bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative or adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: Quality of life results of the randomized phase II AIO-NEONAX trial.
Authors: Buchholz Sina , Ettrich Thomas Jens , Uhl Waldemar , Kornmann Marko , Algül Hana , Friess Helmut , Koenig Alexander , Gallmeier Eike , Lutz Manfred P. , Wille Kai , Schimanski Carl Christoph , Kunzmann Volker , Geissler Michael , Waldschmidt Dirk , Daum Severin , Perkhofer Lukas , Reinacher-Schick Anke C. , Seufferlein Thomas 
Published: January 2023

694 Background: Perioperative chemotherapy (CTX) in resectable pancreatic adenocarcinoma (rPDAC) is still not considered SoC and data regarding efficacy but also quality of life (QoL) are limited. NEONAX is a prospective, randomized phase II trial in patients with rPDAC with two independent experimental arms examining perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. The primary endpoint DFS at 18 mo. as well as DFS, OS and safety have already been reported. Here we present the QoL data of the NEONAX trial. Methods: QoL was evaluated by EORTC QLQ-C30, EORTC QLQ-PAN26 and HADS-D questionnaires at baseline, at the beginning of each CTX cycle (neoadj. and adj. in arm A, only adj. in arm B), after neoadj. treatment in arm A as well as prior and post resection and after 6 cycles of CTX. Results: Global health status score (GHS-score) (QLQ-C30) showed no difference between baseline (t1) and the timepoint after 6 cycles of CTX (t2) in the perioperative arm A (66.7/100 at both timepoints). Here patients experienced the lowest GHS-score pre- and postoperatively (50/100 in both cases). Adjuvant arm B showed a deterioration in the GHS-score of 12.5 points from timepoint 1 to 2 (62.5/100 to 50.0/100). Here the lowest GHS-score was observed within 4 weeks post-surgery (41.7/100). Physical function score (QLQ-C30) was decreased by 6.7 points (86.7/100 to 80/100) in perioperative arm A and by 26.7 points (86.7/100 to 60/100) in arm B between both timepoints. Role function (QLQ-C30) was reduced by 16.7 points (83.3/100 to 66.7/100) in arm A and by 33.3 points (83.3/100 to 50/100) in arm B between both timepoints. In the remaining subscales of the used questionnaires the two arms of the trial showed comparable median scores over the whole study period. The number of submitted questionnaires at each timepoint varied but was at large comparable in both arms. Conclusions: QoL was largely preserved in the perioperative as well as the adjuvant arm of the NEONAX trial. GHS-score was lower pre-and postoperatively in arm A. The lowest GHS-score was observed postoperatively in the adjuvant arm B. QoL was restored at the end of the treatment period in the perioperative arm A and remained slightly reduced in arm B suggesting that QoL is not substantially impaired by perioperative treatment in rPDAC. Clinical trial information: NCT02047513 . [Table: see text]
Effect of pancreatic enzyme replacement therapy (PERT) on body weight in advanced pancreatic cancer (APC).
Authors: Picozzi Vincent J. , Najjar Anas , Harb Diala E , Kort Jens J , Mandelson Meg T. 
