Histogram analysis of magnetic resonance images: evaluation of intra-tumoral heterogeneity and correlation with pathological findings in solid pancreatic tumors.

Objectives To evaluate magnetic resonance (MR)-derived whole-tumor histogram analysis parameters in predicting aggressiveness of pancreatic ductal adenocarcinomas (PDACs) and neuroendocrine neoplasms (panNENs). Methods Pre-operative MR of 169 consecutive patients with PDAC or panNEN were retrospectively analyzed. T1-/T2-weighted images and apparent diffusion coefficient (ADC) maps were analyzed. Histogram-derived parameters were compared to several pathological features (grade, vascular infiltration, nodal and hepatic metastases) using Mann-Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis; sensitivity and specificity were assessed for each histogram parameter. Results No significant differences were found among histogram parameters for prediction of PDACs grade. ADCentropy was significantly higher in G2-3 panNENs with ROC-AUC 0.757; sensitivity was 83.3%. ADCentropy was significantly higher in PDACs with vascular involvement (p=.022; AUC=.641), with specificity of 92.2%. ADCskewness was significantly higher in PDACs with nodal metastases (p=.027; AUC=.642), with 72% specificity. ADCkurtosis was higher in panNENs with vascular involvement, nodal and hepatic metastases (p= .008, .021, and .008; ROC-AUC= 0.820, 0.709, and 0.820); sensitivity and specificity were: 85.7/74.3%; 36.8/96.5%; and 100/62.8%. No significant differences between groups were found for other histogram-derived parameters (p >.05). Conclusions Whole-tumors histogram analysis of ADC values is a valuable tool for predicting aggressiveness of PDACs and panNENs. Our results indicate that histogram metrics related to intra-tumor heterogeneity, as ADCentropy, ADCkurtosis and ADCskewness are the most accurate parameters for the identification of PDACs and panNENs with higher biological aggressiveness. Further and larger studies are needed to incorporate the results of the histogram analysis within decision support models and to mine these data to detect possible correlations with genomic patterns

p 167symptoms reported at initial diagnosis of metastatic pancreatic adenocarcinoma m pac in routine clinical practice and variation in frequencies across europe

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pd 004baseline characteristics and second line treatment for metastatic pancreatic adenocarcinoma mpac patients receiving first line folfirinox gemcitabine nab paclitaxel or gemcitabine monotherapy in routine clinical practice across europe

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o 002geographic variation in systemic treatment of metastatic pancreatic adenocarcinoma mpac patients in real world across europe

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Second-Line Chemotherapy in Elderly Patients with Advanced Biliary Tract Cancer: A Multicenter Real-World Study

Objectives: The ABC-06 and the NIFTY trials recently established the role of second-line chemotherapy (2L) in patients with advanced biliary tract cancer (BTC). Our real-world study aimed to explore 2L in BTC patients aged ≥ 70 years old and to compare their outcomes with younger subjects. Methods: Institutional registries across three academic medical centers were retrospectively reviewed. The Kaplan–Meier methods were used to estimate survival, and the log-rank test was used to make comparisons. Results: A total of 190 BTC patients treated with 2L were identified and included in the analysis. Among them, 52 (27.3%) were aged ≥ 70 years (range 70–87 years). No statistically significant differences in both median overall survival (mOS) and median progression-free survival (mPFS) were recorded between the elderly and younger patients. Absolute lymphocyte count < 1000/mmc (p < 0.001) and albumin level < 3 g/dL (p < 0.001) were independently associated with worse prognoses. Conclusions: The results of this real-world study suggest that for patients aged ≥ 70 years, 2L could be equally effective for younger patients with survival outcomes aligned to those from the ABC-06 and NIFTY trials. The delivery of 2L should be carefully evaluated and monitored in this patient subset

Quality of life in metastatic pancreatic cancer patients receiving liposomal irinotecan plus 5-fluorouracil and leucovorin

