Supriya Chopra, Tjalling Bosse, Nanda Horeweg, Kedar Deodhar, Santosh Menon, Tynisha Rafael, Venkatesh Pai, Lucia Rijstenberg, Folkert van Kemenade, Sadhana Kannan, Umesh Mahantshetty, Barbara Segedin, Fleur Huang, Kjersti Bruheim, Margarita Perez, Bhavana Rai, Li Tee Tan, Nadia Giannakopoulos, Maximilian Schmid, Kari Tanderup, Richard Pötter, Remi A Nout
{"title":"局部晚期宫颈癌化疗和基于磁共振成像引导的近距离放疗国际研究中的生物标志物表达及其对临床结果的影响:BIOEMBRACE.","authors":"Supriya Chopra, Tjalling Bosse, Nanda Horeweg, Kedar Deodhar, Santosh Menon, Tynisha Rafael, Venkatesh Pai, Lucia Rijstenberg, Folkert van Kemenade, Sadhana Kannan, Umesh Mahantshetty, Barbara Segedin, Fleur Huang, Kjersti Bruheim, Margarita Perez, Bhavana Rai, Li Tee Tan, Nadia Giannakopoulos, Maximilian Schmid, Kari Tanderup, Richard Pötter, Remi A Nout","doi":"10.1016/j.ijrobp.2024.07.2316","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods and materials: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":"97-106"},"PeriodicalIF":6.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biomarker Expression and Clinical Outcomes in International Study of Chemoradiation and Magnetic Resonance Imaging-Based Image-Guided Brachytherapy for Locally Advanced Cervical Cancer: BIOEMBRACE.\",\"authors\":\"Supriya Chopra, Tjalling Bosse, Nanda Horeweg, Kedar Deodhar, Santosh Menon, Tynisha Rafael, Venkatesh Pai, Lucia Rijstenberg, Folkert van Kemenade, Sadhana Kannan, Umesh Mahantshetty, Barbara Segedin, Fleur Huang, Kjersti Bruheim, Margarita Perez, Bhavana Rai, Li Tee Tan, Nadia Giannakopoulos, Maximilian Schmid, Kari Tanderup, Richard Pötter, Remi A Nout\",\"doi\":\"10.1016/j.ijrobp.2024.07.2316\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods and materials: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":14215,\"journal\":{\"name\":\"International Journal of Radiation Oncology Biology Physics\",\"volume\":\" \",\"pages\":\"97-106\"},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Radiation Oncology Biology Physics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ijrobp.2024.07.2316\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Radiation Oncology Biology Physics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijrobp.2024.07.2316","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:BIOEMBRACE-I旨在研究EMBRACE研究中除临床病理因素外,生物标志物对局部晚期宫颈癌化疗和核磁共振引导近距离放射治疗(BT)患者疾病预后的影响:2018-2021年间,8个EMBRACE-I研究点提供了肿瘤组织,用于p16、PD-L1和L1CAM的免疫组化。分析了这些生物标志物和临床病理因素(FIGO 2009分期、结节状态、组织学、MRI上的坏死),以预测近距离治疗(BT)时的不良反应(BT时高风险临床靶体积[HR-CTV]≥40cc)以及5年局部控制、盆腔控制和无病生存(DFS)。研究了p16、PD-L1、放疗剂量(HR-CTV D90)与疾病结局之间的相互作用。进行了单变量和多变量分析:结果:共纳入 264 例患者。P16阳性(pos)、PD-L1>1%和L1CAM≥10%的患者分别占86.6%、20.1%和17.8%。P16阴性(OR 2.0 (1.0-5.7),p=0.04)、MRI坏死(OR 2.1 (1.1-4.3),p5cm)和PDL1>1%与肿瘤的生长有关。PDL1>1% 与局部控制率(82% vs. 94%,p=0.02)和盆腔控制率(79% vs. 89%,p=0.02)降低有关。HR-CTV D90 1%是5年局部控制率的唯一独立因素(HR 3.3,P=0.04),L1CAM≥50%是盆腔控制率的唯一独立因素(HR 5.5 (1.3-23.3),P=0.02):结论:P16阴性状态和MRI上的肿瘤坏死与化疗反应差独立相关,而PD-L1>1%和L1CAM≥50%对局部和盆腔控制有独立影响,这表明生物标志物的表达对预后有影响。还需要进一步验证。
Biomarker Expression and Clinical Outcomes in International Study of Chemoradiation and Magnetic Resonance Imaging-Based Image-Guided Brachytherapy for Locally Advanced Cervical Cancer: BIOEMBRACE.
Purpose: 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.
Methods and materials: 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.
Results: 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).
Conclusions: 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.
期刊介绍:
International Journal of Radiation Oncology • Biology • Physics (IJROBP), known in the field as the Red Journal, publishes original laboratory and clinical investigations related to radiation oncology, radiation biology, medical physics, and both education and health policy as it relates to the field.
This journal has a particular interest in original contributions of the following types: prospective clinical trials, outcomes research, and large database interrogation. In addition, it seeks reports of high-impact innovations in single or combined modality treatment, tumor sensitization, normal tissue protection (including both precision avoidance and pharmacologic means), brachytherapy, particle irradiation, and cancer imaging. Technical advances related to dosimetry and conformal radiation treatment planning are of interest, as are basic science studies investigating tumor physiology and the molecular biology underlying cancer and normal tissue radiation response.