Accelerated Partial-Breast Irradiation Using 3D Conformal Radiation Therapy Causes More Adverse Events Compared With Whole-Breast Irradiation 

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The RAPID trial compared accelerated partial-breast irradiation using three-dimensional (3D) conformal external-beam radiation therapy vs whole-breast irradiation in women with invasive or in situ breast cancer ≤ 3 cm. As reported by Ivo A. ­Olivotto, MD, FRCPC, of the British Columbia Cancer Agency, and colleagues in the Journal of Clinical Oncology, interim cosmetic results from the trial show that adverse cosmesis at 3 years was significantly increased among patients treated with accelerated partial-breast irradiation compared with whole-breast irradiation as assessed by trained nurses, patients, or physicians.1 Although grade 3 or 4 toxicities were infrequent in both groups, grade 1 or 2 toxicities were more frequent with partial-breast irradiation.

Study Details

In this multicenter trial, 2,135 women aged greater than 40 years with invasive or in situ breast cancer ≥ 3 cm were randomly assigned after breast-conserving surgery to 3D conformal radiotherapy–based accelerated partial-breast irradiation (38.5 Gy in 10 fractions twice daily; n = 1,070) or whole-breast irradiation (42.5 Gy in 16 or 50 Gy in 25 daily fractions with or without boost irradiation; n = 1,065). The primary outcome was ipsilateral breast tumor recurrence. Secondary outcomes were cosmesis and toxicity. Adverse cosmesis was defined as a fair or poor global cosmetic score on trained nurse and patient assessments and on physician panel assessment using digital photographs. After a planned interim cosmetic analysis, the Data, Safety, and Monitoring Committee recommended release of results. There have been too few ipsilateral breast tumor recurrence events to trigger a primary efficacy analysis.

Patients in the whole-breast irradiation and accelerated partial-breast irradiation groups were well matched for age (≥ 50 years in 88% of both), cancer type (invasive in 81% and 82%), tumor size (≥ 1.5 cm in 38% and 39%), estrogen receptor status (positive in 88% and 91%), tumor grade (I in 40% and 42% and II in 41% and 40%), presence of lymphatic or vascular invasion (6% in both), receipt of chemotherapy (16% and 15% of patients with invasive cancers), and endocrine therapy (67% and 69%). At baseline, for the whole-breast vs partial-breast irradiation groups, 17% vs 19% of patients on nurse assessment and 22% vs 24% on patient assessment had adverse cosmesis (no significant differences between groups).  

Cosmesis Outcomes

Median follow-up was 36 months. The whole-breast irradiation dose was 42.5 Gy in 16 fractions for 82% of whole-breast irradiation patients, and 21% of whole-breast irradiation patients received boost irradiation. At 3 years, adverse cosmesis was increased among those treated with partial-breast irradiation compared with whole-breast irradiation as assessed by trained nurses (29% vs 17%, P < .001), by patients (26% vs 18%, P = .0022), and by physicians (35% vs 17%, P < .001). At 5 years, adverse cosmesis was also increased with accelerated partial-breast irradiation on nurse assessment (32% vs 13%, P < .001) and patient assessment (32% vs 22%, P = .034). There was no physician assessment at 5 years.

An analysis of nurse-assessed cosmesis at 3 years according to fractionation and boost radiation among whole-breast irradiation patients showed adverse cosmesis for 16% of patients receiving 42.5 Gy in 16 fractions vs 17% of those receiving 50 Gy in 25 fractions (P = .77) and in 17% of patients without a boost vs 16% of those who received a boost (P = .88).


Grade 3 toxicities were rare in both the partial-breast irradiation and whole-breast irradiation groups (1% vs 0%) and there were no grade 4 toxicities. Grade 3 toxicities in the accelerated partial-breast irradiation group consisted of telangiectasia, induration or fibrosis, breast pain, and fatty necrosis, with each observed in < 1% of patients. Overall, grade 1 or 2 toxicities were significantly more frequent among patients in the partial-breast irradiation group (P < .001). Telangiectasia (grade 1 or 2 in 17% vs 7%) and breast induration (50% vs 28%) were significantly more common with partial-breast irradiation (P < .001). Grade 1 breast pain was common (25% after whole-breast irradiation, 30% after partial-breast irradiation) and grade 2 to 3 breast pain was uncommon (0.5% and 1%). Fat necrosis was uncommon but was significantly more likely after partial-breast irradiation than whole-breast irradiation (3% vs 0.9%, P = .01). The magnitude of differences in toxicity between treatment groups at 5 years was similar to that at 3 years.

The authors noted that a number of ongoing trials will contribute additional level I evidence regarding the safety and efficacy of different approaches to accelerated partial-breast irradiation. They concluded:  “3D [conformal external-beam radiation therapy–based accelerated partial-breast irradiation] increased rates of adverse cosmesis and late radiation toxicity compared with standard whole-breast irradiation. Clinicians and patients are cautioned against the use of [this approach] outside the context of a controlled trial.” ■

Disclosure: The study authors reported no potential conflicts of interest.


1. Olivotto IA, Whelan TJ, Parpia S, et al: Interim cosmetic and toxicity results from RAPID: A randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. July 8, 2013 (early release online).