Preoperative Chemotherapy for Pancreatic Cancer Improves Survival and R0 Rate Even in Early Stage I

Vega, Eduardo; Kutlu, Onur; Salehi, Omid; James, Daria; Alarcon, Sylvia V.; Herrick, Beth; Krishnan, Sandeep; Kozyreva, Olga; Conrad, Claudius

doi:10.1007/s11605-020-04601-x

Cited by 17 publications

(10 citation statements)

References 26 publications

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“…Radical surgery for patients with locally confined tumors might not provide long-term survival, the median survival interval following diagnosis ranging from eight to ten months and early tumor relapse occurring in most patients [29]. Several factors affect the survival rates, such as cancer type, tumor stage at diagnosis, treatment modality, age, sex, overall health, lifestyle and differences in healthcare systems [36,37].…”

Section: Discussionmentioning

confidence: 99%

“…Although survival duration is mainly related to tumor stage, both long-term and shortterm survivals have been described in patients diagnosed with early-stage tumors [29,36,37]. Recent studies have reported the prognostic utility of circulating miRNAs profiling in several malignancies due to their altered expression during tumorigenesis and their stability in body fluids [17,18].…”

Section: Discussionmentioning

confidence: 99%

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Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

et al. 2021

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Background: Tumor stage predicts pancreatic cancer (PDAC) prognosis, but prolonged and short survivals have been described in patients with early-stage tumors. Circulating microRNA (miRNA) are an emerging class of suitable biomarkers for PDAC prognosis. Our aim was to identify whether serum miRNA signatures predict survival of early-stage PDAC. Methods: Serum RNA from archival 15 stage I-III PDAC patients and 4 controls was used for miRNAs expression profile (Agilent microarrays). PDAC patients with comparable age, gender, diabetes, jaundice and surgery were classified according to survival: less than 14 months (7/15 pts, group A) and more than 22 months (8/15 pts, group B). Bioinformatic data analysis was performed by two-class Significance Analysis of Microarray (SAM) algorithm. Binary logistic regression analyses considering PDAC diagnosis and outcome as dependent variables, and ROC analyses were also performed. Results: 2549 human miRNAs were screened out. At SAM, 76 differentially expressed miRNAs were found among controls and PDAC (FDR = 0.4%), the large majority (50/76, 66%) of them being downregulated in PDAC with respect to controls. Six miRNAs were independently correlated with early PDAC, and among these, hsa-miR-6821-5p was associated with the best ROC curve area in distinguishing controls from early PDAC. Among the 71 miRNAs differentially expressed between groups A and B, the most significant were hsa-miR-3135b expressed in group A only, hsa-miR-6126 and hsa-miR-486-5p expressed in group B only. Eight miRNAs were correlated with the presence of lymph-node metastases; among these, hsa-miR-4669 is of potential interest. hsa-miR-4516, increased in PDAC and found as an independent predictor of survival, has among its putative targets a series of gens involved in key pathways of cancer progression and dissemination, such as Wnt and p53 signalling pathways. Conclusions: A series of serum miRNAs was identified as potentially useful for the early diagnosis of PDAC, and for establishing a prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

et al. 2021

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“…The PREOPANC-1 trial has demonstrated superiority for R0 resection rate after NAC, over DS and adjuvant chemotherapy for borderline resectable pancreatic cancer (70% versus 40%; P< 0.001), but NAC did not improve OS [31]. Recent trends show an increased utilization of PBD and NAC for resectable pancreatic cancer, with evidence that its use can improve R0 resection rate and survival, mirroring the outcomes within borderline and locally advanced tumors [30,[32][33][34]. However, this has not yet been confirmed in randomized controlled trials.…”

Section: Impact Of Chemotherapymentioning

confidence: 99%

Which patients benefit from preoperative biliary drainage in resectable pancreatic cancer?

Blacker

Lahiri

Phillips

et al. 2021

Expert Review of Gastroenterology & Hepatology

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Recent studies have indicated that preoperative biliary drainage (PBD) should not be routinely performed in all patients suffering from obstructive jaundice before pancreatic surgery. The severity of jaundice that mandates PBD has yet to be defined. The evaluated paper examines the impact of PBD on intra-operative, and post-operative outcomes in patients initially presenting with severe obstructive jaundice (bilirubin ≥250 μmol/L). In this key paper evaluation, the impact of PBD versus a direct surgery (DS) approach is discussed. The arguments for and against each approach are considered with regards to drainage associated morbidity and mortality, resection rates, survival and the impact of chemotherapy and malnutrition. Concentrating on resectable head of pancreas tumors, this mini-review aims to scrutinize the authors' recommendations, alongside those of prominent papers in the field.

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“…The type of ACT administered was not reported. In a series of patients with only earlystage PC (IA-IB), Vega et al found that any sequence of chemotherapy given (NAT, ACT or perioperative NAT/ ACT) lead to improved survival compared to if not chemotherapy was given at all (52). They did not provide data on the type of chemotherapy applied either (52).…”

Section: Survival Outcome With Act After Nat-matter Of Timing or Total Dose Of Chemotherapymentioning

confidence: 99%

“…In a series of patients with only earlystage PC (IA-IB), Vega et al found that any sequence of chemotherapy given (NAT, ACT or perioperative NAT/ ACT) lead to improved survival compared to if not chemotherapy was given at all (52). They did not provide data on the type of chemotherapy applied either (52). Thus, the question whether the total dose or the time-point of chemotherapy is more important, remains to be answered.…”

Section: Survival Outcome With Act After Nat-matter Of Timing or Total Dose Of Chemotherapymentioning

confidence: 99%

How to select the most appropriate adjuvant treatment after neoadjuvant treatment and resection for locally advanced pancreatic cancer?

Rangelova

Bratlie

2021

J Gastrointest Oncol

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Adjuvant chemotherapy (ACT) significantly improves survival of patients undergoing upfront surgery for resectable pancreatic cancer. After introducing the concept of neoadjuvant therapy (NAT) with potent chemotherapy regimens, long term survival has been achieved even in patients with borderline and locally advanced pancreatic cancer (BR/LAPC) following radical resection. The observed pathologic tumor response is strongly predictive of survival and provides a unique opportunity to visualize to what extent the cancer has been sensitive to the administered chemotherapy regimen and may potentially give hint how to personalize further oncologic treatment. Current literature provides only limited and heterogeneous data as to whether and what type of ACT is beneficial after NAT and resection for BR/LAPC. Larger studies suggest that ACT may bring survival advantage and should be attempted particularly in node-positive disease and preferably with more potent regimen such as FOLFIRINOX, if tolerable. In case of complete pathologic response, particularly after FOLFIRINOX, it does not seem beneficial to deescalate the treatment during ACT, but whether continuation on the same regimen is worthwhile needs to be further examined. In case of gemcitabine-based treatment as NAT, continuation with more cycles seems to be of value unless tumor biology proves to be too aggressive, with high lymph node ratio. Whether switch to a different regimen should be sought, if tolerability allows it, needs to be further studied. Whether it is the exact treatment sequence (NAT, ACT or both) of the potent chemotherapy regimens like FOLFIRINOX and gemcitabinenab-paclitaxel or the total dose of chemotherapy that has impact on survival in BR/LAPC, is unknown.

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Preoperative Chemotherapy for Pancreatic Cancer Improves Survival and R0 Rate Even in Early Stage I

Cited by 17 publications

References 26 publications

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

Which patients benefit from preoperative biliary drainage in resectable pancreatic cancer?

How to select the most appropriate adjuvant treatment after neoadjuvant treatment and resection for locally advanced pancreatic cancer?

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