Reni M, Milella M, Bergamo F, Di Marco M, Giommoni E, Cardellino G G, Cavanna L, Bonomi M, Zustovich F, Bozzarelli S, Salmaso F, Spada M, Orsi G, Macchini M, Insolda J, Procaccio L, Santoni A, De Simone I, Caldirola L, Galli F, Pinto C
Medical Oncology Department, IRCCS Ospedale San Raffaele, Milan, Italy.
Section of Innovation Biomedicine, Department of Engineering for Innovation Medicine (DIMI), University of Verona and Verona University and Hospital Trust (AOUI), Verona, Italy.
ESMO Open. 2025 Jan;10(1):104001. doi: 10.1016/j.esmoop.2024.104001. Epub 2025 Jan 3.
Non-metastatic pancreatic ductal adenocarcinoma (PDAC) presents a challenging scenario: the rarity of the disease, the limited number of completed prospective trials, and the shortcomings of comparability across series produce several controversial topics and unanswered questions. Guideline recommendations usually include all the different therapeutic options, de facto transferring to the multidisciplinary team the responsibility on the final decision. This secondary analysis of the GARIBALDI study was aimed to explore the correlation of center type, self-declared volume, and commitment with the overall survival (OS) in patients with non-metastatic PDAC.
Treatment-naïve patients aged ≥18 years with a pathological diagnosis of non-metastatic PDAC, enrolled between July 2017 and October 2019, were analyzed. OS was defined as the time from treatment start to death. The impact of centers and clinical-demographic characteristics on OS was evaluated using Cox models.
Overall, 402 patients enrolled in 41 centers were eligible for this analysis. The median age was 68.4 years (range 35.6-88.8 years), 49.5% were females, 93.5% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, 16.7% had prior cancer history, and the median CA 19-9 level was 171.5 IU/ml (first-third quartile 24.5-937.5 IU/ml). For 79.8% of patients treatment started within 1 month from diagnosis. Thirty six point six percent of patients underwent upfront surgery and 91.8% of these received a subsequent adjuvant chemotherapy; 14.2% received chemotherapy followed by surgery and 49.3% chemotherapy without surgery. The preferred chemotherapy schemes were gemcitabine (54.8%) for adjuvant chemotherapy and nab-paclitaxel + gemcitabine (55.3%) for upfront chemotherapy. The median follow-up was 57.6 months and 300 patients died. A statistically significant shorter OS was observed in both low- [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.12-2.32, P = 0.0099] and medium-commitment (HR 1.57, 95% CI 1.10-2.23, P = 0.0120) compared to high-commitment institutions, when adjusting for clinically relevant covariates.
The GARIBALDI study suggests that the volume and the academic brand are not associated with OS in patients with non-metastatic PDAC, while center commitment warrants further exploration.
非转移性胰腺导管腺癌（PDAC）的情况颇具挑战性：该疾病较为罕见，已完成的前瞻性试验数量有限，且各系列研究之间可比性存在不足，从而产生了几个有争议的话题和未解决的问题。指南建议通常涵盖所有不同的治疗选择，实际上将最终决策的责任交给了多学科团队。对加里波第研究的这项二次分析旨在探讨中心类型、自我宣称的治疗量以及投入程度与非转移性PDAC患者总生存期（OS）之间的相关性。
对2017年7月至2019年10月期间入组的年龄≥18岁、经病理诊断为非转移性PDAC且未接受过治疗的患者进行分析。OS定义为从治疗开始至死亡的时间。使用Cox模型评估中心及临床人口统计学特征对OS的影响。
总体而言，41个中心入组的402例患者符合本分析条件。中位年龄为68.4岁（范围35.6 - 88.8岁），49.5%为女性，93.5%的东部肿瘤协作组（ECOG）体能状态为0 - 1，16.7%有既往癌症史，CA 19 - 9水平的中位数为171.5 IU/ml（第一 - 第三四分位数为24.5 - 937.5 IU/ml）。79.8%的患者在诊断后1个月内开始治疗。36.6%的患者接受了 upfront手术，其中91.8%接受了后续辅助化疗；14.2%接受化疗后手术，49.3%接受单纯化疗。辅助化疗的首选方案是吉西他滨（54.8%），upfront化疗的首选方案是白蛋白结合型紫杉醇 + 吉西他滨（55.3%）。中位随访时间为57.6个月，300例患者死亡。在调整临床相关协变量后，与高投入机构相比，低投入（风险比[HR] 1.61，95%置信区间[CI] 1.12 - 2.32，P = 0.0099）和中等投入机构（HR 1.57，95% CI 1.10 - 2.23，P = 0.0120）的OS均显著缩短。
加里波第研究表明，对于非转移性PDAC患者，治疗量和学术声誉与OS无关，而中心投入程度值得进一步探究。
