tbuckley/cabot-search huggingface dataset:
Unveiling inequalities: An analysis of treatment disparities of primary gallbladder neuroendocrine tumors by race, ethnicity, and socioeconomic status from the National Cancer Database.
Authors: Aleenah Mohsin, Mohammad Arfat Ganiyani, Shahzaib Ahmad, Vivek Podder, Rohan Garje
Journal: Journal of Clinical Oncology (2024)

e16385 Background: Gallbladder neuroendocrine tumors (NETs) are exceedingly rare tumors and carry a poor prognosis. Racial/ethnic disparities and socioeconomic status have been known to influence cancer treatment and outcomes. This study explores racial/ethnic and socioeconomic disparities in treatment patterns of primary gallbladder NETs, focusing on factors affecting receipt of chemotherapy and multimodal therapy. Methods: We analyzed primary gallbladder NETs patients using the National Cancer Database (NCDB) from 2004 to 2020. Racial groups were divided into White and Black categories, and then those groups were further divided into Hispanic White, non-Hispanic White, Hispanic Black, and non-Hispanic Black categories according to ethnicity. We considered socioeconomic factors, tumor histology, and facility type. Logistic regression was used to determine the odds of receiving chemotherapy and multimodality therapy. The significance of disparities was determined using odds ratio (OR) and p-value. Results: Of 1,195 primary gallbladder NET patients, 59% (708 patients) underwent surgery. These patients had a median age of 65 years, with a female majority (64%) and predominantly White ethnicity (73.6%). Insurance coverage varied, with 48.9% having Medicare and 35.6% private insurance, while 3.9% were uninsured and 8.6% were covered by Medicaid. The study highlighted key factors affecting the receipt of surgery. Notably, racial disparities were apparent, with Black patients less likely to receive surgery compared to White patients (OR: 0.52; P &lt; .001). Furthermore, patients with typical carcinoid tumors were markedly more likely to receive surgery than those with other histology (OR: 10.93; P &lt; .001). The type of treatment facility was influential, with patients in Academic/Research Programs more likely to receive surgery (OR: 0.41; P &lt; .001) than those in Community Cancer Programs. Conclusions: This study highlights racial and socioeconomic disparities in chemotherapy and multimodality therapy for gallbladder NETs, with Black, uninsured, and Medicaid-insured patients less likely to receive treatment. These findings call for targeted policy and healthcare reforms to ensure equitable access and outcomes for all patients with this condition. [Table: see text]
Longitudinal tissue-based evaluation of TIGIT expression in patients with pancreatic cancer: Effect of expression with advancing clinical stages and across racial groups.
Authors: Madison George, Julie Clark, Kailee Hartway, Samuel Zwernik, Kendyll Gartrelle, Daniel Sålas-Escabillas, Daniel Long, Georges Nassif, Thais Pichardo, Allison Wombwell, Hui-Ju Wen, Simone Benitz, Philip A. Philip, Gazala Khan, Rupen A. Shah, Hakmin Park, Howard Crawford, David S. Kwon, Brian Theisen, Nina Steele
Journal: Journal of Clinical Oncology (2024)

e16314 Background: While ground has been gained, pancreatic ductal adenocarcinoma (PDAC) continues to have a low 5-year survival of 13%. This is owed partially to a lack of early detection biomarkers and resistance to standard therapeutic options. TIGIT, an immune checkpoint receptor, is a marker of T-cell exhaustion and plays a key role in the inhibition of anti-tumor immune responses. TIGIT inhibitors are being explored in clinical trials in PDAC. Here we evaluate TIGIT expression in a cohort of PDAC patients and correlate level and intensity of expression with clinical parameters. We also examine changes in expression as the disease progresses from primary to metastatic disease. Methods: We performed RNAscope in situ hybridization (ISH) with a probe specific for human TIGIT mRNA on 82 formalin-fixed paraffin-embedded (FFPE) tissue samples. The cohort of tissue samples included 9 biopsies, 67 primary resections and 6 metastatic lesions. We evaluated the total TIGIT expression (%) as well as the intensity of TIGIT expression (% of cells with 3+ punctae, signifying