bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total pancreatectomy: Experience within an integrated health care system.
Authors: Chang Amber , Kwak Hyunjee V. , Peng Peter D , Kazantsev George , Spitzer Austin L , Chang CK 
Published: June 2023

e16269 Background: Total pancreatectomy (TP) is most used for pancreatic adenocarcinoma (PC) but also for main duct intra-ductal papillary mucinous neoplasm. The authors report on a retrospective study of 61 patients who underwent TP in an integrated healthcare system. Methods: A retrospective review was performed of all patients treated with TP between January 2012 and December 2022. Patient demographics, tumor characteristics, treatment modalities, and mean overall survival (OS) were evaluated. Results: An intra-operative positive pancreatic neck margin for cancer or high-grade dysplasia was the most common indication for TP in 77% (47/61) of patients. The mean OS for patients with pancreatic cancer was 18 months, however, patients with a pre-op diagnosis of IPMN had a mean OS of 50 months. Multivariate analysis of PC without IPMN showed that neoadjuvant and NPH insulin were associated with a decrease in overall survival ( p< .05). Overall HbA1c were higher in patients after one year after surgery for patients taking NPH (8.6) as opposed to an insulin pump (7.6) or Lantus (7.6) but not significant ( p= .346). Mean OS for patients with PC and type of insulin used was statistically significant at 24.4 months vs 13.1 months respectively for Lantus vs NPH ( p= .033). Conclusions: Conversion to TP for positive neck margins did not improve survival in patients who receive neoadjuvant chemotherapy but may be helpful in patients with IPMN. Blood sugar control after one year was similar among the various indication groups as well the type of insulin use. Although Lantus insulin was associated with improved overall survival for patients with pancreatic cancer, the exact reason is unclear and requires further studies.
A retrospective real-world study of nimotuzumab combined with chemotherapy for advanced pancreatic cancer.
Authors: Wu Yinying , Dong Xuyuan , Li EnXiao , Fan Yangwei , Dong Danfeng , Shi Yu , Wang Meichen , Yang Nan , Ou Fengyun , Wang Jia , Yang Yuqian 
Published: June 2023

e16271 Background: Existing treatment options including gemcitabine-based therapy and 5FU-based chemotherapy have limited prognostic impact in advanced pancreatic cancer (APC): the median overall survival (mOS) was 6-11 months for 1st line therapy and 4-9 months for 2nd line therapy. Nimotuzumab (nimo), anti-EGFR monoclonal antibody, had been shown to be more effective against APC in two previous studies, PCS07 (a phase II study in Germany) and NOTABLE study (a phase III study in China). Although the NOTABLE study obtained an encouraging result in China, it focused on a narrow population, KRAS wild-type patients. This study aimed to explore the efficacy and safety of nimo in the real-world population with APC. Methods: In this retrospective observational study, patients with APC were treated with nimo and followed up in a real-world clinical setting. Demographic and clinical data of these patients were collected from electronic medical records of First Affiliated Hospital of Xi’an Jiaotong University from April 2018 to June 2022. The primary efficacy endpoint was overall survival. Results: A total of 104 patients (median age was 60.5 years, range 34-84) treated with nimo and chemotherapy were analyzed. Among them, 11 (10.6%) were in stage II (AJCC 8th edition), 23 (22.1%) were in stage III, and 70(67.3%) were in stage IV. The treatment regimen included gemcitabine plus nab-paclitaxel (AG, 80.77%), gemcitabine plus S-1 (GS, 10.58%) and others. The dosage of nimo was 200-400mg weekly, of which above 50% of patients received nimo 400 mg weekly. About 66 (63.5%) patients received nimo as 1st line therapy and 38 (36.5%) patients as 2nd line therapy. Up to July 5, 2022, the median follow-up time was 8.12 months and the mOS was not reached. The 1-year and 2-year OS rate were 80.2% and 74.4%, respectively. Further subgroup analysis showed that the mOS was also not reached in 1st line treatment of nimo (median follow-up time 8.77 months) as well as the 2nd line treatment of nimo (median follow-up time 7.62 months), showing a potential survival benefit. No grade 3 or above toxicities were observed. Conclusions: AG regimen was the most common therapy in clinical practice in China. The real world study displayed the addition of nimo would prolong the survival for APC, with a good safety profile.
Real-world impact of olaparib use in patients (pts) with advanced pancreatic cancer (PC) harboring germline BRCA1/2 (gBRCA) mutations.
Authors: Milella Michele , Orsi Giulia , Di Marco Mariacristina , Salvatore Lisa , Procaccio Letizia , Noventa Silvia , Bozzarelli Silvia , Garajova Ingrid , Vasile Enrico , Giordano Guido , Macchini Marina , Cavaliere Alessandro , Gaule Marina , Barsotti Giulia , Palloni Andrea , Tortora Giampaolo , Sperduti Isabella , Reni Michele 
Published: June 2023

