{"title":"基于诱导化疗后肿瘤总体积与诱导前体积的局部晚期鼻咽癌放疗靶区划分:一项开放标签、非劣效、多中心、随机 III 期试验","authors":"","doi":"10.1016/j.ijrobp.2024.08.023","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Radiotherapy target volume delineation based on pre-induction chemotherapy gross tumor volume (pre-IC GTV) is the standard principle in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after IC. However, over 90% patients responded to IC, with a significant volume reduction in GTV. We aimed to address whether radiotherapy target volume delineation based on pre-IC GTV can be safely reduced to post-IC GTV for LANPC patients treated with intensity-modulated radiotherapy.</div></div><div><h3>Materials/Methods</h3><div>In this open-label, non-inferiority, randomized controlled, phase III trial, patients with newly diagnosed, non-keratinising, non-metastatic NPC were recruited from three Chinese medical centers. Key inclusion criteria were aged 18–70 years, stage III-IVa disease (AJCC 8th edition), and a Karnofsky performance status score of at least 70. Eligible patients were required to have completed 3 cycles of IC and then were randomly assigned (1:1; block size of four) to receive radiotherapy with target volume delineation either based on post-IC or pre-IC GTV. Randomization was centrally performed with a random number code stratified by treatment center and stage. The primary endpoint was locoregional relapse-free survival (LRRFS). Non-inferiority was indicated if the lower limit of the 95% confidence interval (CI) of the difference in 3-year LRRFS between 2 groups was greater than -8%. The secondary endpoints were overall survival (OS), distant metastasis-free survival (DMFS), adverse events (AEs) and quality of life (QoL).</div></div><div><h3>Results</h3><div>A total of 445 patients were recruited (225 patients in the post-IC GTV group and 220 patients in the pre-IC GTV group). After a median follow-up of 38.7 months till June 30, 2024, intention-to-treat analysis showed that the post-IC GTV group and pre-IC GTV group had similar 3-year LRRFS (89.9% [95% CI 85.6 to 93.8] <em>v</em> 89.6% [95%CI 85.9 to 94.2], difference 0.3% [lower limit of the one-sided 95% CI -5.3], P<sub>non-inferiority</sub> 0.007), 3-year OS (96.7% <em>v</em> 96.6%, P=0.64) and DMFS (91.2% <em>v</em> 92.7%, P=0.62). In the safety population (n=442), the post-IC GTV group had lower incidence of acute grade 3-4 AEs (37.4% <em>v</em> 55.5%) and late radiation related grade 3-4 AEs (22.5% <em>v</em> 33.6%) to the pre-IC GTV group. During follow up, the post-IC GTV group had significantly better QoL scores for global health (82.1 <em>v</em> 73.4, P<0.001) and emotional functioning (94.4 <em>v</em> 90.3, P=0.25).</div></div><div><h3>Conclusion</h3><div>Radiotherapy target volume delineation based on post-IC GTV was noninferior to that based on pre-IC GTV in LRRFS with less toxicities and better quality of life in LANPC. This study is registered with ClinicalTrials.gov, NCT04384627.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Radiotherapy Target Volume Delineation Based on Post-Induction Chemotherapy Gross Tumor Volume vs. Pre-Induction Volume for Locoregionally Advanced Nasopharyngeal Carcinoma: An Open-label, Non-Inferiority, Multicenter, Randomized Phase III Trial\",\"authors\":\"\",\"doi\":\"10.1016/j.ijrobp.2024.08.023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose/Objective(s)</h3><div>Radiotherapy target volume delineation based on pre-induction chemotherapy gross tumor volume (pre-IC GTV) is the standard principle in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after IC. However, over 90% patients responded to IC, with a significant volume reduction in GTV. We aimed to address whether radiotherapy target volume delineation based on pre-IC GTV can be safely reduced to post-IC GTV for LANPC patients treated with intensity-modulated radiotherapy.