Background

Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1–2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline.

Methods

In this prospective registry study (RAPCHEM, BOOG 2010–03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1–2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed.

Findings

838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4–3·4). The 5-year locoregional recurrence rate was 2·1% (0·9–4·3) in the low-risk group, 2·2% (1·0–4·1) in the intermediate-risk group, and 2·3% (0·8–5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8–5·3) for the low-risk group, 1·0% (0·2–3·4) for the intermediate-risk group, and 1·4% (0·3–4·5) for the high-risk group.

Interpretation

In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1–2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline.

Funding

Dutch Cancer Society.

Translation

For the Dutch translation of the abstract see Supplementary Materials section.

中文翻译：

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cT1-2N1 乳腺癌初次化疗后放疗的降级（RAPCHEM；BOOG 2010-03）：荷兰一项前瞻性注册研究的 5 年随访结果

背景

乳腺癌的初次化疗给辅助局部放疗带来了困境，因为局部放疗指南最初是基于初次手术的病理结果。我们的目的是根据预先确定的、基于共识的研究指南，评估接受初次化疗的 cT1-2N1 乳腺癌患者降级局部放疗的肿瘤学安全性。

方法

在这项前瞻性登记研究中（RAPCHEM，BOOG 2010-03），2011 年 1 月 1 日至 2015 年 1 月 1 日期间，患有 cT1-2N1 乳腺癌（一到三名可疑病例）的患者转诊至荷兰 17 个参与放射肿瘤中心之一该研究纳入了初次化疗前影像学检查中的淋巴结（其中至少一个已得到病理学证实）以及接受初次化疗和乳房和腋窝手术治疗的患者。研究指南包括三个局部复发风险组，以及相应的局部放疗建议：低风险组不进行胸壁放疗且不进行区域放疗，中风险组仅进行局部放疗，高风险组进行局部放疗。团体。放射治疗包括 25 个 2 Gy 的生物学等效剂量，有或没有加强。研究期间，荷兰普遍应用的放射治疗技术是正向计划或逆向计划调强放射治疗。考虑到对研究指南的遵守情况，以局部复发率作为主要终点，对 5 年随访进行了评估。我们假设5年局部复发率低于4%（上限95% CI 7·8%）。该研究已在 ClinicalTrials.gov 注册（NCT01279304）并已完成。

发现

838 名患者符合 5 年随访分析的条件：低风险组 291 名，中风险组 370 名，高风险组 177 名。所有患者的 5 年局部复发率为 2·2%（95% CI 1·4–3·4）。低危组5年局部复发率为2·1%（0·9～4·3），中危组为2·2%（1·0～4·1），2高风险组中·3% (0·8–5·5)。如果遵循研究指南，低风险组的局部区域复发率为 2·3% (0·8–5·3)，中风险组的局部区域复发率为 1·0% (0·2–3·4)组，高危组为 1·4% (0·3–4·5)。

解释

在这项研究中，5年局部区域复发率低于4%，这支持了我们的假设，即在选择接受原发性治疗的cT1-2N1乳腺癌患者中，根据局部区域复发风险逐步降低局部区域放疗在肿瘤学上是安全的。根据这一预先确定的、基于共识的研究指南进行化疗。

资金

荷兰癌症协会。

翻译

有关摘要的荷兰语翻译，请参阅补充材料部分。