e16278 Background: g BRCA mutations are found in approximately 8% of Italian PC pts screened within 3 months from diagnosis. g BRCA PC pts display enhanced sensitivity to platinum-based chemotherapy (CHT) and PARP inhibitors, such as olaparib. In metastatic g BRCA PC pts, maintenance olaparib after platinum-based CHT doubled PFS and resulted in twice as many long-term (3-yr) survivors (34% versus 18%) in the randomized POLO trial. However, despite guideline recommendations, olaparib is currently not reimbursed in Italy in metastatic g BRCA PC pts, based on the absence of significant differences in median OS. Methods: We analyzed the impact of exposure to olaparib on OS from the start of I-line treatment in a cohort of 114 Italian g BRCA PC pts, whose clinical characteristics and outcomes in response to first () and subsequent chemotherapy lines have been previously reported ( 10.1016/j.esmoop.2021.100238 ; 10.1038/s41416-022-02086-w ). Results: Clinical characteristics of patients who did or did not receive olaparib were well balanced, except for baseline CA19.9 levels (significantly lower in patients who received olaparib, p=0.043) and exposure to platinum-containing chemotherapy (significantly less in patients who did not receive olaparib, p<0.0001). In the entire cohort of g BRCA PC pts, OS from the start of I-line treatment for metastatic disease was significantly (p=0.02) longer in pts who had been exposed to olaparib in any treatment line (n=53). Since previous surgery and response to I-line chemotherapy were strong independent predictors of OS at multivariate analysis, we analyzed pts who were diagnosed with stage IV (M+, n=87) disease and pts who did not experience PD as best response to I-line chemotherapy (no PD, n=94), separately. A statistically significant difference in OS favoring g BRCA PC pts who were exposed to olaparib in any line of treatment was observed in the M+ cohort (p=0.0025), in the no PD cohort (p=0.049), but not in the M+/no PD cohort (n=73, p=0.057) or in the POLO-like population (I-line maintenance; n=60, p=0.334). Conclusions: In g BRCA PC pts, exposure to olaparib in any line of treatment in a real-world setting significantly impacts on OS; timing and setting of administration remain to be determined in order to optimize survival advantage. [Table: see text]
Molecular profiling as a predictor of treatment response and survival in unresectable pancreatic ductal adenocarcinoma.
Authors: Paredes Rodrigo , Banegas Marcela , Sucre Santiago , Ponce Cristina , Rattani Ahmed Anwer Ali , Peters Mary Linton Bounetheau 
Published: June 2023

e16279 Background: To date, few targetable mutations have been found to enhance PDAC treatment. Next-generation sequencing (NGS) of somatic mutation profiles may help tailor cytotoxic chemotherapy selection and guide translational research. Methods: We analyzed NGS data from a retrospective cohort of 142 patients with unresectable biopsy-proven PDAC from August 2009 to December 2022. Individual mutations were grouped into 14 distinct signaling pathways: cell cycle, DNA damage repair, KIT, ErbB2, TP53, MAPK-RAS, PIK3, TGF-beta, NOTCH, ALK, FLT3, FGFR, and WNT. Treatment selection, duration of response, and survival were recorded. We stratified patients based on their first-line therapy, either FOLFIRINOX (FFX) or gemcitabine/nab-paclitaxel (GA). We present median time-to-first progression (PFS1) and overall survival (OS) based on the presence or absence of mutations in these pathways. The time-to-event endpoint was estimated by the Kaplan-Meier method. Results: Of 142 samples, 131 were analyzed for PFS1; 57 received FFX, and 60 received GA. In the FFX group, no pathway predicted PFS1 with statistical significance. In the GA group, KIT pathway mutations (n = 10) showed improved PFS1 vs. non-KIT mutated tumors (10.3 mos vs. 6.2 mos, p = 0.02). Similar improvement in PFS1 was seen for mutations in the PIK3 pathway (n = 25, 6.6 vs. 5.7, p = 0.02) and FLT3 pathway (n = 4, 13.1 vs. 6.2, p = 0.02). 125 samples were analyzed for OS. KIT pathway mutations (n = 21) showed a better OS vs. non-KIT mutated samples (21.3 mos vs. 12.2 mos, p = 0.04), as did NOTCH mutated samples (n = 44, 15 vs. 12.3, p < 0.01). FLT3 pathway mutations showed a trend toward improved OS (23.6 vs. 13, p = 0.3). PIK3 mutated tumors had no difference in OS. 8 samples were KRAS WT; removing these from the analysis did not change the results. Conclusions: In this sample, KIT, FLT3, and PIK3 pathway mutated tumors had improved PFS1 with GA (but not FFX) treatment. Tumors with KIT and NOTCH pathway mutations had an improved OS. This and similar analyses could help identify potential drivers of treatment response for unresectable pancreatic tumors. [Table: see text]
Components of total cost of care in real-world patients with mPDAC who received first-line FOLFIRINOX or Gem/Abrax.
Authors: Hirsch Jared , Cockrum Paul , Tomicki Samantha , Dieguez Gabriela , Bhatt Prachi , Kim George P. 
Published: June 2023

