Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Tumori. 2024 Dec;110(6):470-474. doi: 10.1177/03008916241291341. Epub 2024 Oct 27.
There is debate about the optimal management of borderline resectable (bRe) and resectable (Re) pancreatic ductal adenocarcinoma (PDAC). Both preclinical and clinical evidence showed that carbon ion radiotherapy (CIRT) produces superior control on radioresistant histologies compared to conventional photon beam radiotherapy (RT). However, so far there is a lack of data concerning the integration of CIRT in a multimodal approach with chemotherapy and surgery for bRe/Re.
We recently presented the first analysis of a multicenter prospective phase II clinical study aimed at assessing the feasibility and effectiveness of a neoadjuvant chemotherapy + short course of CIRT followed by surgery and adjuvant chemotherapy in the management of bRe/Re PDAC. The study was terminated early due to low patient enrollment.Herein, we reported a post-hoc analysis focusing on toxicity, dosimetry and translational assessment.
In our experience, CIRT can be integrated into a multimodal treatment strategy for bRe/Re PDAC, alongside chemotherapy and surgery. A case of fatal liver failure occurring three months post-surgery has been documented, likely related to the combination approach. Although the treatment plans were satisfactory according to the Local Effect Model (LEM) model, recalculations using the modified Microdosimetric Kinetic Model (mMKM) revealed suboptimal target coverage. Additionally, we observed an increased expression of PD-L1 following CIRT.
This multimodal approach was well tolerated; however, clinicians should carefully monitor for vascular disorders during follow-up and further investigate surgical techniques after CIRT. The increased PD-L1 expression supports the immunogenic effects of particle therapy and lays the groundwork for future studies. To enhance the therapeutic ratio of CIRT treatments, integrating LET-d based objectives into the plan optimization process should be considered.
ClinicalTrials.gov Identifier: NCT03822936.
对于交界可切除（bRe）和可切除（Re）胰腺导管腺癌（PDAC），其最佳治疗方案仍存在争议。临床前和临床证据均表明，与传统光子束放疗（RT）相比，碳离子放疗（CIRT）对放射抗拒组织具有更好的控制效果。然而，目前关于 CIRT 与化疗和手术联合应用于 bRe/Re 治疗的多模态方法的数据仍然缺乏。
我们最近首次分析了一项多中心前瞻性 II 期临床研究，该研究旨在评估新辅助化疗+短程 CIRT 联合手术和辅助化疗治疗 bRe/Re PDAC 的可行性和有效性。由于患者入组数量低，该研究提前终止。在此，我们报告了一项侧重于毒性、剂量学和转化评估的事后分析。
在我们的经验中，CIRT 可以与化疗和手术一起整合到 bRe/Re PDAC 的多模态治疗策略中。术后三个月发生了一例致命性肝衰竭病例，可能与联合治疗有关。尽管根据局部效应模型（LEM）模型，治疗计划是令人满意的，但使用改良微剂量动力学模型（mMKM）重新计算显示靶区覆盖不理想。此外，我们观察到 CIRT 后 PD-L1 表达增加。
这种多模态方法耐受性良好；然而，临床医生在随访过程中应仔细监测血管疾病，并进一步研究 CIRT 后的手术技术。PD-L1 表达的增加支持粒子治疗的免疫原性效应，并为未来的研究奠定了基础。为了提高 CIRT 治疗的治疗比，应考虑将 LET-d 为基础的目标纳入计划优化过程。
ClinicalTrials.gov 标识符：NCT03822936。
