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14 pages, 850 KiB

Open AccessArticle

Comparative Effectiveness of Chemotherapy Alone Versus Radiotherapy-Based Regimens in Locally Advanced Pancreatic Cancer: A Real-World Multicenter Analysis (PAULA-1)

Curr. Oncol. 2023, 30(6), 5690-5703; https://doi.org/10.3390/curroncol30060427 - 10 Jun 2023

Viewed by 1226

Abstract

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a [...] Read more.

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005–2018). Survival curves were calculated using the Kaplan–Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, _95%CI 0.34–0.92, p = 0.022) or SBRT (HR: 0.27, _95%CI 0.13–0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, _95%CI 0.28–0.70, p < 0.001) and SBRT (HR: 0.40, _95%CI 0.22–0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

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13 pages, 1135 KiB

Open AccessArticle

Early Recurrence after Upfront Surgery for Pancreatic Ductal Adenocarcinoma

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Curr. Oncol. 2023, 30(4), 3708-3720; https://doi.org/10.3390/curroncol30040282 - 27 Mar 2023

Viewed by 1104

Abstract

Background. Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor, due to early recurrence (ER) of the disease. A global definition of ER is lacking and different cut-off values (6, 8, and 12 months) have been adopted. The aims of this study [...] Read more.

Background. Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor, due to early recurrence (ER) of the disease. A global definition of ER is lacking and different cut-off values (6, 8, and 12 months) have been adopted. The aims of this study were to define the optimal cut-off for the definition of ER and predictive factors for ER. Methods. Recurrence was recorded for all consecutive patients undergoing upfront surgery for PDAC at our institute between 2010 and 2017. Receiver operating characteristic (ROC) curves were utilized, to estimate the optimal cut-off for the definition of ER as a predictive factor for poor post-progression survival (PPS). To identify predictive factors of ER, univariable and multivariable logistic regression models were used. Results. Three hundred and fifty one cases were retrospectively evaluated. The recurrence rate was 76.9%. ER rates were 29.0%, 37.6%, and 47.6%, when adopting 6, 8, and 12 months as cut-offs, respectively. A significant difference in median PPS was only shown between ER and late recurrence using 12 months as cut-off (p = 0.005). In the multivariate analysis, a pre-operative value of CA 19-9 > 70.5 UI/L (OR 3.10 (1.41–6.81); p = 0.005) and the omission of adjuvant treatment (OR 0.18 (0.08–0.41); p < 0.001) were significant predictive factors of ER. Conclusions. A twelve-months cut-off should be adopted for the definition of ER. Almost 50% of upfront-resected patients presented ER, and it significantly affected the prognosis. A high preoperative value of CA 19-9 and the omission of adjuvant treatment were the only predictive factors for ER. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

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14 pages, 2558 KiB

Open AccessArticle

Predicting Early Disease Recurrence of Pancreatic Cancer following Surgery: Determining the Role of NUDT15 as a Prognostic Biomarker

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Curr. Oncol. 2022, 29(4), 2516-2529; https://doi.org/10.3390/curroncol29040206 - 06 Apr 2022

Viewed by 1903

Abstract

Surgical resection remains the only curative treatment strategy for Pancreatic Ductal Adenocarcinoma (PDAC). A proportion of patients succumb to early disease recurrence post-operatively despite receiving adjuvant chemotherapy. The ability to identify these high-risk individuals at their initial diagnosis, prior to surgery, could potentially [...] Read more.

Surgical resection remains the only curative treatment strategy for Pancreatic Ductal Adenocarcinoma (PDAC). A proportion of patients succumb to early disease recurrence post-operatively despite receiving adjuvant chemotherapy. The ability to identify these high-risk individuals at their initial diagnosis, prior to surgery, could potentially alter their treatment algorithm. This unique patient cohort may benefit from neo-adjuvant chemotherapy, even in the context of resectable disease, as this may secure systemic control over their disease burden. It may also improve patient selection for surgery. Using the Cancer Genome Atlas dataset, we first confirmed the poor overall survival associated with early disease recurrence (p < 0.0001). The transcriptomic profiles of these tumours were analysed, and we identified key aberrant signalling pathways involved in early disease relapse; downregulation across several immune signalling pathways was noted. Differentially expressed genes that could serve as biomarkers were identified (BPI, C6orf58, CD177, MCM7 and NUDT15). Receiver operating characteristic curves were constructed in order to identify biomarkers with a high diagnostic ability to identify patients who developed early disease recurrence. NUDT15 expression had the highest discriminatory capability as a biomarker (AUC 80.8%). Its expression was confirmed and validated in an independent cohort of patients with resected PDAC (n = 13). Patients who developed an early recurrence had a statistically higher tumour expression of NUDT15 when compared to patients who did not recur early (p < 0.01). Our results suggest that NUDT15 can be used as a prognostic biomarker that can stratify patients according to their risk of developing early disease recurrence. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

