• Gastrointestinal
• PET/CT
• Radiation oncology

• Humans
• Gastrointestinal Neoplasms/diagnostic imaging
• Gastrointestinal Neoplasms/radiotherapy
• Positron Emission Tomography Computed Tomography/methods
• Radiation Oncology/methods
• Radiopharmaceuticals

• HIV
• Kaposi sarcoma
• case report
• nab-paclitaxel

• the Zhejiang Traditional Chinese Medicine Science and Technology Program of China

• IRTKS
• PI3K/AKT signaling pathway
• Pancreatic cancer
• Tumor phenotype

• Carcinogenesis/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Cell Proliferation/genetics
• Humans
• Microfilament Proteins
• Pancreatic Neoplasms/pathology
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-akt/metabolism

• 20YF3FA033 Key Science and Technology Foundation of Gansu Province

There is a high mortality rate associated with pancreatic cancer, and the incidence has been rising globally in recent decades. When patients are diagnosed, there is little chance that surgery will be beneficial. Systemic chemotherapy is the currently accepted treatment option for patients with metastatic advanced pancreatic cancer. However, a very limited survival improvement is possible with chemotherapy for advanced pancreatic cancer, and chemotherapy resistance plays a significant role in poor prognosis. Despite the fact that targeting growth factor receptor inhibitors such as anti-vascular endothelial growth factor (VEGFR) antibodies significantly improves survival in pancreatic cancer, only a very small number of patients benefit from the treatment. As emerging drugs, immune checkpoint inhibitors (ICIs) have demonstrated significant therapeutic effects in several tumor types, but monotherapy is not effective in pancreatic cancer. In the first-line treatment of solid tumors, combination therapy may result in remarkable outcomes. Here in, we have reported a younger patient with pancreatic ductal adenocarcinoma with liver metastasis (PDACLM) who had a long-term partial response and good tolerance to the combination of anlotinib and programmed cell death protein 1 (PD-1) inhibitor and chemotherapy. Gene analysis suggested only one mutation in the Kirsten rat sarcoma viral oncogene (KRAS) G12V gene. Consequently, there is some hope for patients with pancreatic cancer, especially for KRAS G12V gene mutated patients. Upon reviewing the literature, this patient’s combination therapy is the first to have been reported.

• Humans
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Immune Checkpoint Inhibitors/therapeutic use
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Proto-Oncogene Proteins p21(ras)/genetics
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/genetics
• Liver Neoplasms/drug therapy
• Liver Neoplasms/genetics

Pancreatic cancer has an extremely poor prognosis, and the clinical drugs for the treatment of pancreatic cancer are usually multi-drug combinations. Therefore, it is necessary to search for and find specific new bioactive agents against pancreatic cancer. Carabrone is a carabrane-type sesquiterpenolide extracted from Carpesium cernuum L., and this natural compound has been reported to be a potential anti-tumor agent. However, there are few reports on the function of carabrone related to anti-tumor activity in pancreatic cancer. Herein, cell experiments indicated that carabrone had anti-proliferation inhibition and anti-migration and anti-invasion activity against SW1990 cells. Furthermore, the tandem mass spectrometry and network pharmacology analysis showed that this activity may be related to the ferroptosis and Hippo signaling pathway. Taken together, our results demonstrated that carabrone exhibited prominent anti-pancreatic cancer activity and could be a promising agent against pancreatic cancer.

• Humans
• Adenocarcinoma/diagnostic imaging
• Adenocarcinoma/therapy
• Carcinoma, Pancreatic Ductal/diagnostic imaging
• Carcinoma, Pancreatic Ductal/therapy
• Fluorodeoxyglucose F18
• Neoadjuvant Therapy/methods
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/therapy
• Prognosis
• Retrospective Studies

• R01 CA272628 NCI NIH HHS

• chemotherapy
• metastasis/lung
• metastatectomy
• pancreatic ductal adenocarcinoma
• survival

In this prospective exploratory study, we evaluated the feasibility of [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) PET/MRI-based chemotherapy response prediction in pancreatic ductal adenocarcinoma at two weeks upon therapy onset.

