Gridley Daila S, Bonnet Reiner B, Bush David A, Franke Christian, Cheek Gregory A, Slater Jerry D, Slater James M
Department of Radiation Medicine, School of Medicine, Loma Linda University and Medical Center, Chan Shuh Pavilion, 11175 Campus Street, Loma Linda, CA 92354, USA.
Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):759-66. doi: 10.1016/j.ijrobp.2004.04.022.
We prospectively measured the levels of basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10, and procollagen III peptide (P III P) in serum from non-small-cell lung cancer patients treated with photons combined with protons or protons alone. These factors were quantified because they may be extremely important in the development of side effects, and the treated volume integral dose may be crucial in inducing them.
Of the 12 participating patients, 6 with squamous cell carcinoma (SCC) and 3 with adenocarcinoma received combined photon/proton beam radiation, whereas 2 with SCC and 1 with large-cell carcinoma (LCC) received only proton radiation. Mean age was 73.6 years. There were 4 male and 8 female patients with a mean smoking history of 87.0 packyears. Nine patients had Stage I, 2 had Stage II, and 1 had stage IIIA lung cancer. Serum samples were obtained at baseline and on Days 15, 30, 45, 60, 90, 120, 150, 180, and 210 after initiation of radiation therapy. Injury scores for pneumonitis and fibrosis based on computed tomography (CT) scans were assigned.
The percentage of lung volume irradiated was significantly less for patients treated with protons alone compared with those receiving photon plus proton therapy (p < 0.001). Injury scores were also lower for proton only treatment (p = 0.039). When evaluated collectively, bFGF, TNF-alpha, and IL-6 concentrations were significantly higher in the photon/proton group (p < 0.05 or less); radiation regimen, but not time after treatment initiation, was a significant factor in their levels. P III P level was also higher in the photon/proton patients (p < 0.001) and both radiation regimen (p = 0.027) and time after treatment (p = 0.019) had an impact.
Although significant changes occurred in some of the measured cytokines and P III P, it was the difference in the volume integral dose that occurred when protons were used alone vs. mixed photon/proton therapy that correlated with the incidence of pneumonitis and/or fibrosis. However, it cannot be ruled out that differences in cytokine levels before radiotherapy initiation may have contributed to the outcome.
我们前瞻性地测量了接受光子联合质子治疗或仅接受质子治疗的非小细胞肺癌患者血清中碱性成纤维细胞生长因子（bFGF）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6、IL-10和前胶原III肽（P III P）的水平。对这些因子进行定量是因为它们在副作用的发生中可能极为重要，且治疗体积积分剂量在诱导这些副作用方面可能至关重要。
12名参与研究的患者中，6例鳞状细胞癌（SCC）患者和3例腺癌患者接受了光子/质子束联合放疗，而2例SCC患者和1例大细胞癌（LCC）患者仅接受了质子放疗。平均年龄为73.6岁。有4名男性和8名女性患者，平均吸烟史为87.0包年。9例患者为I期肺癌，2例为II期肺癌，1例为IIIA期肺癌。在放疗开始时的基线以及放疗后第15、30、45、60、90、120、150、180和210天采集血清样本。根据计算机断层扫描（CT）扫描结果对肺炎和纤维化的损伤评分进行赋值。
与接受光子加质子治疗的患者相比，仅接受质子治疗的患者肺部受照射体积的百分比显著更低（p < 0.001）。仅接受质子治疗的患者的损伤评分也更低（p = 0.039）。综合评估时，光子/质子组中bFGF、TNF-α和IL-6的浓度显著更高（p < 0.05或更低）；放疗方案而非治疗开始后的时间是其水平的一个显著因素。光子/质子治疗患者的P III P水平也更高（p < 0.001），放疗方案（p = 0.027）和治疗后的时间（p = 0.019）均有影响。
尽管在一些测量的细胞因子和P III P中发生了显著变化，但单独使用质子与光子/质子混合治疗时出现的体积积分剂量差异与肺炎和/或纤维化的发生率相关。然而，不能排除放疗开始前细胞因子水平的差异可能对结果有影响。
