bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors for overall survival in patients with advanced digestive neuroendocrine carcinoma treated with first-line cisplatin-based chemotherapy: A post-hoc analysis of JCOG1213.
Authors: Hirano Hidekazu , Hirata Kenro , Honma Yoshitaka , Morizane Chigusa , Machida Nozomu , Kato Ken , Okusaka Takuji , Boku Narikazu , Sekine Shigeki , Hiraoka Nobuyoshi , Ogawa Gakuto , Sano Yusuke , Shibuya Yuichi , Takahashi Masanobu , Fujimori Nao , Nomura Motoo , Doki Yuichiro , Ueno Makoto , Yoshikawa Takaki , TAKEUCHI HIROYA 
Published: January 2024

594 Background: Advanced digestive neuroendocrine carcinoma (ADNEC) is a rare and aggressive malignancy without evidence of prognostic factors assessed in prospective studies. We aimed to evaluate prognostic factors in patients with ADNEC receiving first-line cisplatin-based chemotherapy. Methods: This is a post-hoc analysis of JCOG1213, which is a phase 3 randomized trial showing equivalent overall survival (OS) for cisplatin plus etoposide versus cisplatin plus irinotecan as first-line chemotherapy for patients with ADNEC. The primary endpoint of JCOG1213 was OS. For this post-hoc analysis of prognostic factors, patients who had ineligible histology based on the central pathological review or who lacked the necessary clinical data for analysis were excluded. A Cox proportional hazard model was used to assess the effect of independent variables on OS. Priori variables selected on previous reports (performance status (PS), Ki-67 index, and serum LDH level), as well as variables that remained at a level of p-value <0.20 by backward stepwise selection, were incorporated in the final model of OS. Results: Among 170 patients enrolled in JCOG1213, a total of 129 patients with ADNEC were included in this analysis. In multivariable analysis, serum LDH level (> upper normal limit vs. normal) was identified as a significant prognostic factor for OS (HR = 1.721, 95% CI: 1.144–2.589, p = 0.009). Other clinicopathological factors were not found to be significant, including PS (1 vs. 0; HR = 0.784, 95% CI: 0.507–1.214, p = 0.276), Ki-67 (≥ 55% vs. < 55%; HR = 1.475, 95% CI: 0.588–3.698, p = 0.407), liver metastasis (present vs. absent; HR = 1.434, 95% CI: 0.968–2.124, p = 0.072), sex (female vs. male; HR = 1.387, 95% CI: 0.937–2.053, p = 0.102), and serum ALP level (> upper normal limit vs. normal; HR = 0.948, 95% CI: 0.639–1.406, p = 0.789). OS of patients with elevated serum LDH levels was shorter than those with normal serum LDH levels (median: 9.5 months vs. 15.6 months, p = 0.0019). No statistically significant differences were observed between the two groups regarding objective response rate (58.8% vs. 54.1%, p = 0.594) and progression-free survival (median: 4.5 months vs. 5.9 months, p = 0.141). A numerically lower proportion of patients with elevated serum LDH levels received second-line chemotherapy than those with normal serum LDH levels (76.5% vs. 88.3%). Conclusions: Serum LDH level may serve as a prognostic factor in the daily practice of patients with ADNEC and as a risk stratification factor in future randomized clinical trials. Clinical trial information: UMIN000014795 .
Advances in the treatment of gastroenteropancreatic poorly differentiated neuroendocrine carcinoma at our hospital.
