#VisualAbstract: Targeted intraoperative radiotherapy associated with similar outcomes as whole breast post-operative radiotherapy for breast cancer

1. Targeted intraoperative radiotherapy for breast cancer has comparable long-term cancer-related outcomes as whole breast post-operative radiotherapy, and lower mortality from other causes.

Evidence Rating Level: 1 (Excellent)

Breast cancer is one of the most common cancers worldwide, with 2 million diagnoses and 626 000 deaths in 2018 alone. The treatment for breast cancer consists usually of breast conserving surgery, known as a lumpectomy, postoperative whole breast external beam radiotherapy (ERBT). However, a new radiotherapy treatment was developed known as immediate targeted intraoperative radiotherapy (TARGIT-IORT): This is a single treatment performed immediately following the lumpectomy, while the patient is still under anesthesia. Furthermore, TARGIT-IORT is done only on target tissues to avoid affecting nearby healthy tissues and organs. In this randomized controlled trial, researchers sought to determine whether TARGIT-IORT was non-inferior to EBRT, with the primary outcomes being local recurrence of cancer after five years, as well as long-term survival. The study population consisted of women over 45 years of age, 1140 in the TARGIT-IORT group and 1158 in the ERBT group. The TARGIT-IORT group was risk adapted, meaning that if certain risks/conditions were present following the lumpectomy and TARGIT-IORT treatment, ERBT would then be performed. 80% of TARGIT-IORT patients did not receive additional ERBT. The results found 24 local recurrences in the TARGIT-IORT group and 11 in the ERBT group, which translates to a 2.11% and 0.95% recurrence rate respectively (difference is 1.16%, 90% CI 0.32-1.99). This falls under the 2.5% threshold for non-inferiority, indicating that TARGIT-IORT is not inferior to ERBT. As well, there were fewer deaths in the TARGIT-IORT group, 42 compared to 56 (3.7% versus 4.8%). For long term follow-up (the interquartile range being 7.0-10.6 years), there was no significant difference in overall survival (hazards ratio 0.82, 95% CI 0.63-1.05, p = 0.13) or breast cancer mortality (HR 1.12, 95% CI 0.78-1.60, p = 0.54). Other cause mortality was significantly lower for the TARGIT-IORT group (HR 0.59, 95% CI 0.40-0.86, p = 0.005). Overall, this study demonstrated that risk adapted immediate TARGIT-IORT has comparable long-term cancer-related outcomes as ERBT, with lower non breast-cancer related mortality. This has implications for helping physicians and patients in making informed decisions on their preferred radiotherapy treatment.

Click to read the study in BMJ

Correction 9/4/2020: Previous version of the VA said that TARGIT-IORT was non-inferior to EBRT, when the conclusion of the study is that it is an effective alternative; the conclusion sentence has been updated.

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