tbuckley/cabot-search huggingface dataset:
Phase I study of ProAgio, an αvβ3 integrin cytotoxin, in patients with previously treated advanced pancreatic cancer and other solid tumors.
Authors: Nebojsa Skorupan, Keith Thomas Schmidt, Eve Koehler, Min-Jung Lee, Seth M. Steinberg, William Douglas Figg, Zhi-Ren Liu, Christine Alewine
Journal: Journal of Clinical Oncology (2024)

e16336 Background: The limited clinical benefit of combination chemotherapy in patients with advanced pancreatic cancer is in part attributed to the tumor’s dense, hypoxic stroma that is largely composed of extracellular matrix, cancer-associated fibroblasts (CAFs), and myeloid cells. ProAgio is a pegylated peptide drug that targets and kills cells expressing integrin αvβ3, such as CAFs and endothelial cells. Preclinical activity of ProAgio was demonstrated in murine pancreatic cancer models. Here we describe the dose escalation arm of the first-in-human Phase 1 trial of ProAgio in patients with advanced solid malignancies, including pancreatic cancer. Methods: The dose escalation arm of this single institution study of ProAgio monotherapy enrolled adults with previously treated, histologically confirmed advanced solid tumors for which no curative therapy exists. Participants were required to have evaluable disease. The primary objective was to determine the recommended Phase 2 dose (RP2D) of ProAgio. Secondary objectives assessed the safety (CTCAE v. 4.03), pharmacokinetics, and objective response rate. ProAgio was administered as an intravenous infusion every 1-2 weeks depending on the dose level. Response was determined by serial imaging (CT or MRI) or serum tumor marker assessment. Results: Twenty-eight participants (26 with pancreatic adenocarcinoma and 2 with other gastrointestinal malignancies) were treated as of January 30, 2024, completing enrollment to all 6 planned dose levels. ProAgio has been remarkably well tolerated with only transient grade 1 or 2 treatment-related adverse events observed in most participants. Two participants had grade 2 infusion related reaction but were able to continue treatment with increased dose of diphenhydramine pre-medication. Isolated serious adverse events of hyperglycemia, acute kidney injury, or anemia (all grade 3) considered at least possibly related to ProAgio were observed in 3 separate participants. Five participants with pancreatic cancer receiving weekly dosing of ProAgio had stable disease, 2 of which had interval stabilization in CA 19-9 tumor markers. RP2D determination is pending completion of pharmacokinetic analyses. Conclusions: ProAgio is safe and well-tolerated at all dose levels. A dose expansion phase of 15 participants will begin enrolling once RP2D is determined. Clinical trial information: NCT05085548 .
Factors associated with the receipt of palliative care in Native American patients with hepatocellular carcinoma: A retrospective analysis.
Authors: Lauren Dentinger, Sowmya Prathika Kolluru, Christopher Reese Bine, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

e16202 Background: Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related deaths in the United States. This primary liver malignancy often has a poor prognosis and commonly metastasizes to the lungs, lymph nodes, bones, and adrenal glands. HCC has a high burden of disease with many patients suffering from discomfort and pain related to the disease and its treatment. Palliative care is a unique form of specialized care that provides relief, increasing comfort, and quality of life to patients suffering from illness. Many studies note its effectiveness in helping patients at any point in their illness. Furthermore, recent studies have shown that Native Americans face barriers to receiving palliative and end of life care. Thus, this study aims to examine the factors associated with receipt of palliative care within Native American HCC patients. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 28 and statistical significance was set at α = 0.05. Results: Out of 1536 Native American patients with HCC, 92 (5.9%) received palliative care. Patients who received palliative care experienced shorter mean survival than those who did not receive palliative care (15 vs 42 months; p &lt; 0.001). After controlling for age, year of diagnosis, surgical status and adjuvant therapies, not receiving palliative care was associated with an independent decrease in hazard (HR = 0.625, p &lt; 0.05). Palliative care patients were more likely to present with stage III and IV HCC, experience a longer delay in receiving treatment (69 vs 48 days) and have bone and lung metastasis when compared to those who did not receive palliative care (p &lt; 0.05). Patients who did not receive palliative care were more likely to have Medicare or Medicaid for insurance (p &lt; 0.05). There were no significant differences in the age, income bracket, facility type, tumor size or time to surgery between the patients who received palliative care and those who did not. Conclusions: This study found that patients with HCC are more likely to utilize palliative care if they have severe disease that metastasized to other organ systems. There is a higher mortality among patients who receive palliative care most likely because they had more severe disease. This research demonstrates the common trend of HCC patients underutilizing palliative care in the early stages of disease. Exploring the impacts early palliative care can have on HCC patients’ survival and quality of life would be valuable future areas of research.
Adjuvant tislelizumab combined with capecitabine for patients with biliary tract cancer with high risk of postoperative relapse (ACTIVE): Primary analysis from a prospective cohort study.
Authors: Luyu Yang, Lu Lu, Xiangyu Wang, Haoting Sun, Ying Zhu, Da Xu, Jimeng Yang, Baobing Yin, Xin Yang, Wenwei Zhu, Huliang Jia, Jinhong Chen, Lunxiu Qin
Journal: Journal of Clinical Oncology (2024)

