Patient Characteristics
Table 1 presents patient and tumor characteristics. Patient age ranged from 30 to 87 years old, with a median age of 63 years old (first to third quartile, 54–70 years old). Median tumor size was 0.8 cm (first to third quartile, 0.4–1.4 cm). Overall, 32% of patients had grade 3 disease, 31% had a tumor larger than 1 cm, 17% had close or positive margins, and 5% of patients were HR-negative.
Change in Radiation Therapy Recommendation
Table 2 presents the impact of DCISionRT testing on RT recommendations, by percentage, for the indicated patient subsets. Sixty-nine percent of all women (n = 539) were initially recommended RT pre-test (n = 374), and 46% of these women were recommended to not receive RT post-test (n = 165). Of those initially recommended to not receive RT (n = 165), 35% were recommended to receive RT post-test (n = 58). Consequently, there was a change in the RT recommendation for 42% of women (n = 539, p < 0.001) and a net reduction in the RT recommendation by 20%. A similar overall change (add or omit RT) in the RT recommendation post-DCISionRT testing was seen for radiation oncologists alone (44%), surgeons alone (49%), and radiation oncologists alone or in conjunction with tumor boards (38%). Independently, radiation oncologists were more likely to change a recommendation from ‘no RT’ to ‘yes RT’ (44%) compared with surgeons (28%), while surgeons were more likely to change their recommendation from ‘yes RT’ to ‘no RT’ (57%) compared with radiation oncologists (44%) after DCISionRT testing.
Table 2 Impact of DCISionRT on radiation therapy recommended Table 3 presents the impact of DCISionRT testing on adjuvant RT recommendations within common clinicopathologic features used by clinicians to decide on adjuvant RT. The overall change in RT recommendations was similar between different age groups, varying from 37% of women who were under 50 years of age (n = 82, p < 0.001) to 43% for women who were 50 years and older (n = 457, p < 0.001). With increasing age, the percentage of patients with RT recommended pre-test decreased from 79% to 52%, and among the corresponding cases initially not recommended RT, the percentage with RT recommended post-test increased from 12% to 53%. In patients < 50 years of age (n = 82), 79% (n = 65) were initially recommended RT pre-test; post-test, 43% (n = 28) of these cases were not recommended RT. Overall, in patients < 50 years of age, there was a corresponding net decrease of 31% in RT recommendations, from 65 patients pre-test to 39 patients post-test. For patients of 50 years of age and older, 67% were recommended RT pre-test (n = 306) and 33% were not (n = 151). Of patients initially not recommended RT (n = 151), 38% were recommended RT post-test (n = 57), whereas of patients recommended RT pre-test (n = 306), 46% were not recommended RT post-test (n = 141). Consequently, there was a 43% overall change in the RT recommendations (n = 457, p < 0.001) and an 18% (n = 82) net decrease in the RT recommendations. For patients 70 years of age and older (n = 138), there was a 10% net increase in the RT recommendations, from 72 patients pre-test to 86 patients post-test.
Table 3 Impact of DCISionRT on adjuvant radiation recommended by clinicopathologic features With respect to grade, the RT recommendation was changed overall in 45% of patients with grade 1 or 2 disease (n = 371, p < 0.001) and in 37% of patients with grade 3 disease (n = 168, p < 0.001). For patients with grade 1 or 2 disease, there was a 16% net decrease (n = 229 pre-test vs. n = 169 post-test) in recommending RT, and for patients with grade 3 disease, there was a 31% net decrease (n = 145 pre-test vs. n = 93 post-test) in recommending RT. RT recommendations were changed overall in 46% (n = 359, p < 0.001) of patients with smaller tumors (≤ 1 cm) and in 33% (n = 52, p < 0.001) of patients with larger tumors (>2.5 cm). Clinicians initially recommended that 86% of patients with close margins should receive RT, compared with 66% of patients with clear margins (≥ 2 mm). A similar percentage of RT recommendations were changed pre- to post-test for women with close margins (45%, n = 83; p < 0.001) and clear margins (43%, n = 447; p < 0.001). Positive margins were not evaluated due to the limited number of cases (n = 9).
