Assessment of the level III of Inoue by preoperative endoscopic ultrasound and elastography: a novel approach to predict a periarterial divestment technique in borderline resectable (BR) or locally advanced (LA) pancreatic adenocarcinoma-How I do it.

BACKGROUND: Periarterial divestment is a surgical technique to approach borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) with arterial involvement. There are no reports in the literature regarding the role of endoscopic ultrasound and elastography (EUS-EG) in exploring the integrity of Inoue's level III and its correlation with the periarterial divestment technique feasibility. Our research is aimed at exploring the role of EUS-EG in this scenario. METHODS: We describe our approach to Inoue's level II by EUS-EG in patients with BR and LA pancreatic cancer patients after neoadjuvant chemotherapy. RESULTS: Between June 2019 and December 2020, four patients out of 25 were eligible to perform a preoperative EUS-EG. In all cases, Inoue's level III integrity was corroborated by EUS-EG and confirmed posteriorly in the surgical scenario where a periarterial divestment technique was feasible. Vein resections were necessary in all cases, with no need for arterial resection. An R0 (> 1 mm) margin was achieved in all patients, and the histopathological assessment showed the presence of neurovascular tissue at the peripheral arterial margin. CONCLUSION: Preoperatively, EUS-EG is a novel approach to explore the integrity of Inoue's level III and could be helpful to preclude a periarterial divestment technique in borderline resectable or locally advanced pancreatic adenocarcinoma with arterial involvement.

Landscape of Health-Related Quality of Life in Patients With Early-Stage Pancreatic Cancer Receiving Adjuvant or Neoadjuvant Chemotherapy: A Systematic Literature Review.

OBJECTIVES: Pancreatic resection is associated with postoperative morbidity and reduced quality of life (QoL). A systematic literature review was conducted to understand the patient-reported outcome measure (PROM) landscape in early-stage pancreatic cancer (PC). METHODS: Databases/registries (through January 24, 2019) and conference abstracts (2014-2017) were searched. Study quality was assessed using the Newcastle-Ottawa Scale/Cochrane risk-of-bias tool. Searches were for general (resectable PC, adjuvant/neoadjuvant, QoL) and supplemental studies (resectable PC, European Organisation for Research and Treatment of Cancer QoL Questionnaire [QLQ] - Pancreatic Cancer [PAN26]). RESULTS: Of 750 studies identified, 39 (general, 22; supplemental, 17) were eligible: 32 used QLQ Core 30 (C30) and/or QLQ-PAN26, and 15 used other PROMs. Baseline QLQ-C30 global health status/QoL scores in early-stage PC were similar to all-stage PC reference values but lower than all-stage-all-cancer values. The QoL declined after surgery, recovered to baseline in 3 to 6 months, and then generally stabilized. A minimally important difference (MID) of 10 was commonly used for QLQ-C30 but was not established for QLQ-PAN26. CONCLUSIONS: In early-stage PC, QLQ-C30 and QLQ-PAN26 are the most commonly used PROMs. Baseline QLQ-C30 global health status/QoL scores suggested a high humanistic burden. Immediately after surgery, QoL declined but seemed stable over the longer term. The QLQ-C30 MID may elucidate the clinical impact of treatment on QoL; MID for QLQ-PAN26 needs to be established.

Cost-utility analysis of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine in metastatic pancreatic cancer in Spain: results of the PANCOSTABRAX study.

The PANCOSTABRAX study evaluated the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine (GEM) versus GEM alone in the treatment of patients with metastatic pancreatic cancer in Spain. Efficacy data were obtained from the MPACT study and were modeled to a lifetime horizon using a Markov model. The analysis was performed from the payer's perspective. Use of resources and key assumptions of the analysis were validated by a panel of oncologists. The addition of nab-paclitaxel to GEM showed higher effectiveness results (0.156 additional quality adjusted life years) at a higher cost (€6,477), resulting in a cost per quality-adjusted life years gained of €41,519. The combination of nab-paclitaxel and GEM has been shown to be an effective and well-tolerated option for the treatment of metastatic pancreatic cancer and, in addition to becoming the new standard of care, could also be considered a cost-effective option.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Phase I assessment of new mechanism-based pharmacodynamic biomarkers for MLN8054, a small-molecule inhibitor of Aurora A kinase.

The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the skin mitotic index after dosing. Although some tumors exhibited increases in mitotic cells after dosing, others displayed decreases, a variable outcome consistent with dual mechanisms of mitotic arrest and mitotic slippage induced by antimitotics in tumors. To provide a clearer picture, mitotic cell chromosome alignment and spindle bipolarity, new biomarkers of Aurora A inhibition that act independently of mitotic arrest or slippage, were assessed in the tumor biopsies. Several patients, primarily in the highest dose cohorts, had marked decreases in the percentage of mitotic cells with aligned chromosomes and bipolar spindles after dosing. Evidence existed for an exposure-effect relationship for mitotic cells with defects in chromosome alignment and spindle bipolarity that indicated a biologically active dose range. Outcomes of pharmacodynamic assays from skin and tumor biopsies were concordant in several patients. Together, these new pharmacodynamic assays provide evidence for Aurora A inhibition by MLN8054 in patient skin and tumor tissues.