Authors: Nishina Shinichi , Yokota Mitsuru , Nagahisa Yoshio , Kawata Kenji , Okabe Michio , Masui Toshihiko , Kawamoto Kazuyuki 
Published: January 2024

595 Background: Overall survival after first-line chemotherapy for metastatic or recurrent gastroenteropancreatic poorly differentiated neuroendocrine carcinoma (GEP-NEC) is reported to be less than 1 year. Platinum drugs in combination with etoposide or irinotecan have been used as first-line chemotherapy for GEP-NEC patients, but no standard treatment has been established for second-line and subsequent chemotherapy. Recently, however, we have seen patients with a good prognosis after treatment based on comprehensive cancer genomic profiling (CGP). We retrospectively reviewed GEP-NEC patients treated with chemotherapy. Methods: Patient background, treatment regimen, overall survival, and toxicity were evaluated in 20 GEP-NEC patients who started first-line platinum combination chemotherapy at our hospital between October 2016 and September 2022. Results: Median age was 71 (48 to 81) years, 16 were male, and primary sites were esophagus in 2 patients, stomach in 7 patients, small intestine in 2 patients, large intestine in 6 patients, and pancreas in 3 patients. Five patients had an adenocarcinoma component. Stage III, IV, and recurrence were observed in 2, 16, and 2 patients, respectively. Progression-free survival and overall survival after first-line chemotherapy were 4.0 (2.3 to 7.0) and 8.1 (4.7 to 17.0) months, respectively. Grade 3 or higher toxicity was observed in 13 patients. No differences in overall survival were observed in chemotherapy regimen including etoposide or irinotecan and cisplatin or carboplatin. Patients who underwent CGP had significantly longer survival. After second-line chemotherapy, a regimen containing irinotecan, 5-FU, paclitaxel, ramucirumab, and nivolumab was used, and overall survival was 5.2 (1.8 to NA) months. There were 4 of 20 patients who survived for more than 1000 days after first-line chemotherapy. Durable responses were observed in colonic NEC patients harboring the POLE P286R mutation treated with nivolumab and in those harboring the BRAF V600E mutation treated with cetuximab and encorafenib. Conclusions: Overall survival of GEP-NEC patients treated with platinum combination chemotherapy was very poor at only 8 months. However, in some cases, long-term survival has been achieved with molecular targeted therapy based on CGP results.
Potential biomarkers for treatment response in advanced non-pancreatic neuroendocrine tumors.
Authors: Sonti Sahithi , Wang Katy , Attwood Kristopher , Minderman Hans , Maguire Orla , Ryan Courtney , Sharma Nitika , Konda Bhavana , Iyer Renuka V. , Krishnamurthy Anuradha 
Published: January 2024

599 Background: Well-differentiated NETs are highly vascular and hence, inhibition of angiogenesis is of interest. VEGF, a key molecule in promoting angiogenesis, has also been shown to promote an immunosuppressive tumor microenvironment. Nintedanib, an oral inhibitor of FGFR1–3, VEGFR1–3 and PDGFRA, has previously been evaluated in a phase II clinical trial in well-differentiated, non-pancreatic NETs, where 83% of the evaluable patients were progression-free at 16 weeks and median PFS was 11 months. In preclinical studies, nintedanib has been shown to increase PD-L1 expression in tumor cells, which then results in improved outcomes with immune checkpoint inhibition. There are multiple indicators of T-cell exhaustion, including PD-L1 and LAG-3. LAG-3+ T-cells have been found to correlate with poor response to treatment in neuroendocrine neoplasms. Given these findings, this study evaluates serum VEGF and LAG-3 expression to determine potential biomarkers of response in patients treated with nintedanib. Methods: 27 sets of paired samples collected at baseline and 8-weeks post treatment with nintedanib, from clinical trial NCT02399215 were used for this study. With IRB approval, we tested for serum VEGFa and serum LAG-3 using Luminex test kits: HCKP1-11K-01 (LAG-3) and HCYTA-60K-01 (VEGFa). We compared the baseline, 8-week, and percentage change in serum VEGF and serum LAG-3 levels with Rd Cd8+ pAkt+ T-cells (activated cytotoxic T-cells) as a marker of immune activation, Rd CD25+ pAkt+ T-cells (regulatory T-cells) as a marker of immune suppression, and PFS. Results: The median VEGF levels at baseline and 8-weeks were 10.50 pg/mL and 11.90 pg/mL respectively. The median LAG-3 level at baseline and 8-weeks were 59000 pg/mL and 62900 pg/mL respectively. Higher VEGFa levels in the post-treatment samples were associated with poorer progression free survival (HR= 1.009, 95% HR CI: [0.999, 1.019], with P= 0.0760). Higher levels of VEGF at baseline were also associated with lower numbers of Rd CD8+ pAkt + cells (Pearson coefficient = -0.42, p-value 0.04) at baseline. Increased baseline CD25+ pAkt+ levels were positively correlated with percent change in serum LAG-3 levels between baseline and post-treatment samples. (Pearson Co-efficient: 0.45; p=value: 0.02). Conclusions: Elevated serum VEGFa levels at 8-weeks post treatment correlated with lower PFS. Serum VEGFa level is a potential indicator of effector T-cell suppression, as evidenced by low number of activated cytotoxic T-cells in patients with higher VEGFa levels at baseline. Higher baseline regulatory T-cells were associated with a greater increase in serum LAG-3 levels, suggesting that serum LAG-3 may be an indicator of an immunosuppressive tumor microenvironment.
