The impact of metastatic sites in advanced pancreatic adenocarcinoma, systematic review and meta-analysis of prospective randomized studies

Usón, Pedro Luiz Serrano; Tolentino, Fernanda D'Avila Sampaio; Santos, Vilmara Almeida dos; Rother, Edna Terezinha

doi:10.1371/journal.pone.0230060

Cited by 20 publications

(11 citation statements)

References 26 publications

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“…Our observation, combined by findings from other groups, corroborates the hypothesis that detection of ctDNA mutated KRAS at diagnosis of advanced pancreatic cancer is correlated with reduced time-to-progression and overall survival ( 35 – 37 ). Patients with a KRAS mutation more frequently presented the liver as the primary site of metastasis compared to those without KRAS mutations, several studies indicate that liver metastasis confers worse overall survival probabilities in MPC when compared to other metastatic sites such as the lung or bones ( 38 , 39 ), and further prospective analyses in larger cohorts would be necessary to address those associations. Interestingly, in a subgroup of patients, clearance of TP53 17% (3/18)or KRAS 33% (6/18) mutations after chemotherapy treatment was associated with improved PFS (p=0.0056 and p=0.037, HR of 0.087 and 0.32, respectively), and this observation is corroborated by other groups and highlights additional clinical utility of ctDNA in PDAC ( 27 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival

et al. 2022

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BackgroundPlasma-based circulating cell-free tumor DNA (ctDNA) genomic profiling by next-generation sequencing (NGS)is an emerging diagnostic tool for pancreatic cancer (PC). The impact of detected genomic alterations and variant allele fraction (VAF) in tumor response to systemic treatments and outcomes is under investigation.MethodsPatients with advanced PC who had ctDNA profiled at time of initial diagnosis were retrospectively evaluated. We considered the somatic alteration with the highest VAF as the dominant clone allele frequency (DCAF). ctDNA NGS results were related to clinical demographics, progression-free survival (PFS) and overall survival (OS).ResultsA total of 104 patients were evaluated. Somatic alterations were detected in 84.6% of the patients. Patients with ≥ 2 detectable genomic alterations had worse median PFS (p < 0.001) and worse median OS (p = 0.001). KRAS was associated with disease progression to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (p < 0.001) and worse median OS (p = 0.002). TP53 was associated with worse median PFS (p = 0.02) and worse median OS (p = 0.001). The median DCAF was 0.45% (range 0-55%). DCAF >0.45% was associated with worse median PFS (p<0.0001) and median OS (p=0.0003). Patients that achieved clearance of KRAS had better PFS (p=0.047), while patients that achieved clearance of TP53 had better PFS (p=0.0056) and OS (p=0.037).ConclusionsInitial detection of ctDNA in advanced PC can identify somatic alterations that may help predict clinical outcomes. The dynamics of ctDNA are prognostic of outcomes and should be evaluated in prospective studies.

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Section: Discussionmentioning

confidence: 99%

Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival

et al. 2022

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“…Patients with more prognostic factors showed worse OS in both patient groups. Liver metastasis, NLR, and CA19-9 have already been reported to be significant prognostic factors in patients who received systemic palliative chemotherapy in many large clinical trials worldwide [13,14] . A summary of the main reports sited here is shown in Table 4.…”

Section: Discussionmentioning

confidence: 97%

“…Liver metastasis, NLR, and CA19-9 have already been reported to be significant prognostic factors in patients who received systemic palliative chemotherapy in many large clinical trials worldwide. [ 13 , 14 ] A summary of the main reports sited here is shown in Table 4 . We provide further evidence for this in the present study, using real-world samples in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Simple prognostic markers for optimal treatment of patients with unresectable pancreatic cancer

