Targeted intraoperative radiation therapy (TARGIT-IORT) at the time of lumpectomy has been demonstrated to be noninferior to external beam radiation therapy (EBRT) in a large, randomized trial; however, questions have been raised about the TARGIT-A results, and recently patient advocacy groups in California have called into question patient education practices about the procedure.

TARGIT-A Results

In the international, noninferiority, phase 3 TARGIT-A trial, researchers randomly assigned 3,451 patients age 45 or older with invasive ductal breast carcinoma who were undergoing breast-conserving surgery to receive TARGIT-IORT with the Intrabeam device or EBRT.1

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Most patients in the TARGIT arm received radiation at the time of lumpectomy; however, some patients received the single dose of TARGIT after lumpectomy in which the lumpectomy wound was reopened (“postpathology”). Patients in the TARGIT arm could receive EBRT if predefined, high-risk features were found during or after lumpectomy.

The primary endpoint of the trial was pathologically confirmed local recurrence. Secondary endpoints included local toxicity and mortality.

The noninferiority was calculated in binomial proportions with a predefined margin of 2.5% for the primary endpoint with a 5% significance level. At baseline, the median age was 63, most tumors were between 1 and 2 cm, and 15% of tumors were grade 3.

Nodal involvement was present in 17% of patients. In the TARGIT-IORT arm, 15.2% of patients also received EBRT. The median follow-up time was 2 years and 5 months, and 1,222 of patients had 5 years of follow-up.

Patients who received TARGIT-IORT experienced a 5-year local recurrence rate of 3.3% (95% CI, 2.1 to 5.1) compared with 1.3% (95% CI, 0.7 to 2.5; P=0.042) in the EBRT arm.

However, among patients who received TARGIT-IORT at the time of lumpectomy, the rate of local recurrence was 2.1% (95% CI, 1.1 to 4.2) compared with 1.1% (95% CI, 0.5 to 2.5; P=0.31) in the EBRT arm.

In contrast, the postpathology cohort demonstrated a 5.4% (95% CI, 3.0 to 9.7) rate of local recurrence compared with 1.7% (95% CI, 0.6 to 4.9; P=0.56) in the EBRT arm.

Breast cancer–related death was similar among both arms with rates of 2.6% (95% CI, 1.5 to 4.3) and 1.9% (95% CI, 1.1 to 3.2; P=0.56) in the TARGIT-IORT and EBRT arms, respectively.

The overall mortality rate was 3.9% (95% CI, 2.7 to 5.8) in the TARGIT-IORT arm and 5.3% (95% 3.9 to 7.3; P=0.099) in the EBRT arm.

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However, non–breast cancer–related deaths were significantly less in the IORT arm, with a rate of 1.4% (95% CI, 0.8 to 2.5) compared with 3.5% (95% CI, 2.3 to 5.2; P=0.0086) in the EBRT arm.

The rate of adverse events was similar between both arms; however, grade 3/4 skin effects were reduced in the TARGIT-IORT arm. In addition, death associated with other cancers, as well as heart attacks and stroke occurred more frequently in the EBRT arm.