Socioeconomic variables in the National Cancer Database: Utilization and impact of income and education in survival models for patients with resected pancreas cancer.
Authors: Luo Qianyun , LaRocca Christopher James , Ankeny Jacob , Jensen Eric Hans , Marmor Schelomo , Brauer David 
Published: January 2024

607 Background: The National Cancer Database (NCDB) is commonly used for analyzing survival outcomes in pancreatic cancer and has a robust number of patient-specific socioeconomic variables. Although these aggregated variables are commonly collected, their utility and impact on survival has infrequently been assessed. We aim to assess the distribution of income and education variables on their impact on survival models for patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC). Methods: Patients undergoing definitive surgery for PDAC between 2004-2020 were identified from the NCDB. Variables of interest were income and education according to the patient’s ZIP code of residence. Pearson and Spearman correlation was assessed. Overall survival (OS) was calculated using Kaplan Meier method. The effects of income and education was calculated using Cox proportional Hazard (PH) models. Results: 69,362 patients met inclusion criteria. Median age was 66 (IQR 59-73), with 48.9% female. The correlation coefficient between income and education based on the 2020 American Community Survey data was 0.48 (p<0.01). Median OS from the time of diagnosis was 21 months. The 5-year OS was 19.4 and 22.7 months for groups with lowest and highest education (p<0.01). Group with missing education has a 5-year OS of 22.4 month, comparable to the group with highest education (p=0.82). The 5-year OS based on income quartiles was 18.7 and 22.5 months for the Q1 and Q4 (p<0.01). Group with missing income has a 5-year OS of 22.4 month, similar to the highest income group (p=0.85). When including combinations of income, education and their interaction, the concordance of Cox models was changed by less than 0.002. Conclusions: For patients who underwent definitive surgery for PDAC, the income and education variables are only mildly correlated, and their inclusion do not have significant impact on OS models. Investigators should reconsider the utility of the aggregate NCDB measures, as they many not fully elucidate income and education disparities and impact on survival. [Table: see text]
Demographic and social vulnerability factors associated with late diagnosis of gastrointestinal cancers.
Authors: Khan Muhammad Sohaib , Meier Jennie , Nehrubabu Mithin , Murimwa Gilbert Zvikomborero , Young Sean , Dimartino Lisa , Kazmi Syed Mohammad Ali , Pogacnik Javier Salgado , Wang Sam C. , Yopp Adam C. , Zeh Herbert J. , Polanco Patricio M. 
Published: January 2024

610 Background: Almost 30% of gastrointestinal cancers (GI) are diagnosed at an advanced stage. These patients have a poor prognosis with no curative options. Certain demographic and social factors adversely impact health outcomes. However, these have not been well studied in the context of late diagnosis of GI cancers. Methods: Texas and California cancer registries, merged with CDC’s Social Vulnerability Index (SVI) database, were used to identify patients diagnosed with gastric, colorectal, pancreatic and liver cancer from 2004 to 2019. To determine the association of demographic and 16 social vulnerability factors, while accounting for differences in tumor characteristics, univariate and multivariate logistic regression analysis (MVA) was performed for each cancer separately. Results: In total, 589,405 patients were included. Of these 166,910 (28.3%) patients had metastasis at diagnosis. This included 55%, 39%, 21%, and 17% of all pancreatic, gastric, colorectal and liver cancers respectively. On MVA, odds of metastatic cancer at presentation decreased with increasing age (except for pancreatic cancer where odds increased). Across all 4 cancer types, females and Asians had decreased odds while Blacks, uninsured and patients on Medicaid had increased odds of metastatic cancer at diagnosis. Poverty below 150% increased odds of metastatic pancreas, liver, and colorectal cancers at diagnosis. Odds were decreased for households with adults aged over 65 years for pancreas, colorectal and gastric cancers. Conclusions: This study has identified multiple demographic and social factors associated with odds of having metastatic GI cancer at diagnosis. Interventions aimed towards these at-risk populations offer an opportunity for early diagnosis and improved survival.[Table: see text]
Real-world comparison of low- versus high-dose continuous 5FU infusion in patients receiving triplet chemotherapy plus bevacizumab for newly diagnosed metastatic colorectal cancer (mCRC).
