bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in utilization of first-line palliative care in non-metastatic hepatocellular carcinoma.
Authors: Ozer Muhammet , Goksu Suleyman Yasin , Sahin Ilyas
Published: June 2023

e16234

Background: Palliative care therapies are known to improve the quality of life and even the survival of some patients. Although non-metastatic (stages I-III) hepatocellular carcinoma (HCC) patients often present with significant symptoms, first-line palliative care treatment is uncommon in this setting. Here we characterized rates of palliative care utilization among non-metastatic HCC patients and determined factors associated with palliative care receipt. Methods: We conducted a retrospective review of adult National Cancer Database patients diagnosed with metastatic HCC between 2004 and 2019. We used descriptive analysis for determining palliative care utilization, including palliative chemotherapy, surgery, radiotherapy, and pain management. We performed multivariable logistic regression analysis to assess the association of characteristics with palliative treatment utilization. Results: Among 121,151 patients diagnosed with stage I-III HCC, the utilization of first-line palliative care subsets was only a small portion of 3966 (3.3%). The most commonly used palliative care treatment was pain management (37.4%), followed by systemic chemotherapy (31.1%), radiotherapy (13%), surgery (9.9%), and combination therapies (8.6%). The higher stage, high comorbidity score, and decreased life expectancy were more likely to be associated with received PC. Stage 2 and 3 diseases were associated with increased odds of PC receipt compared to stage 1 disease (odds ratio [OR] = 1.63 [1.45-1.83] and OR = 3.57 [3.22-3.95]; respectively). Comorbidity score 3 was significantly more likely to receive PC than comorbidity score 0 (OR = 1.54 [1.41–1.69]). In addition, life expectancy >24 months was significantly less associated with PC receipt compared to life expectancy < 6 months (OR: 0.23 [0.20-0.26]). Conclusions: First-line palliative care subsets are underutilized to control symptoms among patients with non-metastatic HCC. Targeted efforts should be focused on increasing palliative care delivery in this group which has a vast potential to benefit.
Comprehensive analysis of molecular characteristics, TMB, and MSI in Chinese patients with neuroendocrine neoplasms.
Authors: Li Xiaohan , Xiao Yun , Ma Juan , Ding Ran , Wang Chenxi , Deng Wanglong , Bu Fanfeng
Published: June 2023

e16236

Background: Neuroendocrine neoplasms (NENs) is a heterogeneous and rare tumor type. To date, most genomic profiling studies on NENs have mainly focused on pancreatic NENs (PanNENs), less is known about nonpancreatic NENs (NP-NENs). We explored the molecular characteristics, tumor mutational burdens (TMB) and microsatellite instability (MSI) in Chinese NENs patients based on different primary lesions to discover genomic profiles. Methods: We retrospectively analyzed molecular characteristics, TMB and MSI in 155 Chinese NENs patients from laboratory of Simcere Diagnosis (Nanjing, China) during 2019 to 2022. Tissue and plasma samples were profiled using the 551-gene panel next-generation sequencing (NGS). Results: The median age of 155 patients was 61 years old (range, 22-85 years old), the male to female ratio was 1.63:1. 118 cases with known primary lesions could be divided into PanNENs(n=22) and NP-NENs (n=96). There were no differences in age and ratio of PanNENs and NP-NENs. The most common SNV and indel mutations were TP53(23%), DAXX (22.7%), MEN1 (18.2%), KRAS (18.2%), ATM (13.6%), SMAD4 (13.6%) and TSC2 (13.6%) in PanNENs, in which CDK4/6 amplifications were often detected (31.8%, 27.3%). Gene fusions rarely occurred in this cohort. For NP-NENs, we identified TP53 (58.3%), MUC16 (29.2%), RB1(31.3%), LRP1B (22.9%), SMARCA4 (10.4%), SPTA1 (10.4%) and FAT3 (10.4%) as the most common SNV and indel mutations, with MYC (26%) and CDK4 (15.6%) amplifications. CCNE1 high-level amplification was especially common in digestive system NENs. Multiple gene fusions were found in NP-NENs. 13/155 (8.4%) patients carried pathogenic/likely pathogenic germline mutations in MUTYH(n=3), MSH3 (n=2), FANCG (n=2), RAD51D (n=1), CDH1 (n=1), ERCC3 (n=1), ATM (n=1), MEN1 (n=1), RECQL4 (n=1), most of them were associated with DNA damage repair (DDR) pathway. 92.3% (12/13) patients were NP-NENs with only one PanNENs harboring MUTYH germline mutation. 155 NEN patients could be evaluated for TMB, 24 (15.5%) patients had TMB≥10Muts/Mb, 7% (10/24) were lung-derived NENs. TMB was significantly higher in NP-NENs compared to PanNENs (4.26 muts/Mb vs. 2.13muts/Mb, P<0.01). 138 patients could be evaluated for MSI status, only one NEN whose primary site was liver was MSI-H, the others were all MSS. Conclusions: Our data showed that PanNENs and NP-NENs had different mechanisms of tumorigenesis: DAXX and MEN1 alterations commonly identified in PanNENs primarily mediate DDR and PI3K-mTOR pathway. Frequent TP53, RB1 and CCNE1 aberrations in NP-NENs were associated with CDK signaling pathway. TMB was low in almost all NENs exclude lung-derived NENs. It revealed distinct drivers in different subtypes, potentially being used as relevant therapeutic targets.
Oxaliplatin based chemotherapy for advanced well-differentiated neuroendocrine tumors: A systematic review and meta-analysis.
Authors: Wang Jian , Wang Xiangling , Chu Yunxia , Li Shuguang , Hao Jing
Published: June 2023