putative immune cells), and compared these values between samples. Utilizing linear regression for continuous outcomes and logistic regression for binary outcomes, we tested for associations between TIGIT expression and clinical covariates. Results: Staining analysis showed that TIGIT expression did not differ significantly between racial groups. The mean percentage of TIGIT positive cells was 64.0%. High expression of TIGIT was associated with more advanced clinical stage (p &lt; 0.05). Evaluation of three longitudinal samples from the same patient revealed decreased TIGIT expression from the initial biopsy (41.6%) to resection (33.4%) and metastasis (2.8%). In these specimens, 3+ TIGIT expression also declined (2.1%, 1.2% and 0.02%, respectively). Conclusions: Anti-TIGIT therapy has potential to reverse immune suppression and, with other therapeutic modalities, may provide survival benefit. Here we demonstrate that increased TIGIT expression correlates with more advanced stage at diagnosis and also present data demonstrating that overall TIGIT expression, as detected by RNAscope ISH, may decrease as PDAC progresses to metastasis. As such, anti-TIGIT therapy may have important implications for evading an important mechanism of cancer progression.
Tislelizumab with anlotinib and chemotherapy for second-line treatment of pancreatic ductal adenocarcinoma: A pilot study early result.
Authors: Xuyuan Dong, Yinying Wu, Yangwei Fan, Yu Shi, Meichen Wang, Danfeng Dong, Enxiao Li
Journal: Journal of Clinical Oncology (2024)

e16316 Background: Advanced pancreatic ductal adenocarcinoma is a malignant tumor with poor prognosis. At present, chemotherapy is still the standard treatment, however the efficacy is unsatisfied. The lack of second-line treatment options for pancreatic cancer results in progression-free survival often lasting less than 3 months. For pancreatic cancer is an immune desert type of tumor, immunotherapy has not brought breakthrough therapeutic regimen compared to the remarkable data in other tumors.There is still insufficient therapeutic evidence treated with PD1 antibody in pancreatic cancer. Anlotinib is a tyrosine kinase inhibitor (TKI) with anti-tumor effects. It has been shown the combination of PD1 and multi-target tyrosine kinase inhibitors can increase immunotherapy efficacy. The purpose of this study is to evaluate the efficacy and tolerability of Tislelizumab combined with Anlotinib, as well as chemotherapy (the choice of the investigator) in second-line treatment of patients with pancreatic ductal adenocarcinoma. Methods: In this single arm, phase II, prospective exploratory study, it was planned to recruit 30 adult patients with treated pancreatic ductal adenocarcinoma who have never received any PD (L) 1 and TKI. Eligible patients received Tislelizumab (iv, 200mg, Q3W), Anlotinib (PO, 10mg, QD), and chemotherapy (determined by the researchers) till disease progression or death. The primary endpoint was median progression-free survival (mPFS), the secondary endpoints were objective response rate (ORR), median overall survival(mOS), disease control rate (DCR), and treatment safety profile. Results: 14 eligible patients were recruited till Jan 2024, 12 patients with PFS records were included. Median follow-up time was 208 days (104 days-504 days). mPFS was 106 days, OS is not reached, BOR (best of response) was stable disease. The 3-months DCR rate was 58.3%, 6-months DCR rate was 25%. One patient was observed to have a 20% tumor shrinkage after two cycles of treatment and is still being followed up. The most common treatment-related adverse events(TRAEs) was neutropenia with level ≤grade 3, observed in 8/14 patients. The immune-related adverse event of concern was hypothyroidism(grade 1/2), which occurred in two patients. Two patients experienced grade 4 obstructive jaundice caused by the progression of the disease. Conclusions: The second-line combination regimen of Tislelizumab with Anlotinib based on chemotherapy demonstrated survival improvement trend and no new safety signals identified in pancreatic cancer. These data suggest Tislelizumab + Anlotinib+Chemo may be a promising novel treatment option for patients with pancreatic cancer. Clinical trial information: NCT05681390 .