e16282 Background: FOLFIRINOX (FFX) and Gemcitabine/Abraxane (Gem/Abrax) are two recommended options for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). There is limited research assessing differences in costs between real-world patients with mPDAC who received first-line (1L) FFX or Gem/Abrax. Methods: We used ICD-10 diagnosis codes to identify patients aged 65+ with mPDAC without end-stage renal disease in the 2018-2021 Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Total cost of care (TCOC) represents mean Medicare paid amounts and patient cost sharing. Lines of therapy (LOTs) were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. Study patients were treated with FFX or Gem/Abrax as a 1L therapy. Results: We identified 8,889 patients with mPDAC that received an 1L FFX regimen between 2018 and 2021 and 15,053 patients that received a Gem/Abrax regimen in the same period. Total cost of care was similar among the two cohorts ($7,187 per administration cycle among patients receiving FFX vs. $7,240 among those receiving Gem/Abrax in 1L). Patients receiving Gem/Abrax had higher chemotherapy costs ($2,980) than FFX ($406), however, patients receiving FFX had higher granulocyte colony-stimulating growth factor costs ($1,592 FFX vs. $293 Gem/Abrax) and higher Other Part B costs ($1,301 FFX vs. $876 Gem/Abrax). Inpatient costs were similar between FFX ($1,732) and Gem/Abrax ($1,615), while outpatient costs were higher for patients receiving FFX ($1,549) than patients receiving Gem/Abrax ($847). Conclusions: Among Medicare Fee-For-Service patients with mPDAC, patients receiving FOLFIRINOX (FFX) or Gemcitabine/Abraxane (Gem/Abrax) as a first-line therapy incurred similar costs of care overall, with different distributions across service categories. While therapy costs were lower among patients receiving generic FFX than those receiving branded Gem/Abrax, higher costs from supportive therapies offset those differences.
A phase Ib/II, open-label, multicenter study to evaluate the safety, efficacy, and pharmacokinetics/pharmacodynamics of αvβ3/5 integrin and neuropilin-1 targeting peptide LSTA1 in patients with metastatic pancreatic ductal adenocarcinoma.
Authors: Xu Jianming , Niu Zuoxing , Bai Yuxian , Qiu Wensheng , Cui Jiuwei , Qu Xiujuan , Wu Zheng , Zha Yong , Zhang Tao , Cheng Wei , Han Cuicui , Si Meimei , Li Lingyan , Kang Xiaoyan 
Published: June 2023