e16248 Background: Only 20% of biliary tract cancer (BTC) patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. This rate is even lower in patients with high-risk features. Capecitabine as an adjuvant therapy in biliary tract cancer has been verified to improve overall survival, however, the efficacy still remains limited. PD-1/L1 antibody combined with chemotherapy have been demonstrated to improve survival in advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of adjuvant tislelizumab and capecitabine following surgery for biliary tract cancer with high risk of recurrence. Methods: This was a single-center, prospective cohort phase II study. BTC patients (pts) underwent R0/R1 resection with high postoperative recurrence risk were eligible. The high-risk factors included positive resection margins, positive lymph nodes, positive perineural invasion, and tumor &gt; 5cm in diameter. The patients were divided into two groups, the tislelizumab (TIS 200 mg Q3W for 1 year )+capecitabine (CAP D1-14, 1500mg/m 2 for eight 3-weekly cycles) group and the capecitabine group. The primary endpoint was DFS (disease free survival). The second endpoints was OS (overall survival) and adverse event (AE). Results: A total of 37 pts were enrolled into the study, while 22 pts in the TIS+CAP group and 15 in CAP group, 23 males and 14 females with a median age of 66 years. According to the location of the tumor, 37.8% pts were intrahepatic cholangiocarcinoma, 21.6% were gallbladder cancer, 5.4% were distal cholangiocarcinoma and 35.1% were hilar cholangiocarcinoma. The median DFS was 16.2 months (95% CI, 8.1-26.2) in the TIS+CAP group, which was longer than CAP group (11.4 months, 95% CI 4.2-27.1). 12-month RFS rates were 56.5% and 36.6% , respectively. The most common adverse events (AEs, any grade) were rash (18.2%), vomiting (13.6%), neutropenia (13.6%) and anorexia (13.6%) in the TIS+CAP group. Conclusions: Tislelizumab in combination with capecitabine were effective and safe as adjuvant therapy, which can prolong the DFS of BTC patients with high recurrence risk after resection. Clinical trial information: NCT04782804 .
Second-line (2L) treatment patterns and clinical outcomes among real-world (RW) patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with FOLFIRINOX (FFX) or gemcitabine + nab-paclitaxel (GnP) in the first-line (1L).
Authors: Ravi Kumar Paluri, Michelle Silver, Paul Cockrum, Syvart Dennen
Journal: Journal of Clinical Oncology (2024)

