Short Course of Radiotherapy With Concurrent Radiation Boost for High-Risk, Early-Stage Breast Cancer

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A 3-week course of radiation therapy including a concomitant boost of radiation to the surgical site appears to be as safe and effective as 4 to 6 weeks of radiation therapy given with a sequential boost of radiation for patients with early-stage breast cancer who have a high risk of recurrence. These findings were from the phase III NRG/RTOG 1005 trial presented at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.1

Frank A. Vicini, MD, FASTRO

Frank A. Vicini, MD, FASTRO

“Adding a radiation boost reduces the likelihood of tumor recurrence in the breast by 20% to 30%, but delivering that boost after hypofractionated radiation therapy adds another week to treatment This can be challenging for patients who need to take time from work or travel long distances for treatment. This approach cuts treatment time for these patients in half,” said radiation oncologist Frank A. Vicini, MD, FASTRO, National -Director of Research and Breast Care Services at GenesisCare. “Now, the comfort level is there [for oncologists] to say to higher-risk patients, ‘I can offer you this option, and it works just as well’ [as longer-course treatment].”

These results may help guide treatment decisions for patients who undergo breast-conserving therapy but have an increased risk of recurrence due to larger tumor size, higher tumor grade, older age, receipt of presurgical therapy, or estrogen receptor–negative status. Randomized studies have shown that a 3-week course of radiation therapy is as safe and effective as conventional 6-week therapy for patients with a low risk of ipsilateral breast recurrence. However, patients considered at higher risk for recurrence are typically treated with an additional boost of sequential radiation to the surgical site, adding another 1 to 2 weeks of treatment.

Study Details

NRG/RTOG 1005 was designed to compare hypofractionated whole-breast irradiation with a concomitant boost vs conventionally fractionated or hypofractionated whole-breast irradiation followed by a sequential boost, with the aim of demonstrating noninferiority using the primary endpoint of ipsilateral breast recurrence. Secondary endpoints included noninferiority of cosmetic outcomes and feasibility of delivering whole-breast irradiation with CT-based conformal intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) methods in a multi-institutional setting following lumpectomy in patients with early-stage breast cancer.

The study was conducted at 276 different sites across the United States, Canada, Switzerland, Israel, Hong Kong, Japan, Republic of Korea, and Singapore. A total of 2,262 patients with high-risk stage 0, 1 and 2 breast cancer who underwent lumpectomy were randomly assigned 1:1 to arm 1 (conventionally fractionated or hypofractionated whole-breast irradiation plus a sequential boost; n = 1,124) or arm 2 (hypofractionation with whole-breast irradiation plus a concurrent boost; n = 1,138). For arm 1, radiation therapy was delivered over 4 to 5 weeks, with the sequential boost delivered over 6 to 7 days. For arm 2, radiation therapy was delivered over 3 weeks, with a concurrent boost. Stratification factors were age (< 50 vs ≥ 50), chemotherapy (yes or no), histologic grade (1, 2, vs 3), and estrogen receptor status (positive or negative).

At baseline, median patient age was approximately 55, with about 35% younger than 50. About 34% had stage II disease. A total of 30% were estrogen receptor–negative, and 60% had chemotherapy prior to radiation therapy.

Key Results

For the primary endpoint of ipsilateral breast recurrence, hypofractionated whole-breast irradiation with a concurrent boost was found to be noninferior to whole-breast irradiation plus a sequential boost. At a median follow-up of 7.4 years, there were 56 recurrences: 2.1% in arm 1 (sequential boost) and 2.6% in arm 2 (concurrent boost). The 5-year recurrence rate was 1.9% with the concurrent boost regimen compared with 1% with the sequential boost.

Severe adverse events were uncommon in both study arms. The rate of treatment-related adverse events of grade 3 or higher was comparable, at 3.3% in arm 1 and 3.5% in arm 2.

The Breast Cancer Treatment Outcome Scale (BCTOS) was used to determine cosmesis. Cosmetic outcomes were rated noninferior for the two arms by both patients and physicians. Cosmetic outcomes were rated as “excellent” or “good” by 84% of the concurrent boost arm and 86% of the sequential boost arm.

The study showed that use of target volume–based radiation planning for 3D-CRT and IMRT whole-breast irradiation assessed by dose volume analysis was feasible and resulted in low toxicity in the treatment arms, regardless of fractionation or boost delivery.

The next issues to be addressed include whether the patient population that may benefit from the shortened course of whole-breast irradiation plus concurrent boost can be expanded to include those with positive lymph nodes, as well as whether the treatment time can be shortened even more. For example, Dr. -Vicini noted that researchers in the United Kingdom are looking at a 1-week course of radiation therapy for low-risk patients.

Additional Comment

Lori J. Pierce, MD, FASTRO, FASCO, served as the discussant for Dr. Vicini’s paper. Dr. Pierce looked back to 2011, when there was a lack of consensus regarding boosts with hypofractionated whole-breast irradiation. “This trial is important for confirming noninferiority of hypofractionation with a concurrent boost when compared with conventional

Lori J. Pierce, MD, FASTRO, FASCO

Lori J. Pierce, MD, FASTRO, FASCO

treatment using a sequential boost. This was the right trial at the right time,” Dr. Pierce said. She noted, however, that only treatment approaches that do not increase dose to nearby normal tissues should be utilized with planning a concurrent boost, similar to approaches currently used in the planning of a sequential boost. She also noted the importance of incorporating current dose volume constraints in the planning processes that reflect the advances made in radiation treatment planning since the initiation of RTOG 1005. 

DISCLOSURE: Dr. Vicini reported no conflicts of interest. Dr. Pierce receives royalties from UptoDate and PFS Genomics; and has uncompensated relationships with Bristol Myers Squibb and Exact Sciences.


1. Vicini FA, Winter K, Freedman GM, et al: NRG RTOG 1005: A phase III trial of hypofractionated whole breast irradiation with concurrent boost vs. conventional whole breast irradiation plus sequential boost following lumpectomy for high risk early-stage breast cancer. 2022 ASTRO Annual Meeting. Abstract 1. Presented October 24, 2022.