In a mixed cohort, seventeen patients treated with chemotherapy in neoadjuvant or palliative intent were enrolled. All patients were imaged by [¹⁸F]FDG PET/MRI before and two weeks after onset of chemotherapy. Response per RECIST1.1 was then assessed at 3 months [¹⁸F]FDG PET/MRI-derived parameters (MTV_50%, TLG_50%, MTV_2.5, TLG_2.5, SUV_max, SUV_peak, ADC_max, ADC_mean and ADC_min) were assessed, using multiple t-test, Man–Whitney-U test and Fisher’s exact test for binary features.

At 72 ± 43 days, twelve patients were classified as responders and five patients as non-responders. An increase in ∆MTV_50% and ∆ADC (≥ 20% and 15%, respectively) and a decrease in ∆TLG_50% (≤ 20%) at 2 weeks after chemotherapy onset enabled prediction of responders and non-responders, respectively. Parameter combinations (∆TLG_50% and ∆ADC_max or ∆MTV_50% and ∆ADC_max) further improved discrimination.

Multiparametric [¹⁸F]FDG PET/MRI-derived parameters, in particular indicators of a change in tumor glycolysis and cellularity, may enable very early chemotherapy response prediction. Further prospective studies in larger patient cohorts are recommended to their clinical impact.

The online version contains supplementary material available at 10.1186/s13550-021-00808-4.

• Chemotherapy
• PDAC
• PET/MRI
• Response prediction

Pancreatic ductal adenocarcinomas exhibit a high degree of desmoplasia due to extensive extracellular matrix deposition. Encasement of mesenteric vessels by stroma in locally advanced pancreatic cancer (LAPC) prevents surgical resection. This study sought to determine if the addition of a monoclonal antibody to connective tissue growth factor, pamrevlumab, to neoadjuvant chemotherapy would be safe and lead to improved resectability in this surgically adverse patient population.

In this phase I/II trial, 37 patients with LAPC were randomised 2:1 to gemcitabine/nab-paclitaxel plus (Arm A, n=24) or minus (Arm B, n=13) pamrevlumab. Those who completed six cycles of treatment were assessed for surgical eligibility by protocol-defined criteria. Resection rates, progression-free and overall survival were evaluated.

Eighteen (75%) patients in Arm A and seven (54%) in Arm B completed six cycles of therapy with similar toxicity patterns. In Arms A and B, carbohydrate antigen 19–9 response, as defined by ≥50% decline from baseline, occurred in 13 (65%) and 5 (42%), respectively. Sixteen (16%) per cent of patients were radiographically downstaged by National Comprehensive Cancer Network criteria (5 in Arm A (21%) and 1 (8%) in Arm B). Positron emission tomography normalised in 9 (38%) vs 3 (23%) of patients in Arm A vs Arm B, respectively, and correlated with surgical exploration. Eligibility for surgical exploration was 17 (71%) vs 2 (15%) (p=0.0019) and resection was achieved in 8 (33%) vs 1 (8%) of patients in Arm A vs Arm B (p=0.1193), respectively. Postoperative complication rates were not different between arms.

Neoadjuvant chemotherapy with pamrevlumab holds promise for enhancing resection rates in patients with LAPC without added toxicity. This combination merits evaluation in a larger patient cohort.

• Pancreatic ductal adenocarcinoma, desmoplasia, connective tissue growth factor, monoclonal antibody

• CCL26
• PI3K/AKT/mTOR signaling pathway
• cancer-associated fibroblasts
• invasion
• pancreatic cancer

• PDAC
• diagnostic imaging
• immuno-PET
• pancreatic cancer

• PI18/01665 Instituto de Salud Carlos III
• XIII Beca Fero Fundación Fero

In pancreatic cancer, imaging plays an essential role in surveillance, diagnosis, resectability evaluation, and treatment response evaluation. Pancreatic cancer surveillance in high-risk individuals has been attempted using endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI). Imaging diagnosis and resectability evaluation are the most important factors influencing treatment decisions, where computed tomography (CT) is the preferred modality. EUS, MRI, and positron emission tomography play a complementary role to CT. Treatment response evaluation is of increasing clinical importance, especially in patients undergoing neoadjuvant therapy. This review aimed to comprehensively review the role of imaging in relation to the current treatment strategy for pancreatic cancer, including surveillance, diagnosis, evaluation of resectability and treatment response, and prediction of prognosis.

