RAPID

Background

Phase III, randomized non-inferiority trial. 2135 patients with early breast cancer (T1-2 N0, age ≥40) after BCS with clear margins (≥2mm), treated at 33 centers. Accelerated partial breast irradiation (APBI) using 3D conformal RT (38.5Gy in 10 fractions BID over 5–8 days) vs standard whole-breast irradiation (42.5Gy/16f or 50Gy/25f). RAPID is the largest APBI non-inferiority trial using an accelerated BID regimen.

Interventions and follow up

Arm A: APBI 38.5Gy in 10 fractions BID (twice-daily) over 5–8 days (3D conformal RT to tumor bed + 1cm margin)
Arm B: Standard whole-breast irradiation (42.5Gy/16f over 22 days or 50Gy/25f)
Primary endpoint: Ipsilateral breast tumor recurrence (IBTR) at 8 years (non-inferiority)
mFollow up: 8.6 years

Results

IBTR (8-yr): 3.0% vs 2.8% (APBI vs WBI), HR 1.27, 95% CI 0.84–1.91 — non-inferior
Breast cosmesis (poor/fair, 3-yr): 35.3% vs 17.0% (APBI vs WBI), P<.001 — significantly worse with APBI
OS: Similar between arms

Adverse events

Cosmesis: Physician-assessed poor/fair cosmesis 35.3% (APBI) vs 17.0% (WBI) at 3 years (P<.001).
Late tissue effects: Telangiectasia higher with APBI (17.0% vs 5.0%); fat necrosis 5.1% vs 1.0%.
Other: Breast pain similar; contralateral breast cancer similar.

Conclusions

APBI using 38.5Gy in 10 BID fractions was non-inferior to WBI for IBTR at 8 years. However, cosmetic outcomes were significantly worse with APBI — 35% had poor or fair cosmesis vs 17% with WBI. The cosmesis finding substantially limits the clinical utility of this APBI regimen.

Key Limitations

The primary non-inferiority finding (IBTR) was met, but the dramatic cosmetic deficit (35% poor/fair vs 17%) is a major clinical concern that may negate the convenience benefit of APBI. Twice-daily fractions require patients to return twice per day for 5–8 days. The regimen (38.5Gy BID) differs substantially from IMPORT LOW (40Gy/15f once-daily) — different APBI techniques yield different toxicity profiles. Patient selection (pN0, T1-2) limits applicability to higher-risk patients.

Clinical Context

RAPID demonstrates that not all APBI schedules are equivalent — the BID 38.5Gy regimen has inferior cosmesis despite non-inferior IBTR. In contrast, IMPORT LOW (once-daily 40Gy/15f) showed non-inferior IBTR without excess cosmetic toxicity. ASTRO guidelines conditionally support APBI in selected low-risk patients using appropriate techniques — the RAPID BID regimen is generally not preferred over IMPORT LOW-style once-daily APBI. ESMO-MCBS: not applicable (RT trial).

References