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Cancers
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Neoadjuvant Therapy of Pancreatic Cancer
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Neoadjuvant Therapy of Pancreatic Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 11065

Special Issue Editors

Dr. Judith De Vos-Geelen

E-Mail Website
Guest Editor
Division Medical Oncology, Department Internal Medicine, GROW, Maastricht University Medical Centre, Maastricht, The Netherlands
Interests: hepato-pancreatobiliary cancer; systemic therapy; precision medicine
Special Issues, Collections and Topics in MDPI journals
Dr. Jordan M. Cloyd

E-Mail Website
Co-Guest Editor
Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
Interests: multimodality therapy; neoadjuvant therapy; gastrointestinal and hepatopancreatobiliary cancers; neuroendocrine tumors; surgery; patient-centered outcomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pancreatic cancer is predicted to become the second leading cause of cancer-related death by 2030. As such, and despite advancements in outcome in the past decade, it is necessary to further increase our understanding of this fatal disease.

We are pleased to invite you to contribute to the Special Issue on research refining guidance of patients in the neoadjuvant trajectory for pancreatic cancer. We include basic, translational, and clinical studies regarding neoadjuvant therapy, focusing on predictive and prognostic markers to oppose futile surgery and improve outcome. Furthermore, this Special Issue aims to sharpen therapeutic neoadjuvant strategies, including cutting-edge systemic targets and precision medicine.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) neoadjuvant treatments and supportive strategies to conquer invalidating toxic events and augment patients’ body composition. In addition to pancreatic cancer, research on overarching periampullary cancers will be considered. 

We look forward to receiving your contributions.

You may choose our Joint Special Issue in Current Oncology.

Dr. Judith De Vos-Geelen
Dr. Jordan M. Cloyd
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pancreatic cancer
  • preoperative
  • neoadjuvant
  • systemic therapy
  • prognostic biomarkers
  • predictive biomarkers
  • physical activity
  • body composition
  • toxicity
  • quality of life

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Published Papers (4 papers)

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Research

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9 pages, 1259 KiB  
Article
Adjuvant FOLFIRINOX in Patients with Resectable Pancreatic Cancer Is Effective but Rarely Feasible in Real Life: Is Neoadjuvant FOLFIRINOX a Better Option?
by Yossi Maman, Yaacov Goykhman, Oz Yakir, Alex Barenboim, Ravit Geva, Sharon Peles-Avraham, Ido Wolf, Joseph M. Klausner, Guy Lahat and Nir Lubezky
Cancers 2023, 15(11), 3049; https://doi.org/10.3390/cancers15113049 - 3 Jun 2023
Cited by 2 | Viewed by 2015
Abstract
Background: The recommended treatment for resectable pancreatic cancer (PC) is resection followed by adjuvant FOLFIRINOX. We assessed the proportion of patients that managed to complete the 12 courses of adjuvant FOLFIRINOX and compared their outcome with that of patients with borderline resectable pancreatic [...] Read more.
Background: The recommended treatment for resectable pancreatic cancer (PC) is resection followed by adjuvant FOLFIRINOX. We assessed the proportion of patients that managed to complete the 12 courses of adjuvant FOLFIRINOX and compared their outcome with that of patients with borderline resectable pancreatic cancer (BRPC) who underwent resection after neoadjuvant FOLFIRINOX. Methods: A retrospective analysis was performed on a prospectively maintained database of all PC patients who underwent resection with (2/2015–12/2021) or without (1/2018–12/2021) neoadjuvant therapy. Results: A total of 100 patients underwent upfront resection, and 51 patients with BRPC received neoadjuvant treatment. Only 46 resection patients started adjuvant FOLFIRINOX, and only 23 completed 12 courses. The main reasons for not starting/completing adjuvant therapy were poor tolerance and rapid recurrence. Significantly more patients in the neoadjuvant group received at least six FOLFIRINOX courses (80.4% vs. 31%, p < 0.001). Patients who completed at least 6 courses, either pre- or postoperatively, had better overall survival (p = 0.025) than those who did not. In spite of having more advanced disease, the neoadjuvant group had comparable overall survival (p = 0.062) regardless of the number of treatment courses. Conclusion: Only a minority of patients (23%) undergoing upfront pancreatic resection completed the planned 12 courses of FOLFIRINOX. Patients who received neoadjuvant treatment were significantly more likely to receive at least six treatment courses. Patients receiving at least six courses had better overall survival than those who received fewer than six courses, regardless of the timing of treatment relative to surgery. Potential ways to increase chemotherapy adherence, such as administering treatment before surgery, should be considered. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy of Pancreatic Cancer)
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19 pages, 6941 KiB  
Article
COL12A1 Acts as a Novel Prognosis Biomarker and Activates Cancer-Associated Fibroblasts in Pancreatic Cancer through Bioinformatics and Experimental Validation
by Yao Song, Lei Wang, Kaidong Wang, Yuhua Lu and Pengcheng Zhou
Cancers 2023, 15(5), 1480; https://doi.org/10.3390/cancers15051480 - 26 Feb 2023
Cited by 4 | Viewed by 3169
Abstract
Pancreatic cancer remains one of the most challenging malignancies to date and is associated with poor survival. Cancer-associated fibroblasts (CAFs) are key stromal cells in the tumor microenvironment (TME) that play a crucial role in tumor progression in pancreatic cancer. Thus, uncovering the [...] Read more.
Pancreatic cancer remains one of the most challenging malignancies to date and is associated with poor survival. Cancer-associated fibroblasts (CAFs) are key stromal cells in the tumor microenvironment (TME) that play a crucial role in tumor progression in pancreatic cancer. Thus, uncovering the key genes involved in CAF progression and determining their prognostic value is critically important. Herein, we report our discoveries in this research area. Analysis of The Cancer Genome Atlas (TCGA) dataset and investigation of our clinical tissue samples indicated that COL12A1 expression was aberrantly highly expressed in pancreatic cancer. Survival and COX regression analyses revealed the significant clinical prognostic value of COL12A1 expression in pancreatic cancer. COL12A1 was mainly expressed in CAFs but not in tumor cells. This was verified with our PCR analysis in cancer cells and CAFs. The knocking down of COL12A1 decreased the proliferation and migration of CAFs and down-regulated the expression of CAF activation markers actin alpha 2 (ACTA2), fibroblast activation protein (FAP), and fibroblast-specific protein 1 (FSP1). Meanwhile, the interleukin 6 (IL6), CXC chemokine Ligand-5 (CXCL5), and CXC chemokine Ligand-10 (CXCL10) expressions were inhibited, and the cancer-promoting effect was reversed by COL12A1 knockdown. Therefore, we demonstrated the potential prognostic and target therapy value of COL12A1 expression in pancreatic cancer and elucidated the molecular mechanism underlying its role in CAFs. The findings of this study might provide new opportunities for TME-targeted therapies in pancreatic cancer. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy of Pancreatic Cancer)
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Review

