Lightowlers S V, Machin A, Woitek R, Provenzano E, Allajbeu I, Al Sarakbi W, Demiris N, Forouhi P, Gilbert F J, Kirby A M, Towns C, Somaiah N, Coles C E
Department of Oncology, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Cambridge Clinical Trials Unit-Cancer Theme, University of Cambridge, Cambridge, UK.
Clin Oncol (R Coll Radiol). 2025 Jan;37:103669. doi: 10.1016/j.clon.2024.103669. Epub 2024 Oct 30.
To establish the safety and feasibility of delivering neoadjuvant radiotherapy and endocrine therapy for oestrogen receptor-positive breast cancers with palpable size 20mm or greater, for which radiotherapy might facilitate more conservative surgery.
A single-arm feasibility study was conducted. Patients received whole breast radiotherapy with or without radiotherapy to nodal areas. Dose/fractionation was 40Gy in 15 fractions over 3 weeks, with or without either a simultaneous integrated boost to 48Gy or sequential boost to the tumour bed. This was followed by endocrine treatment for 20 weeks, then surgery. The primary endpoint of the study was the proportion of patients successfully completing neoadjuvant radiotherapy and endocrine treatment followed by breast surgery. Response and toxicity endpoints including mastectomy rate, peri/postoperative complications, and pathological response were also evaluated. The primary analysis is descriptive. The study regimen would be considered feasible if more than 70% of patients completed treatment, while it might not be considered feasible if less than 50% did so. With a one-sided 5% significance level and 80% power, a maximum of 43 patients would be required to detect a rate of ≤50% vs ≥70%.
14 patients were recruited out of the planned 43. Due to slow recruitment, particularly during the COVID-19 pandemic, the decision was made to stop the trial in October 2021. One registered patient was found to be ineligible before starting treatment. 13/13 patients (100%, 90% CI: 75.3%, 100%) who received any trial treatment successfully completed all trial treatments. The lower bound of the Clopper-Pearson (exact) 90% confidence interval was 79%, indicating that the primary endpoint would have been met if the planned recruitment had been achieved. 3/13 patients underwent mastectomy. 7/13 had more conservative surgery than had been planned at baseline. 4/13 patients experienced any peri/postoperative complication. The only acute radiotherapy toxicities reported were grade 1/2 dermatitis and grade 1 fatigue. Long-term breast outcomes were clinician assessed as none/mild at all timepoints in 12/13 patients. All tumours showed evidence of some pathological response to treatment, but none had a pathological complete response.
This treatment schedule is likely feasible. It is difficult to draw strong conclusions on safety/toxicity given the small numbers, but these seem in keeping with other recent reports of neoadjuvant breast radiotherapy.
对于可触及大小为20mm或更大的雌激素受体阳性乳腺癌，确立新辅助放疗及内分泌治疗的安全性与可行性，放疗可能有助于实现更保守的手术。
开展了一项单臂可行性研究。患者接受全乳放疗，部分患者还接受区域淋巴结放疗。剂量/分割方案为3周内分15次给予40Gy，可同时推量至48Gy或序贯推量至瘤床。之后进行20周的内分泌治疗，然后手术。研究的主要终点是成功完成新辅助放疗、内分泌治疗并接受乳腺手术的患者比例。还评估了反应和毒性终点，包括乳房切除术率、围手术期/术后并发症及病理反应。主要分析为描述性分析。如果超过70%的患者完成治疗，则该研究方案被认为可行；如果低于50%，则可能不可行。在单侧5%的显著性水平和80%的检验效能下，最多需要纳入43例患者以检测≤50%与≥70%的完成率。
计划纳入43例患者，实际招募了14例。由于入组缓慢，尤其是在新冠疫情期间，于2021年10月决定停止试验。1例已登记患者在开始治疗前被发现不符合入组标准。13例接受任何试验治疗的患者均成功完成了所有试验治疗（100%，90%CI：75.3%，100%）。Clopper-Pearson（精确）90%置信区间的下限为79%，这表明如果达到计划入组人数，主要终点本可达成。13例患者中有3例行乳房切除术。13例中有7例接受了比基线计划更保守的手术。13例患者中有4例出现围手术期/术后并发症。报告的唯一急性放疗毒性为1/2级皮炎和1级疲劳。在所有时间点，13例患者中有12例经临床医生评估长期乳房结局为无/轻度。所有肿瘤均显示出对治疗有一定病理反应的证据，但无一例达到病理完全缓解。
该治疗方案可能可行。鉴于样本量小，难以就安全性/毒性得出有力结论，但这些结果似乎与近期新辅助乳腺放疗的其他报告一致。
