tbuckley/cabot-search huggingface dataset:
The effect of cachexia and anti-cancer therapies on GDF-15 levels in patients with pancreatic adenocarcinoma.
Authors: Talya Geller, Abrahm Levi, Arsen Osipov, Jun Gong, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2025)

778 Background: Growth differentiation factor 15 (GDF15) is a novel biomarker in the setting of pancreatic adenocarcinoma (PDAC). Preliminary studies have found that downstream effects of GDF-15 promote the progression of pancreatic cancer. PDAC has a high prevalence of cachexia which is commonly treated with enzyme supplementation and nutritional support. Platinum-based therapies often used to treat PDAC increase the likelihood of patients experiencing cachexia. The purpose of this study was to observe the GDF-15 levels in respect to weight change of PDAC patients being treated with cachexia and anti-cancer therapies. Methods: Serum and Plasma samples were collected from locally advanced and advanced PDAC patients on 5 IRB approved studies from 2014-2024. Samples were analyzed using the R-PLEX Human GDF-15 Antibody Set. The study objective was compared using two-sample paired t-tests and Pearson correlation matrices. Elevated GDF-15 was determined as &gt;1500 pg/mL. Results: Samples from 73 patients were utilized for this study (63% female; median age: 69; BMI: 23.31±4.96 kg/m 2 ). At baseline 71.8% (46/64) had elevated GDF-15, at Cycle 3 76% (25/33), and at Cycle 5 86% (25/29). In the total sample set, there was a slight negative correlation in the change of weight (-1.75 kg, p = 0.013) and GDF-15 (577.5 pg/mL, p = 0.278) from C1 to C3 (r = -0.185, p = 0.366). There was a slight negative correlation (r = -0.44, p = 0.076) in the difference of weight and GDF-15 from C1 to C3 in patients receiving chemotherapy. A strong negative correlation was observed in the change of GDF15 and weight from C1D1 to C1D8 in patients treated with platinum-based therapy (r = -0.530, p = 0.212) and a weak negative correlation (r = -0.421, p = 0.065) for patients with non-platinum-based therapy. There was a strong positive association (r = 0.993, p &lt; 0.01) between the change in weight and GDF-15 from C1 to C5 in patients not receiving chemotherapy. There was no significant decrease in GDF-15 levels across the patients at all time points. Conclusions: Despite cachexia and anti-cancer treatment, the GDF-15 levels of PDAC patients continue to remain elevated in consecutive blood draws. Further research in GDF-15 kinetics is warranted. Clinical trial information: NCT02400398 , NCT03207724 , NCT04098237 , NCT05336266 , NCT04634539 . Weight and GDF-15 levels across different chemotherapy regimens. Baseline Cycle 1 Cycle 3 Cycle 5 BMI (kg/m2) Weight (kg) GDF15 (pg/mL) Weight (kg) GDF15 (pg/mL) Weight (kg) GDF15 (pg/mL) Chemotherapy 23.21 63.83 3243.25 63.44 3498.76 60.14 3201.33 No Chemotherapy 23.77 65.85 3113.73 62.32 2949.56 71.05 2944.54 Platinum Based 20.88 59.89 6527.78 51.7 3600.87 58.1 5152.50 Non-platinum-based chemotherapy 23.86 64.89 2442.14 64.67 3487.41 60.39 2957.43
A comparative study of dosage strategies in HIPEC: BSA-based vs fixed dose methods.
