By Frank Vicini, MD
Radiology Today
Vol. 20 No. 5 P. 5
Physicians and women seeking reassurance that opting for accelerated partial breast irradiation (APBI) over whole breast irradiation (WBI) is an acceptable decision can now benefit from the results of a randomized phase 3 trial presented at the 2018 San Antonio Breast Cancer Symposium, which confirmed APBI can serve as a viable alternative.
For the past 50 years or so, lumpectomy paired with WBI has served as the standard of care for breast-conserving therapy. More recently, the attractiveness of APBI has grown for some candidates as emphasis is increasingly placed on efforts to reduce treatment time for patients, improve quality of life, reduce exposure to toxicities, and make breast conservation more accessible for women. Furthermore, advancements in screening and public awareness have resulted in the majority of US breast cancer patients being diagnosed at early stages, meaning more women than ever before must make treatment decisions about breast-conserving therapy. These trends have fostered a desire to better understand how WBI and APBI stack up against each other, and they’ve served as motivation behind this latest trial.
The Trial
To compare outcomes associated with APBI vs WBI, we set out to conduct one of the largest trials with the longest follow-up on the topic designed to see whether the two techniques are equivalent in controlling for ipsilateral breast tumor recurrence (IBTR) in women who desire breast conservation surgery. The trial randomly assigned more than 4,000 women with stage 0, 1, or 2 breast cancer to receive either WBI or APBI with a median follow-up time of just over 10 years. The population was stratified by disease stage, menopausal status, hormone receptor status, and intent to receive chemotherapy. IBTR—both invasive and ductal carcinoma in situ (DCIS)—was the primary endpoint, with secondary endpoints of distant disease-free interval, recurrence-free interval, and overall survival.
Statistically, the trial narrowly missed showing that the two modalities are equivalent. When considering the primary endpoint, the results were marginally outside of the range required to show equivalency, falling 0.08 outside of the upper limit of the hazard ratio confidence interval. However, when looking at the 10-year mark, the absolute difference between APBI and WBI was only 0.7%. That is, admittedly, a remarkable result. Furthermore, when looking at overall survival, disease-free survival, metastases-free survival, and the other endpoints, none of them were statistically significantly different between the two arms of the study. Also of note, differences between the two modalities were very low for grade 3 toxicity and grade 4 toxicity, as well as the rate of second cancers.
Although the trial didn’t prove absolute equivalence, the differences are incredibly small. And there are essentially no differences in survival or metastases. Ultimately, these results build upon the existing body of evidence and serve to reinforce the idea that for many women—probably the majority—APBI is an option for providing good local control of the breast and reducing overall treatment time.
Clinical Implications
The implications of the study are far reaching and could have a tremendous impact on patients and their quality of life. The negative side effects of traditional radiation therapy are well known and include daily hospital trips for treatments that typically occur five days per week over the course of three to six weeks. Additionally, WBI has a larger field and may potentially expose healthy tissue to radiation. With APBI, patients benefit from an abbreviated and more accessible treatment schedule that only lasts five to eight days and from targeted treatment that reduces overall radiation exposure. And, with these trial results, physicians can now feel validated in their decision to recommend the treatment for their patients who quality for APBI.
When considering who the best candidates are for APBI, ASTRO guidelines to identify optimal patients are recommended. The guidelines were updated in 2016 to indicate that younger, early-stage breast cancer patients and those with DCIS may be suitable for this treatment option. Looking to the future, we hope to expand upon the trial with additional insights, such as the cosmetic and quality of life impacts that come from opting for APBI over WBI. With these insights, we could further the field’s understanding of how the modalities impact women from a more holistic viewpoint that looks beyond overall efficacy and survival rates.
It is imperative that clinicians in the field have access to modern information about breast conservation treatment options that can improve access to care, combat overtreatment, reduce the burden of treatment and health care costs, and improve quality of life. Physicians and patients alike have waited a long time for these results, which deliver an affirming message regarding the viability of APBI as a treatment option.
— Frank Vicini, MD, is the principal investigator at MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Michigan, and the lead researcher of NSABP B-39/RTOG 0413 (NRG Oncology): A Randomized Phase III Study of Conventional Whole Breast Irradiation (WBI) Versus Partial Breast Irradiation (PBI) for Women With Stage 0, I, or II Breast Cancer.