tbuckley/cabot-search huggingface dataset:
Pancreatic cancer and diabetes: The effects of race and genes.
Authors: Michael Shu, Katie Moreland, Olugbenga Olanrele Olowokure, Tahir Latif, Adam Rojan, Gregory Wilson, Sameer H. Patel, Jeff Sussman, Syed Ahmad, Jianmin Pan, Shesh Rai, Davendra Sohal
Journal: Journal of Clinical Oncology (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.
A review of comprehensive genomic profiling testing in a Japanese single institution.
Authors: Nozomi Funatsu, Misato Takao, Yusuke Kanemasa, Shinichiro Horiguchi, Daichi Sadato, Yuka Harada, Kazushige Kawai, Tatsuro Yamaguchi
Journal: Journal of Clinical Oncology (2024)

740 Background: In Japan, comprehensive genomic profiling (CGP) testing, including OncoGuide and FoundationOne CDx (F-1), were approved in June 2019 for patients with advanced solid tumors. Here, we report the landscape of CGP testing in our hospital. Methods: This study was conducted with a retrospective design to evaluate the clinico-genomic characteristics of patients who underwent CGP testing. OncoGuide is a panel using matched tumor tissue and blood sample, containing 124 genes, developed by the National Cancer Center. F1 is a tumor-only panel, containing 324 genes, developed by Foundation Medicine Industry. Results: Of the 460 patients enrolled in this study, 376 and 84 underwent F-1 and OncoGuide, respectively. The most common primary tumor was colorectal cancer (93 pts), followed by malignant melanoma (33 pts) and pancreatic cancer (33 pts). Actionable gene alteration was detected in 304 patients (66.1%). The detected actionable genes were TP53 (55.9%), APC (27.8%), KRAS (22.6%), and BRAF (8.5%) in colorectal cancer, BRAF (10.1%), CDKN2A (30.2%), CDKN2B (9.4%), and TERT (33.3%) in malignant melanoma, and KRAS (18.8%), TP53 (54.3%), and CDKN2A (21.8%) in pancreatic cancer. The mean time from sample shipment to result receipt was 42.5 days. As a result of CGP testing, candidate anticancer drugs were found in 304 patients: however, 108 patients were not treated due to poor general condition, complications, or age, which limited access to clinical trials. In germline findings, a pathogenic germline variant of BRCA2 was detected in one patient in OncoGuide, and presumed germline pathogenic variants of MLH1, BRCA2, and PTEN were detected in 1, 13, 26 patients in F-1. Conclusions: In Japan, CGP testing found candidate anticancer drugs, however it requires a significant amount of time to receive treatment because of limiting access to ongoing clinical trials and being typically performed after standard chemotherapy. Therefore, improving access to clinical trials, including determining the timing of testing and selecting appropriate cases, was critical.
Effect of PD-1/ PD-L1 and statin combination therapy on gastrointestinal toxicity related to immune checkpoint inhibitors and on survival.
Authors: Yinghong Wang, Jay Sanjay Shah, Andres Caleb Urias Rivera, Antony Mathew, Anusha Thomas, Mehmet Altan, Dan Zhao
Journal: Journal of Clinical Oncology (2024)

742 Background: Immune Checkpoint Inhibitor (ICI) therapy has greatly expanded its approval to treat a variety of malignancies with high efficacy. Inhibitors of programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are two of the most common classes of ICI therapy. There has been significant research into medications that may have a synergistic effect with ICI therapy, notably statins due to their pro-apoptotic effect. The addition of statins to immunotherapy may also increase the risk of developing certain immune related adverse events (irAEs). We sought to investigate the effect of statin use on the development of gastrointestinal (GI) irAEs and on survival of patients on PD-1/L1 therapy. Methods: We conducted a review of select cancer patients at a tertiary cancer center who received PD-1/L1 inhibitors and statins between 2016 and 2022. The clinical characteristics and overall survival were compared to a control group who received PD-1/L1 inhibitors without statins. Results: A total of 823 patients were included in the statin group and compared to 11101 patients in the control group. In the statin group 707 received a PD-1 inhibitor, 86 received a PD-L1 inhibitor, and 30 received both checkpoint inhibitors. The included cancer types were lung cancer (44%), kidney cancer (26%), head/neck cancer (19%), and GI cancer (7.0%). The overall incidence of GI irAEs in patients receiving statins was 10.8%, which was comparable to patients without statin treatment (11.1%, p=0.83). In addition, statin treatment appeared to be associated with a more favorable survival in patients overall (p= 0.004) and also those with GI irAEs (p=0.047). Conclusions: Synergism between statins and PD-1/L1 inhibitors continues to be a developing field of interest. Our data showed the combination therapy’s survival benefit without exacerbating GI toxicity, which warrants further investigation of this treatment strategy.
Immune-related adverse events in patients with gastrointestinal cancer undergoing pembrolizumab monotherapy: A systematic review of clinical trials.
Authors: Nikolas Naleid, Veronica Mears, Hanna Kakish, Amit Mahipal, Sakti Chakrabarti
Journal: Journal of Clinical Oncology (2024)

