Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.

PURPOSE: 18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. METHODS: Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120 min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. RESULTS: [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. CONCLUSION: [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06056362.

Comparative Analysis of mRNA, microRNA of Transcriptome, and Proteomics on CIK Cells Responses to GCRV and Aeromonas hydrophila.

Grass Carp Reovirus (GCRV) and Aeromonas hydrophila (Ah) are the causative agents of haemorrhagic disease in grass carp. This study aimed to investigate the molecular mechanisms and immune responses at the miRNA, mRNA, and protein levels in grass carp kidney cells (CIK) infected by Grass Carp Reovirus (GCRV, NV) and Aeromonas hydrophilus (Bacteria, NB) to gain insight into their pathogenesis. Within 48 h of infection with Grass Carp Reovirus (GCRV), 99 differentially expressed microRNA (DEMs), 2132 differentially expressed genes (DEGs), and 627 differentially expressed proteins (DEPs) were identified by sequencing; a total of 92 DEMs, 3162 DEGs, and 712 DEPs were identified within 48 h of infection with Aeromonas hydrophila. It is worth noting that most of the DEGs in the NV group were primarily involved in cellular processes, while most of the DEGs in the NB group were associated with metabolic pathways based on KEGG enrichment analysis. This study revealed that the mechanism of a grass carp haemorrhage caused by GCRV infection differs from that caused by the Aeromonas hydrophila infection. An important miRNA-mRNA-protein regulatory network was established based on comprehensive transcriptome and proteome analysis. Furthermore, 14 DEGs and 6 DEMs were randomly selected for the verification of RNA/small RNA-seq data by RT-qPCR. Our study not only contributes to the understanding of the pathogenesis of grass carp CIK cells infected with GCRV and Aeromonas hydrophila, but also serves as a significant reference value for other aquatic animal haemorrhagic diseases.

Diagnostic efficacy of [68Ga]Ga-NY104 PET/CT to identify clear cell renal cell carcinoma.

PURPOSE: Most clear cell renal cell carcinoma (ccRCC) overexpresses carbonic anhydrase IX (CAIX). [68Ga]Ga-NY104 is a small-molecule PET agent selectively targeting CAIX. This study aims to assess the efficacy of [68Ga]Ga-NY104 PET/CT to identify ccRCC. MATERIALS AND METHODS: Participants were prospectively recruited in the study (ClinicalTrials.gov: NCT05902377). They were further divided into two groups: group 1, patients with primary renal mass who were scheduled for surgery, group 2, patients with suspected/confirmed metastatic ccRCC. All patients underwent [68Ga]Ga-NY104 PET/CT. RESULTS: A total of 47 patients (mean age, 58.8 years ± 13.5, 34 men) were recruited, including 20 patients in group 1 and 27 patients in group 2. The patient-level sensitivity, specificity, and accuracy of [68Ga]Ga-NY104 PET scan was 62%, 33%, 58% for group 1 and 95%, 100%, 96% for group 2. [68Ga]Ga-NY104 PET identified additional 26 disease regions in 67% (14/21) of patients that were previously unknown. The tumor uptake was correlated with immunohistochemical staining results. CONCLUSIONS: [68Ga]Ga-NY104 PET/CT has a high diagnostic efficacy for patients with metastatic ccRCC, while it might be of limited value in the diagnosis of primary ccRCC.

Gallium-68 labeled somatostatin receptor antagonist PET/CT in over 500 patients with neuroendocrine neoplasms: experience from a single center in China.