Published: January 2023

698 Background: Malnutrition/cachexia is common in PC and is associated with multiple adverse patient (pt) outcomes. Current NCCN guidelines recommend PERT in PC pts with exocrine pancreatic insufficiency (EPI). However, little evidence exists regarding the impact of PERT on clinical outcomes in PC, especially APC. Data on impact of PERT use on change in body weight is presented here. Methods: Pts in this retrospective cohort study were identified from the Virginia Mason PC database. Eligibility requirements included: 1) no upfront resection 2) no prior PC therapy 3) pancreatic stool elastase 1< 200 µg/g stool or documented clinical evidence of EPI at diagnosis 4) treatment at least to initial restaging event (8 weeks) 5) available data regarding PERT use/dosage. Weight/BMI was assessed at baseline and after 8 weeks on therapy. Two pt groups were compared; a) pts prescribed PERT for EPI at recommended package insert dose (≥ 500KU-2500/kg/meal for ≥ 3 meals/day) for ≥ 50% treatment period and b) pts who received no PERT. Pts on PERT at lower than recommended dose and /or < 50% interval between 1st treatment and reassessment were excluded from analysis. Statistical significance was determined using the T-test for continuous variables, chi-squared for categorical variables. Results: 505 total pts were study eligible; 197 (39%) pts received PERT, 308 (61%) pts did not. Pt characteristics are shown. Despite a more adverse patient population with respect to weight loss, pts receiving PERT after 8 weeks experienced less change in weight (-0.36 kg vs -1.54 kg, P = 0.025) and change in BMI ( -0.64% vs -1.96., p= 0.026). Pts with cachexia experienced a similar outcome (-0.36% vs. -2.02 %, p= 0.026). No other pt characteristics achieved statistical significance. Conclusions: Despite a more adverse population with respect to weight loss at baseline, PERT usage prescribed per package insert guidance reduced wt loss/ change in BMI loss in APC over the 1st 8 weeks of therapy. This was also true in APC pts with cachexia. Further analysis of the impact of PERT therapy in APC with respect to treatment tolerability, and toxicity, quality of life and overall survival is warranted. [Table: see text]
Long-term results from NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC).
Authors: George Thomas J. , Yothers Greg , Rahma Osama E. , Hong Theodore S. , Russell Marcia McGory , You Y. Nancy , Parker William , Jacobs Samuel A. , Lucas Peter C. , Colangelo Linda H. , Gollub Marc J , Hall William A. , Kachnic Lisa A. , Bajaj Madhuri , Gross Howard M. , Peterson Richard A. , Dorth Jennifer Anne , Vijayvergia Namrata , Wolmark Norman 
Published: January 2023

7 Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EAs) in LARC. EAs are not intended for direct comparison, but rather to concurrently randomized control arm (CA) patients. Primary endpoint (EP) and available secondary EPs (from EA1 using veliparib [V], PARPi; and EA2 using pembrolizumab [P], anti-PD-1) have been previously reported. We present long-term outcomes of all pts enrolled (NCT02921256). Methods: Stage II/III pts with MSS LARC (with any ONE of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to CA (neoadjuvant FOLFOX [x 4mo] → chemoRT [capecitabine with 50.4Gy] → surgery 8-12 wks later). EA1 added V (400mg PO BID) and EA2 added P (200mg IV Q3 wks x 6 doses) each concurrent with chemoRT. Primary EP: 4-point reduction in Neoadjuvant Rectal Cancer (NAR) score with a one-sided α=0.10, 80% power. NAR compared by linear model controlling for clinical T4 at entry (Y/N). Secondary EPs: OS, DFS. p-values are two-sided. Results: From 10/2016-2/2018, 178 pts were randomized (88 CA, 90 EA1). From 8/2018-5/2019, 185 pts were randomized (95 CA, 90 EA2). Baseline characteristics were previously reported. Median follow-up is 3.50 yrs for the 1st comparison. Median follow-up is 3.15 yrs for the 2nd comparison. Updated primary and long-term secondary outcomes are in the table. Conclusions: With longer follow-up, addition of V to TNT provided no significant differences in the NAR score or 3yr outcomes. The addition of P to TNT was associated with a statistically significant improvement in 3yr OS, but not DFS. Correlative molecular analyses are ongoing. Support: U10CA180868, -180822; UG1-189867; U24-196067; AbbVie; Merck. Clinical trial information: NCT02921256 . [Table: see text]
Does neoadjuvant treatment in resectable pancreatic cancer improve disease outcomes? Systematic review and metanalysis of randomized controlled trials.