Impact of obesity on immune-related adverse events and tyrosine kinase inhibitor side effects in patients with metastatic renal cell carcinoma (mRCC).
Authors: Malak Alharbi, Muhammad Junaid Tariq, Karan Jatwani, Saby George
Journal: Journal of Clinical Oncology (2024)

4560 Background: A pooled data analysis from clinical trials, including various cancer subtypes, showed that obesity is associated with a heightened incidence of immune-related adverse events (irAEs). However, the heterogeneous patient population across different demographics calls for further investigation into the correlation between obesity and adverse effects from immune checkpoint inhibitors (ICI) in mRCC. Additionally, there is limited available data regarding the association of obesity with tyrosine kinase inhibitors (TKIs) toxicities. We hypothesize that obesity may be linked to an increased rate of irAEs and TKIs toxicities in mRCC patients (pts). Methods: We conducted a retrospective analysis of pts diagnosed with mRCC using TriNetX Research Network (TriNetX LLC., Cambridge, Massachusetts, USA). We searched two cohorts (ICI and TKIs) and toxicities using the ICD-10-CM codes. Pts were categorized into two groups based on body mass index (BMI): obese (BMI ≥30) and non-obese (BMI &gt;19 - &lt; 30). Characteristics of the cohorts were balanced using propensity score matching. Results: A total of 4526 pts with mRCC receiving treatment met the inclusion criteria. 40% of pts were in ICI cohort (n=1811), and 60% (n=2715) in TKI cohort. In the ICI cohort 53% were obese (959/1811), and 47% non-obese (852/1811). Among both cohorts, 50% were male, 30% females, 20% unknown and the average age was 69-72. In TKI cohort, Obese group had 57% (1549/2715) pts while non-obese group included 43% (1166/2715) pts. In ICI cohort, there was no statistically significant difference in risk of developing thyroid dysfunction, liver toxicity, type 1 diabetes, adrenal insufficiency/hypophysitis, skin toxicity, pneumonitis, cardiomyopathy, colitis or myositis/arthropathy between obese and non-obese groups (p&gt;0.05). In TKI cohort, risk of thyroid dysfunction was higher among obese (0.177, n=187/1056) vs non-obese (0.131, n=102/781), p=0.007. Moreover, obese pts had a higher rate of diarrhea compared to non-obese (0.141 vs 0.109, p= 0.017). No significant difference was seen in the rate of developing other toxicities including liver dysfunction, mucositis, cardiovascular toxicities including hypertensive crisis or fatigue. (Table) Conclusions: The use of TKIs has shown an increased risk of developing thyroid dysfunction and diarrhea in obese pts. However, there is no difference in irAE with use of ICI between obese and non-obese pts. Further large studies are needed to support this observation and to study the mechanism by which obesity and metabolic syndromes influence the development of adverse effects. [Table: see text]
Unveiling the nexus: Use of e-frailty index in predicting chemotherapy tolerance in older patients with pancreatic cancer.
Authors: Mohammed Al-Jumayli, Marina Sehovic, Cassandra Vonnes, Martine Extermann
Journal: Journal of Clinical Oncology (2024)

e16315 Background: Pancreatic cancer prevalence is on the rise, particularly among octogenarians—individuals aged 80 years and above. This age group, however, remains notably underrepresented in clinical trials, hindering the applicability of findings to this growing demographic. Methods: We conducted a retrospective study investigating the predictive potential of the E-frailty Index (EFI) in relation to chemotherapy tolerance in octogenarian patients with unresectable/metastatic pancreatic adenocarcinoma. Drawing from EFI's developmental insights in a prior study¹, our cohort comprised 72 octogenarians undergoing chemotherapy. Results: Despite a modest statistical correlation (R = 0.038, p = 0.751), our study revealed a weak, but positive association between EFI and chemotherapy toxicity. Conclusions: Our findings, while subtle, highlight the potential relevance of EFI in predicting chemotherapy outcomes among octogenarians. The non-significant correlation underscores the need for larger-scale, prospective trials to confirm these insights. Inconclusion, This study, rooted in the developmental continuum of EFI, offers a glimpse into its potential significance in predicting chemotherapy tolerance in octogenarian pancreatic cancer patients. The call for prospective trials is evident, especially considering the underrepresentation of this demographic in current research.
