Microscopic lymphovascular invasion is an independent predictor of survival in resected pancreatic ductal adenocarcinoma

Epstein, Jeffrey D.; Kozak, Geoffrey M.; Fong, Zhi Ven; He, Jin; Javed, Ammar A.; Joneja, Upasana; Jiang, Wei; Ferrone, Cristina R.; Lillemoe, Keith D.; Cameron, John L.; Weiss, Matthew J.; Lavu, Harish; Yeo, Charles J.; Castillo, Carlos Fernández‐del; Wolfgang, Christopher L.; Winter, Jordan M.

doi:10.1002/jso.24723

Cited by 34 publications

(29 citation statements)

References 28 publications

(70 reference statements)

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“…We found that PNI status and AJCC T and N categories were associated with LVI status in the PDACs. Using the TCGA cohort, we confirmed that positive LVI status was significantly associated with poor survival in PDAC and an independent risk factor for OS, echoing the previous reports [14,15]. Further, transcriptomic investigation revealed that the PDACs with positive LVI were associated with enhanced cell cycles and promoted TGF-beta signaling pathways, but not with EMT or lymphangiogenesis.…”

Section: Discussionsupporting

confidence: 83%

“…Multivariate analysis revealed that positive LVI was independently associated with shorter OS (p = 0.012, Table 2). Positive LVI was found to affect clinical outcome, which is in agreement with the previous reports [14,15]. LVI was significantly associated with shorter OS in the TCGA cohort, demonstrating that the TCGA-PDAC cohort is a reliable cohort that follows a similar trend as the previous reports in the literature.…”

Section: Status Was Associated With Worse Prognosis In Pdacsupporting

confidence: 91%

“…Lymphovascular invasion (LVI) is pathologically defined as neoplastic invasion into the vascular or lymphatic vessels [ 9 ], and PNI as invasion into the perineural space [ 10 ]. Positive LVI and PNI are pathologic aggressive features of cancer and considered to be risk factors for recurrence and distant metastases in various types of malignancies [ 11 , 12 , 13 , 14 , 15 ]. LVI and PNI are commonly positive in PDAC, and have been reported in as many as 50–75% and 75–100% of specimens, respectively [ 5 , 7 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…There have been multiple studies reporting an association between clinical outcome and pathological features, such as LVI and PNI in patients with PDAC [ 5 , 7 , 14 , 15 ]. Our group recently found that increased vascularity (high expression of CD31) might be associated with better prognoses in patients with PDAC, possibly due to better delivery of tumor-specific immune cells [ 18 ], using the bioinformatics analysis of transcriptomic profiles [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic Profile of Lymphovascular Invasion, a Known Risk Factor of Pancreatic Ductal Adenocarcinoma Metastasis

Takahashi

Katsuta

Yan

et al. 2020

Cancers

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Lymphovascular invasion (LVI) is an aggressive pathologic feature and considered a risk factor for distant metastasis. We hypothesized that pancreatic ductal adenocarcinomas (PDACs) with LVI are associated with shorter survival, as well as aggressive cancer biology and lymphangiogenesis in transcriptomic analysis. Utilizing the cancer genome atlas (TCGA)-PDAC cohort, we found that positive LVI was significantly associated with positive perineural invasion (PNI) (p = 0.023), and higher American Joint Committee on Cancer (AJCC) T (p = 0.017) and N (p < 0.001) categories. Furthermore, positive LVI was associated with shorter overall survival (OS) (p = 0.014) and was an independent risk factor of poor OS. Although there was no association between LVI status and lymphangiogenesis, epithelial-mesenchymal transition (EMT), or metastasis-related genes, Gene Set Enrichment Analysis revealed a strong association with cell-proliferation-related gene sets such as mitotic spindles (Normalized enrichment score (NES) = 1.76, p = 0.016) and G2/M checkpoints (NES = 1.75, p = 0.036), as well as with transforming growth factor beta (TGF-beta) signaling (NES = 1.61, p = 0.043), which is a known mechanism of metastasis in PDACs. In conclusion, positive LVI was an independent risk factor of poor OS in PDACs. We found that PDACs with LVI were possibly associated with accelerated cell proliferation and enhanced TGF-beta signaling independent of lymphangiogenesis. Transcriptomic profiling elucidates more precise tumor biology of LVI-positive PDACs.

