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Joseph A Sparano

Publications and source records attributed to Joseph A Sparano.

2 recordsLinked to original sources
PubMed2026

Development and Validation of a Multimodal Clinical, Pathologic, and Genomic Model for Breast Cancer Recurrence.

PURPOSE: To develop and validate a multimodal recurrence-risk model integrating histology, genomic testing, and clinical variables. METHODS: We developed AI-Path, a whole-slide image biomarker for recurrence prediction trained in CALGB 9344, and validated it in three independent cohorts: TAILORx, a multi-site Chicago cohort, and the MDX-BRCA cohort. We then integrated AI-Path with Oncotype DX Recurrence Score (RS), tumor size, and nodal status into a Cox model, PathClinRS, fit using 60% of cases from TAILORx, with the remaining 40% held out for validation. The primary end point was distant recurrence-free interval. Performance was assessed using Harrell's concordance index (C-index) and Kaplan-Meier analyses. RESULTS: A total of 12,418 patients were included. In TAILORx, AI-Path outperformed RS for distant recurrence (C-index, 0.682 vs 0.647; P = .038), driven by superior prediction of late recurrence (0.656 vs 0.567; P < .001). In node-negative disease, PathClinRS outperformed RSClin in the TAILORx fitting (0.72 vs 0.70; P = .016) and validation sets (0.74 vs 0.70; P = .004). In node-positive disease, PathClinRS outperformed RSClinN+ in Chicago (0.94 vs 0.74; P < .001) and MDX-BRCA (0.71 vs 0.66; P = .004) cohorts. Compared with NATALEE eligibility, PathClinRS identified nearly twice as many high-risk node-negative patients while maintaining a comparable 10-year distant recurrence risk (16.7% vs 16.6% per NATALEE eligibility in TAILORx fitting; 21.0% vs 19.4% in TAILORx validation). PathClinRS identified 68% of intermediate risk premenopausal patients as low-risk with no evidence of chemotherapy benefit, compared to only 36% identified as low risk by standard clinicopathologic criteria. CONCLUSION: Digital histopathology provides prognostic information complementary to genomic assays and has the potential to personalize therapy beyond existing clinicogenomic tools.

Journal Article↗
PubMed2026

Artificial intelligence-based tumour infiltrating lymphocyte quantification in patients with triple-negative breast cancer: an independent validation study.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are a robust prognostic marker in patients with triple-negative breast cancer. Artificial intelligence (AI)-derived computational tools assessing TILs could improve efficiency, but require independent validation against clinical outcomes. We aimed to compare the prognostic performance of AI-derived TIL scores with pathologist-scored TILs in a large, prospectively collected dataset pooled from randomised controlled trials. METHODS: CATALINA was an independent, external validation study using prospectively collected long-term clinical outcome data pooled from seven randomised clinical trials conducted at multiple sites. We independently evaluated two previously validated AI pipelines that generate five computationally assessed tumour-infiltrating lymphocyte (cTIL) scores by masked, independent deployment of locked models. cTIL scores were correlated with the mean of the pathologist-scored stromal TILs (sTILs) in 220 digitised haematoxylin and eosin whole slide images in a cohort of patients with early-stage triple-negative or HER-2 positive breast cancer, previously scored by trained pathologists in a TIL-reproducibility study. Prognostic performance was assessed in a separate cohort of patients with early triple-negative breast cancer pooled from seven prospective, randomised adjuvant trials. Multivariable Cox regression models adjusted for clinicopathological factors and study heterogeneity assessed associations of cTIL score and sTIL score with invasive disease-free survival, distant disease-free survival, and overall survival. 5-year discrimination was estimated using time-dependent area under the receiver operating characteristic curve (AUC). FINDINGS: Individual data were collated from 1759 patients, of whom 1356 had complete clinicopathological data, pathologist sTIL scores, and cTIL scores available. Modest correlation (r 0&#xb7;375-0&#xb7;473) was observed between cTIL scores and the mean pathologist sTIL score. Both sTIL and cTIL were independently associated with 5-year invasive disease-free survival, distant disease-free survival, and overall survival after adjustment for clinicopathological factors (hazard ratio for invasive disease-free survival was 0&#xb7;73 [95% CI 0&#xb7;66-0&#xb7;82]; q<0&#xb7;0001, distant disease-free survival was 0&#xb7;70 [0&#xb7;61-0&#xb7;79]; q<0&#xb7;0001, and overall survival was 0&#xb7;72 [0&#xb7;63-0&#xb7;82]; q<0&#xb7;0001 for sTIL scores and 0&#xb7;80 [0&#xb7;73-0&#xb7;89]; q<0&#xb7;0001, 0&#xb7;77 [0&#xb7;69-0&#xb7;86]; q<0&#xb7;0001, and 0&#xb7;79 [0&#xb7;70-0&#xb7;88]; q=0&#xb7;0002, respectively, for percentage_lymphocyte scores). In models adjusted for clinicopathological variables and sTIL score, cTIL score did not maintain a statistically significant prognostic association. Both sTIL and cTIL scores improved the 5-year AUC over clinicopathological variables alone, while cTIL score did not significantly further improve AUC when combined with clinicopathological variables and sTIL score. INTERPRETATION: Two cTIL models deployed entirely without retraining or modification provided statistically significant prognostic information and improved risk discrimination compared with clinicopathological variables alone in this large, platform-based, independent validation study. Although cTIL score did not incrementally improve prognostication compared with models combining clinicopathological variables with sTIL score, these findings support the application of cTILs as a reproducible prognostic biomarker, particularly in settings where routine or widespread pathologist assessment is unavailable. FUNDING: Breast Cancer Research Foundation (USA).

Humans↗