e16240

Background: Currently, chemotherapy is predominantly considered in advanced well-differentiated neuroendocrine tumors (NENs) with high ki67 proliferation index and tumor burden. So far, no standard regimen is available and alkylating agents alone, such as temozolomide or in combination with 5-fluorouracil or capecitabine are widely used. Besides, oxaliplatin based chemotherapy has shown promising antitumor activity without being influenced by the MGMT status. In the current SRMA, we aim to address the efficacy of oxaliplatin based chemotherapy in advanced well differentiated NENs. Methods: We conducted a systematic database search using PubMed/MEDLINE and EMBASE. Eligible studies included randomized and single-arm trials, prospective observational and retrospective studies documenting the clinical efficacy of oxaliplatin based chemotherapy for advanced well-differentiated NENs. The pooled overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were calculated and weighted using generic inverse variance in a random-effects model, as well as subgroup analysis for pts with pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs), G1-2 and G3 NETs. Results: 14 of 24 identified publications were included with a combined total of 865 patients in 3 phase II trial and 11 retrospective studies. 495 pts received FOLFOX, 155 pts XELOX, 130 pts GEMOX and 138 pts plus bevacizumab. 48.4% (419/865) patients were pNETs, and G3 NETs accounted for 21.7% (188/865). The pooled ORR was 27.9% (237/865, 95% CI: 23.2-32.5). pNETs showed much higher ORRs (37.7%,114/303, 95% CI: 31.1-44.3) than epNETs (14.9%, 40/251, 95% CI: 10.5-19.2), χ2 = 32.17, p < 0.001. ORRs in G1-2 NETs was 23.1% (66/273, 95% CI: 18.2-28.1), while in G3 NETs was 45.7% (42/85, 95% CI: 29.7-61.6), χ2 = 19.60, p < 0.001. FOLFOX plus bevacizumab showed a higher ORR (38.3%, 38/98, 95% CI: 28.8-47.9) than the oxaliplatin based regimens without bevacizumab (26.9%, 166/594, 95% CI: 23.4-30.4), χ2 = 4.745, p = 0.029. The median PFS in pNETs was 8.1 months (n = 247, 95% CI: 6.3-9.9), similar to 8.4 months in epNETs (n = 211, 95% CI 5.7-11.2). The median PFS in G1-G2 and G3 NET was 13.4 months (95% CI 9.1-17.6) and 7.1 months (95% CI 4.1-9.6) respectively. Besides, FOLFOX plus bevacizumab also showed a trend of a longer PFS (12.4months, 95% CI 9.5-15.2) than those without bevacizumab (7.6months, 95% CI 6.8-8.3). The pooled median overall survival was 28.8months (95% CI 26.7-30.9). Conclusions: Among the advanced well-differentiated neuroendocrine tumors, oxaliplatin based chemotherapy alone or plus bevacizumab could be a good alternative regimen, especially in pts with pNETs and G3 NETs.
Association of guideline adherence in diagnosis and treatment of pancreatic neuroendocrine tumors with survival.
Authors: Overheu Oliver , Gisder Doreen M. , Noepel-Duennebacke Stefanie , Kraeft Anna-Lena , Janot-Matuschek Monika , Uhl Waldemar , Tannapfel Andrea , Reinacher-Schick Anke C.
Published: June 2023

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Background: Clinical guidelines and their adherence are important instruments to ensure quality in diagnosis and treatment, especially when treating rare diseases like pancreatic neuroendocrine tumors (PanNET). However, data on guideline adherence and its impact on outcome in PanNET is limited. Methods: Cases of PanNET according to 2017 WHO definition at our university hospital between 2010 and 2019 were retrospectively identified. Adherence to ENETS guideline 2007/2012 and the German S2k guideline was evaluated among four categories (diagnostics: chromogranin A (CgA) testing, somatostatin receptor imaging, discussion in an interdisciplinary tumor board; pathology: reporting of grading, Ki67 and synaptophysin expression; surgical treatment; systemic treatment including aftercare). Guideline adherence within these categories was valued with one point per fulfilled criterion and a final score between 0-8 points was calculated. Data was analyzed using Student’s t-test, Chi-square test and Spearman’s correlation coefficient test. Results were considered significant at α = 0.05. Results: Overall, 115 patients (47% female) with a diagnosis of PanNET were identified. Mean age was 61 (±13.5) years. Mean overall survival (OS) was 45 months, mean recurrence free survival (RFS) was 47 months. During the study period 21 patients (18%) had died, 6 patients (5%) were lost-to-follow-up and 11 patients (10%) had a recurrent disease after initially curative resection. 24 patients (21%) presented with metastatic disease upon diagnosis. Guideline adherence concerning pathology reports (97%) as well as systemic (91%) and surgical treatment (75%) was high, while complete adherence in diagnostic modalities was low (5%). However, the latter was mainly driven by lack of CgA testing (31%), and somatostatin receptor imaging (11%) not being performed on initial diagnosis, but in most cases during follow-up. Subsequently, complete guideline adherence (8/8) across all categories was rare (3%). However, a higher overall score was associated with survival (p = 0.032, V = 0.321). Long term survivors had a higher mean overall adherence score (5.6 vs. 6.1; p = 0.05). In addition, the composite score of surgical and systemic therapy was significantly correlated with RFS (ρ = 0.254, p = 0.016). Conclusions: The quality in diagnosis and treatment of PanNET in our cohort was high. These are the first data to demonstrate a positive impact of guideline adherence on survival and RFS in PanNET.
Correlating peptidylglycine alpha-amidating monooxygenase (PAM) expression with clinicopathologic variables in gastrointestinal (GI) neuroendocrine tumors (NETs).
Authors: Sim Jordan , Marginean Horia , Jirovec Anna , Vickers Michael M. , Marginean E. Celia , Asmis Tim , Marginean Bianca , Goodwin Rachel Anne
Published: June 2023