744 Background: Pembrolizumab, an immune checkpoint inhibitor targeting programmed death 1 (PD-1), is widely employed in the treatment of various gastrointestinal (GI) cancers. This systematic review aims to assess the spectrum and incidence of immune-related adverse events (irAEs) associated with pembrolizumab monotherapy in GI cancer patients. Methods: A comprehensive search of PubMed/MEDLINE was conducted to identify full-text articles of clinical trials investigating pembrolizumab monotherapy in GI cancer patients. Two independent authors reviewed the articles and extracted data, with discrepancies resolved by consensus. Primary endpoints included the incidence of grade 3 or higher irAEs and the treatment discontinuation rate due to irAEs. Secondary endpoints encompassed the incidence of any-grade irAEs and specific irAEs such as pneumonitis, colitis, hepatitis, myositis, myocarditis, nephritis, pancreatitis, peripheral neuropathy, skin toxicity, endocrine toxicity, infusion reactions, and deaths. Results: After excluding duplicates and articles not meeting inclusion criteria, data extraction and analysis were performed on 25 selected articles. Common reasons for exclusion included concomitant use of chemotherapy or targeted therapy and trials involving non-GI cancer patients. The analysis included 2866 patients with a median age of 62 years, of which 29% were female. Tumor types included colorectal (13%), esophagogastric (46%), hepatocellular carcinoma (25%), and others (16%). The aggregate incidence of grade 3 or higher irAEs was 8.7%, with reported rates ranging from 3% to 41% across different trials. The incidence of any grade irAEs varied from 39% to 98%. The treatment discontinuation rate due to irAEs was 6.8%. The most common grade 3 or higher irAEs were hepatitis (3.6%), pneumonitis (0.8%), and colitis (0.7%). irAE-related deaths were infrequent (0.9%). Detailed irAE data are summarized in the Table. Conclusions: In GI cancer patients receiving pembrolizumab monotherapy, severe irAEs are rare. Treatment discontinuation and deaths attributed to pembrolizumab-related irAEs are infrequent, underscoring the safety profile of this therapy in patients with GI cancer. [Table: see text]
Advanced pancreatic cancer outcomes and the impact of COVID-19 pandemic: The experience of an academic cancer center.
Authors: Christian Adams-Carey, Anna Shepard, Katie Moreland, Olugbenga Olanrele Olowokure, Tahir Latif, Adam Rojan, Jianmin Pan, Shesh Rai, Davendra Sohal
Journal: Journal of Clinical Oncology (2024)

626 Background: The COVID-19 pandemic increased all-cause mortality and disrupted healthcare delivery in the United States. Interruptions in cancer screening and surveillance because of the pandemic resulted in delayed diagnosis, diagnosis at later stages, and worse cancer-related outcomes. However, the effect of COVID-19 on pancreatic cancer outcomes has not been reported. This study aimed to investigate this question. Methods: We studied consecutive patients with unresectable and metastatic pancreatic cancer treated at the University of Cincinnati Cancer Center. Patients were divided into 2 cohorts: from January 2018 to December 2019 (pre-COVID) and from January of 2020 to December of 2021 (during-COVID). Descriptive data on patient characteristics, ECOG performance status (PS), laboratory values, therapies, and mortality were obtained by pre- and during-COVID. The 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 time, the Kaplan-Meier curves were compared between pre- and during-COVID using log rank test. We fitted univariable Cox proportional-hazards model for each interest variable, and the multivariable Cox models, which includes only significant variables. Results: There were 81 and 64 patients in the pre- and during-COVID cohorts, respectively. Patients diagnosed during COVID were more likely to be female, have better PS, have higher proportion of alcohol use, and were more likely to receive 5-FU-based (compared with gemcitabine-based) chemotherapy upfront. There was no overall survival difference between the two cohorts. A Cox proportional hazards model showed that PS at diagnosis, history of chronic pancreatitis, any chemotherapy compared to no chemotherapy, serum albumin prior to initial chemotherapy, and body mass index at time of diagnosis were associated with survival. Conclusions: We observed no difference in overall survival in patients diagnosed with advanced stage pancreatic cancer during the first two years of the COVID-19 pandemic compared with the two prior years. While some differences were observed between patient groups and treatment selection before and during the pandemic, a concerted effort to maintain cancer care appears to have minimized the impact of the pandemic. Further analyses on patients undergoing treatment are being conducted.
Optimising utility of selective internal radiation therapy in metastatic pancreatic adenocarcinoma.
Authors: Prasad Cooray, Vijayaragavan Muralidharan, Manfred Spanger, Patrick Page, Adrian Fox, Sean Mackay, Sue Thang, Lisa Miller, Ashleigh Poh, Caroline Le
Journal: Journal of Clinical Oncology (2024)

