Dapper Hendrik, Fleischmann Maximilian, Tselis Nikolaos, Diefenhardt Markus, Hofheinz Ralf-Dieter, Weiß Christian, Grabenbauer Gerhard G, Merten Ricarda, Grosu Anca-Ligia, Kirste Simon, Rieken Stefan, Claßen Johannes, Langer Christian, Kuhnt Thomas, Schmidberger Heinz, Ghadimi Michael, Giordano Frank, Nestle Ursula, Koerber Stefan A, Bock Felix, Geiger Matthias, Polat Bülent, Bruns Christiane J, Dieplinger Georg, Popp Felix, Zander Thomas, Brunner Thomas, Tribius Silke, Arnold Dirk, Wurschi Georg, Piso Pompiliu, Friede Tim, Hörner-Rieber Juliane, Gkika Eleni, Rödel Claus, Fokas Emmanouil
Department of Radiation Oncology, Cyberknife and Radiation Therapy, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University, Frankfurt, Germany.
Clin Transl Radiat Oncol. 2025 Apr 13;53:100958. doi: 10.1016/j.ctro.2025.100958. eCollection 2025 Jul.
Rectal cancer disproportionately affects the elderly population, with more than half of cases diagnosed in individuals aged 70 years or older. Frail patients in this group often face significant challenges tolerating the standard treatment of total mesorectal excision (TME), due to elevated risks of surgical complications and perioperative morbidity. Advances in radiotherapy techniques offer a viable alternative, providing effective tumor control while minimizing treatment-related toxicity. Recent clinical trials, including OPERA and MORPEUS, have demonstrated that dose-escalated radiotherapy, which integrates external beam (chemo)radiotherapy (EBRT) with high-dose-rate endorectal brachytherapy (HDR-BT) or contact X-ray brachytherapy (CXB), can achieve high clinical response rates and facilitate organ preservation in younger, healthier patient cohorts. Building on these findings, the ACO/ARO/AIO-22 study seeks to adapt these innovative approaches to meet the needs of elderly and frail patients with rectal cancer.
METHODS/DESIGN: The ACO/ARO/AIO-22 trial is a prospective multicentre controlled trial. Elderly (age ≥70 years) and/or frail patients with non-metastatic rectal adenocarcinoma (cT1-3d N0/+ M0, mrCRM - / +) localized 0-16 cm from the ano-cutaneous line, unable to undergo radical surgery can be included. The initial treatment comprises an external beam radiation (EBRT) regime with 13 × 3 Gy (total: 39 Gy) over a period of two and a half weeks. Following initial restaging 6.5 weeks after completion of EBRT, endorectal HDR-BT will be delivered with 3 weekly fractions of 8 Gy to a total dose of 24 Gy (prescribed at the radial margin of the tumor; with a maximum prescription depth of 10 mm); alternatively, with CXB with 90 Gy in 3 weekly fractions. The primary objective is complete or near complete clinical response (cCR or ncCR) and the second primary endpoint is quality of life (QoL) measured with the EORTC QLQ-ELD14, both at 12 months after treatment start.
The ACO/ARO/AIO-22 prospective multicentre trial will evaluate organ preservation rates and QoL after combining EBRT with endorectal HDR-BT in elderly and/or frail patients with rectal cancer.Clinicialtrials.gov number: NCT06729645.
直肠癌对老年人群的影响尤为严重，超过半数的病例在70岁及以上的个体中被诊断出来。由于手术并发症和围手术期发病率风险升高，这一群体中的体弱患者在耐受全直肠系膜切除术（TME）的标准治疗时往往面临重大挑战。放射治疗技术的进步提供了一种可行的替代方案，在将与治疗相关的毒性降至最低的同时实现有效的肿瘤控制。最近的临床试验，包括OPERA和MORPEUS试验，已经证明，将外照射（化疗）放疗（EBRT）与高剂量率直肠内近距离放疗（HDR-BT）或接触X线近距离放疗（CXB）相结合的剂量递增放疗，在更年轻、更健康的患者队列中可以实现较高的临床缓解率并有助于器官保留。基于这些发现，ACO/ARO/AIO-22研究旨在调整这些创新方法，以满足老年和体弱直肠癌患者的需求。
方法/设计：ACO/ARO/AIO-22试验是一项前瞻性多中心对照试验。纳入年龄≥70岁和/或体弱的非转移性直肠腺癌（cT1-3d N0/+ M0，mrCRM - / +）患者，肿瘤位于距肛门皮肤线0-16 cm处，无法进行根治性手术。初始治疗包括在两周半的时间内进行13×3 Gy（总计39 Gy）的外照射放疗（EBRT）方案。在EBRT完成后6.5周进行初始再分期，之后直肠内HDR-BT将分3周进行，每周1次，每次8 Gy，总剂量为24 Gy（在肿瘤的径向边缘规定剂量；最大规定深度为10 mm）；或者，采用CXB，分3周进行，每周1次，每次90 Gy。主要目标是完全或接近完全临床缓解（cCR或ncCR），第二个主要终点是在治疗开始后12个月时用欧洲癌症研究与治疗组织QLQ-ELD14量表测量的生活质量（QoL）。
ACO/ARO/AIO-22前瞻性多中心试验将评估在老年和/或体弱直肠癌患者中，EBRT与直肠内HDR-BT联合应用后的器官保留率和生活质量。Clinicaltrials.gov编号：NCT06729645。