PURPOSE: Somatostatin receptor antagonists have shown promising performance for imaging neuroendocrine neoplasms. However, there is a lack of studies exploring the diagnostic performance of SSTR antagonists or comparing them with agonists in a large cohort of patients with NENs. This study aimed to retrospectively review all SSTR antagonist PET/CT scans conducted at Peking Union Medical College Hospital since November 2018 in patients with confirmed or suspected NENs. METHODS: Four types of SSTR antagonists were utilized, including [68Ga]Ga-NODAGA-LM3, [68Ga]Ga-DOTA-LM3, [68Ga]Ga-NODAGA-JR11, and [68Ga]Ga-DOTA-JR11. The reference standard was based on a combination of histopathology, clinical evaluation, imaging results, and follow-up. Patient-based sensitivity, specificity, and accuracy were evaluated. The SUVmax and tumor-to-liver ratio (TLR) of the hottest lesions was recorded and compared between antagonists and [68Ga]Ga-DOTATATE. RESULTS: A total of 622 antagonist scans from 549 patients were included in the analysis. The patient-level sensitivity, specificity, and accuracy of antagonist imaging (all tracers combined) were 91.0% (443/487), 91.9% (57/62), and 91.1% (500/549), respectively. In 181 patients with a comparative [68Ga]Ga-DOTATATE PET/CT scan, the patient-level sensitivity, specificity, and accuracy were 87.5% (147/168), 76.9% (10/13), and 86.7% (157/181), respectively. For the hottest lesions, SSTR antagonists all tracers combined demonstrated an overall comparable SUVmax to [68Ga]Ga-DOTATATE (40.1 ± 32.5 vs. 39.4 ± 23.8, p = 0.772). While [68Ga]Ga-NODAGA-LM3 showed significantly higher uptake than [68Ga]Ga-DOTATATE (57.4 ± 38.5 vs. 40.0 ± 22.8, p<0.001), [68Ga]Ga-NODAGA-JR11 (39.7 ± 26.5 vs. 34.3 ± 23.9, p = 0.108) and [68Ga]Ga-DOTA-LM3 (38.9 ± 32.1 vs. 37.2 ± 22.1, p = 0.858) showed comparable uptake to [68Ga]Ga-DOTATATE, and [68Ga]Ga-DOTA-JR11 showed lower uptake (28.9 ± 26.1 vs. 44.0 ± 25.7, p = 0.001). All antagonists exhibited significantly higher TLR than [68Ga]Ga-DOTATATE (12.1 ± 10.8 vs. 5.2 ± 4.5, p<0.001). CONCLUSION: Gallium-68 labeled SSTR antagonists could serve as alternatives to SSTR agonists for imaging of NENs. Among various antagonists, [68Ga]Ga-NODAGA-LM3 seems to have the best imaging profile.

Development and validation of a nomogram model based on pretreatment ultrasound and contrast-enhanced ultrasound to predict the efficacy of neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer.

OBJECTIVES: To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram's performance, calibration, discrimination and clinical benefit. RESULTS: The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

A real-world analysis of trametinib in combination with hydroxychloroquine or CDK4/6 inhibitor as third- or later-line therapy in metastatic pancreatic adenocarcinoma.

BACKGROUND: There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or CDK4/6 inhibitors for pancreatic adenocarcinoma showed promising efficacy in preclinical studies. However, the regimens have not been well examined in patients with mPDAC. METHODS: Patients with mPDAC who received the combination of trametinib and HCQ or CDK4/6 inhibitors as third- or later-line therapy were reviewed. The efficacy and prognosis were further analyzed. RESULTS: A total of 13 mPDAC patients were enrolled, of whom 8 and 5 patients were treated with trametinib plus HCQ or a CDK4/6 inhibitor (palbociclib or abemaciclib), respectively. All enrolled patients had either KRAS G12D or G12V mutations and had received a median of 3 prior lines of therapy (range, 2-6). The median trametinib treatment duration was 1.4 months. Of the 10 patients with measurable disease, only 1 patient achieved stable disease, and the remaining patients had progressive disease. Moreover, in patients treated with trametinib plus HCQ and a CDK4/6 inhibitor, the median progression-free survival was 2.0 and 2.8 months, respectively, and the median overall survival was 4.2 and 4.7 months, respectively. Moreover, 5 (50%) patients experienced grade 3-4 adverse events in 10 patients with available safety data. CONCLUSIONS: The combination of trametinib and HCQ or CDK4/6 inhibitors may not be an effective later-line treatment for mPDAC, and the current preliminary findings need to be confirmed by other studies with larger sample sizes.

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-naïve advanced pancreatic ductal adenocarcinoma.