Authors: Dias e Silva Douglas , Castro Nicoly Marques , Victor Elivane da Silva , Rother Edna Terezinha , Araújo Sergio Eduardo Alonso , Moura Fernando , Uson Junior Pedro Luiz Serrano 
Published: January 2023

704 Background: Neoadjuvant chemotherapy improves survival in borderline resectable pancreatic cancer (RPC). Whether these results are the same in upfront RPC is unknown. Methods: To evaluate the association of neoadjuvant treatment and outcomes in RPC a systematic review was performed including randomized trials of neoadjuvant treatment versus upfront surgery. Articles indexed in PubMed, Embase and Web of Science were evaluated. Data regarding treatment regimens, R0 rates, disease free survival (DFS) and overall survival (OS) were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Results: Of 3,229 abstracts, 6 randomized controlled trials were considered eligible with a combined sample size of 805 patients. Among the trials, the PACT-15, JSAP-05, and updated long-term results from PREOPANC and NEONAX trials were included. In the meta-analysis, we could see that neoadjuvant treatment in RPC does not improve DFS or OS; HR 0.72 [0.46-1.09] and HR 0.76 [0.52-1.11], respectively. Interestingly, R0 rates were improved about 20% with the neoadjuvant approach (HR 1.2 [1.04-1.37]). It is important to note that most studies evaluated gemcitabine-based regimens in the neoadjuvant setting. Conclusions: This metanalysis of six randomized controlled trials suggests that neoadjuvant chemotherapy with gemcitabine-based regimens does not improve PFS or OS in RPC compared to upfront surgery followed by adjuvant treatment. Neoadjuvant treatment improves R0 rates in about 20%. Randomized ongoing trials are eagerly waited with more active combined regimens including modified FOLFIRINOX.[Table: see text]
Exploring optimal therapeutic management of STAGE IA PDAC in the era of neoadjuvant chemotherapy.
Authors: Macchini Marina , Belfiori Giulio , Crippa Stefano , Orsi Giulia , Gasparini Giulia , Tamburrino Domenico , Schiavolena Marco , Capurso Gabriele , Falconi Massimo , Reni Michele 
Published: January 2023

712 Background: Neoadjuvant chemotherapy (NAT) is currently recommended for non-metastatic pancreatic ductal adenocarcinoma (PDAC). Data on the optimal NAT duration and the proper post-surgical chemotherapy (PSC) are lacking, especially for patients (pts) who yielded a pathological stage IA. Methods: We retrospectively analyzed the outcome of PDAC pts resected between 2015 and 2020 at our institution after NAT yielding a pathologic stage of PDAC ypT1N0. Pts were analyzed basing on NAT duration (aim 1) and PSC indication (yes/no) and type (aim 2). The primary endpoint was median event-free survival (EFS) for aim 1 and median disease free-survival (DFS) for aim 2. As per secondary endpoints, overall survival (OS) and the prognostic role of clinical and pathological variables was assessed (baseline CA19.9 level; pre-operative Ca19.9 level, basal vascular involvement, grading, perineural invasion, R1 resection). Results: During the study period a total of 756 pts were resected, 363 (48%) after NAT. Of them, 72 pts (20%) achieved a pathological ypT1N0 (ypIA). Among this group 16 pts (22%) showed a T1a-T1b, 62 pts (86%) had a G1/G2 tumor, 60 pts (83%) had a R0, 36 pts (50%) had a perineural invasion and 33 (46%) had a tumor regression grade marked or completed. For aim 1 we compared 34 pts (47%) treated with NAT for not more than 4 months (Group A1) and 38 pts (53%) treated for at least 4 months (Group B1). Baseline, biochemical and radiological variables were similar between the 2 groups. No statistical difference was found in EFS (Group A1: median 46 months/ Group B1: median not reached). For aim 2 we compared 10 pts (14%) who received the same chemotherapy regimen in NAT and PSC (Group A2), 35 pts (49%) who received a different chemotherapy regimen in NAT and PSC (Group B2) and 27 (14%) pts who did not receive any PSC (Group C2). PSC were gemcitabine/nab-paclitaxel (10%) and mFOLFIRINOX (90%) in group A2, whereas gemcitabine/nab-paclitaxel (17%), mFOLFIRINOX (3%), gemcitabine (51.5%), capecitabine (17%), gemcitabine/capecitabine (8.5%), PEXG (3%) in group B2. DFS were 24 months for group B2, whereas median was not reached for group A2 e C2 (p=0.006). No statistical difference was found in OS among the groups. At multivariate analysis only grading (G3) emerged as independent factor for poor prognosis. Conclusions: In ypIA pts NAT duration and or type seem to be unrelated to the outcome. PSC performed with alternative and depotentiated chemotherapy as compared to NAT, seem to be related to a higher rate of disease recurrence. Poor differentiated/G3 tumors is confirmed as independent risk factor for poor survival in this population.
