bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic cancer and diabetes: The effects of race and genes.
Authors: Shu Michael , Moreland Katie , Olowokure Olugbenga Olanrele , Latif Tahir , Rojan Adam , Wilson Gregory , Patel Sameer H. , Sussman Jeff , Ahmad Syed , Pan Jianmin , Rai Shesh , Sohal Davendra 
Published: January 2024

627 Background: Pancreatic cancer and diabetes mellitus (DM) have been shown to be connected, but the genetic associations between the two have not been well characterized. The goal of this study was to identify racial and genomic patterns that relate the timing of DM onset with a pancreatic cancer diagnosis. Methods: Consecutive pancreatic cancer patients treated at the University of Cincinnati Cancer Center with available tumor genomic profiles were studied. Descriptive statistics for 133 genes, patient characteristics, cancer stage, treatment details, and family history were analyzed. Categorical variables were compared using the Pearson Chi-square test for contingency tables (or Fisher’s exact test when the expected frequency within any cell was less than 5 in the contingency table), and the t-test or ANOVA was used for continuous variables. For overall survival, we generated Kaplan-Meier curves by DM diagnosis, and fit univariable Cox Proportional-Hazard models for each interest variable for all patients, and multivariable Cox models, which included only significant variables. Results: Of 147 individuals with pancreatic cancer (median age 67 years, 49% female, 12% Black), 46.3% had a DM diagnosis. Of these, 62% had chronic DM, while 38% were diagnosed within one year of their pancreatic cancer diagnosis. Black individuals were more likely to have DM diagnosed (76.5% vs 41.7%, p = 0.007), and were more likely to have been diagnosed within a year of pancreatic cancer (69.2% vs 30.2%, p = 0.023), compared with White individuals. There were 15 genes found to be upregulated in those with DM and pancreatic cancer, and 11 genes found to be downregulated. RNF43 mutation was more prevalent in pancreatic cancer patients with chronic DM than those without DM (71.4% vs 32.5%, p = 0.048), although absolute number of individuals with the mutation were low. No other genomic association on the timing of DM and pancreatic cancer was found. A SMAD4 mutation was associated with a 121% increased risk of mortality (HR = 2.21, 95% CI 1.16-4.19, p=0.016). Conclusions: In a cohort of pancreatic cancer patients at a single center, Black individuals were more likely to have DM diagnosed closer to pancreatic cancer diagnosis (rather than earlier), compared with other races. No remarkable genomic association was found. This highlights that a diagnosis of diabetes may be related to inequities in healthcare, as opposed to true genomic differences, and needs to be explored in larger datasets.
Real-world overall survival and time to next treatment in patients with metastatic pancreatic ductal adenocarcinoma who received FOLFIRINOX and modified FOLFIRINOX in the first line.
Authors: Dennen Syvart , Boppudi Naga Sai Sriteja , Cockrum Paul , Paluri Ravi Kumar 
Published: January 2024

629 Background: FOLFIRINOX (FFX) is a recommended first line (1L) treatment option for patients (pts) with mPDAC but is known for its high toxicity. Efforts to balance pts’ quality of life (QoL) during treatment with treatment effectiveness have led to the use of modified FOLFIRNOX (mFFX) regimens that employ decreased doses of FFX components. Further evidence is needed to assess OS and progression-free survival (PFS) among pts who receive FFX or mFFX treatment in the real world compared to the trial setting. We identified a real-world (RW) sample of pts with mPDAC treated with FFX and mFFX in 1L and assessed their OS, and, as a RW proxy for PFS, TTNT. Methods: This retrospective observational study utilized the Flatiron Metastatic Pancreatic Cancer Enhanced Data Mart. Adult pts diagnosed with mPDAC between January 2014 and May 2022 who initiated treatment with FFX or mFFX in 1L within 90 days of their diagnosis for metastatic disease were included in the study. mFFX was defined as administration of <150mg/m2 of irinotecan or <2,720mg/m2 5-FU total (bolus+infusion) during cycle 1; doses greater than these were considered FFX. TTNT was defined as duration between 1L treatment initiation and the start of second line therapy or death. Kaplan-Meier analyses were used to assess median OS and TTNT from the start of 1L FFX or mFFX treatment and log-rank tests for the statistical significance of differences in OS and TTNT. Results: 2,212 mPDAC pts met the study inclusion criteria, with 507 pts (23%) receiving FFX and 1,705 pts (77%) receiving mFFX in 1L. For FFX vs. mFFX, the median age at 1L initiation was 63yr vs. 65yr, 72% vs. 56% were male, 67% vs. 63% were white, 36% vs. 30% had an ECOG score of 0, 31% vs. 32% had an ECOG score of 1, and 83% vs. 81% received treatment at community oncology centers. For FFX vs. mFFX, median OS was 9.5 (95% CI: 8.9–10.7) vs. 9.0 months (95% CI: 8.4–9.7) (p=.452) and median TTNT was 4.8 (95% CI: 4.5–5.5) vs. 4.8 months (95% CI: 4.5–5.2) (p=.256). Conclusions: In a RW sample of 2,212 pts receiving 1L FFX and mFFX at primarily community oncology practices in the United States from 2014–2022, more than three-quarters received mFFX. Pts experienced similar median OS and TTNT across the two regimens, indicating that full-strength FFX may provide little benefit to OS in exchange for its increased toxicity. In the PRODIGE 4/ACCORD 11 trial of unmodified FFX, conducted earlier (2005–2009) among a group of 342 French pts, median OS was 11.1 months (95% CI: 9.0–13.1) and median PFS was 6.4 months (95% CI: 5.5–7.2). The median RW OS of FFX and mFFX pts in our study was numerically lower than the trial, as was RW TTNT compared with trial PFS. Future research should seek to understand the factors driving differences in RW and clinical trial outcomes as well as to assess the tradeoff between regimen toxicity and survival benefit.