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12 pages, 272 KiB  
Review
Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results
by Robert Connor Chick, Andrew J. Gunderson, Shafia Rahman and Jordan M. Cloyd
Cancers 2023, 15(15), 3967; https://doi.org/10.3390/cancers15153967 - 4 Aug 2023
Cited by 7 | Viewed by 2831
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials of immunotherapy in metastatic PDAC have yielded disappointing results. There is considerable interest in using immunotherapy approaches in the neoadjuvant setting in order to prime the immune system to detect and prevent micrometastatic disease and recurrence. A scoping review was conducted to identify published and ongoing trials utilizing preoperative immunotherapy. In total, 9 published trials and 27 ongoing trials were identified. The published trials included neoadjuvant immune checkpoint inhibitors, cancer vaccines, and other immune-modulating agents that target mechanisms distinct from that of immune checkpoint inhibition. Most of these are early phase trials which suggest improvements in disease-free and overall survival when combined with standard neoadjuvant therapy. Ongoing trials are exploring various combinations of these agents with each other and with chemotherapy and/or radiation. Rational combination immunotherapy in addition to standard neoadjuvant therapy has the potential to improve outcomes in PDAC, but further clinical trials are needed, particularly those which utilize an adaptive trial design. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy of Pancreatic Cancer)
20 pages, 385 KiB  
Review
Venous Thromboembolism and Primary Thromboprophylaxis in Perioperative Pancreatic Cancer Care
by R. A. L. Willems, N. Michiels, V. R. Lanting, S. Bouwense, B. L. J. van den Broek, M. Graus, F. A. Klok, B. Groot Koerkamp, B. de Laat, M. Roest, J. W. Wilmink, N. van Es, J. S. D. Mieog, H. ten Cate and J. de Vos-Geelen
Cancers 2023, 15(14), 3546; https://doi.org/10.3390/cancers15143546 - 8 Jul 2023
Cited by 4 | Viewed by 2369
Abstract
Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the [...] Read more.
Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the neoadjuvant setting. PDAC patients are at a high risk of developing venous thromboembolism (VTE), which is associated with decreased survival rates. As patients with PDAC were historically offered immediate surgical resection, data on VTE incidence and associated preoperative risk factors are scarce. Current guidelines recommend primary prophylactic anticoagulation in selected groups of patients with advanced PDAC. However, recommendations for patients with (borderline) resectable PDAC treated with chemotherapy in the neoadjuvant setting are lacking. Nevertheless, the prevention of complications is crucial to maintain the best possible condition for surgery. This narrative review summarizes current literature on VTE incidence, associated risk factors, risk assessment tools, and primary thromboprophylaxis in PDAC patients treated with neoadjuvant chemo(radio)therapy. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy of Pancreatic Cancer)
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