e16322 Background: FFX and GnP are the most common 1L treatments for pts with mPDAC. Approximately half of pts treated with these regimens continue to 2L, though optimal 2L treatment is unclear. We identified a RW sample of mPDAC pts treated with 1L FFX or GnP and assessed their 2L treatment patterns, duration of therapy (DoT), overall survival (OS), and time to next treatment (TTNT). 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 1L treatment with FFX or GnP ≤90 days from metastatic diagnosis date were included. To observe 2L treatment patterns, pts were required to have ≥1 year of follow-up unless death occurred first. Pts were censored at date of last activity absent death. Kaplan-Meier analyses were used to assess the median OS and TTNT from the start of 1L. Pts were grouped into five treatment categories: 1L FFX-only, 1L FFX + 2L GnP, 1L FFX + 2L other, 1L GnP-only, and 1L GnP + any 2L. Pts with 2L treatments were not restricted by whether they received 3L therapy or later. Results: 936 1L GnP and 712 1L FFX pts met the study inclusion criteria. 572 (61%) 1L GnP pts received 1L GnP-only and 364 (39%) received 1L GnP + any 2L (“any 2L” included 78 Nal-IRI, 59 FOLFOX, 57 FFX pts, and 170 pts with various combinations of chemotherapies and/or targeted therapies, with &lt; 50 pts per regimen). 300 (42%) 1L FFX pts received 1L FFX-only, 287 (40%) received 1L FFX + 2L GnP, and 125 (18%) received 1L FFX + 2L other (“2L other” included 35 capecitabine monotherapy pts, 27 G monotherapy pts, all other regimens &lt; 20 pts). Pts with 1L FFX were younger, slightly more likely to be male, and had slightly better ECOG scores than 1L GnP pts. Median 1L DoT was shorter for 1L-only pts compared to pts with 2L therapies. Median OS was shortest for 1L-only pts and longest for 1L FFX + 2L other. Median OS was similar for 1L FFX + 2L GnP and 1L GnP + any 2L. Median TTNT was similar across treatment categories with a 2L. Conclusions: In a RW sample of mPDAC pts, those with 1L-only had poor survival. Pts with 1L FFX + 2L GnP had a similar survival to 1L GnP + any 2L. [Table: see text]
Inpatient mortality outcomes of patients with hepatocellular carcinoma with congestive heart failure: A nationwide retrospective cohort study.
Authors: Benjamin Olufemi Adegbite
Journal: Journal of Clinical Oncology (2024)

e16256 Background: Chronic conditions create challenges in improving outcomes and treatment strategies for cancer patients. In the general population, for example, congestive heart failure (CHF) has been associated with poor cardiovascular health and thus increased mortality. However, its prognostic implications in patients with hepatocellular carcinoma (HCC) are less clear despite the physiological connection of the cardiohepatic system. This study aims to elucidate the relationship between CHF and mortality among HCC patients, offering insights that could inform clinical management strategies and improve care. Methods: The 2017 – 2019 versions of the National Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP) were used to acquire the sample population. ICD-10 codes were used to identify diagnoses and procedures. The main sample population consisted of all patients diagnosed with HCC. A multivariate regression model was used (adjusted for age, sex, race, median household income based on patient ZIP code, Charleston Comorbidity Index score, hospital region, hospital teaching status based on rural/urban setting) to calculate the adjusted odds ratio (aOR) for outcomes. First, the association between CHF and inpatient outcomes was examined. Then mortality was calculated for HCC patients receiving therapeutic interventions (chemoradiation, liver transplant, radiation, or immunotherapy) based on CHF status. Results: There were 29,396 patients with HCC. Of this amount, 3,810 patients (13%) had CHF diagnoses. For inpatient procedures, 1,120 patients (3.8%) underwent a liver transplant, 265 (0.9%) received chemotherapy, 2 (0.01%) received immunotherapy, and 5 (0.02%) received radiation therapy. The cohort of CHF patients was found to be older than non-CHF patients (70.2 ± 0.3 years and 64.3 ± 0.2 years, respectively, with p &lt; 0.001). The multivariate regression analysis for the entire sample showed that the adjusted odds of mortality for HCC patients with CHF was 0.92 times that of not having CHF but not significant (95% CI 0.8 – 1.07, p = 0.3). The analysis was then applied to HCC patients receiving one of the four treatments during their hospitalization. Results showed that the CHF cohorts had increased odds of mortality if they received a liver transplant (aOR 20.3, 95% CI 2.5 – 165.7; p = 0.005) or chemotherapy (aOR 338.4, 95% CI 10.0 – 11428.9; p = 0.001). Conclusions: Having CHF is not a significant predictor of mortality in patients with HCC. However, when considering HCC patients undergoing liver transplantation, having comorbid CHF significantly carried about a 20-fold odds in mortality. In addition, HCC patients receiving chemotherapy had a 338-fold odds of death if they have CHF. Thus, careful consideration and planning must be taken into account to optimize patients’ cardiac status when considering treatment options.
Impact of preoperative frailty on outcomes of hepatic resection among elderly patients with hepatocellular carcinoma: A comprehensive multicenter cohort study.
Authors: Li Dan, Yong-Kang Diao, Nanya Wang, Yi-Fan Yang, Wei-Min Gu, Ting-Hao Chen, Jie Li, Hong Wang, Ya-Hao Zhou, Xian-Ming Wang, Yong-Yi Zeng, Timothy M. Pawlik, Zhong-Qi Fan, Wan Yee Lau, Feng Shen, Guo-Yue Lv, Tian Yang
Journal: Journal of Clinical Oncology (2024)