622 Background: Selective internal radiation therapy (SIRT) using Yttrium-90 containing microspheres has established benefit for a number of cancers but there is limited data available on the utility of SIRT for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: In this retrospective audit we identified 32 patients who received SIRT using Yttrium-90 microspheres for metastatic PDAC in 2 treatment centres. All patients received SIRT in combination with chemotherapy. Data was analysed from electronic medical records. Results: Thirty two patients with metastatic PDAC who had SIRT were identified. Patients received SIRT (median activity 1.6 GBq) in combination with chemotherapy (platinum-based; n = 23, non-platinum-based; n = 9). Three patients remain alive and 29 patients were included in the survival analysis. For the entire group, the median OS was 15 months (range 4-49), median survival from time of SIRT was 9 months (range 1-48) and median PFS from time of SIRT was 4 months (range 1-25). Median PFS (6 vs 2 months, p=0.0011) and OS (13 vs 4 months, p=0.0004) from SIRT was significantly better when SIRT was given with 1st-line therapy vs with 2nd-line and beyond. Median PFS from SIRT was significantly better (10 vs 2 months, p=0.0020) when combined with 1st line platinum-based chemotherapy (n=14) vs non-platinum based treatment (n=6). 18 month survival was 40% (n=13) with 9/13 patients having had SIRT with 1st line with platinum-based therapy. 24 month survival was 22% (n=7) with 7/7 patients having had SIRT with 1st line with platinum-based therapy. SIRT was well-tolerated with no associated 30-day all-cause mortality. Grade 3 adverse events were liver abscess (7%, n = 2), gastritis (7%, n = 2) and duodenitis (7%, n=2). Conclusions: This is the first report to analyse optimum utility of SIRT with chemotherapy in metastatic PDAC. Our data suggest SIRT in combination with 1st-line platinum agents contribute to the best outcomes in the setting and warrants further study.
Phase Ib adaptive study of dasatinib for the prevention of oxaliplatin-induced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab.
Authors: Anne M. Noonan, Patrick Schnell, Danielle Trunzo, Wendy Thornton, Pannaga G. Malalur, Ashish Manne, Laith I. Abushahin, Shafia Rahman, Ning Jin, John L. Hays, Rifat T. Elkhatib, Arjun Mittra, Sameek Roychowdhury, Maryam B. Lustberg, Alex Sparreboom, Shuiying Hu
Journal: Journal of Clinical Oncology (2024)

745 Background: Neurotoxicity is one of the most significant and disabling side effects of oxaliplatin (OX) and frequently limits the amount of OX that can be used. OX uptake by organic cation transporter 2 (OCT2) into mouse and rat dorsal root ganglia is a prerequisite for OX-induced peripheral neuropathy (OIPN). Preclinical data in rat and mouse models from our group showed that by inhibiting YES1, pre-treatment with dasatinib (D) inactivated OCT2 and prevented acute and chronic OIPN. A phase I trial is ongoing investigating addition of D prior to OX to prevent OIPN. Methods: This was a Bayesian Phase 1b dose-finding study with adaptive dose selection using efficacy-toxicity trade-offs in patients (pts) with GI cancers who are candidates for mFOLFOX6 ± bevacizumab [NCT04164069]. Pts received chemotherapy on day 1 and 15 schedule, every 28 days. D was administered at one of 2 dose levels – 100mg or 140mg PO, given 24 hours and 30 mins prior to OX on C1D14, C1D15 respectively and repeated on C1D28 and C2D1. During cycle 1, pharmacokinetic and pharmacodynamic data was obtained at baseline, during, and up to 24 hours after D or OX administration. Recommended Phase 2 dose (RP2D) was defined as the lowest intermittent dose of D that affects serum biomarkers of OCT2, including methylnicotinamide (NMN) and creatinine, by ≥2-fold without influencing the clearance of oxaliplatin by ≥20%. CIPN20 questionnaire was completed prior to each dose of FOLFOX on screening through to C3D1. Weakly informative Jeffreys priors were used for response and toxicity probabilities, with the latter constrained to be increasing with dose. Results: 13 pts were screened. 5 pts enrolled in cohort 1 (D 100 mg), 2 in cohort 2 (D 140 mg) and 2 in cohort 3 (D 140mg). 6 pts were not evaluable for the efficacy and toxicity endpoints due to screen failure or early study discontinuation. 7 patients were evaluated for efficacy biomarkers and 6 pts were evaluated for both efficacy biomarkers and toxicity. There were no DLTs observed in any cohort. 4/7 pts had ≥2-fold increase in AUC of NMN, and 3/7 pts had ≥2-fold increase in AUC of creatinine. 6/7 pts had ≤20% change in the clearance of OX. Conclusions: Addition of D 100mg or 140mg to traditional FOLFOX regimen was safe and in the majority of pts appeared to alter serum biomarkers of OCT2 in a manner suggesting inhibition of OX uptake in the DRG. 140mg was the chosen RP2D. A randomized phase II study is planned using D to prevent OPIN. Clinical trial information: NCT04164069 . [Table: see text]
Update results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgery: A single arm, multi-center, phase II clinical trial.
Authors: Zheng Wu, Zheng Wang, Lei Zhang, Xiaojing Song
Journal: Journal of Clinical Oncology (2024)

