Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, S-17176, Sweden.
The Skandion Clinic, Uppsala, S-75237, Sweden.
Med Phys. 2019 May;46(5):2512-2521. doi: 10.1002/mp.13514. Epub 2019 Apr 14.
Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on F-HX4 positron emission tomography (PET) imaging of NSCLC.
Positron emission tomography imaging data based on the hypoxia tracer F-HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO ) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy.
Gross target volumes ranged between 6.2 and 859.6 cm , and the hypoxic fraction < 10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO , HTV doses were calculated as 43.6-48.4 Gy for a three-fraction schedule, 51.7-57.6 Gy for five fractions, and 59.5-66.4 Gy for eight fractions. For patients in whom the HTV pO distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single-fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions.
The method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on F-HX4-PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume.
肿瘤缺氧在非小细胞肺癌（NSCLC）中很常见，这意味着对放疗的抵抗力增加。因此，这些患者需要进行肿瘤氧合的预处理评估，因为缺氧功能成像可以作为剂量描绘的基础。本研究旨在探讨使用一种方法来计算在 NSCLC 的 F-HX4 正电子发射断层扫描（PET）成像中分割的缺氧亚体积所需的剂量的可行性。
本研究纳入了 19 例 NSCLC 患者的 F-HX4 缺氧示踪剂正电子发射断层扫描成像数据。将归一化示踪剂摄取值转换为氧分压（pO ），并使用 10mmHg 的阈值分割缺氧靶体积（HTV）。根据之前提出的方法，考虑到分次间再氧合的影响，计算出克服靶体积缺氧耐药所需的均匀剂量，该方法适用于从极端低分割立体定向体部放射治疗（SBRT）到常规分割放疗的分割方案。
大体肿瘤体积范围为 6.2 至 859.6cm ，<10mmHg 的缺氧分数为 1.2%至 72.4%。克服 HTV 中细胞耐药所需的计算剂量与目前临床实践中规定的剂量以及之前在 NSCLC 剂量递增可行性研究中测试的剂量相当。根据 HTV 的大小和 pO 的分布，对于三分割方案，HTV 剂量计算为 43.6-48.4Gy，五分割方案为 51.7-57.6Gy，八分割方案为 59.5-66.4Gy。对于 HTV pO 分布更有利的患者，尽管体积较大，但所需剂量较低。单分割方案的肿瘤控制概率较低，而采用多分割方案的肿瘤控制概率较高。
基于 F-HX4-PET 成像的靶区分割和剂量处方中考虑异质性和动态缺氧的方法在 NSCLC 患者中似乎是可行的。HTV 内氧分压的分布比体积大小对所需的规定剂量的影响更大。