Table 4 presents the impact of DCISionRT for cohorts of patients based on traditional ‘low-risk’ features, by percentage, for indicated patient subsets. In patients meeting the criteria for RTOG 9804, 54% were recommended RT pre-test, with an overall change in RT recommended for 46% of patients (n = 268, p < 0.001) and a net decrease of 13% (n = 144 pre-test vs. n = 110 post-test) in recommending RT. Of the corresponding 46% of patients not recommended RT pre-test (n = 123), 36% were recommended RT post-test (n = 44). Similar findings were seen using the grade 1 or 2 ECOG E5194 study criteria. In contrast, of those patients meeting the grade 3 ECOG E5194 study criteria,11 84% (n = 71) were recommended RT pre-test, with a 42% (n = 42) overall change in the RT recommendation (n = 85, p < 0.001) and a net 36% decrease in the RT recommendation (n = 71 pre-test vs. n = 45 post-test). Of those patients initially recommended RT (n = 71), 47% were not recommended RT post-test (n = 33). When looking at alternative criteria, patients with estrogen-positive disease who were older than 50 years of age had results similar to the grade 1 and 2 RTOG 9804 criteria findings.
Table 4 Impact of DCISionRT on treatment recommended by clinicopathologic features Table 5 presents changes in RT recommendations according to the DS Low and DS Elevated risk groups. Overall, patients with a DS Low risk score (63% of all patients) had a 45% net reduction (n = 248 pre-test vs. n = 95 post-test, of 341) in RT recommendations post-DCISionRT testing, while those with a DS Elevated risk score (37% of patients) had a 21% absolute increase (n = 126 pre-test vs. n = 167 post-test, of 198) in RT recommendations post-DCISionRT testing. When evaluating patients meeting the RTOG 9804 and ECOG E5194 criteria, similar changes were seen with the DS Low risk results compared with all patients. However, in DS Elevated risk patients, there were greater increases in RT recommendations in the RTOG 9804 and ECOG E5194 subpopulations compared with the entire population.
Table 5 Impact of DCISionRT on treatment recommended for the low-risk cohorts Furthermore, when assessing the continuous DS result post-testing, 26% of patients were recommended RT when they had lower scores (DS ≤ 2), while 95% of patients were recommended RT when they had higher scores (DS ≥ 4).
Logistic Regression of Factors Influencing Treatment Decisions
Figure 1 and Table 6 present multivariable logistic regression analyses of factors associated with the recommendation of RT pre- and post-DCISionRT testing. Pre-testing factors associated with increased RT recommendations included grade 3 versus grade 1 or 2 (OR 4.9), size > 1 and ≤ 2.5 cm versus size ≤ 1 cm (OR 1.6), size >2.5 cm versus ≤ 1 cm (OR 8.1), margin status (close/positive) versus negative (OR 5.3), and patient preference to receive RT (OR 4.3). Pre-testing, the factors that decreased the likelihood of an RT recommendation were patient age ≥ 70 years (OR 0.3) and patient preference to not receive RT (OR 0.4). Post-DCISionRT testing, factors associated with an increased likelihood of an RT recommendation included size >1 cm versus ≤ 1 cm (OR 2.4), grade 3 versus grade 1 or 2 (OR 2.2), African American race (OR 2.4), initial patient preference to receive RT (OR 4.9), and DCISionRT DS Elevated risk (OR 43.4). Post-testing, factors associated with a decreased likelihood of an RT recommendation were patient aged ≥ 70 years (OR 0.3) and an initial patient preference to not receive RT (OR 0.5). Following DCISionRT testing, surgeons were less likely to recommend RT than radiation oncologists (OR 0.4). The DCISionRT score had a substantially greater impact (by eightfold) on RT recommendations (OR 43.4) in comparison with all other factors.
Table 6 Factors associated with recommendation for radiation therapy before and after DCISionRT