e16243

Background: Peptidylglycine alpha-amidating monooxygenase (PAM) is a hypoxia-responsive protein which is responsible for peptide alpha-amidation, important in neuroendocrine hormone maturation. A prior study of well-differentiated neuroendocrine tumors of multiple sites, both GI and non-GI, has shown that PAM expression by immunohistochemistry correlates with important clinical and pathologic parameters. We assessed PAM expression by immunohistochemistry using two separate scoring systems in patients with well-differentiated neuroendocrine tumors (NETs) exclusively of the GI tract and assessed its correlation with clinical and pathologic variables. Methods: A tissue microarray was constructed from 58 patients with NETs of the GI tract. Two separate scoring systems were used, the immunoreactive score (IRS) and one as described by Horton et al (2020). The IRS score was derived by scoring for intensity (range 0-3) and percent of cells staining (range 0-4), multiplying these to give an overall IRS between 0 and 12. These results were dichotomized into 0-1 (negative) and 2-12 (positive). The score as described by Horton et al is a 4-tiered system: 0, no staining; 1, very faint and scarce staining; 2, staining easily visible in > 50% of tissue; 3, moderately dark and intense staining across 50% of tissue; 4, very intense dark staining across > 50% of tissue. These were then divided into negative (0), low (1) and high (2-4) scores. Clinical and pathologic variables were collected from the clinical records and correlated with PAM staining. Results: Patients had NETs involving the stomach (n = 1), duodenum (n = 3), ileum (n = 18), small bowel (n = 12), cecum (n = 2), and pancreas (n = 13). Twenty-one patients (36.2%) had 1 metastatic site, 12 patients (20.7%) had > = 2 metastatic sites and 25 patients (43.1%) lacked metastases. IRS and Horton scores were compared and were correlated (p = 0.007). By IRS, 9 patients (31%) had negative staining, and 20 patients (69%) had positive PAM staining. PAM staining did not correlate with functional status of the tumor (p = 1), synchronicity of disease (p = 1), number of metastatic sites (p = 0.69), Octreotide receptor positivity (p = 0.72) or blood chromogranin A (p = 0.58) and urine 5 HIAA levels (p = 0.52). PAM scoring also did not correlate with Ki-67 of primary tumors (p = 0.57). Conclusions: In our GI NET cohort, PAM staining did not correlate with any of the assessed clinical variables or with Ki-67 of primary tumors. A previous study of NETs involving more body sites found that PAM staining did inversely correlate with Ki-67 scoring. This difference may be due to our assessment of solely gastrointestinal NETs.
Effects of pancreatic enzyme replacement therapy (PERT) on overall survival (OS) in patients (pts) with advanced pancreatic ductal adenocarcinoma (APDAC) and evidence of pancreatic enzyme insufficiency (PEI): A single institution, retrospective, cohort study.
Authors: Picozzi Vincent J. , Najjar Anas , Harb Diala E , Kort Jens J , Mandelson Meg T.
Published: June 2023

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Background: Weight loss (WL)/cachexia is common in APDAC and associated with multiple adverse pt outcomes. Current NCCN guidelines recommend PERT in PDAC patients with PEI. However, little evidence exists regarding PERT use and clinical outcomes in PDAC, especially APDAC. We present here data on impact of PERT use from our institution. Methods: Study pts were identified from the Virginia Mason PDAC database (01-2010-12/2019). Eligibility criteria included: 1) No upfront resection, 2) no prior PDAC therapy, 3) FE 1 < 200 µg/g or documented evidence of PEI at diagnosis, 4) treatment at least to initial restaging event (8 wks), and 5) data regarding PERT use/dosage available. Pts were stratified by PERT/non-PERT usage. PERT use was defined by prescription for >50% of time from initial Rx to 1st restage using recommended dosing per package insert. Pts on PERT for < 50% of time during this time frame and/or prescribed less than recommended dose were excluded from analysis. Results: 505 total pts were study eligible, PERT 197(39%), non-PERT 308(61%). WL (80 vs 65%, p< 0.001) and cachexia (74 v 54%, p<0.001) were more common in PERT pts. ECOG PS 2 (4 vs 9%, p=0.02) and non-metastatic disease (51 vs 40%, p=0.02) more common in non-PERT pts. Other pt characteristics (age, sex, diabetes at dx, serum albumin, NLR, BMI distribution, % obese) were similar in both groups. OS after adjustment for PS and stage was 15.7 mo (95% CI 13.6-18.3 mo) among PERT users vs. !2.6 mo non-PERT users (95% CI 11.0 -13.7 mo, p=0.02, adjusted hazard ratio 0.81 (95% CI 0.67-0.99). Pts receiving PERT also tended to have a higher therapeutic response rate by both Ca 19.9 and CT: but without statistical significance (p=0.10, 0.09, respectively). Regarding nutrition, PERT vs. non-PERT pts at 8 weeks experienced less WL (-0.4 vs. -1.5 kg, p=0.03) and less change in BMI (-0.3 vs -1.6, p=0.02). This was true even in cachectic pts at dx (change in BMI + 0.1 vs -1.7, p=0.01). Additional analyses of impact of PERT on QOL are ongoing, including in a subset of patients who underwent serial PG-SGA scoring. Conclusions: In this pt cohort, APDAC pts prescribed PERT per recommended dosing had a statistically significant improvement in median OS vs. those not prescribed PERT. This remained true in multivariate analysis after adjustment for population imbalances. PERT use was also associated with a statistically significant reduction in weight loss and change in BMI at 8 weeks, even in those patients defined as cachectic at diagnosis. Further investigation into a) impact of PERT on quality of life, b) mechanisms producing the above observations, c) confirmatory observations in independent datasets, and d) additional therapeutic interventions designed to mitigate weight loss/cachexia in PDAC are needed.
Dosing patterns and treatment patterns in real-world patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX in the first line.
Authors: MacEwan Joanna P. , Silver Michelle , Cockrum Paul , Sanders Chad , Kim George P.
Published: June 2023