e16254 Background: With the increasing prevalence of hepatic resection for hepatocellular carcinoma (HCC) in the elderly, understanding the impact of preoperative frailty on surgical outcomes is crucial. This multicenter cohort study investigates the association between frailty and both short- and long-term outcomes post-hepatic resection in elderly HCC patients. Methods: This multicenter study involved elderly HCC patients (≥ 70 years) undergoing curative-intent resection at 10 hospitals in China from 2012 to 2021. Frailty was assessed using the Clinical Frailty Scale (CFS), with a score of ≥5 indicating frailty. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS), while secondary outcomes included postoperative 30-day morbidity and mortality, and 90-day mortality. Comparisons were made between patients with and without preoperative frailty. Results: Out of 488 elderly patients, 148 (30.3%) were classified as frail. Frail patients had significantly higher rates of 30-day morbidity (68.9% vs. 43.2%), 30-day mortality (4.1% vs. 0.6%), and 90-day mortality (6.1% vs. 0.9%) compared to non-frail patients (all P &lt; 0.05). Over a median follow-up of 37.7 months, frail patients showed markedly lower median OS (41.6 months [95% CI, 32.0-51.2] vs. 69.7 months [55.6-83.8]) and RFS (27.6 months [23.1-32.1] vs. 42.7 months [34.6-50.8]) than non-frail patients (both P &lt; 0.01). Multivariable Cox regression analysis identified frailty as an independent risk factor for decreased OS (HR 1.61, P = 0.001) and RFS (HR 1.32, P = 0.028). Conclusions: Preoperative frailty is significantly associated with worse short-term and long-term outcomes following hepatic resection in elderly HCC patients. These findings underscore the importance of incorporating frailty assessment into the perioperative and postoperative care of elderly patients undergoing HCC resection.
Impact of personalized peptide neoantigen vaccines on immunologic responses in patients with pancreatic cancer.
Authors: Landian Hu, Yuchao Zhang, Xiangyin Kong, Zhenchuan Wu, Hailong Wang
Journal: Journal of Clinical Oncology (2024)

e16351 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer that often resists conventional therapies. One of the most promising alternative treatments is personalized neoantigen vaccines that target specific mutations in each patient’s tumor. These vaccines aim to activate the immune system to fight cancer cells. However, how this type of vaccine affects immune cells across different vaccination phases is poorly understood. Methods: Here we report the safety and dynamic immunological responses of peptide-based vaccines after chemotherapy in patients with resected PDAC in a single-center open-label phase 1b trial (registered at ClinicalTrials.gov [NCT03558945]). The primary endpoint was safety, assessed by the incidence of adverse events in all vaccinated patients. The key secondary endpoints included prognosis assessed by recurrence-free survival and overall survival rate. Results: We observed only 3 grade ≥3 adverse events in 2 patients (12.5%) and no grade ≥4 events. Vaccinated patients achieved favorable survival outcomes, with a 3-year recurrence-free survival rate of 56% and a 3-year overall survival rate of 74%. Using single-cell sequencing, we revealed the dynamics of vaccine-induced immune responses, with CD8 + cytotoxic T cells expanding at the priming phase and CD4 + T cells at the boosting phase. The CD8 + cytotoxic T cells had a higher proportion (average, 38.4%) of persistent expansion than the CD4 + T cells (average, 3.7%), with a range of 2.8~21.8 months duration. We also discovered a helper B-cell subtype that interacted with T cells and was associated with prognosis, suggesting a role for B-cell epitopes in vaccine effectiveness. Conclusions: These results provide valuable insights for optimizing peptide-based neoantigen vaccine design, regimen, and evaluation strategies. Clinical trial information: NCT03558945 .
Prognoses Associated With Palliative Performance Scale Scores in Modern Palliative Care Practice
Authors: Kara E. Bischoff, Kanan Patel, W. John Boscardin, David L. O’Riordan, Steven Z. Pantilat, Alexander K. Smith
Journal: JAMA Network Open (2024)

