The Role of Tumor Microenvironment in Pancreatic Cancer Immunotherapy: Current Status and Future Perspectives DOI Open Access

Fotini Poyia,

Christiana M. Neophytou, Maria Christodoulou

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9555 - 9555

Published: Sept. 3, 2024

Pancreatic cancer comprises different subtypes, where most cases include ductal adenocarcinoma (PDAC). It is one of the deadliest tumor types, with a poor prognosis. In majority patients, disease has already spread by time diagnosis, making full recovery unlikely and increasing mortality risk. Despite developments in its detection management, including chemotherapy, radiotherapy, targeted therapies as well advances immunotherapy, only about 13% PDAC patients does overall survival exceed 5 years. This may be attributed, at least part, to highly desmoplastic microenvironment (TME) that acts barrier limiting perfusion, drug delivery, immune cell infiltration contributes establishment immunologically ‘cold’ conditions. Therefore, there an urgent need unravel complexity TME promotes progression decipher mechanisms pancreatic tumors’ resistance immunotherapy. this review, we provide overview major cellular non-cellular components TME, their biological interplays. We also discuss current state therapeutic treatments focus on ongoing future immunotherapy efforts multimodal aiming remodeling improve efficacy.

Language: Английский

European cancer mortality predictions for the year 2024 with focus on colorectal cancer DOI Creative Commons
Claudia Santucci, Silvia Mignozzi, Matteo Malvezzi

et al.

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(3), P. 308 - 316

Published: Jan. 29, 2024

We predicted cancer mortality figures for 2024 the European Union (EU), its five most populous countries, and UK. focused on from colorectal (CRC).

Language: Английский

Citations

48
GPT-4 for Information Retrieval and Comparison of Medical Oncology Guidelines DOI
Dyke Ferber, Isabella C. Wiest, Georg Wölflein

et al.

NEJM AI, Journal Year: 2024, Volume and Issue: 1(6)

Published: May 17, 2024

Oncologists face increasingly complex clinical decision-making processes as new cancer therapies are approved and treatment guidelines revised at an unprecedented rate. With the aim of improving oncologists' efficiency supporting their adherence to most recent recommendations, we evaluated use large language model generative pretrained transformer 4 (GPT-4) interpret from American Society Clinical Oncology European for Medical Oncology. The ability GPT-4 answer clinically relevant questions regarding management patients with pancreatic cancer, metastatic colorectal hepatocellular carcinoma was assessed. We also assessed outputs without retrieval-augmented generation (RAG), which provided additional knowledge model, then manually compared results original guideline documents. RAG correct responses in 84% cases (of 218 statements, 184 were correct, 30 inaccurate, wrong). only 57% 163 93 29 41 showed that GPT-4, when enhanced information through RAG, can accurately identify detailed similarities disparities diagnostic proposals across different authoritative sources.

Language: Английский

Citations

28
REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer DOI Creative Commons
Ugo Boggi, Emanuele F. Kauffmann, Niccolò Napoli

et al.

Annals of Surgery, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 26, 2024

Objective: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Summary Background Data: Coupled improvements in chemotherapy radiation, contemporary approach to surgery supports resection BR-PDAC and, a lesser extent, LA-PDAC. Guidelines outlining selection for these are lacking. Methods: Scottish Intercollegiate Network (SIGN) methodology was used develop create recommendations. Delphi reach (agreement ≥80%) among experts. Recommendations were approved after debate vote international experts cancer management. A Validation Committee AGREE II-GRS tool assess methodological quality guidelines. Moreover, an independent multidisciplinary advisory group revised statements ensure adherence non-surgical Results: Overall, 34 recommendations created targeting centralization, training, staging, patient surgery, possibility uncommon scenarios, timing avoidance vascular reconstruction, details resection/reconstruction, arterial divestment, frozen section histology perivascular tissue, extent lymphadenectomy, anticoagulation prophylaxis role minimally invasive surgery. level evidence however low 29 clinical questions. Participants agreed that most conducive mean promptly advance our understanding this field is establish registry addressing population (https://rediscover.unipi.it/) Conclusions: provide pertaining pancreatectomy BR- LA-PDAC, serve as basis new population.

Language: Английский

Citations

20
MRI-guided stereotactic ablative body radiotherapy versus CT-guided percutaneous irreversible electroporation for locally advanced pancreatic cancer (CROSSFIRE): a single-centre, open-label, randomised phase 2 trial DOI
Florentine E. F. Timmer, Bart Geboers, Alette H. Ruarus

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2024, Volume and Issue: 9(5), P. 448 - 459

Published: March 19, 2024

Language: Английский

Citations

16
Futility of Up-Front Resection for Anatomically Resectable Pancreatic Cancer DOI
Stefano Crippa, Giuseppe Malleo, Vincenzo Mazzaferro

et al.

