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Cancers
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Neoadjuvant Therapies in Pancreatic Cancer
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Neoadjuvant Therapies in 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 October 2023) | Viewed by 11894

Special Issue Editors

Prof. Dr. Huamin Wang

E-Mail Website
Guest Editor
1. Department of Anatomical Pathology, MD Anderson UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2. Department of Translational Molecular Pathology, MD Anderson UTHealth Graduate School of Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Interests: pathology; pancreatic, biliary and gastrointestinal cancers
Dr. Dan Zhao

E-Mail Website
Guest Editor
Department of Gastrointestinal (GI) Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: medical oncology; cancer; immunology; clinical trials; targeted therapy; cellular therapy

Special Issue Information

Dear Colleagues, 

Multidisciplinary neoadjuvant therapy (NAT) plays a critical role in treating pancreatic ductal adenocarcinoma (PDAC). Available data suggest that NAT improves survival for patients with borderline resectable/locally advanced disease. The paradigm is shifting from up-front surgery to multidisciplinary NAT followed by surgery even for resectable disease. The field of NAT for PDAC is evolving with the development of modern therapeutic regimens such as FOLFIRINOX and gemcitabine plus nab-paclitaxel with or without radiation. The pre- and post-treatment radiographic and clinical evaluation to select patients who may benefit the most from surgical resection, the standardized pathologic examination, reporting and staging, and the development of clinical prognostic markers and molecular markers are crucial for selecting more effective post-surgical therapies. Clinical trials of immunotherapy in combination with conventional therapies may help establish the role of immunotherapy in the neoadjuvant setting for PDAC in the future. This Special Issue will cover the above-mentioned key issues for NAT in PDAC patients.

Prof. Dr. Huamin Wang
Dr. Dan Zhao
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
  • neoadjuvant therapy
  • biomarker
  • tumor response
  • pathologic staging

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Published Papers (5 papers)

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Research

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14 pages, 1798 KiB  
Article
Comparative Analyses of the Clinicopathologic Features of Short-Term and Long-Term Survivors of Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreatoduodenectomy
by Tom Z. Liang, Matthew H. G. Katz, Laura R. Prakash, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D. Tzeng, Naruhiko Ikoma, Robert A. Wolff, Dan Zhao, Eugene J. Koay, Anirban Maitra, Suprateek Kundu and Huamin Wang
Cancers 2023, 15(12), 3231; https://doi.org/10.3390/cancers15123231 - 18 Jun 2023
Cited by 1 | Viewed by 1409
Abstract
Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically [...] Read more.
Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15–60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data. Full article
(This article belongs to the Special Issue Neoadjuvant Therapies in Pancreatic Cancer)
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15 pages, 3029 KiB  
Article
Prognosticators for Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Therapy and Pancreatectomy
by Yi Tat Tong, Zongshan Lai, Matthew H. G. Katz, Laura R Prakash, Hua Wang, Deyali Chatterjee, Michael Kim, Ching-Wei D. Tzeng, Jeffrey E. Lee, Naruhiko Ikoma, Asif Rashid, Robert A. Wolff, Dan Zhao, Eugene J. Koay, Anirban Maitra and Huamin Wang
Cancers 2023, 15(9), 2608; https://doi.org/10.3390/cancers15092608 - 4 May 2023
Cited by 3 | Viewed by 2042
Abstract
Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients [...] Read more.
Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies. Full article
(This article belongs to the Special Issue Neoadjuvant Therapies in Pancreatic Cancer)
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18 pages, 6709 KiB  
Article
Cross-Dataset Single-Cell Analysis Identifies Temporal Alterations in Cell Populations of Primary Pancreatic Tumor and Liver Metastasis
by Daowei Yang, Rohan Moniruzzaman, Hua Wang, Huamin Wang and Yang Chen
Cancers 2023, 15(8), 2396; https://doi.org/10.3390/cancers15082396 - 21 Apr 2023
Cited by 5 | Viewed by 3681
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a unique tumor microenvironment composed of various cell populations such as cancer cells, cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. Recently, single-cell RNA-sequencing analysis (scRNA-seq) has systemically revealed the genomic profiles of these cell populations in PDAC. [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) has a unique tumor microenvironment composed of various cell populations such as cancer cells, cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. Recently, single-cell RNA-sequencing analysis (scRNA-seq) has systemically revealed the genomic profiles of these cell populations in PDAC. However, the direct comparison of cell population composition and genomic profile between primary tumors (at both early- and late-stage) and metastatic tumors of PDAC is still lacking. In this study, we combined and analyzed recent scRNA-seq datasets of transgenic KPC mouse models with autochthonous PDAC and matched liver metastasis, revealing the unique tumor ecosystem and cell composition of liver metastasis in contrast to primary PDAC. Metastatic PDAC tumors harbor distinct cancer cell subpopulations from primary tumors. Several unique markers, including HMGA1, were identified for metastasis-enriched cancer cell subpopulations. Furthermore, metastatic tumors reveal significantly enriched granulocytic myeloid-derived suppressor cells (G-MDSCs), mature neutrophils, and granulocyte-myeloid progenitors (GMPs). A common GMP population across primary tumors, liver metastases, and healthy bone marrow was identified as the putative cell origin of tumor-associated neutrophils/granulocytes. Full article
(This article belongs to the Special Issue Neoadjuvant Therapies in Pancreatic Cancer)
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Review

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20 pages, 387 KiB  
Review
Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma
by Anish J. Jain, Jessica E. Maxwell, Matthew H. G. Katz and Rebecca A. Snyder
Cancers 2023, 15(16), 4174; https://doi.org/10.3390/cancers15164174 - 19 Aug 2023
Cited by 8 | Viewed by 2334
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical. Full article
(This article belongs to the Special Issue Neoadjuvant Therapies in Pancreatic Cancer)
11 pages, 245 KiB  
Review
Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer
by Brandon G. Smaglo
Cancers 2023, 15(8), 2377; https://doi.org/10.3390/cancers15082377 - 19 Apr 2023
Cited by 6 | Viewed by 1753
Abstract
Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy [...] Read more.
Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools. Full article
(This article belongs to the Special Issue Neoadjuvant Therapies in Pancreatic Cancer)
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