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Background: While FOLFIRINOX (FFX) demonstrated a significant overall and progression-free survival benefit vs. gemcitabine in the PRODIGE 4/ACCORD 11 trial among previously untreated patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC), treatment with FFX was associated with a higher rate of grade 3/4 adverse events (AEs). In an effort to reduce toxicity, modified FFX (mFFX) regimens that employ lower doses of components of the regimen have been developed. To better understand the frequency and degree of dose modifications in practice, we examined real-world (RW) dosing patterns among mPDAC pts receiving FFX in first line (1L). Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between January 2015 and November 2022 who initiated treatment with FFX or mFFX within 90 days of their diagnosis for metastatic disease (1L) were included in the study. Pts were required to have an available body surface area measurement within 7 days of the index date. Doses of each FFX component were measured during cycles in which pts received all four components of the FFX regimen on the same date. mFFX was defined as administration of < 150mg/m2 of irinotecan or < 2,720mg/m2 5-FU total during cycle 1. Results: Of the 1,326 pts eligible meeting inclusion criteria and receiving 1L treatment with FFX or mFFX, 1,325 received mFFX and 1 received FFX. The median age at 1L initiation was 65yr (IQR: 58–70), 57% (754 pts) were male, 69% (916 pts) were white, 15% (197 pts) had an ECOG score of 0, 42% (550 pts) had an ECOG score of 1, and 78% (1028 pts) were stage IV at diagnosis. The bolus of 5-FU was frequently omitted—only 20% (262 pts) received it in the first cycle. If pts received the bolus, they did not receive the 5-FU infusion, with the exception of 1 pt. For pts receiving at least two cycles, the percentage of pts with dose reductions of ≥10% (≥20%) between the first and last cycle were 20% (11%) for the 5-FU infusion, 18% (13%) for the 5-FU bolus, 34% (21%) for irinotecan, 12% (9%) for leucovorin, and 40% (28%) for oxaliplatin. Median starting doses were 2400, 401, 152, 399, and 85 mg/m2 for the 5-FU infusion, bolus 5-FU, irinotecan, leucovorin, and oxaliplatin components, respectively. The median number of cycles was 5 (IQR: 3–10) and the median dose intensity per week was 940 mg/m2 for 5-FU, 179 mg/m2 for leucovorin, 38 mg/m2 for oxaliplatin, and 73 mg/m2 for irinotecan. Conclusions: In a RW cohort of pts with mPDAC treated with 1L FFX, almost all received a modified version of the regimen. The 5-FU bolus was omitted for most pts. Doses of other components fell over time for a notable percentage of patients, which may reflect clinician efforts to manage FFX toxicity.
A pilot study of liposomal irinotecan plus 5-FU/LV combined with paricalcitol in patients with advanced pancreatic cancer whose disease progressed on gemcitabine-based therapy.
Authors: Grierson Patrick , Suresh Rama , Tan Benjamin R. , Pedersen Katrina Sophia , Amin Manik A. , Park Haeseong , Trikalinos Nikolaos , Liu Jingxia , Lim Kian-Huat , wang-gillam Andrea , Bansod Sapana Prakashrao
Published: June 2023

e16263

Background: 5-FU-based chemotherapy is the standard of care for patients with advanced pancreatic cancer progressed on gemcitabine-based therapy. Based on the NAPOLI-1 study, 5-FU/LV/liposomal irinotecan is currently an FDA-approved regimen in the second-line setting with median progression free survival (mPFS) 3.1 months, median overall survival (mOS) 6.1 months and objective response rate (ORR) 16%. In pancreatic cancer mouse models, vitamin D was shown to remodel the desmoplastic stroma and when combined with chemotherapy significantly improved animal survival. Methods: We conducted a pilot study in patients with advanced pancreatic cancer progressed on gemcitabine-based therapy treated with 5-FU (2,400mg/m2)/LV (400mg/m2)/liposomal irinotecan (70mg/m2) with paricalcitol in two dose level cohorts: paricalcitol 75mcg IV on day 1 weekly (N=10, dose level 1) or 7mcg/kg IV on day 1 weekly (N=10, dose level 2). The primary endpoint was safety and toxicity. Dose-limiting toxicities (DLT) were assessed during cycle 1. Secondary endpoints include ORR, PFS and OS. Results: Between 8/29/2019 to 5/6/2021, a total of 20 patients were enrolled in the study. No DLTs or grade 4 adverse events were observed in either paricalcitol cohort. The most common toxicities were gastrointestinal (nausea, diarrhea), fatigue and anemia and were similar in both cohorts. Only one grade 3 adverse event was possibly due to paricalcitol (spinal fracture, dose level 1). 2/17 (12%) evaluable patients experienced an objective response (both in dose level 2), one of which was confirmed. Disease control rate (DCR) was 65%. Median follow up was 6.15 months. At the time of analysis, mPFS of all patients is 3.57 months (95% CI 1.28 – 8.12) and mOS is 6.14 months (95% CI 2.43 – 11.77). The mPFS is 3.55 months (0.79-6.21) for dose level 1 and 4.83 months (0.62-9.96) for dose level 2. The mOS is 6.15 months (0.79-8.12) for dose level 1 and 6.66 months (1.78-14.53) for dose level 2. Correlative analysis shows increased tumor vascularity (via CD31) and a trend toward decreased stromal fibrosis (via Sirius Red) in dose level 2. Conclusions: Administration of paricalcitol in combination with liposomal irinotecan and 5-FU/LV is well tolerated in patients with advanced pancreatic cancer and survival outcomes were comparable to liposomal irinotecan plus 5-FU/ LV. Clinical trial information: NCT03883919 .
Impact of homelessness on outcomes among pancreatic cancer hospitalization: Insight from the 2016-2020 National Inpatient Sample.
Authors: Pagidipally Alekhya , Sharma Shivani , Dandwani Mehndi , Chennapragada Suma Sri , Ramphul Kamleshun , Verma Renuka , Sanikommu Sailaja , Sombans Shaheen , Mejias Stephanie G , Dhillon Balkiranjit Kaur , Lohana Petras , Arti Fnu , Kumar Vijay
Published: June 2023