Authors: Harsimran Kaur Multani
Journal: Journal of Clinical Oncology (2025)

832 Background: Peritoneal metastases commonly occur in ovarian, gastric, and colorectal cancers, significantly contributing to patient morbidity and mortality. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a promising approach for managing peritoneal surface cancers. This procedure involves cytoreductive surgery to remove visible tumors, followed by the perfusion of heated chemotherapy (41-42°C) directly into the peritoneal cavity. HIPEC addresses the limitation of systemic chemotherapy, which often fails to penetrate the peritoneal cavity effectively. HIPEC dosing may either be a flat-fixed dose or be calculated based on Body Surface Area (BSA). BSA can be determined using three methods: actual BSA (based on weight and height), ideal BSA (based on sex and height), and adjusted BSA (considering lean and fat mass). Methods: A retrospective chart review was conducted on 151 metastatic cancer patients at UVMMC. Patient BMI, weight, and height at diagnosis were collected to calculate BSA values (actual, adjusted, and ideal) for estimating a hypothetical chemotherapy dosage. Statistical analysis using SPSS involved linear mixed models and paired t-tests to compare Mitomycin-C dosages between a fixed dose (40 mg) and a BSA-derived dose (30 mg/m²). Results: The average dosage of Mitomycin-C differed significantly depending on whether the dose was calculated using actual, adjusted, or ideal BSA. The largest discrepancy in dosage was observed between the actual BSA method and the flat-fixed dose, with an average difference of 16 mg. The smallest difference in dose was between the adjusted and ideal BSA methods. When stratifying by BMI, the greatest variation in Mitomycin-C dosage was found among overweight and obese patients (BMI ≥ 25). For these patients, the average dosage difference between the flat fixed dose and the actual BSA dose was 20 mg. In comparison, in patients with a BMI under 18.5 (underweight) the actual BSA dose was comparable to the fixed dose. Conclusions: Different institutions utilize a variety of dosing strategies for the HIPEC procedure. Differences in BSA calculation methods and perfusate volumes (literature values of 2, 3 and 4 L is most common) contribute to the complexity of establishing standardized dosing. The significant dosing variations observed, especially in overweight and obese patients, are of concern, as 70% of the U.S. population has a BMI ≥ 25. Our study demonstrates significant variability in HIPEC chemotherapy dosing, especially among patients with higher BMI. The discrepancy between BSA-based methods and flat-fixed doses may impact treatment efficacy and toxicity. Standardizing dosing approaches is important to ensure consistent therapeutic outcomes and patient safety.
Changes in peri-operative chemotherapy and radiation use among patients with resected pancreatic ductal adenocarcinoma (PDAC) between 2004-2021 in the US SEER dataset.
Authors: Alan Su, Flavio G. Rocha, Charles D. Lopez, Jin Yun, Hagen Fritz Kennecke
Journal: Journal of Clinical Oncology (2025)

697 Background: PDAC peri-operative management changed over 20 years. Randomized data supports adjuvant and multiagent chemotherapy (CT), while peri-operative chemoradiotherapy (RT) was used selectively in the US. We examined recent trends in treatment with outcomes in surgically resected PDAC patients. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) 17 dataset, we identified surgically resected primary M0/MX PDAC cases from 2004-2021 over 3-year periods (P1-P6). Neoadjuvant (NCT), adjuvant (ACT), or multiagent (MACT) CT scheduling was included. χ² analysis assessed cohort characteristics over time and multinomial logistic regression assessed odds of CT allocation adjusted by cohort characteristics. Multivariable Cox proportional hazards model assessed treatment-related overall survival (OS) adjusted for cohort characteristics. Results: Among 55,293 cases of M0/MX PDAC, 21,904 (40%) completed surgery. Median age was 66 years; stages were T1/T2/T3/T4 (8.0/25/59/6.0%) and N0/N+ (38/54%). RT use declined (P1:P6, 41%-&gt;18% p&lt;0.001) while CT use increased (P2:P6, 63%-&gt;79%, p&lt;0.001). NACT (P2:P6, 4.1%-&gt;23% p&lt;0.001) and MACT (P2:P6, 1.6%-&gt;20%, p&lt;0.001) use increased while ACT decreased (P2:P6, 58%-&gt;36%, p&lt;0.001). CT is likely to be allocated to young patients (&lt;65yo) with Stage II-III tumors located at the pancreatic head (OR&gt;1.00, p&lt;0.001). Median OS increased over time (P1:P6, 18mo-&gt;32mo, p&lt;0.001). Multivariable analysis shows that Adjuvant RT (HR 0.84 [0.81-0.87], p&lt;0.001) and all CT (NCT: HR 0.71 [0.66-0.77], p&lt;0.001; ACT: HR 0.63 [0.60-0.66], p&lt;0.001; MACT: HR 0.65 [0.60-0.71], p&lt;0.001) improved OS. Conclusions: This study shows decreased RT and increased CT adoption from 2004-2021. Median OS improved over the years, potentially due to peri-operative advances during this study period. Trends in treatment use over 3-year periods. RTN (%) CTN (%) Neo CTN (%) MACTN(%) P1: 2004-2006N=2661 1087 (41) 0 (0) a 0 (0) a 0 (0) a P2: 2007-2009N=3185 1185 (37) 2021 (63) 129 (4.1) 50 (1.6) P3: 2010-2012N=3536 1226 (35) 2460 (70) 267 (7.6) 138 (3.9) P4: 2013-2015N=3947 1210 (31) 2880 (73) 434 (11) 244 (6.2) P5: 2016-2018N=4224 971 (23) 3256 (77) 676 (16) 491 (12) P6: 2019-2021N=4351 787 (18) 3430 (79) 1003 (23) 857 (20) a No cohorts reported chemotherapy use during period 1. RT: Radiation Therapy; CT: Chemotherapy; NCT: Neoadjuvant Chemotherapy; MACT: Multiagent Chemotherapy.