Retrospective analysis of the real-world demographics, clinical characteristics, and treatment patterns in metastatic CRC among patients treated with encorafenib in combination with cetuximab in the United States.
Authors: Parikh Aparna Raj , Vieira Maria Cecilia , Silver Michelle , Rava Andrew , Rau Reina , Li Benjamin 
Published: January 2024

63 Background: The presence of BRAF V600E mutations (BRAF-m) occurs in approximately 7% of patients with metastatic CRC (mCRC). Encorafenib (enco) plus cetuximab (cetux) were approved in April 2020 as the first targeted therapy for the treatment of adult patients with BRAF-m mCRC. The purpose of this study is to assess the demographics, clinical characteristics, and treatment patterns in BRAF-m mCRC among patients treated with enco, based on a claims database in the US. Methods: This was a retrospective cohort study in the IQVIA PharMetrics Plus claims database. Adults ≥18 years old with ≥1 claim for enco (first claim for enco on/after 4/1/2020) with concurrent cetux, as approved, or with EGFR panitumumab (pani), ≥2 ICD-9/10 codes for malignancy of the colon or rectum ≥30 days apart in the 1 year before index date, and ≥1 day of pharmacy and medical continuous enrollment during the index date were included. Patients were excluded if they had a record of melanoma or non-small cell lung cancer during the year before index date, were enrolled in a clinical trial any time after the CRC diagnosis date or did not have a treatment regimen starting on or after CRC diagnosis date. Index date was the date of first treatment of enco+EGFR during the identification period (4/1/2020-3/31/2022). Patient demographics and disease characteristics were assessed at baseline, and treatment patterns were evaluated during the pre-index and follow-up periods. Results: 125 patients were included. Median (Q1 [1st quartile], Q3 [3rd quartile]) age at index was 58 (49, 63) years; 52.0% were female; 47.2% residents in the South, 26.4% in the Midwest, 14.4% in the East and 12.0% in the West. In terms of healthcare coverage, 64.0% were under commercial, 27.2% self-insured and 8.8% under Medicare plans. Most patients (60.8%) at the start of enco had metastases in 3 or more sites, predominantly in the liver (76.8%), lymph nodes (50.4%), and lung (43.2%). The 2011 Modified Quan Charlson Comorbidity Index was 0 for 44.8% of the patients, 1-2 for 39.2%, and 3 or more for 16.0%. Mean (SD [standard deviation]) number of pre-index treatment regimens was 0.87 (0.73). Among the enco patients who had a previous treatment computed in claims, FOLFOX +/- bevacizumab (beva) and FOLFIRI + beva were the most common. Among the ones who had a subsequent treatment computed in claims, FOLFIRI +/- beva was the most common. Conclusions: This study provides current RW demographics, disease characteristics and treatment patterns among BRAF mCRC patients treated with enco in the US.
Are adverse events (AEs) during first-line FOLFIRINOX (FFX) more frequent in real-world (RW) patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not proceed to second-line therapy?