</div></div><div><h3>Materials/Methods</h3><div>In this open-label, non-inferiority, randomized controlled, phase III trial, patients with newly diagnosed, non-keratinising, non-metastatic NPC were recruited from three Chinese medical centers. Key inclusion criteria were aged 18–70 years, stage III-IVa disease (AJCC 8th edition), and a Karnofsky performance status score of at least 70. Eligible patients were required to have completed 3 cycles of IC and then were randomly assigned (1:1; block size of four) to receive radiotherapy with target volume delineation either based on post-IC or pre-IC GTV. Randomization was centrally performed with a random number code stratified by treatment center and stage. The primary endpoint was locoregional relapse-free survival (LRRFS). Non-inferiority was indicated if the lower limit of the 95% confidence interval (CI) of the difference in 3-year LRRFS between 2 groups was greater than -8%. The secondary endpoints were overall survival (OS), distant metastasis-free survival (DMFS), adverse events (AEs) and quality of life (QoL).</div></div><div><h3>Results</h3><div>A total of 445 patients were recruited (225 patients in the post-IC GTV group and 220 patients in the pre-IC GTV group). After a median follow-up of 38.7 months till June 30, 2024, intention-to-treat analysis showed that the post-IC GTV group and pre-IC GTV group had similar 3-year LRRFS (89.9% [95% CI 85.6 to 93.8] <em>v</em> 89.6% [95%CI 85.9 to 94.2], difference 0.3% [lower limit of the one-sided 95% CI -5.3], P<sub>non-inferiority</sub> 0.007), 3-year OS (96.7% <em>v</em> 96.6%, P=0.64) and DMFS (91.2% <em>v</em> 92.7%, P=0.62). In the safety population (n=442), the post-IC GTV group had lower incidence of acute grade 3-4 AEs (37.4% <em>v</em> 55.5%) and late radiation related grade 3-4 AEs (22.5% <em>v</em> 33.6%) to the pre-IC GTV group. During follow up, the post-IC GTV group had significantly better QoL scores for global health (82.1 <em>v</em> 73.4, P<0.001) and emotional functioning (94.4 <em>v</em> 90.3, P=0.25).</div></div><div><h3>Conclusion</h3><div>Radiotherapy target volume delineation based on post-IC GTV was noninferior to that based on pre-IC GTV in LRRFS with less toxicities and better quality of life in LANPC. This study is registered with ClinicalTrials.gov, NCT04384627.</div></div>\",\"PeriodicalId\":14215,\"journal\":{\"name\":\"International Journal of Radiation Oncology Biology Physics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2024-10-01\",\"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://www.sciencedirect.com/science/article/pii/S0360301624032486\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Radiation Oncology Biology Physics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0360301624032486","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的/宗旨:根据诱导化疗前的肿瘤总体积(诱导化疗前 GTV)划定放疗靶区是局部区域晚期鼻咽癌(LANPC)患者接受诱导化疗后的标准原则。然而,超过 90% 的患者对 IC 有反应,GTV 体积显著缩小。材料/方法在这项开放标签、非劣效、随机对照的Ⅲ期试验中,我们从三家中国医疗中心招募了新诊断、非角化、非转移性鼻咽癌患者。主要纳入标准为年龄在18-70岁之间,疾病处于III-IVa期(AJCC第8版),卡诺夫斯基(Karnofsky)表现状态评分至少为70分。符合条件的患者需要完成3个周期的IC治疗,然后被随机分配(1:1;每组4人)接受放疗,靶体积的划分基于IC治疗后或IC治疗前的GTV。随机分配由治疗中心和分期随机数字代码集中进行。