OBJECTIVE: Gemcitabine plus nab-paclitaxel (GnP) is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC). S-1, an oral fluoropyrimidine derivative, as compared with gemcitabine, is non-inferior in terms of overall survival (OS) and is associated with lower hematologic toxicity. Accordingly, S-1 is a convenient oral alternative treatment for advanced PDAC. This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1 (GS) vs. GnP as first-line chemotherapy for advanced PDAC. METHODS: Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated. RESULTS: A total of 300 patients were assessed, of whom 84 received GS and 216 received GnP. The chemotherapy completion rate was higher with GS than GnP (50.0% vs. 30.3%, P = 0.0028). The objective response rate (ORR) was slightly higher (14.3% vs. 9.7%, P = 0.35), and the median OS was significantly longer (17.9 months vs. 13.3 months, P = 0.0078), in the GS group than the GnP group. However, the median progression-free survival (PFS) did not significantly differ between groups. Leukopenia risk was significantly lower in the GS group than the GnP group (14.9% vs. 28.1%, P = 0.049). CONCLUSIONS: As first-line chemotherapy for advanced PDAC, the GS regimen led to a significantly longer OS than the GnP regimen. The PFS, ORR, and incidence of severe adverse events were comparable between the GS and GnP groups.

The prognostic role of WeChat-based instant doctor-patient communication in patients with advanced pancreatic cancer.

BACKGROUND: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) need timely medical assistance since the emergence of complications due to the disease and antitumor treatment. Studies have confirmed that instant messaging can improve the quality of life and compliance of cancer patients. However, the prognostic role of instant doctor-patient communication based on instant messaging applications in PDAC has not been studied. METHODS: Patients with PDAC who received first-line chemotherapy at Peking Union Medical College Hospital between January 2015 and October 2022 were reviewed. We categorized patients into two groups according to whether they received WeChat-based instant doctor-patient communication, and the prognosis and toxicity data between the two groups were compared. RESULTS: A total of 431 PDAC patients were enrolled, of whom 163 had long-term instant communication with their doctors based on WeChat, and 268 did not receive WeChat-based instant communication. There was no significant correlation between WeChat-based communication and first-line chemotherapy overall response rate (14.1% vs. 8.6%, p = 0.074), incidence of grade ≥ 3 adverse events (66.9% vs. 65.7%, p = 0.814) or overall survival (14.7 vs. 13.9 months, p = 0.170) in all enrolled patients. However, patients who received WeChat-based instant communication had a higher completion rate of first-line chemotherapy (42.0% vs. 30.7%, p = 0.023). Consistently, in the patients who developed grade ≥ 3 adverse events (n = 231), those who received WeChat-based instant communication had significantly longer overall survival (17.3 vs. 15.3 months, p = 0.018), even after adjustment for biases. CONCLUSIONS: WeChat-based instant doctor-patient communication demonstrated no superiority in improving the efficacy of chemotherapy or preventing chemotherapy toxicity in PDAC patients, but it may contribute to improving the completion rate of chemotherapy and the prognosis in patients who experienced severe adverse events. IMPLICATIONS FOR CANCER SURVIVORS: Instant doctor‒patient communication may help to timely and appropriately deal with adverse events and prolong the survival time of patients with PDAC, supporting the promotion of mobile technology in clinical practice.

Predicting the Efficacy of Neoadjuvant Chemotherapy for Pancreatic Cancer Using Deep Learning of Contrast-Enhanced Ultrasound Videos.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Expression of p53 and Rb reveal subtypes of gastric neuroendocrine carcinoma with distinct prognosis.

Gastric neuroendocrine carcinoma (NEC) is a rare tumor with a poor prognosis. Due to its rarity and disparity in prevalence across populations, there is limited data on gastric NEC. TP53 and RB1 genetic alterations or expression were reported for predictive value in neuroendocrine neoplasm and classification in pulmonary large cell NEC. This study investigated the genetic alteration and protein expression of TP53 and RB1 in gastric NEC. Thirty-nine patients were categorized as type A and B subtypes by p53 and Rb expression. Patients with concurrent abnormal p53 and Rb expression were defined as the type A group, and the remainder were defined as the type B group. Significant differences in TNM stages, tumor size, and lymph node metastasis were observed between the two subtypes. Type A characteristic is an independent predictor for worse overall survival (HR: 3.27; 95% CI: 1.12-9.58; p = .022). We further evaluated and compared immunotherapy-related markers, including PD-L1 expression, CD8 T cell infiltration, tumor mutation burden, and microsatellite instability in these two subtypes, whereas no significant differences were detected.