Authors: Paluri Ravi Kumar , Silver Michelle , Cockrum Paul , Dennen Syvart 
Published: January 2024

630 Background: mPDAC patients (pts) that tolerate 1L FFX may increase their survival with 2L therapy, most often gemcitabine + nab-paclitaxel (GnP). However, some pts discontinue treatment due to the toxic effects of 1L FFX and consequently experience disease progression and reduced survival. Reasons for discontinuation are typically not available in RW sources. To assess whether AEs are more frequent per unit time in pts that stop treatment after 1L, we calculated the RW incidence rates (IRs) of AEs during 1L treatment for two RW cohorts: mPDAC pts treated with 1L FFX and no 2L (FFX-only) vs. pts treated with 1L FFX and 2L GnP (FFX + GnP). Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2021 who initiated treatment with 1L FFX ≤90 days from their metastatic diagnosis were included. Diarrhea, fatigue, nausea and vomiting, and neuropathy were available in the data as ungraded AEs abstracted from clinician notes. Hematologic and hepatic AEs were based on observed lab values and were graded according to the Common Terminology Criteria for AEs v5. Pts were required to have ≥1 year of follow-up unless death occurred first. We evaluated differences in IRs of AEs per pt-month of 1L treatment for statistical significance using the test-based method. Results: 587 pts met study inclusion criteria. 300 pts received FFX-only prior to death or end of follow-up, while 287 received FFX + GnP. For FFX-only vs. FFX + GnP pts, median age was 66 vs. 64 (IQR: 59–71 vs. 57–69), 57% in both groups were male, 70% vs. 69% were white, 55% vs. 62% had an ECOG of 0–1, and 8% vs. 3% had an ECOG of 2. Median 1L duration of therapy (DoT) was 2.1 (IQR: 0.7–5.0) vs. 4.6 months (IQR: 2.1–7.4). Among ungraded AEs, fatigue was more frequent per pt-month of 1L therapy for FFX-only vs. FFX + GnP pts (IR=0.037 vs. 0.027; p=.041). AEs based on lab values were higher per pt-month of 1L therapy for FFX-only vs. FFX + GnP pts for grade 3/4 thrombocytopenia (IR=0.012 vs. 0.006, p=.013), grade 1/2 anemia (IR=0.203 vs. 0.142, p<.001), grade 1/2 and 3/4 hypokalemia (IR=0.099 vs. 0.074, p<.001; IR=0.040 vs. 0.028, p=.010), grade 1/2 elevated ALT (IR=0.138 vs. 0.098, p<.001), grade 1/2 and 3/4 elevated AST (IR=0.150 vs. 0.109, p<.001; IR=0.018 vs. 0.011, p=.021), and grade 1/2 and 3/4 elevated ALP (IR=0.172 vs. 0.123, p<.001; IR=0.034 vs. 0.025, p=.035). IRs of all other AEs were numerically higher for FFX-only pts but differences were not statistically significant. Conclusions: A RW cohort of mPDAC pts receiving FFX-only experienced more AEs per pt-month of 1L and reduced likelihood of proceeding to subsequent lines of therapy compared to pts treated with FFX + GnP. Identifying predictive biomarkers may distinguish FFX non-responders and obviate AEs.
Patterns of surgery and adjuvant therapy in pancreatic carcinoid tumor: An NCDB analysis.
Authors: Lanoue Connor , Braaten Marco , Bine Christopher Reese , Silberstein Peter T. 
Published: January 2024

631 Background: Pancreatic Carcinoid Tumor (PCT) is a neuroendocrine tumor (NET) of the gastrointestinal (GI) tract composed of Argentaffin cells. Of the primary pancreatic cancers, NETs are exceedingly rare in comparison to pancreatic adenocarcinoma, accounting for less than 2% of pancreatic cancer diagnoses. PCTs constitute for only a subset of these and hold a better prognosis than adenocarcinoma (What Is a Pancreatic Neuroendocrine Tumor? | American Cancer Society, n.d.). GI carcinoid tumors classically originate in the appendix, ileum, or rectum, and are seldom a primary neoplasm of the pancreas. PCTs generate secretory products with Serotonin being the most frequently isolated. Some cases may produce a carcinoid syndrome with characteristic diarrhea, cutaneous flushing, and bronchospasm (Ha & Tan, 2012). Surgical resection is the hallmark of treatment, though other modalities of management are available. Due to the rarity of PCT, no significant study exists in the literature analyzing the association of survival with receipt of surgery or predictors of receipt of surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PCT from 2004 to 2019 using the histology codes 8240 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, Binary Logistic Regression and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α = 0.05. Results: 2237 patients with PCT formed the final sample, with an average age of 61 years of age. 724 patients (32.3%) underwent surgery of the primary site, 72 (3.2%) received adjuvant chemotherapy, and 9 (0.4%) received adjuvant radiation. Surgery alone was associated with the longest median survival ( 198.5 months) compared to the other treatments ( Adjuvant chemotherapy=155.3 months, Adjuvant radiation=122.7 months, No surgery=73.95 months; p<0.05). After controlling for covariates, receipt of surgery was independently associated with decreased overall mortality ( HR=.380; p<0.05). Decreased age, lower grade tumors, and fewer positive regional lymph nodes were significantly associated with increased odds of receiving surgery. Additionally, treatment at an academic facility and private insurance status was associated with significantly higher rates of surgery. Patients who did not receive surgery were significantly older, had later stage disease, higher co-morbidity scores, and larger tumor size. Income level and race had no effect on treatment selection. Conclusions: This study found that surgery alone without adjuvant therapy is independently associated with improved survival. Favorable clinical characteristics may be contributing to this discrepancy in survival. Further exploration of treatment strategies in PCT may benefit patients through the creation of definitive treatment guidelines to manage this disease.