Overall survival in patients with metastatic or locally advanced pancreatic cancer following chemoradiation with novel combination of aldoxorubicin, N-803 IL-15 superagonist, and PDL1- NK cell therapy.
Authors: Seery Tara Elisabeth , Nangia Chaitali Singh , Reid Phillip D. , Fang Bruno , McKean Heidi Ann , Sender Leonard S. , Reddy Sandeep K. , Soon-Shiong Patrick 
Published: January 2023

720 Background: Pancreatic cancer claimed an estimated 47,050 lives in the USA in 2020, with an expected median overall survival (OS) of 3 months in 3rd line. (Manax ASCO GI 2019), with no evidence of disease control in these late stage patients. We hypothesize that effective response against pancreatic cancer requires orchestration of both the innate and adaptive immune system to accomplish immunogenic cell death with survival benefit. Herein we report updated results of the fully enrolled cohort of a novel combination immunotherapy protocol of low-dose chemoradiation, cytokine-induced NK and T cell activation via N-803 (an IL-15 cytokine superagonist ), and allogeneic off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion. Methods: We report data from a multi-center study, on 83 3rd line or greater, subjects treated with low dose, chemo radiation Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV); Cyclophosphamide (50 mg PO BID) and low dose SBRT. This induction immuno-modulation therapy to induce DAMPs was followed with investigational agents activating the innate and adaptive systems: Aldoxorubicin (150 mg/m2 IV), N-803, an IL-15 superagonist (15 μg/kg SC) and PD-L1 t-haNK (~2 × 109cells/dose IV). Prophylactic G-CSF or EPO was not allowed. All treatments were administered on an outpatient basis. Results: As of submission, median follow-up is 4.9 months. Median age 62, M:F ratio 46:36. ECOG 0-1,97%. 74/83 (89%) reported at least 1 investigational product related AE (TRAE) with 63/83 (76%) reporting at least 1 TRA grade 3 or higher. The most common were anemia 41%, neutropenia 20%, thrombocytopenia 10%, all others <10%. SAEs attributed to investigational agents were reported in 8/83 (10%) patients. Treatment is ongoing for 6 subjects (7%), with 17.1 months as the longest duration on therapy to date. Median OS is 5.7 months (95% CI: 4.9, 6.4) with 26/83 alive to date. Median PFS is 2.3 months (95% CI: 2.0, 3.6) and 37% of subjects achieving stable disease >=8 weeks. Median OS in 3rd line (N=38) is 6.3 months, Median OS in 4th line or greater (N=40) is 5.0 months. Conclusions: Historical 3 month median OS in 3rd line metastatic pancreatic cancer patients has been exceeded. A doubling of survival in 3rd line is seen in QUILT 88 investigating a novel combination immunotherapy protocol of low-dose chemoradiation, N-803 and PDL1 t-haNK therapy. Updated data will be presented. Clinical trial information: NCT03563144 .
Feasibility of implantable microdosing devices to perform in vivo pharmacotyping in pancreatic cancer.