Evolving landscape of clinical trials in gastroenteropancreatic neuroendocrine neoplasms in the past two decades.

Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogenous malignancies that require well-designed trials to develop effective management strategies. This cross-sectional study aimed to illustrate the current landscape of clinical trials in GEP-NENs to provide insights for future research. Materials and methods: We reviewed all clinical trials registered on ClinicalTrials.gov between 1 January 2000 and 31 December 2021 with GEP-NEN in the 'condition or disease' field. Results: We included 206 eligible trials. Most trials enrolled less than 50 patients (59.8%) and were sponsored by institutions other than government or industry (67.0%). Most trials were conducted in high-income countries (86.6%) and countries located in Europe (30.1%) or Northern America (29.6%). The overall result reporting rates of GEP-NEN trials was 41.4%, and the median time from primary completion to result reporting was 101 months. Characteristics that improved the reporting of results included larger sample size, tumor differentiation specification for inclusion, progression-free survival as primary endpoint, industry sponsorship, and multicenter or multinational participation (all P < 0.05). Compared with trials registered between 2000 and 2011 (n = 28), trials registered between 2012 and 2021 (n = 178) were more likely to specify the Ki-67 index for inclusion (68.0% vs 35.7%, P = 0.002) and to be conducted outside Europe or Northern America (16.4% vs 3.7%, P = 0.02), while the sample size and the sponsorship did not change significantly. Conclusions: Novel management options have been explored for GEP-NENs with more specific inclusion criteria during the past two decades. More efforts are needed to promote international collaborations in clinical trials and enhance timely result dissemination.

Case report: Peritumoral hepatic steatosis in a patient with a metastatic somatostatin-producing oligosymptomatic neuroendocrine neoplasm.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous collection of tumors derived from various neuroendocrine cells and are divided into functioning NEN and non-functioning NEN. Some NENs present with mild symptoms and can secrete somatostatin. These neoplasms are known as somatostatin-producing oligosymptomatic NENs. In this report, we describe a case of metastatic somatostatin-producing oligosymptomatic NEN with peritumoral hepatic steatosis and review the relevant literature. The patient was a 45-year-old woman who presented with mild steatorrhea and melena. A computed tomography scan revealed an enlarged pancreas protruding into the duodenum. Pathology after total pancreatectomy showed a grade 2 pancreatic NEN with positive somatostatin immunostaining. Enlarging masses on the liver were observed after the operation. Ultrasound examination revealed several lesions in the liver, with inner hypoechoic areas that showed rapid enhancement and fast washout on contrast-enhanced ultrasonography and with outer hyperechoic areas with continuous iso-enhancement. Therefore, the inner hypoechoic areas seen on contrast-enhanced ultrasonography were suspected to be true metastases. A biopsy confirmed this suspicion and indicated that the outer areas were peritumoral liver steatosis. This case highlights the importance of the imaging pattern described in this report for accurate diagnosis of metastatic NEN to avoid incorrect estimation of tumor size or a missed diagnosis on biopsy.

Patients with non-functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20-year single-center retrospective analysis.

Pancreatic neuroendocrine tumor (pNET) is the most common subset (31.5%) of gastroenteropancreatic neuroendocrine tumor in China. Based on real-world data from a single center, the present study aimed to evaluate the influence of clinical characteristics, medical treatment and surgery on the survival of non-functional metastatic G2 pNET. In total, 114 metastatic non-functional G2 pNET patients, who were treated and followed up in the Department of Medical Oncology, Peking Union Medical College Hospital (PUMCH) from 2001 until 2019, were analyzed retrospectively. The primary endpoint, overall survival (OS), was calculated from the date of diagnosis to the date of death. The second endpoint, progression-free survival (PFS), was calculated from the date of diagnosis to the date of disease progression. Statistical data were analyzed to evaluate the effects of a clinical characteristic, medical treatment and surgery on OS and PFS. Sixty-nine (60.5%) patients were male and 87 (76.3%) were aged < 60 years. The liver was the most common metastatic organ, with a total of 84 cases (73.7%). With respect to surgery, 32 (28.1%) patients underwent radical surgery and 37 (32.5%) underwent palliative surgery. Survival analysis showed that the 5-year and 10-year survival rates were 79.36% and 70.0%, respectively. Univariate and multivariate Cox regression analyses suggested that both radical (p < .001/.003) and palliative surgery (p < .001/.002) significantly prolonged OS, as revealed by the Kaplan-Meier test (p < .001). Subgroup analysis showed that palliative resection also significantly improves the prognosis in patients with multiple liver metastases. However, the first-line systemic anti-tumor therapy option showed no statistical differences in the present study. Overall, patients with non-functional metastatic G2 pNET receiving palliative or radical surgery demonstrated significantly better survival. Prospective clinical trials are suggested to validate our findings.