e16290 Background: LSTA1, formerly known as CEND-1, is a novel cyclic peptide which selectively binds to αv/β3 and β5 integrins, which are upregulated in solid tumors, where it undergoes protease cleavage producing a C-end rule peptide fragment (CendR) that selectively binds to and activates neuropilin-1 (NRP1). Once CendR binds NRP1, the CendR pathway is activated, leading to increased vascular permeability of tumors resulting in increased drug delivery and tumor accumulation of co-administered chemotherapeutic agents. Here we report the safety and efficacy results from a Phase Ib/II, multicenter study of LSTA1 plus (SoC) gemcitabine and locally produced nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: The study included a 7-day safety run-in and dose expansion/extension parts. Previously untreated patients with histologically confirmed mPDAC and ≥1 target lesion were treated with systemic chemotherapy and received LSTA1 (1.6 mg/kg or 3.2 mg/kg), gemcitabine (1000 mg/m²) and nab-paclitaxel (125 mg/m2) on days 1, 8, 15, of each 28-day treatment cycle. LSTA1 alone was given during run-in to observe PK/PD. Treatment continued until disease progression or other discontinuation events. The primary endpoints were safety and preliminary efficacy. Results: As of 30 Nov 2022, 38 patients were enrolled at 10 sites in China (12 at 1.6 mg/kg; 26 at 3.2mg/kg). The median follow-up time was 6.28 months. 37 (97.4%) patients experienced TEAEs and 31 (81.6%) patients experienced grade≥3 TEAEs. The most common TEAEs were hematologic toxicity related to chemotherapy. The ORR was 42.9% (15/35) and DCR was 82.9% (29/35). The ORR in 1.6 mg/kg and 3.2 mg/kg groups was 45.5% and 41.7%, respectively. The mPFS in 1.6 mg/kg and 3.2 mg/kg groups was 7.43 months (95% CI: 0.59-NE) and 5.75 months (95% CI: 3.25-7.46) respectively. mOS was not reached. NRP1 expression levels were tested at baseline; six of whom had expression ≥40%. Of those, 4 had PRs and 2 had SD (ORR=66.7%; DCR=100%). The mPFS was 7.5 months. Conclusions: LSTA1 combined with SoC showed an acceptable safety profile in patients with mPDAC. Compared with historical SoC data, LSTA1 plus SoC numerically improved ORR and PFS. Higher NRP1 expression is associated with better ORR and PFS, suggesting NRP1 may be a potential biomarker of LSTA1 plus chemotherapy for mPDAC treatment. Further study is ongoing. Clinical trial information: NCT05052567 .
Integrated clinico-genomic characterization of pancreatic ductal adenocarcinoma in an Asian population.
Authors: Jung Kwangrok , Jung Jae Hyup , Ahn Jinwoo , Kim Bomi , Lee Jong-Chan , Kim Jaihwan , Hwang Jin-Hyeok 
Published: June 2023

e16291 Background: Pancreatic cancer is a devastating malignancy with an extremely poor prognosis. However, the clinico-genomic understanding of pancreatic cancer that could play an important role to improve prognosis is highly limited, especially in Asian population. Methods: Using blood sample and primary pancreas tissues by endoscopic ultrasound guided fine needle biopsy (EUS-FNB) from 237 patients diagnosed with pancreatic ductal adenocarcinoma (PDA) at Seoul National University Bundang Hospital, WES and WTS were performed. Integrated clinico-genomic analysis was conducted by combining genomic data with diverse clinical information. Results: WES and WTS data were obtained from 205 and 93 patients, respectively. In WES, recurrent somatic mutations were identified in KRAS (89.3%), TP53 (68.8%), SMAD4 (22.4%) and CDKN2A (20.5%), and the overall mutation profile was not significantly different from TCGA dataset. Germline mutations related with hereditary cancer syndrome were found in 19 (9.3%), and BRCA2 mutation was the most common as in the Western data. At least one actionable mutation was reported in 61 (29.8%), and KRAS p.G12C, the emerging actionable mutation, was found in five (2.4%). In mutational signature analysis with single-base substitution (SBS), SBS1, SBS3 and SBS13 were identified in this cohort, and SBS3, a potential biomarker for DDR pathway related therapy, was positive in 25 (12.2%). Since this cohort contained 112 stage I-III (47.3%) and 125 stage IV (52.7%), genetic features according to stage or metastatic patterns were analyzed. There was no difference of mutation frequency and burden according to stage. However, liver metastasis was associated with higher frequency of TP 53 mutation (OR = 3.40; P = 0.010) and mutation burden was significantly lower in the lung metastasis (35.4 vs 50.9; P = 0.023). In the gene-set enrichment analysis using WTS, distinct pathways were observed according to the potential mechanism related with each metastatic pattern. Conclusions: Integrative clinico-genomic analysis of Asian PDA cohort provided various clues to better understand the genomic landscape of PDA.
Efficacy and safety of Kras inhibitors in pancreatic cancer: A systematic review of clinical trials.
Authors: Veeraballi Sindhusha , Aiman Wajeeha , Ahmad Amaar , Grewal Navjot , Qirem Murad , Jumean Samer , Montazerin Sahar Memar , Ali Muhammad Ashar , Guron Gunwant K. , Shaaban Hamid Salim 
Published: June 2023

