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Pancreatic Cancer: Recent Advances and Future Challenges

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 12499

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Special Issue Editors

Dr. Vincent P. Groot

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Guest Editor

Department of Surgery, Regional Academic Cancer Centre Utrecht, St Antonius Hospital, Nieuwegein and University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands
Interests: pancreatic ductal adenocarcinoma (PDAC); translational research on biomarkers; PDAC recurrence; post-operative surveillance

Dr. Lois A. Daamen

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1. Department of Surgery, Regional Academic Cancer Centre Utrecht, St Antonius Hospital, Nieuwegein and University Medical Centre Utrecht, 3584 CX Utrecht, Netherlands
2. Division of Imaging, UMC Utrecht Cancer Center, Utrecht University, 3584 CX Utrecht, The Netherlands
Interests: pancreatic ductal adenocarcinoma (PDAC); artificial intelligence; PDAC recurrence; post-operative surveillance

Prof. Dr. Izaäk Quintus Molenaar

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Guest Editor

Department of Surgery, Regional Academic Cancer Centre Utrecht, St Antonius Hospital, Nieuwegein and University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands
Interests: pancreatic ductal adenocarcinoma (PDAC); minimally invasive pancreatic surgery; peri-operative outcomes

Special Issue Information

Dear Colleagues,

As Guest Editors, we are pleased to announce the launch of a new Special Issue entitled “Pancreatic Cancer: Recent Advances and Future Challenges” to be published in the Journal of Clinical Medicine (JCM, Impact Factor 4.964, https://www.mdpi.com/journal/jcm).

Pancreatic cancer is a lethal disease with the poorest survival rate of any solid malignancy. Alarmingly, incidence and mortality rates for pancreatic cancer have continued to rise during the past two decades, in stark contrast with other common cancer types. However, remarkable strides have been made in the molecular understanding of pancreatic cancer, clinical trials using novel multi-drug chemotherapies have shown promising survival outcomes, and pancreatic surgery is less invasive and saver than ever before. Due to these advances in multi-modality care, treatment indications and options have expanded even for patients with locally advanced, oligometastatic or recurrent disease. On the other hand, these improvements add to the complexity of providing multi-disciplinary treatment for pancreatic cancer patients.

This multi-modality care opens the door to new strategies and innovations related to, for instance, artificial intelligence (AI), neoadjuvant and adjuvant therapies, robotic surgery, radiation therapy and immune therapy. To work towards truly personalized care for pancreatic cancer, we need improved tools for patient and treatment selection, superior biomarkers and radiomics to measure treatment response and novel therapies that target tumor-specific genetic vulnerabilities. This Special Issue hopes to address these current advances and future challenges in the field of pancreatic cancer research to help achieve profoundly improved outcomes for patients.

As such, we cordially invite you to submit your original or review article on clinical or translational research to this Special Issue of JCM on “Pancreatic Cancer: Recent Advances and Future Challenges”.

Dr. Vincent P. Groot
Dr. Lois A. Daamen
Prof. Dr. Izaäk Quintus Molenaar
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 short 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. Journal of Clinical Medicine 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 2600 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 ductal adenocarcinoma
pancreatic neoplasms
pancreatic surgery
pancreatectomy
biomarkers
survival outcomes
postoperative complications
cancer recurrence
artificial intelligence
neoadjuvant therapy
locally advanced pancreatic cancer

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Published Papers (6 papers)

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Editorial

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9 pages, 230 KiB

Open AccessEditorial

Recent Advances and Future Challenges in Pancreatic Cancer Care: Early Detection, Liquid Biopsies, Precision Medicine and Artificial Intelligence

