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TOPLINE:

Concurrent radiation dose escalation to the lumpectomy cavity during whole-breast irradiation (WBI) demonstrated noninferior ipsilateral breast recurrence (IBR) compared with sequential boost in patients with high-risk early-stage breast cancer, while reducing overall treatment time from more than 4 weeks to 3 weeks. At 7-year follow-up, IBR was 2.2% with sequential boost and 2.6% with concurrent boost, with no differences in toxicity or cosmetic outcomes between approaches.

METHODOLOGY:

• Traditional boost delivery extends treatment duration by 1-1.5 weeks and potentially causes poorer cosmesis from excess soft tissue fibrosis, representing negative effects that persist even as WBI has transitioned from conventional fractionation over 5 weeks to moderately hypofractionated schedules over approximately 3 weeks.
• Researchers conducted a randomized, unblinded, phase 3 noninferiority trial (NRG/RTOG 1005) across 278 sites in North America and six other countries, enrolling 2354 patients with higher-risk early-stage breast cancer between May 24, 2011, and June 30, 2014, with 2255 eligible for analysis.
• Patients were randomly assigned 1:1 to receive either sequential boost of 12 Gy in six fractions or 14 Gy in seven fractions after WBI of 50 Gy in 25 fractions or 42.7 Gy in 16 fractions (sequential arm, n = 1118) or concurrent boost of 8 Gy in 15 fractions of 0.53 Gy per day with WBI of 40 Gy in 15 fractions for a cumulative total dose of 48.0 Gy in 15 fractions of 3.2 Gy (concurrent arm, n = 1137), using three-dimensional conformal radiation therapy or intensity-modulated radiation therapy.
• Eligible participants were female patients aged ≥ 18 years with pathologic stage I and II breast cancer who underwent lumpectomy and axillary surgical staging, meeting high-risk criteria including age younger than 50 years, positive axillary nodes, lymphovascular space invasion, close or positive resection margins, negative hormone receptors, grade 3 histology, Oncotype recurrence score > 25, prior neoadjuvant systemic therapy, or nuclear grade 3 ductal carcinoma in situ in patients younger than 50 years.
• Analysis used cause-specific hazards regression for the primary endpoint of IBR, with noninferiority defined as a hazard ratio (HR) upper limit on the 90% CI of 2.12, requiring 2312 patients to provide 80% power, with the median follow-up of 7.3 years.
• Secondary endpoints included overall survival, disease-free survival, distant disease-free survival, regional nodal recurrence, adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, and patient-reported cosmetic outcomes using the validated Breast Cancer Treatment Outcome Scale (BCTOS). Physician cosmetic assessment and centrally reviewed digital photographs were collected at baseline, 1 year, and 3 years after radiation therapy.

TAKEAWAY:

• At 7-year follow-up, IBR rates were 2.2% in the sequential arm and 2.6% in the concurrent arm, meeting the noninferiority criterion (HR, 1.31; 90% CI, 0.84-2.04; P = .037), with the upper bound less than the prespecified noninferiority margin of 2.12.
• Treatment-related grade 3-4 adverse events were uncommon and similar between arms, with 3.3% in the sequential arm and 3.5% in the concurrent arm (P = .81), with no grade 5 events reported and no significant differences in radiation dermatitis, fatigue, or breast pain.
• Patient-reported cosmetic outcomes using BCTOS showed noninferiority for the concurrent arm, with mean change scores from baseline to 3 years of 0.16 for sequential and 0.18 for concurrent boost, meeting the noninferiority threshold of < 0.4 standard deviation.
• No significant differences were observed between treatment arms for regional nodal recurrence, disease-free survival, distant disease-free survival, or overall survival, with 7-year overall survival of 93.5% for sequential and 93.6% for concurrent arms.

IN PRACTICE:

“Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time,” the authors of the study wrote.

SOURCE:

This study was led by Frank A. Vicini, MD, Michigan Healthcare Professionals Farmington, Farmington Hills, Michigan, and Gary M. Freedman, MD, University of Pennsylvania/Abramson Cancer Center, Philadelphia. It was published online on May 11 in Journal of Clinical Oncology.

LIMITATIONS:

According to the authors, the trial had limitations including its nonblinded randomized design, which may introduce bias in outcome assessment. The study excluded patients receiving regional nodal irradiation and included few cases of ductal carcinoma in situ, limiting generalizability to these populations. The observed IBR incidence was much lower than initially expected, necessitating a statistical redesign while blinded to treatment effects to allow timely reporting, though this maintained statistical integrity through independent review and National Cancer Institute approval. The applicability of concurrent boost delivery may not extend to 1-week WBI schedules or proton therapy, as these approaches were not evaluated in this trial. The larger boost target volumes used in this study, averaging 17.3% of breast volume compared with 1.5% in other trials, may have limited comparisons across studies, though this did not result in worse outcomes and may have allowed treatment of patients with larger surgical resections.

DISCLOSURES:

This study received support from the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), and U24CA180803 (IROC). Vicini disclosed being employedemployment with 21st Century Oncology and MHP Radiation Oncology Institute; consulting or advisory roles with ImpediMed, Prelude Therapeutics, and Accuray; and receiving travel, accommodations, and expenses from PreludeDx. Freedman disclosed having no relevant conflicts of interest. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.