• Diagnosis
• Imaging
• Pancreatic cancer
• Prognosis
• Resectability
• Response evaluation

• Gastrointestinal
• PET/CT
• Prognosis
• Staging

• Fluorodeoxyglucose F18/pharmacokinetics
• Humans
• Magnetic Resonance Imaging/methods
• Outcome Assessment, Health Care/methods
• Outcome Assessment, Health Care/statistics & numerical data
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/therapy
• Positron Emission Tomography Computed Tomography
• Positron-Emission Tomography/methods
• Prognosis
• Proportional Hazards Models
• Radiopharmaceuticals/pharmacokinetics
• Pancreatic Neoplasms

• HIFU
• PDAC
• gemcitabine
• multimodality therapy
• prognosis

• antibiotics
• bacteria
• gemcitabine
• multivariate analysis
• univariate analysis

• unresectable advanced pancreatic cancer
• chemotherapy regimens
• benefits and risks

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Clinical Trials as Topic
• Female
• Humans
• Male
• Middle Aged
• Pancreas
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/mortality
• Progression-Free Survival
• Randomized Controlled Trials as Topic
• Treatment Outcome
• Pancreatic Neoplasms

• EHMT2
• SKP2
• cell cycle
• p27
• pancreatic cancer

• U01 DK107013 NIDDK NIH HHS

Cancer‐associated fibroblasts (CAF), derived from stroma of cancer tissues, interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Nab‐paclitaxel (nab‐PTX) is a 130 nm albumin‐binding paclitaxel and recommended for many types of cancer chemotherapy. The nab‐PTX stromal‐disrupting effect during pancreatic cancer treatment has been reported. The aim of the present study was to determine the role of nab‐PTX in cancer cells and CAF interaction. Cancer cells (MIA PaCa‐2 and Panc‐1) were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial‐mesenchymal transition (EMT)‐related marker expression and C‐X‐C motif chemokine 10 (CXCL10) expression and secretion were detected. Nab‐PTX treatment was carried out during the coculture system or during preparation of CAF conditioned medium. Then cancer cell migration and invasion ability, EMT‐related marker expression, CXCL10 expression and secretion, and interleukin‐6 (IL‐6) expression and secretion by CAF were checked After coculture with CAF, migration and invasion ability of cancer cells increased. CAF also downregulated E‐cadherin and upregulated N‐cadherin and vimentin expression in cancer cells. During coculture or stimulation with cancer cell‐cultured medium, CAF significantly increased IL‐6 expression and secretion. However, nab‐PTX in the coculture system canceled CAF‐induced migration and invasion promotion and EMT‐related gene changes. Moreover, nab‐PTX increased CXCL10 expression of cancer cells which blocked CAF IL‐6 expression and secretion. Nab‐PTX treatment could increase CXCL10 expression of cancer cells which blocks CAF cancer cell migration and invasion‐promoting effect by inhibiting IL‐6 expression.

• 130 nm albumin-bound paclitaxel
• cancer-associated fibroblast
• chemokine CXCL10
• epithelial-mesenchymal transition
• pancreatic neoplasms

Autoimmune pancreatitis (AIP) shares overlapping clinical features with pancreatic cancer (PC). Importantly, treatment of the two conditions is different. We investigated the clinical usefulness of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with suspected AIP before treatment. From September 2008 to July 2016, 53 patients with suspected AIP at National Taiwan University Hospital had PET/CT prior to therapy to exclude malignancy and evaluate the extent of inflammation. Their scans were compared with those from 61 PC patients. PET imaging features were analyzed using logistic regression. Significant differences in pancreatic tumor uptake morphology, maximum standardized uptake value, high-order primary tumor texture feature (i.e. high-gray level zone emphasis value), and numbers and location of extrapancreatic foci were found between AIP and PC. Using the prediction model, the area under curve of receiver-operator curve was 0.95 (P < 0.0001) with sensitivity, specificity, positive predictive, and negative predictive values of 90.6%, 84.0%, 87.9%, and 87.5% respectively, in differentiating AIP from PC. FDG PET/CT offers high sensitivity, albeit slightly lower specificity in differentiating AIP from PC. Nonetheless, additional systemic inflammatory foci detected by the whole body PET/CT help confirm diagnosis of AIP in these patients before initiating steroid therapy, especially when biopsy is inconclusive.