Authors: Chapin William Joseph , Hwang Wei-Ting , Mamtani Ronac , O'Hara Mark H. 
Published: January 2024

62 Background: Several randomized trials demonstrated an overall survival (OS) benefit to triplet chemotherapy (5-FU, oxaliplatin, and irinotecan) plus bevacizumab compared to doublet chemotherapy plus bevacizumab in patients with newly diagnosed mCRC, though with higher rates of neutropenic fever and diarrhea. These trials used high-dose continuous infusion 5-FU (3,200 mg/m2/48 hours), but national guidelines suggest low-dose continuous infusion 5-FU (2,400mg/m2/48 hours) due to lower tolerance in U.S. patients. We performed a retrospective cohort study in a U.S. population to compare the effectiveness of low- vs high-dose continuous infusion 5FU in patients undergoing triplet chemotherapy plus bevacizumab for newly diagnosed mCRC. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data curated via technology-enabled abstraction from ~280 cancer clinics. Patients with newly diagnosed mCRC who initiated triplet chemotherapy plus bevacizumab between 10/23/14 and 10/31/22 with non-missing height, weight, and dosing data were included. 5FU infusion doses of 2,000 – 2,799 mg/m2 were categorized as low-dose while those >/= 2,800 mg/m2 were categorized as high-dose. OS from first-line treatment initiation was assessed by dosing group using the Kaplan Meier method with log-rank testing. Multivariable analysis with adjustment for pre-specified variables with imbalance (defined by standardized difference < - 0.10 or > 0.10) was performed using multivariable Cox proportional hazards modeling. Missing data were imputed using multiple imputation with chained equations. Results: Among 320 patients included, 244 received low-dose and 76 patients received high-dose continuous infusion 5FU. Imbalance between low- and high-dose groups was observed in the use of 5FU bolus (23% vs 3%), year of metastatic diagnosis 2018 - 2022 (80% vs 55%), mean irinotecan dose (156.4 vs 160.5 mg/m2), left-sided primary (73% vs 64%), MMR deficiency (3% vs 6%) and mean CEA (478 vs 691 µg/L). In univariate analysis, median OS was 33 months (95% CI 26 – 39) in the low-dose group compared to 34 months (95% CI 24 – 48) in the high-dose group (HR 1.16; 95% CI 0.79 – 1.69; p = 0.44). After adjusting for imbalanced covariates, there was no difference in hazard of death between low- and high-dose groups (HR 0.99; 95% CI 0.64 – 1.53; p = 0.97). Conclusions: In this real-world, U.S. population with newly diagnosed mCRC receiving triplet chemotherapy plus bevacizumab, there was no association with survival between low- vs high-dose continuous infusion 5FU. This supports current guidelines recommending low-dose continuous infusion 5FU (2,400mg/m2/48 hours) for patients with mCRC receiving triplet chemotherapy in the U.S.
Nutritional impact and prognostic role of systemic inflammatory response index (SIRI) in advanced pancreatic cancer: PANTHEIA-Spanish Society of Medical Oncology (SEOM) study results.