Importance The Palliative Performance Scale (PPS) is one of the most widely used prognostic tools for patients with serious illness. However, current prognostic estimates associated with PPS scores are based on data that are over a decade old. Objective To generate updated prognostic estimates by PPS score, care setting, and illness category, and examine how well PPS predicts short- and longer-term survival. Design, Setting, and Participants This prognostic study was conducted at a large academic medical center with robust inpatient and outpatient palliative care practices using electronic health record data linked with data from California Vital Records. Eligible participants included patients who received a palliative care consultation between January 1, 2018, and December 31, 2020. Data analysis was conducted from November 2022 to February 2024. Exposure Palliative care consultation with a PPS score documented. Main Outcomes and Measures The primary outcomes were predicted 1-, 6-, and 12-month mortality and median survival of patients by PPS score in the inpatient and outpatient settings, and performance of the PPS across a range of survival times. In subgroup analyses, mortality risk by PPS score was estimated in patients with cancer vs noncancer illnesses and those seen in-person vs by video telemedicine in the outpatient setting. Results Overall, 4779 patients (mean [SD] age, 63.5 [14.8] years; 2437 female [51.0%] and 2342 male [49.0%]) had a palliative care consultation with a PPS score documented. Of these patients, 2276 were seen in the inpatient setting and 3080 were seen in the outpatient setting. In both the inpatient and outpatient settings, 1-, 6-, and 12-month mortality were higher and median survival was shorter for patients with lower PPS scores. Prognostic estimates associated with PPS scores were substantially longer (2.3- to 11.7-fold) than previous estimates commonly used by clinicians. The PPS had good ability to discriminate between patients who lived and those who died in the inpatient setting (integrated time-dependent area under the curve [iAUC], 0.74) but its discriminative ability was lower in the outpatient setting (iAUC, 0.67). The PPS better predicted 1-month survival than longer-term survival. Mortality rates were higher for patients with cancer than other serious illnesses at most PPS levels. Conclusions and Relevance In this prognostic study, prognostic estimates associated with PPS scores were substantially longer than previous estimates commonly used by clinicians. Based on these findings, an online calculator was updated to assist clinicians in reaching prognostic estimates that are more consistent with modern palliative care practice and specific to the patient’s setting and diagnosis group.
Clinicopathologic and treatment characteristics of mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC).
Authors: Muhammet Ozer, Suleyman Yasin Goksu, Ilyas Sahin
Journal: Journal of Clinical Oncology (2024)

e16218 Background: Mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC) represents a rare subtype of primary hepatic malignancy demonstrating morphological and biological features characteristic of both Hepatocellular Carcinoma (HCC) and Intrahepatic Cholangiocarcinoma (ICC). In this study, we describe the clinical and tumor characteristics of survival in HCC-ICC by using a large cohort. Methods: We selected patients diagnosed with HCC‐ICC, HCC, or ICC between 2011 and 2018 and were identified from the National Cancer Data Base (NCDB) using the International Classification of Diseases for Oncology codes. Baseline characteristics were delineated using percentages. Median overall survival (OS) was calculated using the Kaplan-Meier method. Demographic variables (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment features were included. Short‐ and long‐term outcomes were evaluated through univariate analysis. Results: Out of 124,723 patients, 84.6% were diagnosed with HCC, 14.5% with ICC, and 1% with HCC‐ICC. Median survival was significantly better in HCC compared to HCC-ICC and ICC patients (16.2 months, 10.8 months, and 9.4 months, respectively, p &lt; 0.001). Surgical intervention was used by 26.3% of HCC-ICC cases, 19.2% of ICC cases, and 9% of HCC cases. Multiagent chemotherapy was notably more utilized in ICC compared to HCC-ICC and HCC (42.6%, 22.8%, and 5.4%, respectively, p &lt; 0.001). Meanwhile, single-agent chemotherapy was more commonly administered in HCC than in HCC-ICC and ICC (32.3%, 16.5%, and 11.4%, respectively, p &lt; 0.001). Conclusions: HCC-ICC is an aggressive primary liver malignancy with a worse prognosis than HCC and ICC. The primary treatment approach for operable cases continues to be major hepatectomy combined with resection of hilar lymph nodes. Further research is urgently needed to better understand the exact role of the systemic therapies in managing HCC-ICC.