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12 pages, 1009 KiB

Open AccessArticle

Implication of ERBB2 as a Predictive Tool for Survival in Patients with Pancreatic Cancer in Histological Studies

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Miguel A. Ortega

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Leonel Pekarek

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Oscar Fraile-Martinez

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Cielo Garcia-Montero

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Miguel A. Saez

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Angel Asúnsolo

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Miguel A. Alvarez-Mon

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Jorge Monserrat

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Lidia Ruiz-Llorente

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Natalio García-Honduvilla

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Curr. Oncol. 2022, 29(4), 2442-2453; https://doi.org/10.3390/curroncol29040198 - 30 Mar 2022

Cited by 6 | Viewed by 2609

Abstract

Pancreatic cancer will be positioned by the year 2030 as the second cause of oncological death after lung cancer. The pathophysiology of the most common variety, which involves the adenocarcinoma of the pancreas, represents one of the main challenges for current oncology to [...] Read more.

Pancreatic cancer will be positioned by the year 2030 as the second cause of oncological death after lung cancer. The pathophysiology of the most common variety, which involves the adenocarcinoma of the pancreas, represents one of the main challenges for current oncology to explain its tumorigenesis and create a targeted treatment. The tumor microenvironment, metastatic capacity, and lack of early diagnosis lead patients to present advanced stages at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcomes and with respect to the improved survival of these patients. For this reason, in recent years, numerous diagnostic tests, treatments, and possible approaches in the fields of radiotherapy, chemotherapy, immunotherapy, and surgery have been developed to find a combination of methods that improves life expectancy in patients diagnosed with this disease. On the other hand, the scientific community has made numerous advances in the molecular bases of pancreatic cancer since several oncogenetic pathways have been described and the markers expressed by the tumor have proven to be useful in the prognosis of pancreatic adenocarcinoma. These molecular alterations allow the study of possible therapeutic targets that improve the prognosis of these patients, but even numerous tumor cell-individual interactions must be explained to understand the underlying pathophysiology causing the high mortality. Therefore, the purpose of our study is to examine the expression of markers such as EGFR, Cyclin D1, andCDK4 in order to find a relationship with the possible long-term prognostic factors of patients affected by pancreatic ductal adenocarcinoma. Our results show that there is a prognostic role for ErbB2, EGFR, beta catenin, cyclin D1, and CDK4. Of these, we highlight the clinical importance of ErbB2 in the survival rates of patients who overexpress this component. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

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Review

Jump to: Research

18 pages, 414 KiB

Open AccessReview

Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma—A Critical Review of Randomised Trials

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Mathilde Weisz Ejlsmark

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Michael Bau Mortensen

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Per Pfeiffer

Curr. Oncol. 2023, 30(7), 6820-6837; https://doi.org/10.3390/curroncol30070499 - 18 Jul 2023

Viewed by 1191

Abstract

Pancreatic cancer is rising as one of the leading causes of cancer-related death worldwide. Patients often present with advanced disease, limiting curative treatment options and therefore making management of the disease difficult. Systemic chemotherapy has been an established part of the standard treatment [...] Read more.

Pancreatic cancer is rising as one of the leading causes of cancer-related death worldwide. Patients often present with advanced disease, limiting curative treatment options and therefore making management of the disease difficult. Systemic chemotherapy has been an established part of the standard treatment in patients with both locally advanced and metastatic pancreatic cancer. In contrast, the use of radiotherapy has no clear defined role in the treatment of these patients. With the evolving imaging and radiation techniques, radiation could become a plausible intervention. In this review, we give an overview over the available data regarding radiotherapy, chemoradiation, and stereotactic body radiation therapy. We performed a systematic search of Embase and the PubMed database, focusing on studies involving locally advanced pancreatic cancer (or non-resectable pancreatic cancer) and radiotherapy without any limitation for the time of publication. We included randomised controlled trials involving patients with locally advanced pancreatic cancer, including radiotherapy, chemoradiation, or stereotactic body radiation therapy. The included articles represented mainly small patient groups and had a high heterogeneity regarding radiation delivery and modality. This review presents conflicting results concerning the addition of radiation and modality in the treatment regimen. Further research is needed to improve outcomes and define the role of radiation therapy in pancreatic cancer. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

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15 pages, 307 KiB

Open AccessReview

Review of Current Systemic Therapy and Novel Systemic Therapy for Pancreatic Ductal Adenocarcinoma

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Curr. Oncol. 2023, 30(6), 5322-5336; https://doi.org/10.3390/curroncol30060404 - 26 May 2023

Cited by 1 | Viewed by 1570

Abstract

Background: This review aims to describe the systemic treatment options for pancreatic ductal adenocarcinoma and includes a summary of the current treatments as well as the ongoing clinical trials which may be efficacious in the treatment of this aggressive malignancy. Methods: A literature [...] Read more.