Authors: Pacheco-Barcia Vilma , Mariño Méndez Axel , Carmona-Bayonas Alberto , Gallego Javier , Fabregat Franco Carles , Adeva Jorge , Cerdà Paula , Cabezon-Gutierrez Luis , Custodio-Cabello Sara , Ghanem Ismael , Hernandez Irene , Lamarca Angela , Laquente Berta , López-Alfonso Ana , Martinez Lago Nieves , Macarulla Teresa , Peiro Inmaculada , Visa Laura , Jimenez-Fonseca Paula , Muñoz Andrés 
Published: January 2024

623 Background: Whilethe systemic inflammatory response assessed by SIRI has been recognized as a prognostic factor in advanced pancreatic cancer, understanding its association with patients' nutritional status may provide deeper insights into disease biology and outcomes. Methods: This is an observational, non-interventional and multicenter study (15 Spanish hospitals) promoted by SEOM, including retrospective and prospectively patients with metastatic pancreatic cancer in routine clinical practice. Clinical and nutritional data was recorded, and SIRI was calculated using the formula: (neutrophils x monocytes) / lymphocytes. We considered SIRI score as low (SIRI-L) or high (SIRI-H) using a cutoff of <2.3 or ≥2.3, respectively based in our previous findings. PANDORA-SEOM tool was used for electronic data collection. The main outcome is to correlate SIRI with the nutritional status. Other aims were to correlate the overall survival (OS) and progression-free survival (PFS) with SIRI and weight loss in the 3 months prior to diagnosis using the Kaplan-Meier method and multivariate Cox regression model. Data from the pilot study is presented in this abstract, and more data is expected to be available prior to the Congress. Results: We included 144 patients retrospectively: 65% men, with median age of 66 years (range 45-81). The most common 1st line chemotherapy regimen were gemcitabine + nab/paclitaxel (63.2%), mFOLFIRINOX (20.1%) and FOLFOX (11.8). Prior to diagnosis, 54.2% of patients had weight loss >5 Kilograms (Kg) and 22.9% lost >10 Kg. SIRI-H was significantly associated with weight loss >5Kg compared to SIRI-L, 35.7 vs 24% respectively (p=0.028). Patients with a pretreatment SIRI-H showed shorter OS compared to SIRI-L (median OS 5 vs 12 months, Hazard Ratio (HR) 3.047, 95% Confidence Interval (CI) 2.069-4.488, p<0.001), as well as shorter PFS (median PFS 5 vs 10 months, HR 2.364, 95% CI 1.650-3.387, p<0.001). In the patient subgroup that experienced >5Kg weight loss, SIRI-H was associated with worse OS (median OS 4 vs 12 months). We didn’t find an association between CA19.9 level and SIRI or weight loss. Multivariate analysis identified SIRI as an independent prognostic factor for OS (HR 2.962, 95% CI 1.911-4.591, P<0.001). Conclusions: Our findings underscore the importance of SIRI as a significant predictor of nutritional status and disease aggressiveness in patients with metastatic pancreatic cancer. Prospective data will help us to validate these findings.
Predictive machine learning models for survival outcomes in patients with pancreatic cancer.
Authors: Shen Yang-Chen , Chen Po-See , Lin Cheng-Feng , Liu Ping-Yen , Lin Peng-Chan , Yen Chia-Jui , Shan Yan-Shen 
Published: January 2024

625 Background: Identifying prognostic markers is essential for accurately assessing risk levels in pancreatic cancer patients, leading to more personalized treatment approaches. In light of this, our study endeavors to build a survival prediction model for pancreatic cancer patients using various machine learning (ML) techniques, taking into account both clinical and inflammatory factors. Methods: The research included 311 pancreatic cancer patients on a prospective basis. Their data was sourced from the Clinical Data Warehouse of National Cheng Kung University Hospital. For the purpose of predicting 6 and 12-month survival, patients were randomly allocated into training, validation, and test groups in an 8:1:1 ratio. We utilized machine learning techniques and assessed them on the QOCA Aim (Quanta Omni Cloud Care for AI Medical Platform, version 2.0) platform. The model's effectiveness was gauged using the area under the receiver operating characteristic curve (AUC). Results: The cohort exhibited a mean age of 63.5 years with a standard deviation of 11. The median overall survival was documented at 16.8 months (95% confidence interval [CI] = 15.6–18). Analytical evaluation indicated that the optimal model for prognostication of 6-month survival was the balanced bagging classifier, yielding an AUC of 93.7%. Conversely, for the 12-month survival prediction, the k-nearest neighbors (kNN) classifier was superior, demonstrating an AUC of 86.1%. Subsequent variable importance analysis elucidated that salient predictors encompassed C-Reactive protein (CRP), surgical intervention, carbohydrate antigen (CA)19-9, age at diagnosis, and the neutrophil–lymphocyte ratio (NLR). Conclusions: The findings indicated that machine learning can be employed to develop high-efficacy predictive models for survival in pancreatic cancer patients. Such models offer promise for enhanced risk categorization and personalized prognostic assessment in this patient cohort.