{"title":"均匀和非均匀剂量分布在中等氧含量肿瘤放射治疗中的生物有效性。","authors":"Alexei V Chvetsov, Andrei Pugachev","doi":"10.1088/2057-1976/ad87f8","DOIUrl":null,"url":null,"abstract":"<p><p><i>Objective</i>. We propose a criterion of biological effectiveness of nonuniform hypoxia-targeted dose distributions in heterogeneous hypoxic tumors based on equivalent uniform aerobic dose (EUAD). We demonstrate the utility of this criterion by applying it to the model problems in radiotherapy for tumors with different levels of oxygen enhancement ratio (OER) and different degrees of dose nonuniformity.<i>Approach</i>. The EUAD is defined as the uniform dose that, under well-oxygenated conditions, produces equal integrated survival of clonogenic cells in radiotherapy for heterogeneous hypoxic tumors with a non-uniform dose distribution. We define the dose nonuniformity effectiveness (DNE) in heterogeneous tumors as the ratio of the EUAD(<b>D</b><sub>N</sub>) for a non-uniform distribution<b>D</b><sub>N</sub>and the reference EUAD(<b>D</b><sub>U</sub>) for the uniform dose distribution<b>D</b><sub>U</sub>with equal integral tumor dose. The DNE concept is illustrated in a radiotherapy model problem for non-small cell lung cancer treated with hypoxia targeted dose escalation. A two-level cell population tumor model was used to consider the hypoxic and oxygenated tumor cells.<i>Results</i>. Theoretical analysis of the DNE shows that the entire region of the OER can be separated in two regions by a threshold OER<sub>th</sub>: (1) OER > OER<sub>th</sub>where DNE > 1 indicating higher effectiveness of nonuniform dose distributions and (2) OER < OER<sub>th</sub>where DNE < 1 indicating higher effectiveness of uniform dose distributions. Our simulations show that the value of the threshold OER<sub>th</sub>in radiotherapy with conventional fractionation is significant in the range of about 1.2-1.6 depending on selected radiotherapy parameters. In general, the OER<sub>th</sub>increases with reoxygenation rate, relative hypoxic volume and dose escalation factor. The threshold value of OER<sub>th</sub>is smaller of about 1.1 for hypofractionated radiotherapy.<i>Significance</i>. The analysis of dose distributions using the DNE shows that the uniform dose distributions may improve biological cell killing effect in heterogeneous tumors with intermediate oxygen levels compared to targeted nonuniform dose distribution.</p>","PeriodicalId":8896,"journal":{"name":"Biomedical Physics & Engineering Express","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biological effectiveness of uniform and nonuniform dose distributions in radiotherapy for tumors with intermediate oxygen levels.\",\"authors\":\"Alexei V Chvetsov, Andrei Pugachev\",\"doi\":\"10.1088/2057-1976/ad87f8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Objective</i>. We propose a criterion of biological effectiveness of nonuniform hypoxia-targeted dose distributions in heterogeneous hypoxic tumors based on equivalent uniform aerobic dose (EUAD). We demonstrate the utility of this criterion by applying it to the model problems in radiotherapy for tumors with different levels of oxygen enhancement ratio (OER) and different degrees of dose nonuniformity.<i>Approach</i>. The EUAD is defined as the uniform dose that, under well-oxygenated conditions, produces equal integrated survival of clonogenic cells in radiotherapy for heterogeneous hypoxic tumors with a non-uniform dose distribution. We define the dose nonuniformity effectiveness (DNE) in heterogeneous tumors as the ratio of the EUAD(<b>D</b><sub>N</sub>) for a non-uniform distribution<b>D</b><sub>N</sub>and the reference EUAD(<b>D</b><sub>U</sub>) for the uniform dose distribution<b>D</b><sub>U</sub>with equal integral tumor dose. The DNE concept is illustrated in a radiotherapy model problem for non-small cell lung cancer treated with hypoxia targeted dose escalation. A two-level cell population tumor model was used to consider the hypoxic and oxygenated tumor cells.