Influence of time to first therapy (TTFT) variable on survival outcomes of neoadjuvant chemotherapy versus upfront surgery approach in resectable pancreatic ductal adenocarcinoma.
Authors: Qusai Almasad, Aryanna Sousa, Paola Pena, Steve Kwon
Journal: Journal of Clinical Oncology (2025)

720 Background: Evidence demonstrating overall survival (OS) benefit of neoadjuvant chemotherapy (NAC) followed by surgical resection over upfront surgical resection for resectable pancreatic ductal adenocarcinoma (PDAC) has been mixed. The time to first therapy (TTFT) variable has not been studied as a contributing factor. Methods: A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T1 and T2 PDACs from 2010 to 2020. Cox proportional hazards model was used to evaluate the impact of NAC followed by definitive surgery compared to upfront surgery on OS with and without TTFT. Results: Total of 43,196 patients were included – 9,880 patients with clinical stage T1 and 33,316 patients with T2 PDACs. There were increasing trends in the NAC approach from 2.9% in 2010 to over 25% by 2020 and decreasing trends in the upfront surgery approach from 69.35% in 2010 to 31.84% by 2020. There were significant differences in TTFT according to the treatment choice with upfront surgery group having a significantly shorter TTFT – proportion of those receiving first treatment within the 1 st week was 24.32% in the upfront surgery compared to 4.22% in the NAC group. In the adjusted cox regression without the TTFT variable, there was a 25% higher rate of death in the upfront surgery compared to the NAC group (HR 1.25, 95% CI 1.19 – 1.30). When the adjusted regression was performed with addition of a TTFT interaction term, there was survival disadvantage of upfront surgery approach in patients whose TTFT occurred after 1 week, but not in those with TTFT occurring in less than 1 week (HR 1.01, 95% CI 0.86 - 1.17). Conclusions: Our study emphasizes the importance of incorporating TTFT variable when comparing NAC versus upfront surgery approach in PDAC. Future studies comparing NAC to upfront surgery in resectable PDAC should consider incorporating the TTFT variable.
The impact of prediabetes on cerebrovascular risk among patients with gastrointestinal malignancies.
Authors: Kanishka Uttam Chandani, Siddharth Pravin Agrawal, Maharshi Raval, Mohamed Ayaan Sait, Apoorva Kondapally, Ahmed Nadeem, Tanuj Sharma, Ambreen Ijaz, Sajid Siddiq, Ashish V. Chintakuntlawar, Kriti Mittal
Journal: Journal of Clinical Oncology (2025)

817 Background: Cancer screening ingastrointestinal (GI) malignancies has translated into an improvement in overall survival due to detection at an earlier stage. The majority of survivors (up to 67%) are over the age of 65. The impact of metabolic profiles on cerebrovascular events amongst this population of cancer survivors is unclear. Methods: Data from the NIS database from 2016 to 2020 were reviewed for patients with seven GI malignancies. Analysis was performed based on the presence or absence of prediabetes using ICD-10 codes. Baseline characteristics, comorbidities, and cerebrovascular outcomes were studied in these 2 cohorts. Results: 1,532,250 hospitalizations of patients with seven GI malignancies, namely colorectal cancer (CRC), pancreatic cancer, hepatocellular carcinoma (HCC), gastric cancer, small intestinal cancer, cholangiocarcinoma, and esophageal cancer, were evaluated and divided into two subgroups: prediabetics (15,610) and non-prediabetics (1,516,640). Prediabetics with GI malignancies as compared to non-prediabetics with GI malignancies were noted to be older (67.7 years vs. 65.64 years), with higher total hospitalization charges (USD 87,267 vs. USD 80,173), greater rates of elective admissions (34.92% vs. 25.89%) but a lower length of stay (6.018 days vs. 6.53 days). Prediabetic patients with GI malignancies were noted to have a higher prevalence of obesity (18.64% vs. 7.69%), dyslipidemia (52.99% vs. 26.16%), and hypertension (49.59% vs. 39.37%). Prediabetics with CRC, as compared to non-prediabetics, had higher adjusted odds ratios (aORs) of occlusion/stenosis of precerebral or cerebral arteries not leading to cerebral infarction, and cerebral infarction, with aORs of 2.03 (95% CI 1.24-3.30, p 0.004), and 1.63 (95% CI 1.01-2.63, p 0.045) respectively. Additionally, prediabetics with pancreatic cancer had a higher aOR of cerebral infarction as compared to non-prediabetics, with aOR of 2.42 (95% CI 1.70-3.44, p&lt;0.001). Conclusions: Prediabetic patients with CRC had higher aORs of cerebral infarction and occlusion/stenosis of precerebral arteries not leading up to cerebral infarction, and prediabetics with pancreatic cancer had twice the risk of cerebral infarction as compared to non-prediabetics. This study highlights the impact of prediabetes, a modifiable risk factor, on cerebrovascular outcomes in patients with GI malignancies.