Comparison of adjuvant gemcitabine plus S-1 with S-1 monotherapy for pancreatic ductal adenocarcinoma: Retrospective real-world data.

BACKGROUND: S-1 has been recognized as one of the standard adjuvant chemotherapies for pancreatic ductal adenocarcinoma (PDAC) in East Asia, but the optimal adjuvant chemotherapy regimen has not been determined. We aimed to compare the efficacy and safety of adjuvant gemcitabine plus S-1 (GS) with S-1 monotherapy for PDAC. METHODS: Patients with resected PDAC who received adjuvant GS or S-1 chemotherapy in Peking Union Medical College Hospital between May 2014 and May 2022 were reviewed. Data retrieved from medical records were used to evaluate efficacy and toxicity. RESULTS: A total of 241 patients were included, with 167 receiving GS and 74 receiving S-1. The patients who received GS were generally younger (median [range] age: 62 [36-78] versus 64 [44-87] years, p = 0.004), but chemotherapy began later (median [range] interval between chemotherapy and surgery: 49 [17-125] versus 40 [16-100] days, p < 0.001). The median disease-free survival (DFS, 15.1 versus 15.9 months, p = 0.52) and overall survival (OS, 34.8 versus 27.1 months, p = 0.34) did not differ significantly between the GS and S-1 groups, even after adjustment for the biases. However, the chemotherapy completion rate was higher in the patients treated with S-1 (52.4% versus 75.7%, p = 0.006), while grade 3-4 neutropenia occurred more frequently in the GS group (49.5% versus 18.2%, p = 0.015). CONCLUSIONS: Adjuvant S-1 monotherapy demonstrated noninferiority to the GS regimen in DFS and OS with better tolerability for PDAC following surgery.

Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

Health-related quality of life in patients with advanced well-differentiated pancreatic and extrapancreatic neuroendocrine tumors treated with surufatinib versus placebo: Results from two randomized, double-blind, phase III trials (SANET-p and SANET-ep).

AIM: To investigate the health-related quality of life (HRQoL) of patients who had neuroendocrine tumors (NETs) from SANET trials. METHODS: Eligible patients were randomized in a 2:1 ratio to receive surufatinib or placebo. HRQoL questionnaires, including the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-G.I.NET21, were collected. The prespecified HRQoL outcome was the mean change of scores from baseline to the last available visit for each domain. Time until definitive deterioration (TUDD) was defined as the time from randomization to deterioration of ≥10 points from baseline in domain score, disease progression, or death. RESULTS: 370 patients were enrolled and randomly assigned to surufatinib (n = 242) or placebo (n = 128). No significant difference in mean scores change from baseline to the last available visit was observed for QLQ-C30 and QLQ- G.I.NET21 domains, with the exception of diarrhea. The mean score of diarrhea increased 11.7 points from baseline in the surufatinib arm and decreased 1.2 points in the placebo arm, and the between-group difference was 12.9 points. Compared with placebo, surufatinib treated patients had a significantly longer TUDD for dyspnea (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.39-0.86; P = 0.0058) and a significantly shorter TUDD for diarrhea (HR 2.91; 95% CI, 1.66-5.10; P < 0.0001). There were no significant differences in TUDD for the remaining domains of QLQ-C30 and G.I.NET-21. CONCLUSIONS: HRQoL was similar in patients treated with surufatinib and placebo except for diarrhea. The preservation of HRQoL supports surufatinib as a treatment option for NETs. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT02589821, NCT02588170.