Background: This review aims to describe the systemic treatment options for pancreatic ductal adenocarcinoma and includes a summary of the current treatments as well as the ongoing clinical trials which may be efficacious in the treatment of this aggressive malignancy. Methods: A literature review was performed using MEDLINE/PubMed between August 1996 and February 2023. The reviewed studies are categorized into these categories: current standard of care treatments, targeted therapies, immunotherapy and clinical trials. The current treatment modality for the treatment of advanced pancreatic cancer is mainly systemic chemotherapy. Results: The introduction of polychemotherapy regimens including gemcitabine/nab-paclitaxel and FOLFIRINOX (oxaliplatin, irinotecan, folinic acid and fluorouracil) has improved the clinical outcome of advanced pancreatic cancer. For further improvement in clinical outcomes, several novel approaches have been extensively studied in pancreatic cancer. The review discusses the current standard chemotherapy regimen and the novel treatment options in the field. Conclusions: While there are novel treatments being explored for metastatic pancreatic, it remains a debilitating and aggressive disease with high mortality that warrants continued efforts to advance therapeutic options. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

22 pages, 4357 KiB

Open AccessReview

Complement and Fungal Dysbiosis as Prognostic Markers and Potential Targets in PDAC Treatment

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Curr. Oncol. 2022, 29(12), 9833-9854; https://doi.org/10.3390/curroncol29120773 - 14 Dec 2022

Viewed by 1516

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is still hampered by a dismal prognosis. A better understanding of the tumor microenvironment within the pancreas and of the factors affecting its composition is of utmost importance for developing new diagnostic and treatment tools. In this context, the [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is still hampered by a dismal prognosis. A better understanding of the tumor microenvironment within the pancreas and of the factors affecting its composition is of utmost importance for developing new diagnostic and treatment tools. In this context, the complement system plays a prominent role. Not only has it been shown to shape a T cell-mediated immune response, but it also directly affects proliferation and apoptosis of the tumor cells, influencing angiogenesis, metastatic spread and therapeutic resistance. This makes complement proteins appealing not only as early biomarkers of PDAC development, but also as therapeutic targets. Fungal dysbiosis is currently the new kid on the block in tumorigenesis with cancer-associated mycobiomes extracted from several cancer types. For PDAC, colonization with the yeast Malassezia seems to promote cancer progression, already in precursor lesions. One responsible mechanism appears to be complement activation via the lectin pathway. In the present article, we review the role of the complement system in tumorigenesis, presenting observations that propose it as the missing link between fungal dysbiosis and PDAC development. We also present the results of a small pilot study supporting the crucial interplay between the complement system and Malassezia colonization in PDAC pathogenesis. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

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13 pages, 1568 KiB

Open AccessReview

Prognostic Impact of Resection Margin Status on Distal Pancreatectomy for Ductal Adenocarcinoma

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Maia Blomhoff Holm

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Caroline Sophie Verbeke

Curr. Oncol. 2022, 29(9), 6551-6563; https://doi.org/10.3390/curroncol29090515 - 14 Sep 2022

Cited by 3 | Viewed by 1642

Abstract

Pancreatic cancer is associated with a poor prognosis. While surgical resection is the only treatment option with curative intent, most patients die of locoregional and/or distant recurrence. The prognostic impact of the resection margin status has received much attention. However, the evidence is [...] Read more.

Pancreatic cancer is associated with a poor prognosis. While surgical resection is the only treatment option with curative intent, most patients die of locoregional and/or distant recurrence. The prognostic impact of the resection margin status has received much attention. However, the evidence is almost exclusively related to pancreatoduodenectomies, while corresponding data for distal pancreatectomy specimens are limited. The key data, such as the rate of microscopic margin involvement (“R1”), the site of margin involvement, and the impact of R1 on patient outcome, are divergent between studies and do not currently allow any general conclusions. The main reasons for the variability in the published data are the small size of the study cohorts and their heterogeneity, as well as the marked divergence in pathology examination practices. The latter is a consequence of the lack of concrete guidance, both for grossing and microscopic examination. The increasing administration of neoadjuvant chemo(radio)therapy introduces a further factor of uncertainty as the conventional definition of a tumour-free margin (“R0”) based on 1 mm clearance is inadequate for these specimens. This review discusses the published data regarding the prognostic impact of margin status in distal pancreatectomy specimens along with the challenges and uncertainties that are related to the assessment of the margins. Full article

(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)

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