Abstract Background The NAPOLI-1 study (NCT01494506) reported that liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) improved overall survival vs 5-FU/LV with manageable toxicity in patients with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy. Yet, clinicians need treatment strategies that also maintain the patient's health-related quality of life (HRQOL). Here, we report the HRQOL data. Methods Patients completed the European Organisation for Research and Treatment of Cancer QOL core questionnaire C30 (EORTC QLQ-C30) at baseline, every 6 weeks, and at 30 days after discontinuation of study treatment. Patient-reported outcomes (PROs) were scored according to EORTC guidelines. nal-IRI+5-FU/LV HRQOL was compared with 5-FU/LV. The PRO population comprised intent-to-treat patients who completed baseline and at least one subsequent assessment on the EORTC QLQ-C30. Data were also analysed for missingness. Results Of 236 patients in the intent-to-treat population, 128 (54.2%) comprised the PRO population (71 in the nal-IRI+5-FU/LV arm; 57 the in 5-FU/LV arm). Of the remaining 108 patients (45.8%) not included in the PRO population, most progressed rapidly, making participation difficult. Median change from baseline was ≤10 points at weeks 6 and 12 in global health status or functional and symptom scale scores, except for fatigue, which deteriorated by 11.1 points with nal-IRI+5-FU/LV but did not change vs 5-FU/LV. The proportion of patients whose HRQOL improved or deteriorated was not significantly different between the arms. Conclusion In the NAPOLI-1 study, HRQOL was maintained with nal-IRI+5-FU/LV in patients with metastatic pancreatic adenocarcinoma previously treated with a gemcitabine-based regimen, while survival was significantly extended

Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab-paclitaxel plus gemcitabine as second or later-line treatment

Background: Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods: The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results: AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS. Conclusions: This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy

Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort

Objective: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. Materials and methods: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient’s family history was considered as potentially BRCAassociated. Patients or disease characteristics were examined using the c2 test or Fisher’s exact test for qualitative variables and the Student's t-test or ManneWhitney test for continuous variables, as appropriate. Results: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/ gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P ¼ 0.01). The gBRCApv rate was 17.1% among patients <40 years old, 10.4% among patients 41-50 years old, 9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients >70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients <74 years old was 9%. Patients with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations. Conclusion: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients with incident PDAC, we recommend screening all PDAC patients <74 years old, regardless of family history and stage, due to the therapeutic implications and cancer risk prevention in patients' relatives. Key words: germline BRCA, epidemiology, pancreatic cancer genetics, familial cance

Peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early phase of pulmonary hypertension

Pulmonary-artery-hypertension (PAH) is a life-threatening and highly invalidating chronic disorder. Chronic oxidation contributes to lung damage and disease progression. Peroxiredoxin-2 (Prx2) is a typical 2-cysteine (Cys) peroxiredoxin but its role on lung homeostasis is yet to be fully defined. Here, we showed that Prx2 mice displayed chronic lung inflammatory disease associated with (i) abnormal pulmonary vascular dysfunction; and (ii) increased markers of extracellular-matrix remodeling. Hypoxia was used to induce PAH. We focused on the early phase PAH to dissect the role of Prx2 in generation of PAH. Hypoxic Prx2 mice showed (i) amplified inflammatory response combined with cytokine storm; (ii) vascular activation and dysfunction; (iii) increased PDGF-B lung levels, as marker of extracellular-matrix deposition and remodeling; and (iv) ER stress with activation of UPR system and autophagy. Rescue experiments with in vivo the administration of fusedrecombinant- PEP-Prx2 show a reduction in pulmonary inflammatory vasculopathy and in ER stress with down-regulation of autophagy. Thus, we propose Prx2 plays a pivotal role in the early stage of PAH as multimodal cytoprotector, targeting oxidation, inflammatory vasculopathy and ER stress with inhibition of autophagy. Collectively, our data indicate that Prx2 is able to interrupt the hypoxia induced vicious cycle involving oxidation-inflammationautophagy in the pathogenesis of PAH