Standard versus reduced-dose chemoradiotherapy in anal cancer (PLATO-ACT4): short-term results of a phase 2 randomised controlled trial.

Cure rates are high, but treatment can result in substantial acute and long-term morbidity.

治愈率很高，但治疗可能导致显著的急性和长期的发病率。

We aimed to assess whether lower dose chemoradiotherapy maintains high local control rates in patients with early-stage disease, with the secondary aim of reducing toxicity.

我们旨在评估低剂量放化疗是否能在早期疾病患者中维持高局部控制率，次要目的是减少毒性。

Methods

ACT4 is a phase 2, prospective, multicentre, open-label, two-arm non-comparative, randomised, controlled trial, investigating reduced-dose intensity-modulated radiotherapy (rd-IMRT: 41·4 Gy in 23 fractions) in patients with early-stage anal cancer; T1-2 (≤4 cm) N0-NxM0.

ACT4是一项第2阶段、前瞻性、多中心、开放标签、两臂非比较性、随机对照试验，研究在早期肛门癌患者中使用降低剂量强度调制放射治疗（rd-IMRT：23次分割，总剂量41.4 Gy）；T1-2（≤4厘米）N0-NxM0。

Eligible patients were at least 16 years of age, with an Eastern Cooperative Oncology Group performance status of 0-1.

符合条件的患者年龄至少为16岁，且东部肿瘤协作组表现状态为0-1。

The primary outcome is 3-year loco-regional failure rates.

主要结果是3年局部区域失败率。

Patients were randomly assigned 1:2 (with stratification by T stage, N stage, gender, HIV status, and randomising site) to standard-dose IMRT (sd-IMRT: 50·4 Gy in 28 fractions) or rd-IMRT with concurrent mitomycin and capecitabine chemotherapy.

患者按1:2的比例随机分配（按T分期、N分期、性别、HIV状态和随机化地点进行分层），接受标准剂量的IMRT（sd-IMRT：28次分割，总剂量50.4 Gy）或rd-IMRT联合米托蒽醌和卡培他滨化疗。

Here, we report the pre-planned, modified intention-to-treatanalysis of secondary endpoints 6 months after treatment end-complete clinical response, compliance, patient-reported outcomes (EORTC QLQ-C30 and ANL27), and safety data.

在这里，我们报告了治疗结束6个月后预先计划的、修改后的意向治疗分析的次要终点，包括完全临床反应、依从性、患者报告的结果（EORTC QLQ-C30和ANL27）和安全性数据。

The trial is registered at the ISRCTN registry (ISRCTN88455282) and is ongoing but no longer recruiting.

该试验已在ISRCTN注册（ISRCTN88455282），目前正在进行中，但已停止招募。

Results

163 patients were recruited from 28 UK tertiary centres between April 24, 2017, and Dec 1, 2020. 160 patients were included in the primary analysis (sd-IMRT n=55; dr-IMRT n=105).

从2017年4月24日至2020年12月1日，共有163名患者从英国28个三级中心被招募。在主要分析中包括了160名患者（sd-IMRT n=55；dr-IMRT n=105）。

Data on ethnicity were not collected.

未收集种族数据。

The median patient age was 66 years (IQR 58-72 years); 117 (73%) were female and 43 (27%) male; and 129 (94%) of 138 evaluable samples were p16 positive.

患者的中位年龄为66岁（四分位数间距58-72岁）；117名（73%）为女性，43名（27%）为男性；在138个可评估样本中，129个（94%）p16阳性。

Complete clinical responses at 6 months were 87% (46 of 53) for sd-IMRT and 92% (89 of 97) for rd-IMRT.

6个月时完全临床反应率为sd-IMRT组的87%（53人中有46人），rd-IMRT组的92%（97人中有89人）。

Radiotherapy interruptions of 3 days or more occurred in 14 (26%) of 55 patients in sd-IMRT and 16 (15%) of 105 patients in rd-IMRT.

在sd-IMRT组中，有14名（26%）患者发生了3天或更长时间的放疗中断，而在rd-IMRT组中，有16名（15%）患者发生了类似中断。

Chemotherapy modifications occurred in 27 (49%) of 55 patients in sd-IMRT and 39 (37%) of 105 patients in rd-IMRT.

在55名接受sd-IMRT治疗的患者中，有27名（49%）发生了化疗方案的调整；而在105名接受rd-IMRT治疗的患者中，有39名（37%）发生了化疗方案的调整。

Grade 3 or worse acute toxicity was reported in 25 (46%) of 55 patients in sd-IMRT and 37 (35%) of 105 patients in rd-IMRT.

在sd-IMRT治疗的55名患者中，有25名（46%）报告了3级或更严重的急性毒性反应；而在rd-IMRT治疗的105名患者中，有37名（35%）报告了3级或更严重的急性毒性反应。

The most common grade 3 or worse adverse events were radiation dermatitis (seven [13%] of 55 in sd-IMRT and ten [10%] of 105 in rd-IMRT), and diarrhoea (four [7%] of 55 in sd-IMRT and nine [9%] of 105 in rd-IMRT).

最常见的3级或更严重的不良事件是放射性皮炎（sd-IMRT组55人中有7人[13%]，rd-IMRT组105人中有10人[10%]），以及腹泻（sd-IMRT组55人中有4人[7%]，rd-IMRT组105人中有9人[9%]）。

Serious adverse events occurred in eight (15%) of 55 patients in sd-IMRT and ten (10%) of 105 patients in rd-IMRT.

严重不良事件发生在sd-IMRT组的55名患者中的8名（15%）和rd-IMRT组的105名患者中的10名（10%）。

Patient-reported outcomes for most issues deteriorated at the end of treatment and resolved to baseline by 6 weeks in both groups.

在治疗结束时，两组患者的大多数问题的患者报告结果恶化，并在6周内恢复到基线水平。

Poorer sexual function for men and women was observed at 6 months following sd-IMRT.

在sd-IMRT治疗后6个月，观察到男性和女性的性功能较差。

interpretation

Good 6-month complete clinical responses rates were seen in both groups.

两组均显示出良好的6个月完全临床反应率。

Early results suggest rd-IMRT is well tolerated with oncological outcomes maintained. 3-year locoregional failure rates are awaited.

初步结果显示，rd-IMRT耐受性良好，肿瘤学结果得以保持。期待3年局部区域失败率数据。

funding

Cancer Research UK and Stand Up to Cancer.

癌症研究英国和抗击癌症。