• CT
• MRI
• Pancreatic cancer
• RECIST

• Animals
• Carcinoma, Pancreatic Ductal/diagnostic imaging
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/pathology
• Diffusion Magnetic Resonance Imaging
• Diphenylamine/analogs & derivatives
• Diphenylamine/therapeutic use
• Disease Models, Animal
• Humans
• Image Processing, Computer-Assisted
• MAP Kinase Kinase Kinases/antagonists & inhibitors
• MAP Kinase Kinase Kinases/metabolism
• Mice
• Neoadjuvant Therapy
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/pathology
• Protein Kinase Inhibitors/therapeutic use
• Response Evaluation Criteria in Solid Tumors
• Sulfonamides/therapeutic use
• Pancreatic Neoplasms

This single-arm, phase II trial is to investigate efficacy and safety of nab-paclitaxel plus S-1 as first-line treatment in advanced pancreatic cancer. Nab-paclitaxel was administered at 120 mg/m² intravenously on day 1 and 8, S-1 was given twice a day orally on day 1-14 of each 21-day cycle, for 6 cycles. The primary endpoint was objective response rate (ORR), the secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. The ORR in intent-to-treat population (N=60) by either blinded independent review (BIR) or investigator assessment was 50.0%. Median PFS (mPFS) by BIR and median OS (mOS) were 5.6 months (95%CI, 4.6 to 6.6 m) and 9.4 months (95%CI, 8.0 to 10.8m), respectively. The most common grade 3 or 4 toxicities were leukopenia/neutropenia (35%) and fatigue (8.3%). Subgroup analyses based on BIR showed a remarkable ORR (>70%) was achieved in patients with female gender, ≥ 50% decline from baseline CA19-9, and developed grade 3 or 4 leukopenia/neutropenia. Remarkable survival benefit was statistically significant in female (mPFS: 7.7m, mOS: 18.2m), ≥ 50% decline from baseline CA19-9 (mPFS: 6.8m, mOS: 11.8m), objective responders (mPFS: 6.9m, mOS: 12.2m), and ECOG of 0 at baseline (mPFS: 7.5m, mOS: 16.1m). Nab-paclitaxel plus S-1 showed encouraging ORR and manageable toxicities, which is an effective alternative treatment regimen for advanced pancreatic cancer. (https://clinicaltrials.gov/ number, NCT02124317)

• S-1
• advanced pancreatic adenocarcinoma
• nab-paclitaxel
• objective response rate
• survival

• Folfirinox
• Gemcitabine
• Metastatic disease
• Nano albumin bound-paclitaxel
• Pancreatic cancer

• Albumins/metabolism
• Albumins/pharmacokinetics
• Albumins/therapeutic use
• Antineoplastic Agents, Phytogenic/pharmacokinetics
• Antineoplastic Agents, Phytogenic/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/mortality
• Carcinoma, Pancreatic Ductal/pathology
• Clinical Trials as Topic
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/pharmacokinetics
• Deoxycytidine/therapeutic use
• Disease-Free Survival
• Humans
• Neoplasm Staging
• Osteonectin/metabolism
• Paclitaxel/pharmacokinetics
• Paclitaxel/therapeutic use
• Pancreas/metabolism
• Pancreas/pathology
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Permeability
• Treatment Outcome
• Gemcitabine

• Immune resistance
• Immunotherapy
• PD-1/PD-L1
• Pancreatic cancer
• Tumour microenvironment

• Chemoradiation
• Chemotherapy
• Pancreatic cancer
• Randomized control trails
• Randomized trials

• Gemcitabine
• Pancreatic cancer
• Phase 1/2 clinical trial
• Positron emission tomography
• nab-Paclitaxel

A recent analysis from the MPACT trial supported the use of carbohydrate antigen 19-9 (CA19-9) decrease as a predictive marker for survival in patients receiving nab-paclitaxel plus gemcitabine or gemcitabine alone for metastatic pancreatic cancer; however, CA19-9 cannot be used in this capacity for the 15% to 20% of patients who do not produce elevated levels at baseline, leaving fewer tools for predicting outcomes in these patients. Decreases in tumor metabolic activity as measured by positron emission tomography (PET) also predicted longer survival in the MPACT trial. Here we report that tumor metabolic response measured by PET significantly predicted longer survival in patients in the MPACT trial who did not produce elevated CA19-9 at baseline.