delineation and relying solely on MRI sections with the maximum tumor diameter may have compromised the accuracy and stability of the ITH score.
