Preoperative chemo-CIRT in Re/BRe pancreatic cancer: Insights from a multicenter prospective phase II clinical study (NCT03822936).

IF 2 4区 医学 Q3 ONCOLOGY
Tumori Pub Date : 2024-12-01 Epub Date: 2024-10-27 DOI:10.1177/03008916241291341
Amelia Barcellini, Silvia Molinelli, Alessandro Vanoli, Viviana Vitolo, Piero Fossati, Alessandro Vai, Anna Pagani, Frediano Inzani, Mattia Pecorilla, Giovanni Butturini, Catherine Klersy, Lorenzo Preda, Angelica Facoetti, Francesca Valvo, Ester Orlandi
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引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration number: ClinicalTrials.gov Identifier: NCT03822936.

Re/BRe胰腺癌术前化疗-CIRT:一项多中心前瞻性 II 期临床研究的启示(NCT03822936)。
目的:关于边界可切除(bRe)和可切除(Re)胰腺导管腺癌(PDAC)的最佳治疗方法存在争议。临床前和临床证据都表明,与传统的光子束放射治疗(RT)相比,碳离子放射治疗(CIRT)能更好地控制耐放射组织学。然而,迄今为止,还缺乏有关碳离子放疗与化疗和手术治疗 bRe/Re 的多模式整合的数据:我们最近首次对一项多中心前瞻性 II 期临床研究进行了分析,该研究旨在评估新辅助化疗+短期 CIRT 疗程,然后进行手术和辅助化疗治疗 bRe/Re PDAC 的可行性和有效性。在此,我们报告了一项事后分析,重点关注毒性、剂量学和转化评估:结果:根据我们的经验,CIRT可与化疗和手术一起被纳入bRe/Re PDAC的多模式治疗策略。有记录显示,一例致命的肝衰竭发生在手术后三个月,很可能与联合治疗方法有关。虽然根据局部效应模型(LEM)进行的治疗方案令人满意,但使用改良的微剂量动力学模型(mMKM)重新计算后发现,靶点覆盖率并不理想。此外,我们还观察到 CIRT 治疗后 PD-L1 的表达增加:结论:这种多模式方法的耐受性良好,但临床医生在随访过程中应仔细监测血管病变,并进一步研究 CIRT 后的手术技术。PD-L1 表达的增加支持了粒子疗法的免疫原性效应,为未来的研究奠定了基础。为提高CIRT治疗的治疗率,应考虑将剂量平均LETd(基于LETd的目标)纳入计划优化过程:试验注册号:ClinicalTrials.gov Identifier:NCT03822936.
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来源期刊
Tumori
Tumori 医学-肿瘤学
CiteScore
3.50
自引率
0.00%
发文量
58
审稿时长
6 months
期刊介绍: Tumori Journal covers all aspects of cancer science and clinical practice with a strong focus on prevention, translational medicine and clinically relevant reports. We invite the publication of randomized trials and reports on large, consecutive patient series that investigate the real impact of new techniques, drugs and devices inday-to-day clinical practice.
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