et al. 2021

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Most patients with pancreatic cancer are ineligible for curative resection at diagnosis, resulting in poor prognosis. This study aimed to evaluate the prognostic factors in patients with unresectable pancreatic cancer.We retrospectively collected clinical data from 196 patients with unresectable pancreatic cancer who received palliative chemotherapy (N = 153) or palliative care alone (N = 43) from January 2011 to December 2013. Patients' background data and overall survival were analyzed using the Cox proportional hazard regression model.In patients receiving palliative chemotherapy (gemcitabine-based regimen, 88.2%) and palliative care alone, the median (range) ages were 68 (43-91) and 78 (53-90) years, and metastatic diseases were present in 80% (N = 123) and 86% (N = 37), respectively. Multivariate analysis in the palliative chemotherapy patients showed that liver metastasis (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.58-3.20, P < .001), neutrophil-to-lymphocyte ratio (>4.5 vs 4.5; HR 3.45, 95% CI 2.22-5.36, P < .001), and cancer antigen 19-9 (CA19-9) (≥900 vs <900 U/mL; HR 1.45, 95% CI 1.02-2.05, P = .036) were independent prognostic factors. In those receiving palliative care alone, lung (HR 3.27, 95% Cl 1.46-7.35, p = 0.004) and peritoneum (HR 2.50, 95% CI 1.20-5.18, P = .014) metastases and the C-reactive protein-to-albumin ratio (≥1.3 vs <1.3; HR 3.33, 95% Cl 1.51-7.35, P = .003) were independent prognostic factors. Furthermore, patients with multiple factors had worse prognosis in both groups. Median survival time of palliative chemotherapy patients with risk factors 0, 1, 2, and 3 were 13.1 (95% CI 8.0-16.9), 9.4 (95% CI 7.9-10.1), 6.6 (95% CI 4.9-7.8), and 2.5 (95% CI 1.7-4.0) months, respectively. Similarly, median survival time was 5.7 (95% CI 1.3 -8.0), 2.1 (95% CI 1.5-3.9), and 1.3 (95% CI 0.6-1.7) months, respectively, for palliative care alone patients with risk factor 0, 1, and 2 to 3.Prognostic markers for pancreatic cancer were neutrophil-to-lymphocyte ratio, liver metastasis, and CA19-9 in patients undergoing palliative chemotherapy and C-reactive protein-to-albumin ratio and lung/peritoneum metastases in patients undergoing palliative care alone. These simple markers should be considered when explaining the prognosis and therapeutic options to patients.

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“…However, unlike the number of metastatic sites which has no impact on OS, liver involvement proved to be a poor prognostic sign both in terms of OS and PFS. [ 27 ] Furthermore, the liver involvement appears to be a predictive factor as well. In fact, patients with pancreatic cancer and liver metastases benefit more from nab-P/Gem than Gem alone, although liver mets are associated with worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

The effectiveness of nab-paclitaxel plus gemcitabine and gemcitabine monotherapy in first-line metastatic pancreatic cancer treatment: A real-world evidence

et al. 2022

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Pancreatic cancer is one of the most lethal malignancies with a rise in mortality rates. FOLFIRINOX and nab-paclitaxel plus gemcitabine demonstrated a survival benefit compared to gemcitabine alone. Both protocols are now considered the standard of first-line treatment with no significant difference between them, primarily based on observational studies. Although new therapeutic options have emerged recently, the prognosis remains poor. We conducted a retrospective single-center study on 139 patients treated for metastatic pancreatic adenocarcinoma (mPDAC) with gemcitabine monotherapy (Gem) or nab-paclitaxel + gemcitabine (Nab-P/Gem) in the first line. The aim of our study was to evaluate the effectiveness in terms of overall survival (OS) and progression-free survival (PFS) as well as the influence of patient and disease characteristics on outcomes. Nab-P/Gem resulted in OS of 13.87 months compared to 8.5 months in patients receiving Gem. The same trend was achieved in PFS, 5.37 versus 2.80 months, respectively, but without reaching statistical significance. Furthermore, the 6-month survival in the Nab-P/Gem group was also higher, 78.1% versus 47.8%. In terms of survival, the group of elderly patients, patients of poorer performance, with higher metastatic burden and liver involvement, benefited the most from combination therapy. In our analysis ECOG performance status (p.s.), previous primary tumor surgery, and liver involvement were found to be independent prognostic factors. The addition of nab-paclitaxel to gemcitabine resulted in a significant improvement in the OS of patients with mPDAC. Subgroup analysis demonstrated that patients with some unfavorable prognostic factors benefited the most.

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The impact of metastatic sites in advanced pancreatic adenocarcinoma, systematic review and meta-analysis of prospective randomized studies

Cited by 20 publications

References 26 publications

Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival

Circulating Cell-Free Tumor DNA in Advanced Pancreatic Adenocarcinoma Identifies Patients With Worse Overall Survival

Simple prognostic markers for optimal treatment of patients with unresectable pancreatic cancer

The effectiveness of nab-paclitaxel plus gemcitabine and gemcitabine monotherapy in first-line metastatic pancreatic cancer treatment: A real-world evidence

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