Pei Yulei, Ning Renli, Hu Wei, Li Ping, Zhang Zhenshan, Deng Yong, Hong Zhengshan, Sun Yun, Guo Xiaomao, Zhang Qing
Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China.
Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, China.
Front Oncol. 2022 Jul 22;12:845583. doi: 10.3389/fonc.2022.845583. eCollection 2022.
As local recurrence remains a challenge and the advantages of the simultaneous integrated boost (SIB) technique have been validated in photon radiotherapy, we applied the SIB technique to CIRT. The aim was to investigate the metabolomic changes of the CIRT with concurrent androgen deprivation therapy (ADT) in localized prostate cancer (PCa) and the unique metabolic effect of the SIB technique.
This study enrolled 24 pathologically confirmed PCa patients. All patients went through CIRT with concurrent ADT. The gross target volume (GTV) boost was defined as positive lesions on both Ga-PSMA PET/CT and mpMRI images. Urine samples collected before and after CIRT were analyzed by the Q-TOF UPLC-MS/MS system. R platform and MetDNA were used for peak detection and identification. Statistical analysis and metabolic pathway analysis were performed on Metaboanalyst.
The metabolite profiles were significantly altered after CIRT. The most significantly altered metabolic pathway is PSMA participated alanine, aspartate and glutamate metabolism. Metabolites in this pathway showed a trend to be better suppressed in the SIB group. A total of 11 identified metabolites were significantly discriminative between two groups and all of them were better down-regulated in the SIB group. Meanwhile, among these metabolites, three metabolites in DNA damage and repair related purine metabolism were down-regulated to a greater extent in the SIB group.
Metabolic dysfunction was one of the typical characteristics of PCa. CIRT with ADT showed a powerful inhibition of PCa metabolism, especially in PSMA participated metabolic pathway. The SIB CIRT showed even better performance on down-regulation of most metabolism than uniform-dose-distribution CIRT. Meanwhile, the SIB CIRT also showed its unique superiority to inhibit purine metabolism. PSMA PET/CT guided SIB CIRT showed its potentials to further benefit PCa patients.
由于局部复发仍然是一个挑战，并且同步整合加量（SIB）技术在光子放射治疗中的优势已得到验证，我们将SIB技术应用于碳离子放疗（CIRT）。目的是研究局部前列腺癌（PCa）中CIRT联合雄激素剥夺治疗（ADT）后的代谢组学变化以及SIB技术独特的代谢效应。
本研究纳入了24例经病理证实的PCa患者。所有患者均接受了CIRT联合ADT治疗。大体靶区（GTV）加量定义为Ga-PSMA PET/CT和mpMRI图像上的阳性病变。采用Q-TOF超高效液相色谱-串联质谱系统分析CIRT前后采集的尿液样本。使用R平台和MetDNA进行峰检测和鉴定。在Metaboanalyst上进行统计分析和代谢途径分析。
CIRT后代谢物谱发生了显著变化。变化最显著的代谢途径是PSMA参与的丙氨酸、天冬氨酸和谷氨酸代谢。该途径中的代谢物在SIB组中显示出更好的抑制趋势。两组之间共有11种已鉴定的代谢物具有显著差异，且所有这些代谢物在SIB组中下调程度更大。同时，在这些代谢物中，DNA损伤与修复相关嘌呤代谢中的三种代谢物在SIB组中下调程度更大。
代谢功能障碍是PCa的典型特征之一。CIRT联合ADT对PCa代谢具有强大的抑制作用，尤其是在PSMA参与的代谢途径中。与均匀剂量分布的CIRT相比，SIB CIRT在下调大多数代谢方面表现出更好的效果。同时，SIB CIRT在抑制嘌呤代谢方面也显示出其独特的优势。PSMA PET/CT引导的SIB CIRT显示出进一步使PCa患者受益的潜力。