Clinical outcomes of malignant portal vein thrombosis in patients with pancreatic cancer: A retrospective analysis.
Authors: Rabia Iqbal, Henry Kimball, Supriya Peshin, Maha Zafar, Samridhi Sinha, Ana Colon Ramos, Asmat Ullah
Journal: Journal of Clinical Oncology (2025)

784 Background: Portal vein thrombosis (PVT) includes portal vein blockage with a blood clot. Recently, there has been an increase in the incidence of PVT with solid malignancy. Portal vein thrombosis (PVT) is a potentially high-risk complication associated with pancreatic cancer. A hypercoagulable state is frequently observed in pancreatic cancer, with the incidence of thromboembolic events reported to range between 17% and 57%. We wanted to analyze the prevalence of PVT in patients with pancreatic cancer and its impact on hospital outcomes. Methods: We performed a retrospective analysis using the National Inpatient Sample Database (NIS) from 2018 to 2020. Patients with the primary diagnosis of pancreatic cancer and age &gt;18 were diagnosed using ICD-10 codes. They were then stratified based on the presence of portal vein thrombosis. The Chi-square test was used to analyze categorical variables, and the T-test was used to analyze continuous variables. The confounders were adjusted using multivariate regression analysis. We observed the outcomes on mortality, length of stay, and total hospital charges. Results: A total of 336894 patients were diagnosed with a primary diagnosis of pancreatic cancer. Of them, 0.04% (n=13475 patients) were diagnosed with metastatic portal vein thrombosis. The mean age of the patients was 64 years (p &lt;0.001). Out of them, 47% of patients were female. In comparison, the remaining 53% were male (p-value: 0.5). Almost 71% f the patients were White, 13% were African American and 0.09% were Hispanics (p-value &lt;0.001). The presence of PVT was found to be associated with increased mortality in pancreatic patients (aOR 1.6, p-value &lt;0.001) as compared to those without PVT. It was also associated with an increase in mean length of stay (LOS)(7.1 vs 6 days, p-value 0.009) and total hospital charges ($86,000 vs $73794, p-value &lt;0.001). It was also observed that the presence of PVT was associated with increased odds of secondary outcomes, including venous thromboembolism (p-value &lt;0.001), stroke (p-value 0.5), and acute kidney injury (p-value &lt;0.001). Conclusions: The presence of portal vein thrombosis (PVT) in pancreatic cancer patients is associated with significantly worse hospital outcomes. These findings emphasize the importance of early detection and aggressive management of PVT in this patient population. Comparison of hospital outcomes between pancreatic cancer patients with and without portal vein thrombosis. Hospital Outcomes Pancreatic cancer patients with PVT Pancreatic cancer patients without PVT Adjusted Odds Ratio (aOR) 95% CI P-value Mortality 9.4% (n=1310) 7.2% (n=23300) 1.3 0.3-1.5 &lt;0.001 LOS (Days) 7.1 6.0 1.6 1.1-2.3 0.009 Venous thromboembolism (VTE) 11% (n=1645) 4.2% (n=13734) 2.9 2.5-3.3 &lt;0.001 Stroke 0.03% (n=5) 0.02 (n=79) 1.8 0.2-14 0.5 Acute Kidney Injury 21% (n=2970) 20% (n=68499) 1.2 1.09-1.3 &lt;0.001
Annual incidence of colorectal cancer among patients with average risk in the United States between 2017 and 2023.
