Abstract PS19-08: Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction

Abstract

Abstract Second harmonic generation (SHG) is an intrinsic optical signal that can be generated from fibrillar collagen. The directionality of SHG emission is influenced by the diameter and spacing of collagen fibrils, and the disorder in their packing within collagen fibers. One measure of SHG directionality is the ratio of forward- to backward-scattered SHG, or “F/B”. F/B has been used to assess healthy vs diseased tissue in breast, ovarian, and lung cancer, and is an independent prognostic indicator of metastasis free survival time in ER+, lymph node-negative (N0), invasive ductal carcinoma (IDC). Here we assess the heterogeneity in F/B within tumor sections from ER+ N0 IDC, and its effect on the use of F/B for metastatic risk prediction. We find that F/B of tumor collagen varies between the tumor/host interface and the more cellular tumor bulk (p<0.0001, Student’s t-test), and that F/B from the tumor/host interface, but not tumor bulk, is prognostic of metastasis free survival in 95 IDC ER+ N0 patients (p=0.0020 and 0.10, respectively, log rank test for trend). This result was repeated with two additional image analysis procedures to generate F/B with reduced user input and hence reduced possibility of bias. Using Random Survival Forests to generate a data-driven predictive model, we find that F/B from the tumor/host interface, but not bulk, as well as a 21-gene prognostic score inferred from Affymetrix data, both contribute to predicting metastasis-free survival in this cohort. Any tool to help predict metastasis and assist with treatment decisions is likely to be applied in combination with the now well-established genomic scores. To understand how F/B can support genomic methods for guiding treatment decisions we divided our patient samples into two cohorts based upon the value of their 21-gene score relative to the TAILORx cutoff of 26 (separating low-intermediate and high-risk groups). The F/B value from tumor-host interface identifies a subgroup of patients in the low-intermediate risk group with poor clinical outcome (p=0.045, log rank test for trend). Overall, this data reveals that intratumor heterogeneity can impact the ability of F/B to predict patient outcome, and that F/B specifically from the tumor-host interface may provide a tool to better identify patients in need of adjuvant treatment or enrollment in clinical trials. Citation Format: Edward Brown, Danielle Desa, Wencheng Wu, Robert Hill, John Martens, Robert Strawderman, Bradley Turner. Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-08.