Chopra Supriya, Bosse Tjalling, Horeweg Nanda, Deodhar Kedar, Menon Santosh, Rafael Tynisha, Pai Venkatesh, Rijstenberg Lucia, van Kemenade Folkert, Kannan Sadhana, Mahantshetty Umesh, Segedin Barbara, Huang Fleur, Bruheim Kjersti, Perez Margarita, Rai Bhavana, Tan Li Tee, Giannakopoulos Nadia, Schmid Maximilian, Tanderup Kari, Pötter Richard, Nout Remi A
Department of Radiation Oncology and Medical Physics, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Int J Radiat Oncol Biol Phys. 2025 Jan 1;121(1):97-106. doi: 10.1016/j.ijrobp.2024.07.2316. Epub 2024 Jul 26.
BIOEMBRACE was designed to study the impact of biomarkers in addition to clinicopathological factors on disease outcomes in patients treated with chemoradiation and magnetic resonance imaging (MRI)-guided brachytherapy (BT) for locally advanced cervical cancer in the EMBRACE study.
Between 2018 and 2021, 8 EMBRACE-I sites contributed tumor tissue for the immunohistochemistry of p16, PD-L1, and L1CAM. These biomarkers and clinicopathological factors (International Federation of Gynecology and Obstetrics 2009 stage, nodal status, histology, and necrosis on MRI) were analyzed to predict poor response at BT (high-risk clinical target volume [HR-CTV] ≥ 40 cc) at BT) and 5-year local control, pelvic control, and disease-free survival. Interaction between p16, PD-L1, radiation therapy dose (HR-CTV D90), and disease outcomes was investigated. Univariable and multivariable analyses were performed.
Two hundred sixty-four patients were included. The median HR-CTV D90 was 89 Gy (86-95). P-16 positive status, PD-L1 > 1%, and L1CAM ≥ 10% was noted in 86.6%, 20.1%, and 17.8% of patients, respectively. P16 negative status (odds ratio, 2.0; 95% CI, 1.0-5.7; P = .04) and necrosis on MRI (odds ratio, 2.1; 95% CI, 1.1-4.3; P < .02) independently predicted for HR-CTV ≥ 40 cc, as did the International Federation of Gynecology and Obstetrics stage and tumor width >5 cm. PD-L1 > 1% was associated with reduced local (82% vs 94%; P = .02) and pelvic control (79% vs 89%; P = .02). HR-CTV D90 < 85 Gy was associated with inferior 5-year local control in p16-positive patients, especially if PD-L1 was coexpressed. On multivariable analysis, PD-L1 > 1% was the only independent factor for 5-year local control (hazard ratio, 3.3; P = .04) and L1CAM ≥ 50% for pelvic control (hazard ratio, 5.5; 95% CI, 1.3-23.3; P = .02).
P16 negative status and tumor necrosis on MRI are independently associated with poor response to chemoradiation, whereas PD-L1 > 1% and L1CAM ≥ 50% have an independent impact on local and pelvic control, suggesting an impact of biomarker expression on outcomes. Further validation is needed.
在EMBRACE研究中，BIOEMBRACE旨在研究生物标志物以及临床病理因素对接受放化疗和磁共振成像（MRI）引导下近距离放射治疗（BT）的局部晚期宫颈癌患者疾病转归的影响。
2018年至2021年期间，8个EMBRACE - I研究点提供了用于p16、PD - L1和L1CAM免疫组化的肿瘤组织。对这些生物标志物和临床病理因素（国际妇产科联盟2009分期、淋巴结状态、组织学类型以及MRI上的坏死情况）进行分析，以预测BT时反应不佳（高危临床靶体积[HR - CTV]≥40 cc）以及5年局部控制率、盆腔控制率和无病生存率。研究了p16、PD - L1、放射治疗剂量（HR - CTV D90）与疾病转归之间的相互作用。进行了单变量和多变量分析。
共纳入264例患者。HR - CTV D90的中位数为89 Gy（86 - 95）。分别有86.6%、20.1%和17.8%的患者p - 16呈阳性、PD - L1>1%以及L1CAM≥10%。p16阴性状态（比值比，2.0；95%可信区间，1.0 - 5.7；P = 0.04）和MRI上的坏死情况（比值比，2.1；95%可信区间，1.1 - 4.3；P < 0.02）与HR - CTV≥40 cc独立相关，国际妇产科联盟分期和肿瘤宽度>5 cm也与HR - CTV≥40 cc独立相关。PD - L1>1%与局部控制率降低（82%对94%；P = 0.02）和盆腔控制率降低（79%对89%；P = 0.02）相关。HR - CTV D90 < 85 Gy与p16阳性患者5年局部控制率较差相关，尤其是当PD - L1共表达时。多变量分析显示，PD - L1>1%是5年局部控制的唯一独立因素（风险比，3.3；P = 0.04），而L1CAM≥50%是盆腔控制的独立因素（风险比，5.5；95%可信区间，1.3 - 23.3；P = 0.02）。
p16阴性状态和MRI上的肿瘤坏死与放化疗反应不佳独立相关，而PD - L1>1%和L1CAM≥50%对局部和盆腔控制有独立影响，提示生物标志物表达对转归有影响。需要进一步验证。