e16297 Background: Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive tumor and is one of the leading causes of cancer related deaths worldwide. Kirsten Rat Sarcoma (KRAS)mutation resulting in tumor cell proliferation and cancer progression is a frequently mutated oncogene in various cancers and is approximately seen in 90% of pancreatic ductal adenocarcinoma. Efforts are being done to target Kras mutation in the last 3–4 decades. Here in, we report the results of the systemic review of clinical trials done on chemotherapeutic agents targeting Kras mutated pancreatic cancer. Methods: We followed PRISMA guidelines to conduct this systematic review. A literature search was performed on PubMed, Clinicaltrials.gov, and Embase with mesh terms, “pancreatic neoplasm’’ and “kras” from the inception of data till 01/05/2023. We screened 4191 articles and included 3 clinical trials with published study results and 3 ongoing clinical trials. Results: In this systematic review, data on 2 chemotherapeutic agents Sotorasib (AMG510) and Adagrasib (MRTX849) which are Kras G12C inhibitors, are obtained from Code Break-100 and preliminary results of KRYSTAL-1 clinical trials, respectively. In these 2 clinical trials (N-48), all the patients had advanced pancreatic cancer with Kras G12C mutation and were previously treated with chemotherapy. 10 patients in Krystal-1 trial, who received adagrasib showed progression-free survival (PFS) of 6.6 months, disease control rate (DCR) of 100 % and partial response (PR) of 50%. 38 patients in the Code Break-100 trial, who received Sotorasib showed PFS of 4 months, DCR of 84.2% and PR of 21.1%. However, 50% of patients in the KRYSTAL-1 trial are still receiving treatment. Grade 3 /4 adverse events were seen in 21% and 16% of patients in the KRYSTAL-1 and Code Break-100 trial, respectively. Other Kras G12C inhibitors like D-1553, Sotorasib in combination with 2nd line chemotherapy are under investigation. Results of a clinical trial on anti KrasG12D siRNA done on locally advanced pancreatic cancer patients showed a median overall survival of 15.12 months with no dose limiting adverse events. A multinational randomized phase 2b clinical trial is ongoing for the evaluation of efficacy of siRNA based drug in combination with chemotherapy. Conclusions: Both Adagrasib and Sotorasib showed promising results in the pretreated Kras G12C pancreatic cancer patients with acceptable safety profile. Further exploration of these drugs and their combination with other chemotherapeutic agents is necessary. [Table: see text]
LDE-paclitaxel in second or later lines in advanced pancreatic cancer: A phase I trial.
Authors: Bighetti Bruna , Maranhão Raul Cavalcante , Forones Nora Manoukian 
Published: June 2023

e16298 Background: Nanoparticles have been studied in association with chemotherapy, with objective of increasing the concentration of the drug in neoplastic cells and, thus, increasing its antitumor action. Nab-paclitaxel is a well-known nanotechnology association between paclitaxel and albumin and can be used in the treatment of advanced pancreatic cancer. LDE-Paclitaxel is a combination of paclitaxel and a synthetic molecule of low-density lipoprotein (LDE). It was previously evaluated in patients with gynaecological malignancies undergoing third-line treatment and showed higher rates of disease control than conventional regimens described in the literature. Our objective was to evaluate the efficacy of LDE-paclitaxel in the treatment of advanced pancreatic cancer (stage III and IV) in second or third line of therapy. Methods: This was a prospective phase I/II, single-arm study, in which we delivered LDE-Paclitaxel at a weekly dose of 85mg/m² to patients with pancreatic adenocarcinoma in second or third-line. The patients must had been through treatment of at least one standard chemotherapy scheme. Results: From October 2020 to November 2021, nine patients with advanced pancreatic adenocarcinoma were enrolled in this prospective, single-arm, phase 1/2 study in which we offered LDE-Paclitaxel at a dose of 85mg/m² intravenously, after progression to gemcitabine. During this period, patients underwent a maximum of 5 cycles, with no need to reduce the medication dose in any of the cycles, for any of the patients. LDE-paclitaxel presented mostly grade 1 and 2 toxicities, mainly anaemia and neuropathy; Grade 3 toxicity was presented by only 1 patient, which was acute kidney injury. Median overall patient survival was 20.14 months, and patient survival after enrolment in the study and initiation of LDE-paclitaxel use was close to 5 months, with no decline in the assessed quality of life indices. Conclusions: LDE-paclitaxel appears to be more tolerable, viable and less toxic than other standard chemotherapy in this setting. Our results suggest that LDE-paclitaxel could be a therapeutic possibility for patients with metastatic pancreatic cancer. For a better evaluation, further studies would be necessary, to obtain more data on the use of this medication in clinical practice and for a better understanding of other important outcomes. Clinical trial information: 4237198 .