Kupelian Patrick A, Willoughby Twyla R, Meeks Sanford L, Forbes Alan, Wagner Thomas, Maach Mourad, Langen Katja M
Radiation Oncology, M. D. Anderson Cancer Center Orlando, Orlando, FL 32806, USA.
Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1291-6. doi: 10.1016/j.ijrobp.2005.01.005.
The use of intraprostatic fiducials as surrogates for prostate gland position assumes that the markers are rigidly positioned within the prostate. To test this assumption, the intermarker distances (IMD) of implanted markers was monitored during the full course of radiation therapy to determine marker stability within the prostate gland.
The analysis is performed on 56 patients treated with intensity-modulated radiotherapy. A total of 168 markers (3 markers per patient) were implanted. Two high-resolution X-rays were acquired before treatment delivery to visualize the position of the implanted markers. A total of 2,037 daily alignments were performed on the 56 cases (average: 36 alignments per patient). Each pair of X-ray images allows the computation of the 3 IMDs. A total of 6,111 IMDs were available for analysis. To study variations in marker position, daily IMDs were compared with the IMD that was observed during the first alignment. We defined the variation in the IMD as the important measure of intrinsic marker position variation. The standard deviation (SD) of IMD variations was studied as a measure of the extent of marker position variation. Particular attention was given to cases in which significant intermarker variations were observed.
The average directional variation of all IMDs (+/- SD) was -0.31 (+/-1.41) mm. The average absolute variation of all IMDs (+/- SD) was 1.01 (+/-1.03) mm. The largest observed variation in IMD was 10.2 mm. Among the individual 56 patients, the SDs of the IMD variations were computed and found to range from 0.4 to 4.2 mm. In 54 of the 56 patients (96%), the variations of all 3 IMDs had SD of 4.0 mm or less, which indicates little variation in the relative position of the markers. Only in 2 patients did any of the IMDs vary, with SD that exceeded 4.0 mm, which indicated noticeable and consistent marker-position variation. The maximum observed SD in the IMD variation was 4.2 mm. In each of the 2 cases, 2 IMDs were found to fluctuate, while the third IMD remained fairly constant. This finding means that 1 of 3 markers varied frequently in its relative position throughout the treatment. Therefore, only 2 of the 168 markers (1%) showed frequent changes in their relative positions. A review of these 2 cases revealed that the observed marker mobility was likely not caused by migration of the marker itself but caused by prostate deformation, secondary to rectal filling. To investigate the frequency of extreme situations, the maximum observed IMD variation was determined for each patient. In 47 of the 56 patients (84%), the maximum difference in IMDs was at least 2 mm. The corresponding numbers for 3, 4, and 5 mm were 23 (41%), 10 (18%), and 5 (9%) patients, respectively.
This study is the largest reported series of localized prostate cancer patients with implanted intraprostatic markers used for daily target localization in which individual marker positions were registered and IMDs were computed to test for marker position variation. Only 2 of 168 implanted markers showed a relatively significant and consistent change in their relative position throughout a course of treatment. However, these variations in position were most likely not caused by marker migration but caused by prostate deformation. Typically, the IMDs varied minimally, which indicated relatively little deformation of the gland as well as the absence of significant marker migration. However, during a typical course of treatment, the IMD is likely to vary by several millimeters in some instances, which indicates infrequent but significant deformation. In these instances, an alignment based on the 3 markers' center of mass will still provide a meaningful alignment of the prostate within the radiation field. Intraprostatic implanted fiducials in the prostate allow a reliable and simple localization of the prostate gland, even in the presence of organ deformation.
使用前列腺内基准点作为前列腺位置的替代物，前提是标志物在前列腺内固定就位。为验证这一假设，在整个放射治疗过程中监测植入标志物的标志物间距离（IMD），以确定前列腺内标志物的稳定性。
对56例接受调强放疗的患者进行分析。共植入168个标志物（每位患者3个标志物）。在开始治疗前采集两张高分辨率X线片，以显示植入标志物的位置。对56例患者共进行了2037次每日配准（平均每位患者36次配准）。每对X线图像可计算出3个IMD。共有6111个IMD可供分析。为研究标志物位置的变化，将每日的IMD与首次配准期间观察到的IMD进行比较。我们将IMD的变化定义为标志物固有位置变化的重要指标。研究IMD变化的标准差（SD），作为标志物位置变化程度的指标。特别关注观察到显著标志物间变化的病例。
所有IMD的平均方向变化（±SD）为-0.31（±1.41）mm。所有IMD的平均绝对变化（±SD）为1.01（±1.03）mm。观察到的最大IMD变化为10.2mm。在56例个体患者中，计算出IMD变化的SD，范围为0.4至4.2mm。在56例患者中的54例（96%），所有3个IMD的变化SD均为4.0mm或更小，这表明标志物相对位置变化很小。仅2例患者的任何IMD发生变化，SD超过4.0mm，这表明标志物位置有明显且持续的变化。观察到的IMD变化中的最大SD为4.2mm。在这2例中的每一例中，发现2个IMD波动，而第三个IMD保持相当稳定。这一发现意味着168个标志物中的1个在整个治疗过程中其相对位置频繁变化。因此，168个标志物中只有2个（1%）显示出相对位置的频繁变化。对这2例病例的回顾显示，观察到的标志物移动性可能不是由标志物本身的迁移引起的，而是由直肠充盈继发的前列腺变形引起的。为研究极端情况的发生频率，确定每位患者观察到的最大IMD变化。在56例患者中的47例（84%），IMD的最大差异至少为2mm。3mm、4mm和5mm对应的患者数量分别为23例（41%）、10例（18%）和5例（9%）。
本研究是已报道的最大系列局部前列腺癌患者，使用植入前列腺内的标志物进行每日靶区定位，其中记录了各个标志物的位置并计算了IMD，以检测标志物位置变化。168个植入标志物中只有2个在整个治疗过程中显示出相对显著且持续的相对位置变化。然而，这些位置变化很可能不是由标志物迁移引起的，而是由前列腺变形引起的。通常，IMD变化极小，这表明腺体变形相对较小，且不存在明显的标志物迁移。然而，在典型的治疗过程中，IMD在某些情况下可能会有几毫米的变化，这表明虽不常见但有显著变形。在这些情况下，基于3个标志物质心的配准仍将为前列腺在放射野内提供有意义的配准。前列腺内植入的基准点即使在存在器官变形的情况下也能可靠且简单地定位前列腺。