Demographic and socioeconomic analysis of patients with glucagonoma: Insights from the National Cancer Database.
Authors: Yaye Fatou Diagne, Sierra Alban, Nisha Reddy, Michael Loomer, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e16319 Background: Glucagonoma is a rare glucagon-producing alpha islet cell tumor primarily of the pancreas, and a type of pancreatic neuroendocrine tumor. These types of cancers have a 10-year survival rate of about 38%. Metastasis may be found in approximately 50% of glucagonoma cases. As a result of the low incidence of glucagonoma, analysis of the diagnostic patterns may provide more insight into the disease’s epidemiology. This study analyzed the National Cancer Database (NCDB) to examine demographic factors of individuals diagnosed with glucagonoma. Methods: ICD-8152-3 Data from the NCDB between 2004-2020 was gathered to perform a retrospective cohort analysis on patients diagnosed with glucagonoma (N = 88). Descriptive statistics were used to investigate demographic factors such as age, sex, race, Hispanic status, years of education, insurance, facility type, distance from facility, and Charlson-Deyo score. Regression analysis was utilized to evaluate incidence trends. Results: We found that patients had an average age of 61 years (SD = 13, range = 23-90), with an average tumor size of 53 mm (SD = 39, range = 12-140), and the majority were male (61%) and White (90%). The majority of patients (97%) did not receive palliative care, with surgery (57%) and chemotherapy (28%) being the primary treatments. Post-surgery, 90% had no residual tumor, and survival rates were 98% after thirty days and 96% after ninety days. Most were treated in academic/research facilities (43%) and had private insurance (59%) or Medicare (34%). The largest median household income quartile of these patients was $74,063 or more (39%).The study noted a 2-year survival rate of 74%, a 5-year rate of 54%, and a 10-year rate of 31%, with a mean survival of 89.3 months. The primary disease sites were the tail of the pancreas (32%) and pancreas, NOS (22%). The distribution across NCDB Analytic Stage Groups was 19% for Stage I, 11% for Stage II, 2% for Stage III, and 23% for Stage IV. Conclusions: This study represents the first analysis of glucagonoma patients using the National Cancer Database, filling a gap in our understanding of the disease. The findings indicate that the majority of glucagonoma patients were non-Hispanic, White, and had tumors primarily located in the tail of the pancreas, aligning with earlier case report descriptions. Socioeconomically, patients most likely had earnings above the median income quartile, resided in densely populated metropolitan areas, and received treatment in academic facilities. Further investigation is necessary to have a more thorough grasp of the impact of demographic and socioeconomic characteristics on glucagonoma patients' diagnosis, course of treatment, and overall survival rates.
Anatomical and demographic prognosticators of pancreatic cancer.