Authors: Demyan Lyudmyla , Standring Oliver , Chung Taemoon , Gazzara Emma , Lyons Scott , Weiss Matthew John , Park Youngkyu , Jonas Oliver , Tuveson David A. , King Daniel 
Published: January 2023

742 Background: Current biomarkers offer modest predictive capacity for drug sensitivity testing in pancreatic cancer. Patient-specific pharmacotyping offers the potential for a more direct, personalized prediction model. Recently, an implantable microdevice was developed to facilitate in situ multi-agent pharmacotyping and has since entered clinical trials in multiple cancer types, but had not yet been tested in pancreatic cancer. Here we evaluated the use of a microdosing device (microdevice) in a mouse xenotransplant model of pancreatic cancer as proof of principle to inform future translation to the clinic. Methods: A microdevice consists of a cylindrical frame and 18 wells embedded with standard chemotherapy agents (5 FU, gemcitabine, SN 38, paclitaxel, oxaliplatin), a non-toxic polyethylene glycol (PEG) matrix as control, and doxorubicin, the auto-fluorescent properties of which allow us to determine the distance of drug diffusion for each tumor. Devices were implanted into murine xenotransplanted human organoids (hM1A and hM1E Table 1). Microdevices retrieved at 4h, 8h, and 24h post-implantation together with tumors were fixed in 10% formalin. The tissue was embedded in paraffin and sectioned parallel to the device. A distance-dependent drug diffusion rate and concentration profiles with doxorubicin were evaluated. Co-immunohistochemistry (IHC) for cleaved caspase-3 (CC3), gamma H2AX (apoptosis markers), and human mitochondria (human cancer cell marker) was performed in the area of drug diffusion to determine the cytotoxic effects of chemotherapy. Results: 15 animals were enrolled in the experiment with 100% postoperative survival. One device per animal was placed, and all devices were successfully retrieved. Microdevice insertion and exposure to PEG had no effect on tumor integrity. At 250-350µm from the well, we observed intensity from doxorubicin, suggesting drug diffusion. The signal on differential response to drugs was detected as early as 4 hours. Conclusions: Utilization of implantable microdevice to predictcancer drug sensitivity is feasible in organoid transplantation animal models of pancreatic cancer. Future work is needed to expand this model to other cancer drugs and biomarkers to evaluate the cancer drug sensitivity and to test the feasibility of this model to study the effects of chemotherapy on the tumor microenvironment. [Table: see text]
Clinical significance of CA125 in unresectable pancreatic cancer treated with first-line chemotherapy.
Authors: Motoo Iori , Ando Takayuki , Yuki Satoshi , Ito Ken , Ueda Akira , Kito Yosuke , Sakumura Miho , Kajiura Shinya , Matsuno Jun , Nakamura Yoshifumi , Inoue Yuma , Hayashi Nobuhiko , Hosokawa Ayumu , Shibuya Kazuto , Tanaka Haruyoshi , Fukasawa Mina , Fujii Tsutomu , Yasuda Ichiro 
Published: January 2023

745 Background: Serum CA125 is a potential biomarker for diagnosis of peritoneal metastasis in gastric cancer. However, its significance of pancreatic cancer (PC) has not been investigated. Therefore, we aimed to clarify association between serum CA125 and ascites burden, and its kinetics during first-line chemotherapy for PC. Methods: This multicenter retrospective study comprised PC patients who received FOLFIRINOX or gemcitabine plus nab-paclitaxel in first-line setting between Jan 2014 and Dec 2021. Patient background and treatment outcome was assessed in CA125 elevated and non-elevated group before chemotherapy. The CA125 kinetics after chemotherapy was calculated based on baseline and first measure of CA125. Further, the association between early CA125 change and clinical response during chemotherapy were evaluated based on optimal cut off value calculated receiver operating characteristic (ROC) curve analysis. Results: A total 109 patients from 3 hospitals were assessable. The overall survival (OS) was significantly shorter in elevated group than that in non-elevated group (median, 10.7 vs. 21.3 months, p = 0.0002). The median value of CA125 before chemotherapy was elevated according to ascites burden (Non, 36U/ml; mild, 173U/ml; moderate/severe, 575U/ml; p < 0.0001). CA125 elevation, CA19-9 elevation, poor performance status and poor glasgow prognostic score were independent prognostic factors in multivariate analysis. After chemotherapy, the median first-time measure of CA125 was performed in day 41. Among patients with peritoneal dissemination, the median change of CA125 was correlated with clinical response (CR/PR, -0.55%/day; SD, -0.24%/day; PD, 3.35%/day, p = 0.004). After chemotherapy, first-time measure of CA125 was performed in a median of day 41. According to the ROC curve analysis, the optimal cut-off value of increase in CA125 for progressive disease was 1.56 %/day (specificity 94.1%, sensitivity 80%). The median PFS and OS were 1.4 and 6.6 months in increased group and 3.3 months and 14.0 months in non-increased group, respectively (p = 0.016 and p = 0.028). Conclusions: CA125 is considered a clinically useful marker in unresectable PC treated with first-line chemotherapy because CA125 above the ULN is a poor prognostic factor for OS and an increased CA125 can be an early predictor of progression in patients with peritoneal dissemination.