Abstract P3-03-01: Functional tumor volume at 3 and 6-week MRI as an indicator of patients with inferior outcome after neoadjuvant chemotherapy

Abstract Purpose. Functional tumor volume (FTV) is a quantitative measure of tumor burden derived from dynamic contrast-enhanced breast MRI1, 2. In the I-SPY 2 TRIAL, FTV is measured during neoadjuvant chemotherapy (NAC) at pre-treatment (T0), 3 weeks (T1), 12 weeks (T2), and pre-surgery (T3) time points. In I-SPY2 protocol amendment 18, activated in Dec 2017, an optional MRI at 6 weeks (T1a) recommended at clinician’s discretion was added for patients with low response at T1. Patients are treated with standard NAC with or without addition of experimental agents. A treatment escalation option being planned for future I-SPY2 implementation will give patients with suboptimal response the opportunity to pursue more aggressive therapy. T1 and T1a MRI may be helpful to select candidates for this option. We retrospectively investigated the ability of FTV reduction at 3 and 6 weeks to detect non-responders. Methods. We included 104 patients who underwent T1a MRI between Jan 2018 and Mar 2021. FTV was measured using in-house software developed in IDL (Exelis Visual Information Solutions, Boulder, CO). FTV reduction at 3 and 6 weeks was dichotomized to under and over with a cutoff of 20% reduction from T0 to T1 and 65% reduction (the 3D equivalent of size-based partial response criteria by RECIST) from T0 to T1a, respectively. Treatment outcome was evaluated based on residual cancer burden (RCB) on surgical pathology, an established surrogate for survival outcome3. Patients with RCB 0/I were considered as responders and those with RCB II/III as non-responders. Fisher’s exact test was used to examine the association between FTV reduction and treatment outcome, with P <0.05 considered statistically significant. Ability of FTV reduction to detect non-responders was assessed by positive predictive value (PPV) and sensitivity, where non-responder was defined as “positive”. Results. Of the 104 patients, 49 patients (31 HR+HER2–;16 HR–HER2–; 2 HR+HER2+) who had both RCB and analyzable FTVs were included. Other patients were excluded because of missing RCB or FTV data (n = 18) or not having completed the assigned therapy (n = 37).FTV reduction at T1 and T1a was associated with outcome (P = 0.022 and <0.001, respectively) (Table 1). FTV reduction at T1a was also associated with outcome in 26 patients with <20% reduction at T1 (P = 0.047). The combined criteria of <20 % reduction at T1 and <65 % reduction at T1a detected non-responders with PPV of 82% and sensitivity of 95%, which outperformed the T1 only or T1a only criterion (Table 2†).Ability of combined criteria was experimentally tested using 20% cutoff for T1 and various cutoffs for T1a (Table 2). Criteria of <20 % reduction at T1 and <50 % reduction at T1a detected non-responders with PPV of 89% and sensitivity of 89%(Table 2‡). Conclusion. In this early small study, combined criteria using FTV reduction at 3 and 6 weeks of NAC showed high PPV and high sensitivity in early detection of non-responders as candidates for the treatment escalation option. Reference. 1. Radiology 263:663–672, 2012. 2. Radiology 279:44–55, 2016. 3. J Clin Oncol. 2007 Oct 01; 25(28) 4414-4422 Table 1.Association between FTV Reduction and Treatment ResponseCriteria based on FTV reduction at T1Total n = 49<20% reduction at T1 (n = 26)>20% reductionat T1 (n = 23)P-valueNon-responder (RCB II or III)281990.022*Responder (RCB 0 or I)21714Criteria based on FTV reduction at T1aTotal n = 49<65% reduction at T1a (n = 30)>65% reduction at T1a (n = 19)P-valueNon-responder (RCB II or III)28244< 0.001*Responder (RCB 0 or I)21615Combined criteria based on FTV reduction at T1 and T1aTotal n = 26<20% reduction at T1 & <65% reduction at T1a (n = 22)<20% reduction at T1 & >65% reduction at T1a (n = 4)P-valueNon-responder (RCB II or III)191810.047*Responder (RCB 0 or I)743 Table 2.Performance of FTV Reduction-based CriteriaCriteria to detect non-respondersPPVNPVSensitivitySpecificityTrue positiveFalse negativeFalse positiveTrue negativeTotalT1 <20% reduction†73%61%68%67%19971449T1a <65% reduction†80%79%86%71%24461549T1 <20% reduction & T1a <40% reduction88%56%79%71%1542526T1 <20% reduction & T1a <45% reduction89%62%84%71%1632526T1 <20% reduction & T1a <50% reduction ‡89%71%89%71%1722526T1 <20% reduction & T1a <55% reduction86%80%95%57%1813426T1 <20% reduction & T1a <60% reduction86%80%95%57%1813426T1 <20% reduction & T1a <65% reduction †82%75%95%43%1814326T1 <20% reduction & T1a <70% reduction78%67%95%29%1815226T1 <20% reduction & T1a <75% decrease75%50%95%14%1816126Note: Unless otherwise specified, data represent the number of patients Citation Format: Natsuko Onishi, Jessica E Gibbs, Wen Li, David C Newitt, Elissa R Price, Barbara LeStage, William F Symmans, Angela M DeMichele, Christina Yau, the I-SPY 2 TRIAL Imaging Working Group, the I-SPY 2 TRIAL Consortium, Laura J Esserman, Nola M Hylton. Functional tumor volume at 3 and 6-week MRI as an indicator of patients with inferior outcome after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-01.