主要终点是局部无复发生存期(LRRFS)。如果两组间 3 年无局部复发生存率差异的 95% 置信区间 (CI) 下限大于 -8%,则表示非劣效性。次要终点为总生存期(OS)、无远处转移生存期(DMFS)、不良事件(AE)和生活质量(QoL)。截至 2024 年 6 月 30 日,中位随访时间为 38.7 个月,意向治疗分析显示,IC 后 GTV 组和 IC 前 GTV 组的 3 年 LRRFS 相似(89.9% [95% CI 85.6 to 93.8] v 89.6% [95%CI 85.9 to 94.2],差异为 0.3% [单侧 95% CI 下限 -5.3],P 非劣效性为 0.007)、3 年 OS(96.7% v 96.6%,P=0.64)和 DMFS(91.2% v 92.7%,P=0.62)。在安全人群(n=442)中,IC后GTV组的急性3-4级AE(37.4% v 55.5%)和晚期放射相关3-4级AE(22.5% v 33.6%)发生率低于IC前GTV组。结论在LRRFS中,基于IC后GTV的放疗靶区划分并不劣于基于IC前GTV的放疗靶区划分,而且在LANPC中毒性更小,生活质量更高。本研究已在 ClinicalTrials.gov 登记,编号为 NCT04384627。
Radiotherapy Target Volume Delineation Based on Post-Induction Chemotherapy Gross Tumor Volume vs. Pre-Induction Volume for Locoregionally Advanced Nasopharyngeal Carcinoma: An Open-label, Non-Inferiority, Multicenter, Randomized Phase III Trial
Purpose/Objective(s)
Radiotherapy target volume delineation based on pre-induction chemotherapy gross tumor volume (pre-IC GTV) is the standard principle in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after IC. However, over 90% patients responded to IC, with a significant volume reduction in GTV. We aimed to address whether radiotherapy target volume delineation based on pre-IC GTV can be safely reduced to post-IC GTV for LANPC patients treated with intensity-modulated radiotherapy.
Materials/Methods
In this open-label, non-inferiority, randomized controlled, phase III trial, patients with newly diagnosed, non-keratinising, non-metastatic NPC were recruited from three Chinese medical centers. Key inclusion criteria were aged 18–70 years, stage III-IVa disease (AJCC 8th edition), and a Karnofsky performance status score of at least 70. Eligible patients were required to have completed 3 cycles of IC and then were randomly assigned (1:1; block size of four) to receive radiotherapy with target volume delineation either based on post-IC or pre-IC GTV. Randomization was centrally performed with a random number code stratified by treatment center and stage. The primary endpoint was locoregional relapse-free survival (LRRFS). Non-inferiority was indicated if the lower limit of the 95% confidence interval (CI) of the difference in 3-year LRRFS between 2 groups was greater than -8%. The secondary endpoints were overall survival (OS), distant metastasis-free survival (DMFS), adverse events (AEs) and quality of life (QoL).
Results
A total of 445 patients were recruited (225 patients in the post-IC GTV group and 220 patients in the pre-IC GTV group). After a median follow-up of 38.7 months till June 30, 2024, intention-to-treat analysis showed that the post-IC GTV group and pre-IC GTV group had similar 3-year LRRFS (89.9% [95% CI 85.6 to 93.8] v 89.6% [95%CI 85.9 to 94.2], difference 0.3% [lower limit of the one-sided 95% CI -5.3], Pnon-inferiority 0.007), 3-year OS (96.7% v 96.6%, P=0.64) and DMFS (91.2% v 92.7%, P=0.62). In the safety population (n=442), the post-IC GTV group had lower incidence of acute grade 3-4 AEs (37.4% v 55.5%) and late radiation related grade 3-4 AEs (22.5% v 33.6%) to the pre-IC GTV group. During follow up, the post-IC GTV group had significantly better QoL scores for global health (82.1 v 73.4, P<0.001) and emotional functioning (94.4 v 90.3, P=0.25).
Conclusion
Radiotherapy target volume delineation based on post-IC GTV was noninferior to that based on pre-IC GTV in LRRFS with less toxicities and better quality of life in LANPC. This study is registered with ClinicalTrials.gov, NCT04384627.
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.