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Section: Discussionsupporting

confidence: 83%

Section: Status Was Associated With Worse Prognosis In Pdacsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptomic Profile of Lymphovascular Invasion, a Known Risk Factor of Pancreatic Ductal Adenocarcinoma Metastasis

Takahashi

Katsuta

Yan

et al. 2020

Cancers

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“…Tumour size, lymph node status, resection margin and differentiation grade are the most widely studied prognostic factors and were often included in the identified models. Relatively newer relevant (but used less in the models) prognostic factors include perineural invasion, lymphovascular invasion and several biomarkers. A first relevant subgroup is patients receiving neoadjuvant therapy versus those having upfront surgery.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer

Strijker

Chen

Mungroop

et al. 2019

British Journal of Surgery

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Background: As more therapeutic options for pancreatic cancer are becoming available, there is a need to improve outcome prediction to support shared decision-making. A systematic evaluation of prediction models in resectable pancreatic cancer is lacking.Methods: This systematic review followed the CHARMS and PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched up to 11 October 2017. Studies reporting development or validation of models predicting survival in resectable pancreatic cancer were included. Models without performance measures, reviews, abstracts or more than 10 per cent of patients not undergoing resection in postoperative models were excluded. Studies were appraised critically.Results: After screening 4403 studies, 22 (44 319 patients) were included. There were 19 model development/update studies and three validation studies, altogether concerning 21 individual models. Two studies were deemed at low risk of bias. Eight models were developed for the preoperative setting and 13 for the postoperative setting. Most frequently included parameters were differentiation grade (11 of 21 models), nodal status (8 of 21) and serum albumin (7 of 21). Treatment-related variables were included in three models. The C-statistic/area under the curve values ranged from 0⋅57 to 0⋅90. Based on study design, validation methods and the availability of web-based calculators, two models were identified as the most promising. Conclusion: Although a large number of prediction models for resectable pancreatic cancer have been reported, most are at high risk of bias and have not been validated externally. This overview of prognostic factors provided practical recommendations that could help in designing easily applicable prediction models to support shared decision-making.Prediction models enable clinicians and patients to calculate the risks of a specific endpoint individualized to a patient, using combinations of predictors. Such models are used widely in some fields, including the CHADS 2 -VASc score for estimation of stroke risk in atrial fibrillation 3 , and the Acute Physiology and Chronic Health Evaluation (APACHE) score 4 for mortality in intensive care. In breast cancer, the PREDICT 5 and Adjuvant! 6 models have been employed in the decision-making process to determine adjuvant treatment administration. Data analysisData extraction was performed independently by two authors. Articles were categorized into development/model update studies and validation studies 12 .

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Comparison of survival for metastatic pancreatic cancer patients treated with CPI‐613 versus resected borderline‐resectable pancreatic cancer patients

Mangieri

Valenzuela

Solsky

et al. 2023

Journal of Surgical Oncology

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IntroductionTreatment of advanced pancreatic adenocarcinoma remains suboptimal. Therapeutic agents with a novel mechanism of action are desperately needed; one such novel agent is CPI‐613 targets. We here analyze the outcomes of 20 metastatic pancreatic cancer patients treated with CPI‐613 and FOLFIRINOX in our institution and evaluate their outcomes to borderline‐resectable patients treated with curative surgery.MethodsA post hoc analysis was performed of the phase I CPI‐613 trial data (NCT03504423) comparing survival outcomes to borderline‐resectable cases treated with curative resection at the same institution. Survival was measured by overall survival (OS) for all study cases and disease‐free survival (DFS) for resected cases with progression‐free survival for CPI‐613 cases.ResultsThere were 20 patients in the CPI‐613 cohort and 60 patients in the surgical cohort. Median follow‐up times were 441 and 517 days for CPI‐613 and resected cases, respectively. There was no difference in survival times between CPI‐613 and resected cases with a mean OS of 1.8 versus 1.9 year (p = 0.779) and mean PFS/DFS of 1.4 versus 1.7 years (p = 0.512). There was also no difference in 3‐year survival rates for OS (hazard ratio [HR] = 1.063, 95% confidence interval [CI] 0.302–3.744, p = 0.925) or DFS/PFS (HR = 1.462, 95% CI 0.285–7.505, p = 0.648).ConclusionThe first study to evaluate the survival between metastatic patients treated with CPI‐613 versus borderline‐resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI‐613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.

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Microscopic lymphovascular invasion is an independent predictor of survival in resected pancreatic ductal adenocarcinoma

Cited by 34 publications

References 28 publications

Transcriptomic Profile of Lymphovascular Invasion, a Known Risk Factor of Pancreatic Ductal Adenocarcinoma Metastasis

Transcriptomic Profile of Lymphovascular Invasion, a Known Risk Factor of Pancreatic Ductal Adenocarcinoma Metastasis

Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer

Comparison of survival for metastatic pancreatic cancer patients treated with CPI‐613 versus resected borderline‐resectable pancreatic cancer patients

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