Introduction

The phase 3 FAST-Forward trial reported outcomes for 26 and 27 Gy schedules delivered in 5 fractions over 1 week versus 40 Gy in 15 fractions over 3 weeks in 4000 patients. We discuss concerns raised by the radiotherapy community in relation to implementing this schedule.

Ipsilateral Breast Tumour Relapse (IBTR)

Published estimated 5-year IBTR with 95% CI after 40 Gy in 15 fractions was 2.1% (95% CI 1.4–3.1), 1.7% (1.2–1.6) after 27 Gy and 1.4% (0.2–2.2) after 26 Gy, emphatically showing non-inferiority of the 5-fraction regimens. Subgroup analyses comparing IBTR in 26 Gy versus 40 Gy show no evidence of differential effect regarding age, grade, pathological tumour size, nodal status, tumour bed boost, adjuvant chemotherapy, HER2 status and triple negative status. The number of events in these analyses is small and results should be interpreted with caution. There was only 1 IBTR event post-mastectomy.

Normal tissue effects

The 26 Gy schedule, on the basis of similar NTE to 40 Gy in 15 fractions, is the recommended regimen for clinical implementation. There is a low absolute rate of moderate/marked NTE, these are predominantly moderate not severe change. Subgroup analyses comparing clinician-assessed moderate or marked adverse effect for 26 Gy versus 40 Gy show no evidence of differential effects according to age, breast size, surgical deficit, tumour bed boost, or adjuvant chemotherapy.

Radiobiological considerations

The design of the FAST-Forward trial does not control for time-related effects, and the ability to interpret clinical outcomes in terms of underlying biology is limited. There could conceivably be a time-effect for tumour control. A slight reduction in α/β estimate for the late normal tissue effects of test regimens might be a chance effect, but if real could reflect fewer consequential late effects due to lower rates of moist desquamation.

Conclusion

The 26 Gy 5-fraction daily regimen for breast radiotherapy can be implemented now.

中文翻译：

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乳腺癌五次放射治疗：快速推进实施

介绍

3 期 FAST-Forward 试验报告了 26 和 27 Gy 计划在 1 周内分 5 次给药的结果，而 4000 Gy 计划在 3 周内分 15 次给药，4000 名患者。我们讨论了放射治疗界提出的与实施该时间表有关的问题。

同侧乳房肿瘤复发 (IBTR)

已发表的 5 年 IBTR 估计值，15 次 40 Gy 后 95% CI 为 2.1%（95% CI 1.4-3.1），27 Gy 后为 1.7%（1.2-1.6），26 Gy 后为 1.4%（0.2-2.2），强调显示 5 部分方案的非劣效性。比较 26 Gy 和 40 Gy IBTR 的亚组分析显示，没有证据表明在年龄、分级、病理性肿瘤大小、淋巴结状态、肿瘤床加强、辅助化疗、HER2 状态和三阴性状态方面存在差异。这些分析中的事件数量很少，应谨慎解释结果。乳房切除术后仅有 1 次 IBTR 事件。

正常组织效应

26 Gy 方案基于与 40 Gy 相似的 15 次 NTE，是临床实施的推荐方案。中度/显着 NTE 的绝对率较低，主要是中度而非重度变化。比较临床医生评估的 26 Gy 和 40 Gy 的中度或显着不良反应的亚组分析显示，没有证据表明年龄、乳房大小、手术缺陷、肿瘤床增加或辅助化疗存在不同的影响。

放射生物学考虑

FAST-Forward 试验的设计不控制与时间相关的效应，从基础生物学角度解释临床结果的能力有限。可以想象，肿瘤控制可能存在时间效应。测试方案晚期正常组织效应的 α/β 估计值略有下降可能是一种偶然效应，但如果真实，则可以反映较少的后续效应，因为潮湿脱屑率较低。

结论

现在可以实施 26 Gy 每天 5 次乳房放疗方案。