TY - JOUR
T1 - Preoperative chemo-CIRT in Re/BRe pancreatic cancer
T2 - Insights from a multicenter prospective phase II clinical study (NCT03822936)
AU - Barcellini, Amelia
AU - Molinelli, Silvia
AU - Vanoli, Alessandro
AU - Vitolo, Viviana
AU - Fossati, Piero
AU - Vai, Alessandro
AU - Pagani, Anna
AU - Inzani, Frediano
AU - Pecorilla, Mattia
AU - Butturini, Giovanni
AU - Klersy, Catherine
AU - Preda, Lorenzo
AU - Facoetti, Angelica
AU - Valvo, Francesca
AU - Orlandi, Ester
N1 - Publisher Copyright:
© Fondazione IRCCS Istituto Nazionale dei Tumori 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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 dose-averaged LETd (LETd-based objectives into the plan optimization process should be considered. Trial Registration Number: ClinicalTrials.gov
AB - 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 dose-averaged LETd (LETd-based objectives into the plan optimization process should be considered. Trial Registration Number: ClinicalTrials.gov
KW - Carbon ion radiotherapy
KW - LET
KW - PDL1
KW - borderline/resectable pancreatic adenocarcinomas
KW - Pancreatic Neoplasms/therapy
KW - Prospective Studies
KW - Humans
KW - Middle Aged
KW - Male
KW - Treatment Outcome
KW - Combined Modality Therapy
KW - Carcinoma, Pancreatic Ductal/therapy
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Female
KW - Aged
KW - Heavy Ion Radiotherapy/methods
KW - Neoadjuvant Therapy/methods
UR - http://www.scopus.com/inward/record.url?scp=85207936842&partnerID=8YFLogxK
U2 - 10.1177/03008916241291341
DO - 10.1177/03008916241291341
M3 - Journal article
C2 - 39462835
SN - 0300-8916
VL - 110
SP - 470
EP - 474
JO - Tumori
JF - Tumori
IS - 6
ER -