Authors: Krishna Desai, Kristal Pereira, Sivaguha Yadunath Prabhakaran, Hassan Ali, Yu Yu Thar, Eugene Choi, Rajesh Thirumaran
Journal: Journal of Clinical Oncology (2024)

e16310 Background: Pancreatic cancer is known to have one of the poorest median of survival (mOS) of all cancers. It is now the third leading cause of cancer-related mortality after lung &amp; colorectal cancer. With the current trends, understanding &amp; knowing prognosticators can aid in determining outcomes of pancreatic cancer. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted pancreatic cancer cases based on primary site encoding for head, body &amp; tail of pancreas, Islets of Langerhans (IoL), other specified parts &amp; overlapping lesion of pancreas, pancreas, NOS (no other specific). The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 221,304 cases were extracted between 2000-2020. The median age of diagnosis was 71 years. 50.54% were males, &amp; 49.45% were females. The incidence rates are shown below. Whites (69.99%) were commonly affected, followed by Blacks (11.05%), Hispanics (10.79%), Asians &amp; Pacific islanders (7.41%), Alaskan natives &amp; American-Indians (0.57%). A distribution in anatomy was notable for head of the pancreas (46.00%), followed by tail (13.20%), body (11.34%), pancreatic duct (0.49%), IoL (0.10%). A survival curves were compared on different variables. Gender showed no statistical difference. mOS for patients diagnosed &gt;70 years was 3 months &amp; &lt;70 years was 8 months (p value &lt;0.0001, CI 0.3716 to 0.3784, HR 1.731). mOS for calculated for Whites (5), Blacks (4), Asian &amp; Pacific islanders (6), Alaskan natives &amp; American-Indians (4), &amp; hispanics (5) (p value &lt;0.0001). mOS based on involved parts of pancreas were compared for: head (6), body (6), tail (5), pancreatic duct (8), IoL (59) (p &lt;0.0001). Conclusions: Median age of diagnosis was in 71, with a slight male predilection. Overall incidence rate is trending up. It is significantly higher for males, &amp; is significantly lower for females than that of the general population. Whites are most commonly affected, &amp; Alaskan natives &amp; American natives are rarely affected. Survival is significantly greater if diagnosed &lt;70 years. Most common site involved is the head of pancreas, &amp; the least is IoL. mOS is ~10 times greater for IoL, but it's an endocrine pancreatic cancer which is treated differently. From the exocrine pancreas, survival is the best for pancreatic duct cancer, &amp; the worst for pancreatic duct. If anatomic &amp; demographic prognosticators are combined with molecular, radiologic factors, it can be beneficial in predicting the outcomes of this cancer with poor prognosis. [Table: see text]
A preliminary enrichment analysis of tumor genes in patients suffering from rectal cancer with and without CNS metastasis.
Authors: Andrew Polyak, Michelle Cholankeril
Journal: Journal of Clinical Oncology (2024)

e16381 Background: Colorectal cancers have been touted as the third most common cancer and the third leading cause of cancer death worldwide. Of these, rectal cancers often have a more favorable outcome, and are generally responsive to chemotherapy and radiation, due to metastasis limited to local tissues via lymphatics. However, in recent years, cases of rectal cancer with distant metastasis to the CNS have been noted at an urban community hospital serving a primarily Hispanic population in central New Jersey. Methods: We used genetic data from 51 patients at our local cancer center over 5 years to delineate risk factors associated with CNS metastasis. Of these patients, two had CNS metastasis with available tumor genetic information. We performed a gene enrichment analysis to determine phenotypic terms and molecular pathways associated with each gene set using Enrichr. Results: Of 51 patients, genetic data was available on 20, of which 18 had rectal cancer without CNS metastasis. Mutations involving 23 genes were found in this cohort, analysis of which found enrichment of the terms “Lynch Syndrome” and “Constitutional mismatch repair deficiency syndrome”, which are classically implicated in CRCs. In addition, enrichment of the terms “rectal cancer childhood”, “colorectal cancer childhood”, and “Familial colorectal cancer” were found. Of the two patients who had metastasis to the CNS, mutations involving 14 genes were found. Interestingly, both patients had mutations involving KRAS. Analysis of these genes found enrichment of the terms “pilomyxoid astrocytoma”, “giant cell glioblastoma” and “gliosarcoma”. Interestingly, common to both cohorts were the classic CRC-associated genes KRAS, APC and TP53, further solidifying their role in general CRCs. Conclusions: While this study is ongoing, preliminary data suggest that genetic analysis of tumors in patients with rectal cancer can determine whether a patient is susceptible to CNS metastasis. Given the heterogeneity of these cancers, further studies involving tumor and germ-line genetic analysis, which follow patients longitudinally may benefit in predicting which tumors are prone to CNS metastasis before they metastasize.