Than Ngu Wah, Pritchard D Mark, Hughes David M, Duckworth Carrie A, Wong Helen, Ul Haq Muneeb, Sripadam Rajaram, Myint Arthur Sun
Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, The University of Liverpool; Papillon Suite, The Clatterbridge Cancer Centre National Health Service Foundation Trust, Bebington, Wirral, United Kingdom.
Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, The University of Liverpool.
Int J Radiat Oncol Biol Phys. 2025 Jul 1;122(3):709-720. doi: 10.1016/j.ijrobp.2024.11.113. Epub 2024 Dec 12.
Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A contact x-ray brachytherapy (CXB) boost can alternatively be used to treat residual disease postneoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low- to intermediate-risk patients. We have now evaluated the utility of CXB boost in high-risk rectal cancers after their tumors have been significantly downstaged by neoadjuvant (chemo)radiation.
Oncological outcomes and treatment tolerability were evaluated in 328 patients based on rectal cancer treatment risk stratification: low-/intermediate-risk (cT1-3ab, N0-1, M0, no extramural venous invasion, mesorectal fascia involvement >1 mm) and high-risk (cT3cd-4/N2, M0, mesorectal fascia ≤1 mm, and/or extramural venous invasion positive).
With a median follow-up of 33 (IQR, 15-54) months and a median age of 73 (IQR, 62-80) years, no significant differences were found between low/intermediate and high-risk groups in clinical complete response (78% vs. 73%, P = .32), local regrowth (16.6% vs. 22.4%, P = .41), nodal (1.8% vs. 5.8%, P = .051) or regional (1.3% vs. 2.9%, P = .33) relapse, or postradiation toxicities (P = .16). However, the high-risk group had a higher distant relapse rate (21.2% vs. 10.7%, P = .01), with no significant differences in 3-year organ preservation (80% vs. 87%, P = .25), 5-year disease-free survival (62% vs. 64%, P = .46), or overall survival (67% vs. 64%, P = .88). Longer treatment time, treatment gap >24 weeks between therapies, and administration of a higher than standard CXB dose were newly identified factors that negatively impacted outcomes.
High-risk patients with rectal cancer treated with CXB boost had more distant relapses, but comparable locoregional tumor control, organ preservation, disease-free survival, and overall survival to lower risk patients, with acceptable toxicities. CXB boost is, therefore, a viable option for selected high-risk patients with rectal cancer. Timely reassessment, prompt referral, and CXB dose optimization are crucial for improving outcomes.
新辅助治疗后行根治性手术是局部晚期直肠癌的标准治疗方案。接触式X线近距离放疗（CXB）增敏可用于治疗新辅助（化疗）放疗后的残留病灶，尤其是对于不适合或不愿接受手术的患者。迄今为止，其作用主要在低至中危患者中进行了研究。我们现在评估了在新辅助（化疗）放疗使肿瘤明显降期后的高危直肠癌患者中CXB增敏的效用。
根据直肠癌治疗风险分层，对328例患者的肿瘤学结局和治疗耐受性进行了评估：低/中危（cT1-3ab，N0-1，M0，无壁外静脉侵犯，直肠系膜筋膜受累>1 mm）和高危（cT3cd-4/N2，M0，直肠系膜筋膜≤1 mm，和/或壁外静脉侵犯阳性）。
中位随访时间为33（四分位间距，15-54）个月，中位年龄为73（四分位间距，62-80）岁，低/中危组和高危组在临床完全缓解率（78%对73%，P = 0.32）、局部复发率（16.6%对22.4%，P = 0.41）、淋巴结（1.8%对5.8%，P = 0.051）或区域（1.3%对2.9%，P = 0.33）复发率或放疗后毒性反应方面均无显著差异（P = 0.16）。然而，高危组的远处复发率较高（21.2%对10.7%，P = 0.01），在3年器官保留率（80%对87%，P = 0.25）、5年无病生存率（62%对64%，P = 0.46）或总生存率（67%对64%，P = 0.88）方面无显著差异。新发现治疗时间较长、治疗间隔>24周以及给予高于标准的CXB剂量是对结局产生负面影响的因素。
接受CXB增敏治疗的高危直肠癌患者远处复发较多，但在局部区域肿瘤控制、器官保留、无病生存率和总生存率方面与低危患者相当，且毒性反应可接受。因此，CXB增敏是部分高危直肠癌患者的可行选择。及时重新评估、及时转诊和CXB剂量优化对于改善结局至关重要。