Trends in incidence and survival of early-stage pancreatic ductal adenocarcinoma in the United States.
Authors: Perrotta Gerardo , Abboud Yazan , Osipov Arsen , Mohamed Ghada , El Helou Mohamad , Pandol Stephen Jacob , Lo Simon K. , Gaddam Srinivas 
Published: January 2024

633 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor survival with nearly 80% mortality within the first year after diagnosis. There have been modest incremental improvements in survival over the last decade, however the reason for this improvement is unclear. The aim of this study is to evaluate the trends of diagnosis and survival in the last two decades using large public national databases. Methods: Incidence rates of PDAC between 2001 and 2020 (age-adjusted to the 2000 US standard population) were evaluated in the United States Cancer Statistics (USCS) database, representing approximately 98% of the US population. The data was analyzed with SEER*Stat using Joinpoint regression. A survival analysis was subsequently conducted using the American College of Surgeons’ (ACS) National Cancer Database (NCDB), of PDAC cases diagnosed between 2004 and 2015.Survival outcomes were stratified by AJCC stage. Kaplan-Meier survival curves were generated, and log-rank tests were conducted to assess differences in survival between stages. Cox proportional hazards model was employed to estimate hazard ratios and adjust for potential confounders. The analysis was performed with IBM SPSS 24. Results: From 2001 to 2020, the age-adjusted incidence rate of early-stage PDAC increased from 1.1 to 2.8 (per 100,000 person-years), while locally advanced PDAC increased from 3.6 to 4.3, and from 6.4 to 7.7 for metastatic PDAC (all p<0.01). The Annual Percent Change (APC) was 5.7 for Early-Stage PDAC (95% CI 5.1-6.4), 1.4 for locally advanced (95% CI 0.8-1.9), and 0.8 for Metastatic PDAC (95% CI 0.6-1.1). The incidence rate ratio (IRR) almost doubled for early-stage PDAC, increasing from 0.10 to 0.19. Conversely, for metastatic and locally advanced stages, the IRR decreased from 0.58 to 0.52 and 0.32 to 0.29, respectively. Survival analysis revealed 5-year overall survival rates of 74%, 69%, 57%, and 33% for stages 0, IA, IB, and IIA, respectively, with an overall improvement from 2004 to 2015. This increase was consistent among all age groups, genders, and races. Stages IA and IB demonstrated larger increases 45.9% and 56.6%, respectively (IA: 47% in 2004 to 75% in 2015; IB: 38% in 2004 to 68% in 2015). Conclusions: This study highlights a marked increase in the incidence of early-stage PDAC, surpassing the overall incidence increase, suggesting improving diagnostic capabilities over the last two decades. Furthermore, the substantial improvement in 5-year survival rates for stages IA and IB indicates progress in the management of early-stage PDAC. These findings emphasize the importance of continued efforts in early detection and treatment strategies for PDAC.
Associations between BMI, morphomics and survival in 528 patients with metastatic pancreatic cancer.