by Lois A. Daamen, I. Quintus Molenaar and Vincent P. Groot

J. Clin. Med. 2023, 12(23), 7485; https://doi.org/10.3390/jcm12237485 - 4 Dec 2023

Cited by 5 | Viewed by 3095

Abstract

The incidence of pancreatic ductal adenocarcinoma (PDAC) is rising. While surgical techniques and peri-operative care have improved, the overall survival for PDAC remains poor. Thus, novel and bold research initiatives are needed along the spectrum of clinical care, a few of which will be discussed in this article. Early detection is crucial, with specific high-risk groups possibly benefiting from targeted screening programs. Liquid biopsies (such as circulating exosomes, tumor DNA, or tumor cells) offer promise as multifunctional biomarkers for early detection, treatment guidance, and recurrence monitoring. Precision medicine is being explored via targeted therapies for actionable mutations, such as PARP inhibitors for BRCA mutations, and immunotherapy strategies. Artificial intelligence (AI) is emerging as a powerful tool in medical imaging, biomarker discovery, genetics research, and treatment planning, and it can aid in diagnosis, treatment selection, and patient monitoring. However, its associated challenges include ethics, data security, algorithm reliability, and validation. Collaborative efforts between medical professionals, researchers, and AI experts are vital for unlocking AI’s potential to enhance pancreatic cancer care. In conclusion, despite the challenges, advancements in liquid biopsies, precision medicine, and AI offer hope for enhancing the diagnosis, treatment, and management of pancreatic cancer. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Recent Advances and Future Challenges)

Research

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13 pages, 820 KiB

Open AccessArticle

Salvage Ablative Radiotherapy for Isolated Local Recurrence of Pancreatic Adenocarcinoma following Definitive Surgery

by Edward Christopher Dee, Victor C. Ng, Eileen M. O’Reilly, Alice C. Wei, Stephanie M. Lobaugh, Anna M. Varghese, Melissa Zinovoy, Paul B. Romesser, Abraham J. Wu, Carla Hajj, John J. Cuaron, Danny N. Khalil, Wungki Park, Kenneth H. Yu, Zhigang Zhang, Jeffrey A. Drebin, William R. Jarnagin, Christopher H. Crane and Marsha Reyngold

J. Clin. Med. 2024, 13(9), 2631; https://doi.org/10.3390/jcm13092631 - 30 Apr 2024

Cited by 1 | Viewed by 1583

Abstract

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98–100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan–Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37–87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6–71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26–56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46–72%) and 22% (95%CI, 14–37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17–40%) and 36% (95%CI 24–48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3–4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Recent Advances and Future Challenges)

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11 pages, 426 KiB

Open AccessArticle

The Difficulty of Detecting Occult Metastases in Patients with Potentially Resectable Pancreatic Cancer: Development and External Validation of a Preoperative Prediction Model

by Marieke Walma, Laura Maggino, F. Jasmijn Smits, Alicia S. Borggreve, Lois A. Daamen, Vincent P. Groot, Fabio Casciani, Vincent E. de Meijer, Frank J. Wessels, George P. van der Schelling, Vincent B. Nieuwenhuijs, Koop Bosscha, Erwin van der Harst, Ronald van Dam, Mike S. Liem, Sebastiaan Festen, Martijn W. J. Stommel, Daphne Roos, Fennie Wit, Ignace H. de Hingh, Bert A. Bonsing, Olivier R. Busch, Bas Groot Koerkamp, Geert Kazemier, Marc G. Besselink, Roberto Salvia, Giuseppe Malleo, I. Quintus Molenaar and Hjalmar C. van Santvoort Show full author list Hide full author list

J. Clin. Med. 2024, 13(6), 1679; https://doi.org/10.3390/jcm13061679 - 14 Mar 2024

Cited by 1 | Viewed by 1445

Abstract

Occult metastases are detected in 10–15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013–December 2017). Multivariable logistic regression analysis based on the Akaike Information Criteria was performed with intraoperative pathologically proven metastases as the outcome. The model was externally validated with a cohort from the University Hospital of Verona (January 2013–December 2017). For model development, 2262 patients were included of whom 235 (10%) had occult metastases, located in the liver (n = 143, 61%), peritoneum (n = 73, 31%), or both (n = 19, 8%). The model included age (OR 1.02, 95% CI 1.00–1.03), BMI (OR 0.96, 95% CI 0.93–0.99), preoperative nutritional support (OR 1.73, 95% CI 1.01–2.74), tumor diameter (OR 1.60, 95% CI 1.04–2.45), tumor composition (solid vs. cystic) (OR 2.33, 95% CI 1.20–4.35), and indeterminate lesions on preoperative imaging (OR 4.01, 95% CI 2.16–7.43). External validation showed poor discrimination with a C-statistic of 0.56. Although some predictor variables were significantly associated with occult metastases, the model performed insufficiently at external validation. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Recent Advances and Future Challenges)

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12 pages, 724 KiB

Open AccessArticle

Incidence of Diabetes Mellitus and Its Impact on Outcomes in Patients Undergoing Surgical Pancreatectomy for Non-Malignant and Malignant Pancreatobiliary Diseases—A Retrospective Analysis

by Anna Schranz, Christoph Sternad, Faisal Aziz, Doris Wagner, Peter Kornprat, Robert Sucher, Philipp J. Jost, Albert Wölfler, Thomas R. Pieber, Harald Sourij, Jakob M. Riedl and Felix Aberer