Authors: Brad Stieber, Mallik Greene, Quang Anh Le, Joshua Mou, Lakshya Sakthisivabalan, Danielle Lynch, A Burak Ozbay, Joseph LeMaster, Igor Stukalin, Joseph Anderson, Paul J. Limburg
Journal: Journal of Clinical Oncology (2025)

83 Background: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and third most common cancer in the United States. In 2021, 141,902 new cases of CRC were reported. With recent increases in early onset of CRC incidence, a shift in patterns amongst various demographics has been observed. Together with an estimated 60% increase in burden of CRC globally, it is important to continuously assess the nationwide incidence rates and monitor the changing patterns. In this study, we examined the annual incidence rates of CRC in average risk adults using a large national claims database and report patterns of incidence based on various demographic characteristics. Methods: CRC diagnoses were retrospectively identified from a large national claims database, which covers over 165 million lives and is representative of the U.S. population, for each calendar year during the study period from 2017 to 2023. Individuals aged 45 to 75 years, with an average risk of CRC before each index calendar year were included in the study. Individuals were required to be continuously enrolled in the same health plan for at least 1 year prior to and 1 year following the index year. Annual CRC incidence rates per 100,000 people were calculated for each year from 2017 to 2023 within various subgroups based on baseline demographics. Results: Overall, annual CRC incidences remained consistent during the study period with 186.86 (95% CI, 184.87-188.86) cases in 2017 and 183.40 (95% CI, 181.32-185.5) cases in 2023 per 100,000. Among younger adults aged 45-49 years, the annual CRC incidence increased by 66% from 2017 (92.04 cases/100,000) to 2023 (153.12 cases/100,000). Conversely, annual CRC incidence decreased by 25% between 2017 (328.52 cases/100,000) and 2023 (244.93/100,000) in older adults aged 65-75 years. Over the study period, CRC incidence in men was higher than women with an overall rate ratio (RR) of 1.206 (95% CI, 1.122-1.297). African American adults had higher CRC incidence than White Americans with an overall rate ratio (RR) of 1.216 (95% CI, 1.152-1.283). Conclusions: Based on this large study of national claims data, CRC incidence rates remained relatively stable in the total population among average-risk patients from 2017 to 2023. The continuing increase in recommended CRC screening utilization showed a decreased incidence rate in the older population, while observing increased incidences among younger patients.
Impact of intrathecal targeted drug delivery (ITDD) on oral morphine equivalents and pain scores in advanced pancreatic cancer pain.
Authors: Nicole Eye, Tim Metz, Francine Arneson, Heidi Ann McKean
Journal: Journal of Clinical Oncology (2025)

686 Background: Pancreatic cancer accounts for approximately 3% of all cancers and affects ~64,000 adults in the United States each year. Seventy five percent of patients present with abdominal pain, leading to diagnosis. This is one of the most painful cancers, with pain severity strongly correlating to prognosis. Severe intractable abdominal pain negatively impacts quality of life. Traditionally, opioids have been used as the first line agent for the treatment of severe abdominal pain. However, opioids carry significant risk and often unwarranted side effects. With escalating doses to treat refractory pain there is also potential for unintentional overdose. Intrathecal targeted drug delivery (ITDD) provides pain medications directly to the intrathecal space limiting systemic side effects. Our study aimed to determine the impact ITDD has on pain scores as well as the amount of systemic opioid needed in patients with advanced pancreatic cancer. Methods: A retrospective review was conducted on 217 advanced cancer patients that underwent ITDD placement from March 2019 through July 2024. Thirty- five patients with a diagnosis of pancreatic cancer met inclusion criteria. Pain scores and oral morphine equivalent (OME) use was evaluated at baseline (prior to ITDD), at 1 month and 3 months post ITDD implant. A numeric scale of 0-10 was used to determine pain scores, while a comprehensive chart review and patient response was used to determine OME use. Results: We found that post ITDD placement, pain scores were reduced on average by 4.55 points at 1month and 4 points at 3-months after implantation. This was statistically significant with a two-paired t-test analysis (p &lt;0.05). Post ITDD placement, there was a 96.7% reduction in OME at 1-month (p &lt;0.005) and 98.1% reduction in OME at 3 months (p &lt;0.04). Conclusions: Despite the small sample size of patients, ITDD showed a significant reduction in pain scores and OME use compared to baseline with systemic opioid use only in patients with advanced pancreatic cancer. This reduction appeared to be maintained for 3 months post ITDD placement. Further studies conducted on a larger sample size would be beneficial to demonstrate statistical outcomes of ITDD therapy on pain scores and OME use.