A Novel Biosignature Identifies Patients With DCIS With High Risk of Local Recurrence After Breast Conserving Surgery and Radiation Therapy

Vicini, Frank A.; Mann, G. Bruce; Shah, Chirag; Weinmann, Sheila; Leo, Michael C.; Whitworth, Pat W.; Rabinovitch, Rachel; Torres, Mylin A.; Margenthaler, Julie A.; Dabbs, David J.; Savala, Jess; Shivers, Steven C.; Mittal, Karuna; Wärnberg, Fredrik; Bremer, Troy

doi:10.1016/j.ijrobp.2022.06.072

Cited by 16 publications

(9 citation statements)

References 20 publications

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“…17 The test demonstrated high analytical sensitivity, specificity, accuracy, reproducibility, and precision, 18 and was prognostic of IBR risk and predictive of RT benefit in multiple validation studies. 17,[19][20][21][22] These clinical validation studies, which include a large randomized clinical trial (SweDCIS), demonstrate that patients who were classified by DCISionRT as being at low risk received no significant benefit from RT, whereas patients with higher DS results had much higher IBR rates, which were significantly reduced with adjuvant RT. The test had a 99% negative predictive value for RT benefit for patients in the low-risk group, while 96% of all patients benefiting from RT were correctly classified into the high-risk group.…”

Section: Abstract Ductal Carcinoma In Situ • Radiation Therapy • Deci...mentioning

confidence: 97%

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study

Shah,

Whitworth,

Vicini

et al. 2024

Ann Surg Oncol

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Background Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. Methods Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient’s preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. Results RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2–4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3–30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. Conclusions The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological ‘low-risk’ and ‘high-risk’ DCIS patients. Trial Registration ClinicalTrials.gov identifier: NCT03448926 (https://clinicaltrials.gov/study/NCT03448926).

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Section: Abstract Ductal Carcinoma In Situ • Radiation Therapy • Deci...mentioning

confidence: 97%

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study

Shah,

Whitworth,

Vicini

et al. 2024

Ann Surg Oncol

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“…The DS was also validated in the SweDCIS randomized trial study population [174], where the test was predictive for RT benefit in reducing invasive LRs using a DS threshold above 2.8, while the p-value for interaction of RT effect with the cutoff of three was not statistically significant for either total or invasive LRs. A new version of the DS biosignature taking into consideration the EGFR/HER2/KRAS biomarkers expression with a prespecified algorithm was tested by Vicini et al [178] to pinpoint patients who remained at higher risk after RT, the so-called residual risk subtype (RRt). The EGFR/HER2/KRAS pathway is known to be associated with tumour progression and drug resistance [179].…”

Section: The Dcision Scorementioning

confidence: 99%

“…The EGFR/HER2/KRAS pathway is known to be associated with tumour progression and drug resistance [179]. In a combined cohort of patients from three institutions [178], three categorical risk groups were defined: (1) Low-risk group (DS ≤ 2.8 without RRt), (2) Elevated-risk group (DS > 2.8 without RRt), and (3) RRt group (DS > 2.8 with RRt). DCIS in the RRt group showed a more aggressive profile (grade 3, large size, and HER2 overexpression) and higher LR risk without RT, with a 10-year rate of total LRs of 42.1% and invasive LRs of 18.5%.…”

Section: The Dcision Scorementioning

confidence: 99%

Tools to Guide Radiation Oncologists in the Management of DCIS

Leonardi,

Zerella,

Lazzeroni

et al. 2024

Healthcare

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Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.

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“…The DS is a numeric value ranging from 0-100. Patients are categorized into three risk groups based on different cut offs of the DS, defined as: low (<39), intermediate (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54), and high risk (≥55). An analysis from the E5194 study demonstrated the DS as an independent predictor of LR after treatment with BCS alone (hazard ratio (HR) = 2.31, 95% confidence interval [CI]:1.15 to 4.49; p = 0.02) [49].…”

Section: Can Molecular Biomarkers Help De-escalate the Treatment Of D...mentioning

confidence: 99%

“…The Oncotype DX DCIS score (DS) is one of the first molecular expression assays evaluated in DCIS. The DS comprised 12 of the 21 genes of the Oncotype DX Recurrence score [ 54 ]; there are seven genes related to cancer (Ki67, STK15, Survivin, Cyclin B1, MYBL2, progesterone receptor, and GSTM1) along with five genes for reference (ACTB (beta-actin), GAPDH, RPLPO, GUS, and TFRC). The DS is a numeric value ranging from 0–100.…”

Section: Can Molecular Biomarkers Help De-escalate the Treatment Of D...mentioning

confidence: 99%

Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

et al. 2023

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Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS—Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one—the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial—incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.

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A Novel Biosignature Identifies Patients With DCIS With High Risk of Local Recurrence After Breast Conserving Surgery and Radiation Therapy

Cited by 16 publications

References 20 publications

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study

Tools to Guide Radiation Oncologists in the Management of DCIS

Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

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