Dok Rüveyda, Vanderwaeren Laura, Verstrepen Kevin J, Nuyts Sandra
Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, University of Leuven, 3000 Leuven, Belgium.
Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, 3000 Leuven, Belgium.
Cancers (Basel). 2024 May 22;16(11):1959. doi: 10.3390/cancers16111959.
Photon-based radiotherapy (XRT) is one of the most frequently used treatment modalities for HPV-negative and HPV-positive locally advanced head and neck squamous cell carcinoma (HNSCC). However, locoregional recurrences and normal RT-associated toxicity remain major problems for these patients. Proton therapy (PT), with its dosimetric advantages, can present a solution to the normal toxicity problem. However, issues concerning physical delivery and the lack of insights into the underlying biology of PT hamper the full exploitation of PT. Here, we assessed the radiobiological processes involved in PT in HPV-negative and HPV-positive HNSCC cells. We show that PT and XRT activate the DNA damage-repair and stress response in both HPV-negative and HPV-positive cells to a similar extent. The activation of these major radiobiological mechanisms resulted in equal levels of clonogenic survival and mitotic cell death. Altogether, PT resulted in similar biological effectiveness when compared to XRT. These results emphasize the importance of dosimetric parameters when exploiting the potential of increased clinical effectiveness and reduced normal tissue toxicity in PT treatment.
基于光子的放射疗法（XRT）是治疗人乳头瘤病毒（HPV）阴性和HPV阳性局部晚期头颈部鳞状细胞癌（HNSCC）最常用的治疗方式之一。然而，局部区域复发和放疗相关的正常组织毒性仍是这些患者面临的主要问题。质子疗法（PT）具有剂量学优势，可为正常组织毒性问题提供解决方案。然而，物理递送问题以及对PT潜在生物学机制缺乏深入了解阻碍了PT的充分应用。在此，我们评估了HPV阴性和HPV阳性HNSCC细胞中PT涉及的放射生物学过程。我们发现，PT和XRT在HPV阴性和HPV阳性细胞中激活DNA损伤修复和应激反应的程度相似。这些主要放射生物学机制的激活导致克隆形成存活率和有丝分裂细胞死亡水平相当。总体而言，与XRT相比，PT产生的生物学效应相似。这些结果强调了在利用PT提高临床疗效和降低正常组织毒性潜力时剂量学参数的重要性。