Authors: Gunchick Valerie , Brown Edward , Wang Stewart , Su Grace , Sahai Vaibhav 
Published: January 2024

637 Background: Literature describing associations between patient body mass index (BMI) and survival in pancreatic ductal adenocarcinoma (PDA) remains inconsistent. This heterogeneity may be due to studies using pre-diagnosis BMI and including few metastatic patients despite high prevalence at diagnosis. Furthermore, BMI may not adequately reflect other body compositions such as those reflected via morphomic variables (subcutaneous fat, visceral fat, muscle, and fascia) that may have unique associations with survival. In this study, we sought to explore the relationships between detailed body composition in patients with metastatic PDA on both overall survival (OS) and progression-free survival (PFS). Methods: We evaluated data and scans from a phase 3 clinical trial in which 528 patients with metastatic PDA with no prior chemotherapy were randomized to either FOLFIRINOX or modified FOLFIRINOX plus devimistat. No differences in response rate, median PFS or OS were observed. Of the 528 enrolled patients, 377 had baseline CT scans eligible for morphomic evaluation for which Analytic Morphomics was used to measure body composition. For analysis, morphomic variables were summed across the T10-T12 and L1-L4 vertebrae and then divided into tertiles. BMI at diagnosis was evaluated in tertiles and per WHO standards. Cox proportional hazards models and cubic splines were used to evaluate associations between BMI, morphomic variables and PFS, OS. Univariate and multivariate models were evaluated. Kaplan-Meier plots were created to evaluate median survival times between those in the highest and lowest tertiles (R v4.3.1). Results: We did not observe an association between BMI and PDA patient survival: HR (95% CI) comparing BMI ≥30 (obese) to 18.5-24.9 (healthy weight), PFS 0.96 (0.66, 1.39), p-trend=0.80; OS 0.87 (0.64, 1.18), p-trend=0.30. However, multiple morphomic variables were significantly associated with PFS and/or OS in univariate and multivariate models when comparing the highest to lowest tertile. More subcutaneous fat was associated with longer median OS (12.4 vs 10.5 mos, p=0.006; HR (95% CI) 0.41 (0.25-0.68), p-trend=0.001). More dense visceral fat was associated with shorter median PFS (6.0 vs 9.1 mos, p=0.05, HR (95% CI) 1.52 (1.00-2.33), p-trend=0.047). A higher muscle to fascia ratio was associated with longer PFS (9.3 vs 6.5 mos, p=0.03; HR (95% CI) 0.58 (0.38-0.88), p-trend=0.01) and median OS (13.9 vs 10 mos, p=0.005; HR (95% CI) 0.53 (0.38-0.76), p-trend=0.0004). Conclusions: BMI was not associated with PFS or OS in this large prospective study of patients with metastatic PDA receiving chemotherapy. However, morphomic variables including subcutaneous fat area, visceral fat density, and the muscle to fascia ratio were statistically significantly associated with metastatic PDA patient survival.
Germline testing in patients with early-onset pancreatic cancer (EOPC).
Authors: Ehsan Hamid , Symanowski James Thomas , Krishnan Arunkumar , Athens Aly , Wilson Katherine , Tobik Katie , Elrefai Sara , Salem Mohamed E. , Hwang Jimmy J. , Chang Darryl , Kadakia Kunal C. 
Published: January 2024

639 Background: EOPC, defined as pancreatic cancer (PC) diagnosed at 60 years of age or younger, is associated with significant life years lost. Approximately 5-10% of average-onset PC have an underlying germline etiology. Currently NCCN & ASCO guidelines recommend germline testing in all pts w PC. However, there is limited data regarding to what extent pts with EOPC pursue recommended germline testing. We examined the findings from genetic evaluation in EOPC. Methods: A retrospective review of EOPC pts at the Levine Cancer Institute who underwent clinical genetic assessment between January 2019 and December 2021 was performed. Data on clinicodemographic, family history, and genetic testing results were obtained and analyzed descriptively. Results: We identified 69 EOPC pts who were evaluated by genetics. Baseline characteristics include median age of 55 years (range 25-60) with 52% male, 48% white, 23% black, and 52% with current or prior tobacco use. At presentation, 41% and 59% had metastatic and non-metastatic disease, respectively. Eight (12%) pts declined germline testing. Among the 61 who underwent germline testing, 30 (49%) pts had negative testing, 21 (34%) had only variants of uncertain significance, and 10 (16%) had pathogenic/likely pathogenic germline variants (PVs). The most frequently seen PVs were ATM (20%), BRCA1 (20%), BRCA2 (10%), MLH1 (10%), NTHL1 (10%), PTCH1 (10%), CFTR (10%) and one (10%) with multiple pathogenic germline findings including RAD51 and BRCA1. Among the 10 pts with PVs, only two reported any first or second-degree family members with cancer. Conclusions: In this cohort of EOPC at a large community multi-site cancer center, 16% of patients had germline PVs, higher than reported in older patients with PC. Only 20% of pts w PVs reported first or second-degree family members with cancer and highlights the importance to recommend germline testing independent of family history even among EOPC cohorts. Further investigation to clarify reasons for refusal of germline testing in EOPC should be evaluated.