Clinical and biological markers predictive of treatment response associated with metastatic pancreatic adenocarcinoma

被引：2

作者：

Dayimu, Alimu ^{[1
]}

Di Lisio, Lorena ^{[2
]}

Anand, Shubha ^{[2
]}

Roca-Carreras, Isart ^{[2
]}

Qian, Wendi ^{[3
]}

Al-Mohammad, Abdulrahman ^{[4
]}

Basu, Bristi ^{[5
]}

Valle, Juan W. W. ^{[6
,7
]}

Jodrell, Duncan ^{[5
]}

Demiris, Nikos ^{[3
,8
]}

Corrie, Pippa ^{[4
]}

机构：

[1] Univ Cambridge, Dept Oncol, Clin Trials Unit, Cambridge, Cambs, England

[2] Univ Cambridge, Dept Oncol, Canc Mol Diagnost Lab, Cambridge, Cambs, England

[3] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Clin Trials Unit, Cambridge, Cambs, England

[4] Cambridge Univ Hosp NHS Fdn Trust, Oncol Dept, Cambridge, Cambs, England

[5] Univ Cambridge, Dept Oncol, Cambridge, Cambs, England

[6] Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England

[7] Christie NHS Fdn Trust, Manchester, Lancs, England

[8] Athens Univ Econ & Business, Dept Stat, Athens, Greece

来源：

BRITISH JOURNAL OF CANCER | 2023年 / 128卷 / 09期

关键词：

PROGNOSTIC VALUE; CANCER; GEMCITABINE; SURVIVAL; TRIALS; SCORE; DNA;

D O I：

10.1038/s41416-023-02170-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundChemotherapy for metastatic pancreatic adenocarcinoma (PDAC) offers limited benefits, but survival outcomes vary. Reliable predictive response biomarkers to guide patient management are lacking.MethodsPatient performance status, tumour burden (determined by the presence or absence of liver metastases), plasma protein biomarkers (CA19-9, albumin, C-reactive protein and neutrophils) and circulating tumour DNA (ctDNA) were assessed in 146 patients with metastatic PDAC prior to starting either concomitant or sequential nab-paclitaxel + gemcitabine chemotherapy in the SIEGE randomised prospective clinical trial, as well as during the first 8 weeks of treatment. Correlations were made with objective response, death within 1 year and overall survival (OS).ResultsInitial poor patient performance status, presence of liver metastases and detectable (mut)KRAS ctDNA all correlated with worse OS after adjusting for the different biomarkers of interest. Objective response at 8 weeks also correlated with OS (P = 0.026). Plasma biomarkers measured during treatment and prior to the first response assessment identified >= 10% decrease in albumin at 4 weeks predicted for worse OS (HR 4.75, 95% CI 1.43-16.94, P = 0.012), while any association of longitudinal evaluation of (mut)KRAS ctDNA with OS was unclear (beta = 0.024, P = 0.057).ConclusionsReadily measurable patient variables can aid the prediction of outcomes from combination chemotherapy used to treat metastatic PDAC. The role of (mut)KRAS ctDNA as a tool to guide treatment warrants further exploration.

引用

页码：1672 / 1680

页数：9

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