Background
A majority of women with ductal carcinoma in situ (DCIS) treated with breast conserving surgery (BCS) do not benefit from adjuvant radiation therapy (RT). However, evidence from randomized clinical trials supports the role of RT in reducing the risk of local recurrence. Given the understanding that more than two-thirds of women with DCIS do not recur after BCS alone, NCCN guidelines recommend utilization of RTOG-9804 criteria (screening detected, grade I/II, size < 2.5 cm, margins > 3 mm) to consider omitting RT after BCS for DCIS. To overcome limitations of clinicopathologic (CP) risk assessment, a validated biosignature that integrates the protein expression of 7 genes and 4 CP features (DCISionRT, PreludeDx) is currently in use in many breast centers. The 7-gene biosignature has been clinically validated to be both prognostic for ipsilateral breast recurrence (IBR) risk and predictive for response to RT. Recent evidence demonstrates that approximately half of patients meeting RTOG-9804-like criteria will be identified by the 7-gene biosignature as having elevated IBR risk and significant radiation benefit. The study assesses factors impacting shared decision-making, including physician recommendations and patient preferences, when incorporating the biosignature test results along with clinicopathologic factors. The main outcome is the impact of test results on individual preferences and treatment recommendations.
Design and Methods
PREDICT II is a multicenter (30 site), prospective, observational registry, open to 3000 women with DCIS. Primary end points are changes in treatment recommendations for surgery, radiation, and hormonal therapy. Secondary end points are identification of key drivers for treatment recommendations, such as age, size, grade, patient preference, biosignature status, and IBR risk. The study is open to females aged 30 to 85 years who are candidates for BCS and eligible for RT and/or systemic treatment. Subjects must not have been previously treated for DCIS or invasive breast cancer. DCIS patients, breast surgeons, and radiation oncologist participate in informed, shared, decision-making based on standard clinicopathologic criteria. The preference and strength of preference for mastectomy vs BCS and RT vs no RT, following shared decision-making, is recorded before and after biosignature results are available. Recurrence rates at 5 and 10 years will be documented. Changes in treatment recommendations will be analyzed using McNemar’s test (alpha level = 0.05). Multivariable logistic regression will be used to determine odds ratios of clinicopathologic factors affecting pre- and post-test treatment recommendations. Covariates include hormone receptor status, nuclear grade, tumor necrosis, family history of breast cancer, race, ethnicity, patient preference, physician specialty, and the biosignature score. Differences in recurrence-free and overall survival will be assessed by Kaplan-Meier survival analysis using the log-rank test and/or the Cox proportional hazards model. The study has been approved by WCG IRB (Tracking #20172841) and/or local IRBs at each site. ClinicalTrials.gov: NCT03448926.