e16264

Background: Homelessness is a major socio-economic issue in the United States, affecting an estimated 171 per 100,000 persons in certain states. While pancreatic cancer (PC) tends to have a poor prognosis, the disease requires an early diagnosis, proper care, and follow-ups. As there is a paucity of data highlighting differences in patient characteristics and outcomes of homeless patients with PC, a retrospective study was conducted via a national database. Methods: We used data from the 2016-2020 National Inpatient Sample (NIS), the most extensive hospital database, to identify patients with a diagnosis of pancreatic cancer. Patients with a status of “homeless” were located via the ICD-10 code “Z590”, per suggestions from HCUP and past studies. Several differences in patient characteristics were explored between homeless cases of PC and non-homeless cases via Pearson’s Chi-Square tests. Finally, the adjusted odds ratio (aOR) and 95% Confidence intervals (CI) of various outcomes such as mortality, pulmonary embolism, septicemia, and hepatic failure were calculated via multivariable logistic regression models. Results: Our study identified 544855 pancreatic cancer cases, including 1380 patients classified as homeless (0.3%). 81.5% of homeless patients were males (vs. 52.1%), and 24.6% were admitted on weekends (vs. 20.6%). Moreover, Medicaid was the prime insurer among homeless patients (47.6% vs. 8.6%) with a higher mean hospital charge ($86796 vs. $70610). Racial differences were also observed as 51.9% of homeless cases were Whites (vs. 71.2%), while 31.6% (vs. 13.8%) were Blacks, and 11.3% (vs. 8.2%) were Hispanics. A higher proportion of homeless cases had palliative care utilization (27.9% vs. 19.1%), a Do-Not-Resuscitate (DNR) order (25.7% vs. 23.1%), and required pancreatic and proximal biliary dilation/stenting (4.0% vs. 2.2%). Homeless patients admitted with pancreatic cancer also expressed higher odds of in-hospital mortality (8.7% vs. 7.4%, aOR 1.625, 95% CI 1.280-2.064, p<0.01). No statistical significance was found for events of pulmonary embolism (aOR 1.231, p=0.160), septicemia (aOR 1.044, p=0.674), and hepatic failure (aOR 0.892, p=0.549). Conclusions: Homeless patients with PC were linked with higher in-patient mortality. Various racial and socio-economic differences were also observed. Several efforts to ameliorate access to care among homeless patients and an early diagnosis may help improve the outcomes.
Outcomes among patients with pancreatic malignancy on long-term anticoagulation hospitalized for acute pulmonary embolism: A nationwide analysis.
Authors: Syal Arshi , Arya Yajur , Casipit Bruce Adrian , Dourado Claudia
Published: June 2023

e16266

Background: Pancreatic cancer is known to have an increased risk of thromboembolic events. Acute pulmonary embolism further complicates the clinical picture and confers a poor prognosis in this population. Data regarding prophylactic anticoagulation in patients with pancreatic malignancy is lacking, although there is evidence that prophylaxis does reduce incidence of venous thromboembolism in pancreatic malignancy. Whether this benefit equates to improved clinical outcomes needs further clarification. Methods: We utilized the 2018-2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study. We identified patients who have pancreatic malignancy and acute pulmonary embolism using appropriate ICD-10 CM codes. We stratified patients based on the presence or absence of long-term anticoagulation. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of <0.05 was considered statistically significant. The aim of this study is to investigate the outcomes among patients with pancreatic malignancy hospitalized for acute pulmonary embolism looking primarily at the in-hospital mortality, hospital length of stay (LOS) as well as total hospital charges. Results: We identified a total of 160,000 hospitalized patients with acute pulmonary embolism, of which 0.6% (1,120/160,000) had malignant neoplasm of the pancreas and 20.09% (225/1120) are on long-term anticoagulation. The overall in-hospital mortality among those with pancreatic malignancy hospitalized for acute PE was 5.91% (66/1,120). Among those who are on long-term anticoagulation, the overall in-hospital mortality rate was lower at 4.44% (10/225), however, it was not significantly different from those who are not on anticoagulation 6.29% (14/225) (p value=0.64). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, the use of long-term anticoagulation among hospitalized acute PE patients with history of pancreatic malignancy did not significantly decrease risk for in-hospital mortality (adjusted OR 0.37; 95% confidence interval [CI], 0.09-1.57; p=0.18), hospital LOS (adjusted OR 0.80; 95% confidence interval [CI], 0.63-10.26; p=0.86) or total hospital charges (p=0.32). Conclusions: Our analysis showed that among patients with pancreatic malignancy hospitalized for acute pulmonary embolism, the use of prior long-term anticoagulation did not significantly decrease the risk for in-hospital mortality, hospital LOS as well as total hospital charges. Prospective studies with control of possible confounders are warranted to further clarify the use of prophylactic anticoagulation in pancreatic malignancy and its impact on outcomes.
Effect of operative time and blood lost on overall survival after pancreaticoduodenectomy.
Authors: Kwak Hyunjee V. , Chang Amber , Peng Peter D , Kazantsev George , Spitzer Austin L , Chang CK
Published: June 2023

