van Goor Iris W J M, Raymakers Leon, Andel Daan S H, Brosens Lodewijk A A, Kranenburg Onno, Leusen Jeanette H W, Meijer Gert J, Molenaar I Quintus, van Santvoort Hjalmar C, de Vries J H Wilfred, Wopereis Andre J M, Intven Martijn P W, Daamen Lois A
Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands.
Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands.
Clin Transl Radiat Oncol. 2024 Jul 27;48:100829. doi: 10.1016/j.ctro.2024.100829. eCollection 2024 Sep.
The effectiveness of radiotherapy for pancreatic cancer is debated. Patient-derived organoids (PDOs) already mimicked clinical radiation response in other cancer types, which could be valuable in pancreatic cancer as well. This study aimed to investigate whether PDOs can be used to model RT response in pancreatic cancer and to explore the presence of a dose-response correlation.
PDOs derived from two pancreatic cancer patients (HUB-08-B2-022A and HUB-08-B2-026B) were irradiated with doses ranging from 0 to 40 Gray. Viability assessments were conducted after seven and 10 days by measuring ATP-levels. Results were normalized, defining the viability at 0 Gray as 100 % and an absolute viability of 0 as 0 %. The relative area under the curve (rAUC) was calculated (0 = total sensitivity, 1 = total resistance).
With a readout time of seven days, both HUB-08-B2-022A and HUB-08-B2-026B exhibited viability above 50 % at the highest dose of 12 Gy (rAUC of 0.79 and 0.69, respectively). With a readout time of 10 days, both PDOs showed a dose-response relation although HUB-08-B2-022A was more sensitive than HUB-08-B2-026B (rAUC of 0.37 and 0.51, respectively). Increasing the radiation dose to 40 Gy did not further affect viability, but the dose-response relation remained present (rAUC of 0.13 and 0.26, respectively). In the final experiment with a readout time of 10 days and a maximum dose of 14 Gy, the dose-response correlation was paramount in both PDOs (rAUC 0.28 and 0.45, respectively), with HUB-08-B2-022A being most sensitive.
In this setup, both pancreatic cancer PDOs showed an irradiation dose-response correlation. These preliminary findings suggest that pancreatic cancer PDOs are suitable for assessing radiation response . Further experiments are needed to eventually simulate treatment responses to personalized treatment strategies.
胰腺癌放疗的有效性存在争议。患者来源的类器官（PDO）已在其他癌症类型中模拟了临床放射反应，这在胰腺癌中可能也具有价值。本研究旨在调查PDO是否可用于模拟胰腺癌的放疗反应，并探索剂量反应相关性的存在。
对两名胰腺癌患者（HUB-08-B2-022A和HUB-08-B2-026B）来源的PDO进行0至40格雷剂量的照射。在照射7天和10天后通过测量ATP水平进行活力评估。结果进行归一化处理，将0格雷时的活力定义为100%，绝对活力为0时定义为0%。计算曲线下相对面积（rAUC）（0 = 完全敏感，1 = 完全耐药）。
在7天的读数时间下，HUB-08-B2-022A和HUB-08-B2-026B在最高12格雷剂量下的活力均高于50%（rAUC分别为0.79和0.69）。在10天的读数时间下，两个PDO均显示出剂量反应关系，尽管HUB-08-B2-022A比HUB-08-B2-026B更敏感（rAUC分别为0.37和0.51）。将辐射剂量增加到40格雷并未进一步影响活力，但剂量反应关系仍然存在（rAUC分别为0.13和0.26）。在最终读数时间为10天且最大剂量为14格雷的实验中，两个PDO中剂量反应相关性均最为显著（rAUC分别为0.28和0.45），其中HUB-08-B2-022A最为敏感。
在此设置下，两种胰腺癌PDO均显示出照射剂量反应相关性。这些初步发现表明胰腺癌PDO适用于评估放射反应。需要进一步实验以最终模拟对个性化治疗策略的治疗反应。
