Clinical and genomic characterization of pancreatic ductal adenocarcinoma patients with lung oligometastasis

N.S. Tissera , M. Chiaravalli , A. Turpin , R. Luca , F. Castet , C. Fabregat-Franco , G. Castillo , D. López-Valbuena , G. Tortora , P. Hammel , J.M. O’Connor , J. Matito , A. Vivancos , T.V. Tian , T. Macarulla
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Abstract

Background

Lung-only relapse following resection of pancreatic ductal adenocarcinoma (PDAC) is rare. While oligometastatic lung disease (OMLD) is detected after PDAC resection, its clinical and molecular features remain unclear. Our goal was to assess if lung metastatic lesion quantity and mutations could predict a better prognosis.

Materials and methods

We carried out a multicentric retrospective analysis of clinical and genomic characteristics in PDAC patients with OMLD and compared them with those with non-oligometastatic lung-only disease (non-OMLD).

Results

Thirty-nine patients meeting inclusion criteria were analyzed (OMLD n = 18, non-OMLD n = 21). OMLD exhibited more frequent unilateral location (87.5% versus 0%) and late recurrence (88.9% versus 47.6%) compared to non-OMLD. The median disease-free survival in patients with OMLD was 23.2 months versus 10.7 months in those with non-OMLD [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.27-1]. Moreover, OMLD patients had a longer median overall survival (35.7 months) compared to non-OMLD patients (26.2 months) (HR 0.34, 95% CI 0.12-0.96). Both groups shared common PDAC driver mutations (KRAS, TP53, CDKN2A, and SMAD4). Two OMLD patients had pathogenic DNA damage repair gene mutations.

Conclusions

Our study shows an OMLD incidence of 3.4% in PDAC patients after surgical resection. Patients with OMLD have distinct clinical characteristics compared to those with non-OMLD. PDAC driver mutations were found at similar rates in both groups. Further studies are needed for better understanding of OMLD and treatment strategies.

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胰腺导管腺癌合并肺少转移患者的临床和基因组特征
背景:胰腺导管腺癌(PDAC)切除术后仅肺部复发是罕见的。虽然PDAC切除术后检测到肺少转移性疾病(OMLD),但其临床和分子特征尚不清楚。我们的目的是评估肺转移灶的数量和突变是否可以预测更好的预后。材料和方法我们对PDAC合并OMLD患者的临床和基因组特征进行了多中心回顾性分析,并将其与非低转移性肺部疾病(non-OMLD)患者进行了比较。结果39例患者符合纳入标准,其中OMLD患者18例,非OMLD患者21例。与非OMLD相比,OMLD表现出更频繁的单侧位置(87.5%对0%)和晚期复发(88.9%对47.6%)。OMLD患者的中位无病生存期为23.2个月,非OMLD患者的中位无病生存期为10.7个月[风险比(HR) 0.52, 95%可信区间(CI) 0.27-1]。此外,与非OMLD患者(26.2个月)相比,OMLD患者的中位总生存期(35.7个月)更长(HR 0.34, 95% CI 0.12-0.96)。两组都有共同的PDAC驱动突变(KRAS, TP53, CDKN2A和SMAD4)。2例OMLD患者存在致病性DNA损伤修复基因突变。结论我们的研究显示PDAC患者手术切除后的OMLD发生率为3.4%。与非OMLD患者相比,OMLD患者具有明显的临床特征。两组的PDAC驱动突变发生率相似。需要进一步的研究来更好地了解OMLD和治疗策略。
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