<i>Results</i>. Theoretical analysis of the DNE shows that the entire region of the OER can be separated in two regions by a threshold OER<sub>th</sub>: (1) OER > OER<sub>th</sub>where DNE > 1 indicating higher effectiveness of nonuniform dose distributions and (2) OER < OER<sub>th</sub>where DNE < 1 indicating higher effectiveness of uniform dose distributions. Our simulations show that the value of the threshold OER<sub>th</sub>in radiotherapy with conventional fractionation is significant in the range of about 1.2-1.6 depending on selected radiotherapy parameters. In general, the OER<sub>th</sub>increases with reoxygenation rate, relative hypoxic volume and dose escalation factor. The threshold value of OER<sub>th</sub>is smaller of about 1.1 for hypofractionated radiotherapy.<i>Significance</i>. The analysis of dose distributions using the DNE shows that the uniform dose distributions may improve biological cell killing effect in heterogeneous tumors with intermediate oxygen levels compared to targeted nonuniform dose distribution.</p>\",\"PeriodicalId\":8896,\"journal\":{\"name\":\"Biomedical Physics & Engineering Express\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Physics & Engineering Express\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1088/2057-1976/ad87f8\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Physics & Engineering Express","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1088/2057-1976/ad87f8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
摘要
目的:我们提出了一种基于等效均匀有氧剂量(EUAD)的异质缺氧肿瘤非均匀缺氧靶向剂量分布生物有效性标准。我们将这一标准应用于不同氧增强比(OER)水平和不同剂量不均匀程度的肿瘤放疗模型问题,从而证明了这一标准的实用性。EUAD 的定义是:在良好的氧合条件下,对具有非均匀剂量分布的异质缺氧肿瘤进行放疗时,能使克隆生成细胞的综合存活率相等的均匀剂量。我们将异质肿瘤的剂量不均匀有效性(DNE)定义为非均匀分布 DN 的 EUAD(DN) 与肿瘤积分剂量相等的均匀剂量分布 DU 的参考 EUAD(DU) 之比。DNE 概念在非小细胞肺癌放疗模型问题中得到了说明。采用两级细胞群肿瘤模型来考虑缺氧和氧合肿瘤细胞。对 DNE 的理论分析表明,OER 的整个区域可以通过阈值 OERth 分为两个区域:1)OER>OERth,其中 DNE>1 表示非均匀剂量分布的有效性更高;2)OER
Biological effectiveness of uniform and nonuniform dose distributions in radiotherapy for tumors with intermediate oxygen levels.
Objective. We propose a criterion of biological effectiveness of nonuniform hypoxia-targeted dose distributions in heterogeneous hypoxic tumors based on equivalent uniform aerobic dose (EUAD). We demonstrate the utility of this criterion by applying it to the model problems in radiotherapy for tumors with different levels of oxygen enhancement ratio (OER) and different degrees of dose nonuniformity.Approach. The EUAD is defined as the uniform dose that, under well-oxygenated conditions, produces equal integrated survival of clonogenic cells in radiotherapy for heterogeneous hypoxic tumors with a non-uniform dose distribution. We define the dose nonuniformity effectiveness (DNE) in heterogeneous tumors as the ratio of the EUAD(DN) for a non-uniform distributionDNand the reference EUAD(DU) for the uniform dose distributionDUwith equal integral tumor dose. The DNE concept is illustrated in a radiotherapy model problem for non-small cell lung cancer treated with hypoxia targeted dose escalation. A two-level cell population tumor model was used to consider the hypoxic and oxygenated tumor cells.Results. Theoretical analysis of the DNE shows that the entire region of the OER can be separated in two regions by a threshold OERth: (1) OER > OERthwhere DNE > 1 indicating higher effectiveness of nonuniform dose distributions and (2) OER < OERthwhere DNE < 1 indicating higher effectiveness of uniform dose distributions. Our simulations show that the value of the threshold OERthin radiotherapy with conventional fractionation is significant in the range of about 1.2-1.6 depending on selected radiotherapy parameters. In general, the OERthincreases with reoxygenation rate, relative hypoxic volume and dose escalation factor. The threshold value of OERthis smaller of about 1.1 for hypofractionated radiotherapy.Significance. The analysis of dose distributions using the DNE shows that the uniform dose distributions may improve biological cell killing effect in heterogeneous tumors with intermediate oxygen levels compared to targeted nonuniform dose distribution.
期刊介绍:
BPEX is an inclusive, international, multidisciplinary journal devoted to publishing new research on any application of physics and/or engineering in medicine and/or biology. Characterized by a broad geographical coverage and a fast-track peer-review process, relevant topics include all aspects of biophysics, medical physics and biomedical engineering. Papers that are almost entirely clinical or biological in their focus are not suitable. The journal has an emphasis on publishing interdisciplinary work and bringing research fields together, encompassing experimental, theoretical and computational work.