e16270

Background: Blood transfusion is associated with a negative impact on cancer survival. This study aims to evaluate intra-operative time (OR time) and estimated blood loss (EBL) and their impact on survival. Methods: A retrospective review was undertaken to identify patients who had pancreaticoduodenectomy, treated at one of our 4 HPB centers of excellence for Northern California Kaiser Permanente members. All patients received their treatments between January 2015 and July 2022. The two parameters of OR time and EBL were assigned into a 2x2 grid with the creation of four separate groups. The 4 combination groups identified patients with an OR time of more than 400 minutes as time being compared and EBL of more than 600 ml as the absolute volume compared. Results: We identified 999 patients who underwent a pancreaticoduodenectomy. The mean OR time was 377 minutes, and the mean EBL was 349 ml. Portal vein resection was performed on 10.8% of patients. Neoadjuvant chemotherapy (NAT) was used in 27.8% of patients and associated with longer OR time, EBL, and portal vein resection (p<.001). Patients with OR time >400 minutes and EBL >600 ml was associated with male, higher percentage of pancreatic/bile duct cancer, portal vein resection, a longer length of stay, re-admission at 7- and 30-days post-op, neoadjuvant chemotherapy, and adjuvant chemotherapy (Table 1). Mean overall survival for the patients with an OR time >400 minutes and EBL >600 ml was 37 months, while for those with an OR time <400 minutes and EBL <600 ml was 59 months (p<.001). Conclusions: The combination of prolonged intra-operative time and blood loss is associated with decreased overall survival. The two parameters of EBL and OR time are a proxy for advanced tumors and vascular involvement gave the need for portal vein resection and higher utilization of adjuvant and neoadjuvant chemotherapy.
Disparities in pancreatic cancer among Asian-Pacific Islander and American Indian-Alaskan Native populations.
Authors: Cullen Jennifer , Rao Tharun , Dong Weichuan , Hartman Holly , Koroukian Siran
Published: June 2023

e16275

Background: Pancreatic cancer (PanCan) is the third deadliest cancer in the United States, causing 8.2% of all U.S. cancer deaths. A steady rise in incidence rates has been observed nationally, with striking variation by geographic region and across race/ethnicity. Several studies have demonstrated a disproportionate burden of PanCan incidence on non-Hispanic Black (NHB) as compared to non-Hispanic White (NHW) populations. Yet little attention has been given to the burden of disease on Asian-Pacific Islander (API) and American Indian-Alaskan Native (AI/AN) populations. Additionally, there are limited data on disparities in PanCan incidence by U.S. geographical region. This study investigates age-adjusted incidence rates and annual percent change in PanCan incidence over a 20-year period, emphasizing burden of disease among API and AI/AN persons as well as by U.S. geographic region. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End-Results (SEER) database of 22 registries was used to study newly diagnosed pancreatic cancer cases (ICD-O-3/WHO 2008) for the period 2000-2019. Incidence rates and annual percent change were age-adjusted to the 2000 U.S. standard population and calculated per 100,000 persons using SEER*Stat software. Results: The overall age-adjusted PanCan incidence rates, from lowest to highest, for AI/AN, API, NHW and NHB populations were 6.6, 9.6, 12.5 and 15.3, respectively (per 100,000 persons). When examining each registry separately, two notable outliers were observed in the state of Hawaii where API and AI/AN persons had incidence rates of 13.4 and 24.5 per 100,000 persons, respectively. For all racial/ethnic groups, except AI/AN, the annual percent change in PanCan incidence significantly rose from 2000-2019, with increases of 0.9, 0.6 and 0.3 percent per year for NHW, API and NHB persons, respectively (p < 0.05). Conclusions: A striking observation in this study was the unusually high PanCan incidence rates among API and AI/AN persons in the state of Hawaii, as compared to national rates. Moreover, a significant increase in annual percent change in PanCan incidence was observed over the study period for all racial/ethnic groups, except AI/AN. A key strength of this analysis is the examination of a large, population-based database over an extended time period. The SEER regions examined cover approximately 48% of the U.S. population and intentionally balance on racial/ethnic composition of the U.S. However, the database does not capture cancer incidence data from all U.S. states. Furthermore, this study did not examine sub-categories of API and AI/AN persons, which are groupings that may be heterogeneous with respect to disease burden over time and across U.S. regions. Future efforts will include refining the analysis into more granular racial/ethnic groups and exploring incidence rates among API and AI/AN subgroups in Hawaii.
Genetic testing in patients with pancreatic cancer to reveal pathogenic variants in cancer susceptibility genes.
Authors: Tsoulos Nikolaos , Potska Kevisa , Agiannitopoulos Konstantinos , Tsaousis Georgios , Ozdogan Mustafa , Karabulut Bulent , Croitoru Adina-Emilia , Ziogas Dimitrios C. , Theochari Maria , Christodoulou Christos , Samantas Epaminondas , Janinis Dimitrios , Athanasiadis Ilias , Koutras Angelos , Papadopoulou Eirini , Nasioulas George
Published: June 2023