JAMA Surgery, Journal Year: 2024, Volume and Issue: 159(10), P. 1139 - 1139

Published: July 24, 2024

There are currently no clinically relevant criteria to predict a futile up-front pancreatectomy in patients with anatomically resectable pancreatic ductal adenocarcinoma.

Language: Английский

Citations

14
Stereotactic body radiotherapy for pancreatic cancer – A systematic review of prospective data DOI Creative Commons
M. Shouman, Frederik Fuchs, Franziska Walter

et al.

Clinical and Translational Radiation Oncology, Journal Year: 2024, Volume and Issue: 45, P. 100738 - 100738

Published: Jan. 28, 2024

Language: Английский

Citations

10
A Quest for Survival: A Review of the Early Biomarkers of Pancreatic Cancer and the Most Effective Approaches at Present DOI Creative Commons
Muhammad Begawan Bestari, Ignatius Ronaldi Joewono, Ari Fahrial Syam

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 364 - 364

Published: March 19, 2024

Pancreatic cancer (PC) is the most lethal type of cancer; it has lowest 5-year survival rate among all other types cancers. More than half PC cases are diagnosed at an advanced stage due to PC’s insidious and non-specific symptoms. Surgery remains efficacious treatment option currently available, but only 10–20% resectable upon diagnosis. As now, sole biomarker approved by United States Food Drug Administration (US-FDA) for carbohydrate antigen 19-9 (CA19-9); however, its use limited early An increasing number studies have investigated a combination biomarkers. Lately, there been considerable interest in application liquid biopsy, including utilization microRNAs (miRNAs), circulating tumor DNA (ctDNA), cells (CTCs). Screening indicated high-risk patients; on new diagnostic models combined with biomarkers detection also shown promising results terms ability these aid clinicians deciding whether start screening. This review seeks provide concise overview advancements relation existing explore novel strategies PC.

Language: Английский

Citations

9
Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study DOI

Jean–Luc Van Laethem,

Ivan Borbath, Hans Prenen

et al.

The Lancet Oncology, Journal Year: 2024, Volume and Issue: 25(7), P. 853 - 864

Published: June 1, 2024

Language: Английский

Citations

9
18F−Prostate−Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN−2): a phase I/II study DOI Creative Commons
Jisce R. Puik,

Thomas T. Poels,

Gerrit K. Hooijer

et al.

Cancer Imaging, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 14, 2025

Abstract Background Current diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, lack accuracy in detecting lymph node metastases. 18 F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as ductal adenocarcinoma (PDAC). This phase I/II study aimed assess the feasibility F-PSMA detect PDAC. Methods Seventeen patients with clinically resectable PDAC underwent prior surgical resection. Images were analyzed both visually (semi)quantitatively by deriving maximum standardized uptake value (SUV max ) tumor-to-background ratio (TBR). TBR was defined SUV primary tumor divided aortic blood pool. Finally, tracer on PET correlated tissue expression PSMA specimens. Results Out 17 scans, 13 scans demonstrated positive uptake, a mean 5.0 ± 1.3. The suspected detectable (TBR ≥ 2) 3.3 For confirmed PDAC, 4.9 1.2 1.5, respectively. Although eight had regional metastases two distant metastases, none these uptake. There no correlation Conclusions able several cancers, including However, generally low, not specific observed or added this setting appears be limited. Trial registration trial registered PANSCAN-2 European Clinical Trials Database (EudraCT number: 2020–002185-14). Graphical

Language: Английский

Citations

1
Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX DOI
Thomas F. Stoop, Toshitaka Sugawara,

Atsushi Oba

et al.

JAMA Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Importance The effect of adjuvant chemotherapy following resection pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) on overall survival (OS) is unclear because current studies do not account for the number cycles regimen. Objective To investigate association with OS, taking into Design, Setting, Participants This retrospective cohort study included patients localized treated 2 to 11 followed by across 48 centers 20 countries from 2010 2018. Patients who died within 3 months surgery were excluded (landmark). Data analyzed February 1 December 31, 2023. Exposures Preoperative eventually chemotherapy. Main Outcomes Measures primary outcome was calculated 3-month landmark. Cox regression analysis, including interaction analyses, performed OS. Results Overall, 767 (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant independently associated prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed adjusted curves. analysis assess estimated treatment subgroups statistically significant. forest plot test suggest that lower among receiving 8 more (m)FOLFIRINOX, those had radiological response, ypN0 disease. Compared no chemotherapy, both (HR, 0.57; 0.40-0.80) other multiagent regimens 0.61; 0.41-0.92) whereas single-agent 0.75; 0.55-1.03). Conclusions Relevance In this study, improved not. impact may be such as having ypN0.

Language: Английский

Citations

1