J. Clin. Med. 2023, 12(24), 7532; https://doi.org/10.3390/jcm12247532 - 6 Dec 2023

Viewed by 1808

Abstract

Diabetes mellitus (DM) is a prominent risk factor for malignant and non-malignant pancreatic diseases. Furthermore, the presence of DM predicts an unfavourable outcome in people with pancreatic cancer. This retrospective observational study investigated 370 patients who underwent pancreatic resection surgery for various indications (84.3% in malignant indication) in a single surgery centre in Graz, Austria. The preoperative and postoperative diabetes statuses were evaluated according to surgery method and disease entity and predictors for diabetes development after surgery, as well as outcomes (survival and cancer recurrence) according to diabetes status, were analysed. In the entire cohort, the postoperative diabetes (postopDM) incidence was 29%. PostopDM occurred significantly more frequently in malignoma patients than in those with benign diseases (31.3% vs. 16.7%; p = 0.040, OR = 2.28). In the malignoma population, BMI, longer surgery duration, and prolonged ICU and hospital stay were significant predictors of diabetes development. The 1- and 2-year follow-ups showed a significantly increased mortality of people with postopDM in comparison to people without diabetes (HR 1-year = 2.02, p = 0.014 and HR 2-years = 1.56, p = 0.034). Local cancer recurrence was not influenced by the diabetes status. Postoperative new-onset diabetes seems to be associated with higher mortality of patients with pancreatic malignoma undergoing pancreatobiliary surgery. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Recent Advances and Future Challenges)

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12 pages, 1484 KiB

Open AccessArticle

Clinicopathological Features and Prognosis of Resected Pancreatic Ductal Adenocarcinoma Patients with Claudin-18 Overexpression

by Sejun Park, Kabsoo Shin, In-Ho Kim, Taeho Hong, Younghoon Kim, Jahee Suh and Myungah Lee

J. Clin. Med. 2023, 12(16), 5394; https://doi.org/10.3390/jcm12165394 - 19 Aug 2023

Cited by 5 | Viewed by 2041

Abstract

Claudin-18.2 (CLDN18.2) is specifically expressed in pancreatic precancerous lesions and pancreatic ductal adenocarcinoma (PDAC). We assessed the clinical characteristics of patients with CLDN18.2-overexpressing pancreatic cancer to identify patients who might benefit from CLDN18-targeted treatment. A total of 130 patients with surgically resected PDAC were investigated for the immunohistochemical expression of claudin-18 (CLDN18). The CLDN18 staining intensities (0–3+) and relative proportion of positive tumor cells were analyzed by two independent raters. Tumors positive for CLDN18 expression were defined as ≥80% of tumor cells with 2+ or 3+ staining intensity in a CLDN18 immunohistochemical assay. Positive CLDN18 expression was present in 41/130 (31.5%) surgically resected PDACs and the relative proportion of positive tumor cells and the staining intensity were directly correlated (p < 0.001). Positive CLDN18 expression was significantly associated with well-differentiated tumors (p < 0.001) and less regional node involvement (p = 0.045). The positive CLDN18-expressing group showed no statistical difference in median overall survival (17.4 months vs. 20.6 months, p = 0.770) compared to the negative CLDN18-expressing group. Distant nodal metastasis was more frequent in the positive CLDN18-expressing group (p = 0.011). CLDN18 is frequently expressed in PDAC, and high CLDN18-expressing PDACs showed some different clinicopathologic characteristics. High CLDN18 expression was not associated with prognosis in patients with surgically resected PDAC. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Recent Advances and Future Challenges)

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Other

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13 pages, 790 KiB

Open AccessSystematic Review

Recurrence following Resection of Intraductal Papillary Mucinous Neoplasms: A Systematic Review to Guide Surveillance

by Aneesa Salahuddin, Varna Thayaparan, Ahmad Hamad, Willi Tarver, Jordan M. Cloyd, Alex C. Kim, Robyn Gebhard, Timothy M. Pawlik, Bradley N. Reames and Aslam Ejaz

J. Clin. Med. 2024, 13(3), 830; https://doi.org/10.3390/jcm13030830 - 31 Jan 2024

Cited by 2 | Viewed by 1652

Abstract

Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5–57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance. Full article

(This article belongs to the Special Issue Pancreatic Cancer: Recent Advances and Future Challenges)

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