e16276

Background: Pancreatic cancer is one of the most fatal malignancies. It accounts for 2% of all cancers and 5% of cancer-related deaths. Hence, it is essential to identify pancreatic cancer at an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance plans. PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring germline variant in the Homologous recombination repair (HRR) genes. Our aim was to determine the prevalence of germline pathogenic/likely pathogenic variants in cancer predisposing genes in patients with pancreatic cancer. Methods: In total, 113 patients diagnosed with pancreatic cancer were referred to our laboratory for genetic testing. The analysis of 52 genes involved in hereditary cancer predisposition was performed using a NGS approach. Results: A germline pathogenic/likely pathogenic variant was identified in 20% of patients analyzed. Among individuals with germline pathogenic/likely pathogenic variants, 60% had a positive finding in a pancreatic cancer susceptibility gene; ATM (20%), BRCA1 (20%), BRCA2 (12%), CDKN2A (4%), PALB2 (4%) while 40% carried positive findings in other cancer susceptibility genes. More specifically, in CHEK2 (16%), MRE11 (4%), RAD50 (4%), RAD51C (4%), MUTYH (8%) and NTLH1 (4%). Notably, 84% of pathogenic variants were identified in genes associated with the HRR pathway ( ATM, BRCA1, BRCA2, CHEK2, MRE11, PALB2, RAD50 and RAD51C). Conclusions: Our results indicate that multigene genetic testing is meaningful for pancreatic cancer patients as in 20% of tested individuals we identified findings associated with pancreatic or other cancer predisposition. Moreover, pathogenic/likely pathogenic variants in HRR genes, were identified in 16.6% patients and these patients might benefit from targeted treatments, such as PARP inhibitors or platinum-based treatment.
Adverse events in real-world patients covered by Medicare with metastatic pancreatic ductal adenocarcinoma who received first-line FOLFIRINOX.
Authors: Dieguez Gabriela , Tomicki Samantha , Cockrum Paul , Hirsch Jared , Bhatt Prachi , Kim George P.
Published: June 2023

e16280

Background: FOLFIRINOX (FFX) is often associated with side effects and toxicity. This study examines real-world incidence of adverse events (AEs) and associated costs among Medicare fee-for-service (FFS) beneficiaries with metastatic pancreatic ductal adenocarcinoma (mPDAC) receiving first-line (1L) FFX. Methods: We identified patients aged 65+ with a record indicating a diagnosis of mPDAC between 2018-2021 in the Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Patients were required to have at least two malignant neoplasm of pancreatic duct diagnosis codes on different dates AND at least one diagnosis of a metastasis anytime on or after the first pancreatic cancer diagnosis. Patients with end-stage renal disease were excluded. Patients were assigned to cohorts based on drugs present within a 48-hour (2-day) period of a FFX chemo infusion cycle: 1) FFX with all 4 component drugs (oxaliplatin, irinotecan, leucovorin, 5-FU bolus and infusion), 2) FFX with no 5-FU bolus, but with 5-FU infusion, 3) FFX with a 5-FU bolus, but no 5-FU infusion, 4) FFX with no 5-FU of any kind and, 5) FFX with no leucovorin. 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. Incidence rates of adverse events per administration for each cohort were determined along with the total costs of care and growth factor spending per administration. Results: We identified a total of 45,755 administrations of 1L FFX. Administrations of FFX without 5-FU of any kind (N = 842 administrations) had the lowest incidence of AEs (nausea 21.4%, neutropenia 12.5%, anemia 11.4%, fatigue 9.7%, diarrhea 10.1%, and neuropathy 5.9%), total cost of care ($6,715), and growth factor spending ($792). Administrations with all four FFX component drugs (N = 15,565 administrations) had the highest incidence of neutropenia (27.5%) and fatigue (17.5%) as well as the highest total cost of care ($7,515) and growth factor spending ($1,761). Conclusions: Among patients receiving 1L FFX, administrations with all four component drugs were associated with the highest incidence of adverse events as well as the highest total cost of care per administration cycle. In particular, neutropenia was seen in over twice as many administration cycles in patients receiving FFX with all four components (27.5%) compared to those receiving FFX with no 5-FU of any kind (12.5%). A higher incidence of neutropenia contributes to higher growth factor utilization and therefore higher costs.
Real-world treatment patterns and total cost of care in Medicare patients with metastatic pancreatic ductal adenocarcinoma who received first-line FOLFIRINOX.
Authors: Hirsch Jared , Cockrum Paul , Tomicki Samantha , Dieguez Gabriela , Bhatt Prachi , Kim George P.
Published: June 2023

e16283

Background: Modifications to the FOLFIRINOX (FFX) regimen are used in the real world to attempt to decrease side effects and increase tolerability for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). This study assesses patterns in real-world modifications to first-line (1L) FFX and total cost of care per administration cycle in the Medicare Fee-For-Service (FFS) population. 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. Study patients had 2+ claims with a pancreatic cancer diagnosis and at least one diagnosis of a metastasis anytime on or after the first pancreatic cancer diagnosis. 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 assigned to cohorts based on drugs present within a 48-hour (2-day) period of a 1L FFX chemo infusion cycle: FFX with all 4 component drugs (oxaliplatin, irinotecan, leucovorin, 5-Fluorouracil (5-FU) bolus and infusion), FFX with no 5-FU bolus but with 5-FU infusion, FFX with a 5-FU bolus but no 5-FU infusion, FFX with no 5-FU of any kind, and FFX with no leucovorin. Results: We found 45,755 administrations of 1L FFX regimens across 8,889 patients with mPDAC between 2018 and 2021. Among 1L FFX regimens, the largest cohort was comprised of administrations involving a 5-FU infusion but no 5-FU bolus (21,619 administrations, or 47%). The second largest cohort received all 4 FFX component drugs (15,565 administrations, or 34%). The other cohorts were patients receiving FFX with no leucovorin (6,300 administrations, or 14%), FFX with a 5-FU bolus but no infusion (1,425 administrations, or 3%) and patients receiving FFX with no 5-FU of any kind (842 administrations, or 2%). Administrations containing all 4 drug components had the highest cost per cycle ($7,515), and those with no 5-FU of any kind had the lowest ($6,715). Conclusions: Among Medicare beneficiaries receiving 1L FOLFIRINOX (FFX) regimens to treat mPDAC, only 34% of administrations of FFX contained all four components. Administrations most frequently omitted the 5-FU bolus. Administrations containing all 4 drug components had higher costs per cycle and those with no 5-FU of any kind had the lowest cost per cycle.
Response monitoring with ctDNA in metastatic pancreatic cancer.
Authors: Ahn Jinwoo , Hwang Jin-Hyeok , Kim Bomi , Jung Kwangrok , Kim Jaihwan , Lee Jong-chan
Published: June 2023