513 Background: High recurrence rate after curative resection significantly compromised the long-term survival of patients with HCC patients (pts). TACE as adjuvant therapy was proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy. However, the prognosis of TACE reminded unsatisfactory and controversial. Therefore, this study aimed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. The update results were reported here with longer follow-up duration. Methods: HCC pts with one of the following high risk factors after hepatectomy: ≥5 cm and &lt;10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II) were recruited. Eligible pts received cTACE treatment within 1-2 months after hepatectomy, on the 3-5th day after cTACE, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: The data cut-off date was March 2023, 29 pts were enrolled and 27 pts received at least once tumor assessment. The median follow-up was 21.8 (IQR, 17.3-26.3) months. Of 27 with assessable efficacy, mDFS was 24.2 (95% CI, not applicable-not applicable) months, with 12-, and 24-month DFS rates of 72.2% (95% CI, 50.4%-85.7), and 61.8% (95% CI, 38.8%-78.3%), respectively. 18 of 27 pts (66.7%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 4 pts (14.8%) included hypertension (7.4%), leukocytopenia (7.4%) and ascites (3.7%). No grade 4 or 5 TRAEs occurred. Conclusions: Anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in large scale clinical trials subsequently. Clinical trial information: NCT04213118 .
In-hospital outcomes of acute pulmonary embolism in patients with gastrointestinal cancer: A nationwide study.
Authors: SAJANA POUDEL, Manoj Ghimire, Kalpana Ghimire, Ayusha Poudel, Karun Shrestha, Prakriti Subedi, Sandesh Karki, Anurag Adhikari, Wendy Tatiana Garzon_Siatoya, Humera Batool, Khaled Elfert, Muhammad Bilal Ibrahim
Journal: Journal of Clinical Oncology (2024)

624 Background: Cancer is a well-established risk factor for the development of pulmonary embolism (PE), especially the. gastrointestinal (GI) cancers. While multiple studies have reported the burden of PE in cancer patients, recent data comparing in-hospital outcomes among different types of cancer patients are lacking. This study aimed to investigate the clinical and healthcare utilization outcomes of hospitalized patients with acute PE in the context of gastrointestinal (GI) cancers. Methods: A cross-sectional study was conducted using data from the National Inpatient Sample (2016-2020). International Statistical Classification of Diseases (ICD-10) codes were employed to identify hospitalized patients admitted with primary diagnosis acute PE. Data regarding GI cancer diagnosis along with demographic information, baseline clinical characteristics, and outcome variables, including mortality, hospital length of stay, total hospital charges, complications and risk factors were collected and analyzed. Statistical analysis was performed using the survey procedures function in STATA v.17, with statistical significance defined by the t-test at a significance level of p &lt; 0.05. Results: Among the 181,060 patients admitted with primary diagnosis of acute pulmonary embolism, 550 (0.3%) had underlying gastric cancer, 1,790 (0.98%) had pancreatic cancer, 875 (0.48%) had hepatobiliary cancer, and 2,600 (1.61%) had small intestine and colorectal cancer. Mortality was found to be significantly higher in all types of GI cancer, with gastric cancer demonstrating the highest mortality rate (10%). After adjusting for age, sex, race, payment category, comorbidities, and risk factors of PE, gastric cancer (OR 2.6; 95% CI: 1.1-6.2) and pancreatic cancer (OR 2.2; 95% CI: 1.4-3.4) were found as independent risk factors for mortality. There was no significant difference in mean length of hospital stays and mean total hospital charges in patients with or without cancer. Similarly, no significant differences were observed in complications such as requirement for mechanical ventilation, arrhythmia, cardiac arrest, need for vasopressor and thrombolysis. Conclusions: In-hospital mortality in patients with acute pulmonary embolism is significantly higher in all types of GI cancer, however; there is no significant differences in hospital length of stay and total hospital charges in patients with or without cancer.