Accelerated Partial-breast Irradiation Using 3D Conformal Radiation Therapy Causes More Adverse Events Compared with Whole-breast Irradiation
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, and physicians. 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%, invasive cancers only), and endocrine therapy (67% and 69%). At baseline, for the whole-breast vs partial-breast irradiation groups, 17.0% vs 18.9% of patients on nurse assessment and 21.6% vs 23.8% 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 16.5%, P < .001), by patients (25.8% vs 18.1%, P = .0022), and by physicians (35.1% vs 16.6%, P < .001). At 5 years, adverse cosmesis was also increased with accelerated partial-breast irradiation on nurse assessment (32% vs 13.4%, P < .001) and patient assessment (32.4% vs 21.5%, 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 16.3% of patients receiving 42.5 Gy in 16 fractions vs 17.3% of those receiving 50 Gy in 25 fractions (P = .77) and in 16.7% of patients without a boost vs 15.5% of those who received a boost (P = .88).
Toxicities
Grade 3 toxicities were rare in both the partial-breast irradiation and whole-breast irradiation groups (1.4% 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 1.2%). 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.”
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