e16284

Background: Various studies about clinical usefulness of serial monitoring with liquid biopsy are being conducted actively in many types of cancer. However, there is not much in pancreatic cancer. We explored whether serial ctDNA monitoring in metastatic pancreatic cancer (MPC) can be beneficial for evaluating treatment response and predicting prognosis. Methods: A total of 51 MPC patients were prospectively enrolled. Blood samples were collected at every response evaluation until progression of disease (PD) or 5th evaluation. Quantitative ctDNA were measured by droplet digital polymerase chain reaction using KRAS G12/G13 screening multiplex Kit (Bio-Rad) and reported as variant allele fraction (VAF). Percent change of ctDNA VAF (DctDNA(%) = (current VAF - previous VAF)/previous VAF*100) were correlated to radiographic responses by RECIST 1.1. Furthermore, Progression free survival (PFS) and overall survival (OS) were analyzed by DctDNA. Results: Among the 51 enrolled patients, baseline ctDNA were detected in 35 patients. During a median follow-up of 9.4 months, PD by radiographic response was observed in 24 patients. As expected, PD group showed higher DctDNA compared with non-PD group (p<0.001). DctDNA for PD yielded Area Under Curve of 0.914 (p<0.001) with 83.3% sensitivity at 90% specificity. Patients who showed early ctDNA clearance (undetectable level at first response evaluation) had longer PFS (8.1 m vs 4.7 m; HR 0.46; 95% CI 0.20 to 1.03; p=0.059) and OS (not reached vs 8.0 m; HR 0.20; 95% CI 0.06 to 0.74; p=0.009) than those who did not. In multivariable analysis, early ctDNA clearance was still associated with significantly longer PFS (HR 0.27; 95% CI 0.08 to 0.92, p=0.036) and OS (HR 0.08; 95% CI 0.02 to 0.54, p=0.007). Conclusions: Serial monitoring with ctDNA in MPC has considerable clinical potential in monitoring treatment response and predicting prognosis.
Patterns of treatment switching and healthcare resource utilization differences among real-world Medicare patients with metastatic pancreatic ductal adenocarcinoma who received first-line FOLFIRINOX.
Authors: Dieguez Gabriela , Hirsch Jared , Cockrum Paul , Bhatt Prachi , Tomicki Samantha , Kim George P.
Published: June 2023

e16286

Background: Modifications to the FOLFIRINOX (FFX) regimen are used in the real world to attempt to decrease side effects and increase tolerability. This study assesses differences in healthcare resource utilization (HCRU) among patients who switched regimens following initial administration of first-line (1L) FFX among the Medicare fee-for-service (FFS) population with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: We identified patients aged 65+ with mPDAC between 2018-2021 in the Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Patients were required to have at least two malignant neoplasm of pancreatic duct diagnosis on different dates AND at least one diagnosis of a metastasis anytime on or after the first pancreatic cancer diagnosis. Patients were assigned to cohorts based on drugs present within a 48-hour (2-day) period of a FFX chemo infusion cycle: 1) FFX with all 4 component drugs (oxaliplatin, irinotecan, leucovorin, 5-FU bolus and infusion), 2) FFX with no 5-FU bolus, but with 5-FU infusion, 3) FFX with a 5-FU bolus, but no 5-FU infusion, 4) FFX with no 5-FU of any kind and, 5) FFX with no leucovorin. 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. The number of patients receiving FFX and the percentage of patients who switched cohorts (e. g. had a change in the FFX drug components received) at any time during the study was identified. HCRU differences were examined for patients at 60, 120, and 180 days after the initial administration for patients who did and did not switch cohorts. Results: We identified a total of 8,889 unique patients receiving 45,755 total administrations of 1L FFX. Cohort switching was observed in 16.7% of patients. Among patients receiving FFX with all 4 component drugs in the first cycle, 19% of subsequent administrations were different. Among patients who received modified FFX regimens, switching on subsequent regimens varied (7% for FFX with no 5-FU bolus, 47% for FFX with a 5-FU bolus but with no 5-FU infusion, 18% for FFX with no 5-FU of any kind, and 5% for FFX with no leucovorin). Inpatient costs were lower and hospital outpatient and growth factor costs were higher for patients who switched cohorts vs those that did not at 60 days, 120 days, and 180 days. Conclusions: One in six patients with mPDAC receiving first-line FFX switched component drugs at least once throughout the course of their treatment. These patients had higher hospital outpatient, higher growth factor, and lower inpatient costs compared to patients who did not switch. Over time, differences in inpatient costs between the two groups were sustained, while differences in hospital outpatient and growth factor exacerbated.