bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of PD-1 inhibition on macrophage population in human tissue cultures.
Authors: Hoang Ngoc , Welling Charlotte , Husstegge Marlon , Koerfer Justus , Monecke Astrid , Weimann Arved , Gockel Ines , Lordick Florian , Kallendrusch Sonja 
Published: January 2023

463 Background: Moderate response rates of PD-1 inhibition in gastric and esophagogastric junction cancers (GC/EGJC) urge for reliable biomarkers. To further improve treatment outcomes, patients need targeted therapy based on clinically relevant biomarkers and predictive test systems for assessing individual drug susceptibility. We have previously established patient derived tissue cultures (PDTC) as a comprehensive ex-vivo drug testing system for GC/EGJC patients. Methods: The standardized PDTC) model was developed using tissue from surgical resection specimens to investigate response to the PD-1 inhibitor Nivolumab and the macrophage depriving bisphosphonates clodronate and zoledronic acid. Resident macrophage population (CD68, CD163), tumor proliferation (Ki67) and apoptosis (cPARP), as well as bulk gene expression data (nanoString technology) were analysed after 72 hours of PD-1 inhibition. Additionally, supernatants were collected, and cytokine concentrations are measured based on Luminex technology. Results: Macrophage depletion could lead to enhanced anti-tumoral effects in PDTCs after PD-1 inhibition. Gene signatures for Interferon γ-mediated inflammation and myeloid cell activity were identified and found to be relevant indicators for tissue response upon immune checkpoint inhibition. We observed alterations in cytokine and soluble surface marker concentrations, such as IL-8, IL-17A and IL-23 or PD-L2, LAG3 and CTLA4. Conclusions: Yielding an organotypic cell composition, we were able to demonstrate individual response patterns and immunological characteristics to identify responsiveness to PD-1 inhibition in GC and EGJC tissue. PDTCs are potent to define biological marker sets ex vivo and to differentiate and predict clinical patient response as well as their inherent immune cell capacity and plasticity.
Effect of temperature on gastro-esophageal cancer outcomes: A SEER study.
Authors: Gupta Kush , Gupta Ashish , George Anthony , Attwood Kristopher , Gandhi Shipra , Siromoni Beas , Mukherjee Sarbajit 
Published: January 2023

467 Background: Cold stress suppresses antitumor response in animal models, leading to tumor growth . Recent studies have also shown a negative correlation between the average annual temperature (AAT) and cancer incidence. We hypothesized that esophageal cancer (EC) and gastric cancer (GC) patients living in warmer climates have improved overall (OS) and disease-specific survival (DSS) than those living in colder climates. Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database from 1996 to 2015. AAT at the county level was calculated based on the National Centers for Environmental Information. Cox multivariate regression models were performed to measure the association between temperature (measured continuously at diagnosis and in 5-degree increments) and OS/DSS, adjusting for variables. All associations were compared at a significance level of 0.05. The OS and DSS were summarized using Kaplan-Meier methods. All statistics were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC). Results: A total of 17,408 EC patients were analyzed. The average age of the cohort was 65 years, 79% of which were male and 21% were female. Of them, 61.6% had adenocarcinoma, and 37.6% were squamous. After adjusting for covariates, patients in regions with AAT >53.5°F had an 11% improvement in OS [HR 0.89 (95% CI 0.86-0.92), p<0.0001] and 12% in DSS [HR 0.88 (95% CI 0.85-0.91), p<0.0001]. When the temperature was analyzed in 5°F increments, with each increment, there was a 3% improvement in OS [HR 0.97 (95% CI 0.96-0.98), p<0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95-0.97), p<0.0001]. Subgroup analysis of squamous and adenocarcinoma showed similar results. These findings were validated in 20,553 GC patients. After adjusting for covariates, patients in regions with AAT >53.5 had a 12% improvement in OS [HR 0.88 (95% CI 0.85-0.90), p<0.0001] and 14% in DSS [HR 0.86 (95% CI 0.83-0.89), p<0.0001]. When analyzed in 5°F increments, with each increment, there was a 4% improvement in OS [HR 0.96 (95% CI 0.95-0.97), p<0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95 - 0.97), p<.0001]. Conclusions: We showed for the first time that higher environmental temperatures are associated with significant improvements in OS and DSS in patients with gastro-esophageal cancer. Further confirmatory and mechanistic studies are required to implement specific interventional strategies.[Table: see text]
The role of primary tumor resection in synchronous stage IV colorectal cancer: Subgroup analysis.
Authors: An Hojung , Shin Ji Eun , Shim Byoung Yong , Kim Hyunho , Park Hyung Soon , Cho Hyeon-Min , Kye Bong-Hyeon , Yoo Ri Na , Kim Sung Hwan , Lee Jong Hoon , Lee Kang-Moon , Lee Ji Min , Jung Ji-Han 
Published: January 2023

47 Background: The standard treatment for synchronous stage IV colorectal cancer (CRC) is systemic chemotherapy. There have been attempts to conduct elective primary tumor resection (PTR) as an upfront treatment to prevent complications in primary tumor sites, or improve prognosis. However, there are controversies about the role of PTR in stage IV CRC. We investigated the prognostic role of PTR and tried to find subgroups who might get benefit from upfront PTR in this population. Methods: Between 2010 and 2020, 330 patients diagnosed with synchronous stage IV CRC at St. Vincent Hospital in Korea were retrospectively reviewed. We excluded patients underwent PTR and metastasectomy at the same time, PTR for emergencies (perforation, acute bleeding with hemodynamic instability, fistula, and/or obstruction), or received chemoradiotherapy as an initial treatment. Overall survival (OS) was measured from the date of diagnosis until death resulting from any cause or the last censored date during follow-up. OS were calculated using the Kaplan-Meier method, and differences in survival between groups were compared by the log-rank test. Variables with p value <0.05 were included in the Cox regression multivariable model. Results: Total 223 patients were analyzed. Patients were divided into two groups; 45 patients receiving upfront elective PTR (PTR group), and the 178 patients receiving upfront systemic treatment (non-PTR group). Two groups were not different in terms of age ( p = 0.979), ECOG performance status ( p = 0.488), and serum CEA levels ( p = 0.252). However, the PTR group showed lesser number of metastatic organ compared to the non-PTR groups ( p = 0007). The PTR group survived longer than the non-PTR group ( p = 0.015). Multivariate analysis revealed that age≥60 (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.15-2.09; p = 0.004,), CEA≥30 ng/mL (HR, 1.32; 95% CI, 0.99-1.75, p = 0.061), PTR (HR, 0.66; 95% CI, 0.45-0.95; p =0.027), adding targeted agent (HR, 0.71; 95% CI, 0.53-0.96; p = 0.026), and ECOG≥3 (HR, 1.649; 95% CI, 1.15-2.37, p = 0.007) were associated with OS. Subgroup analysis showed that PTR might be beneficial in patients with low CEA (<30 ng/mL, p = 0.032), old age (≥60, p = 0.028), ECOG (≤2, p = 0.006), M1a stage ( p = 0.008), and receiving bevacizumab ( p = 0.016). Conclusions: Upfront PTR was conducted in selected patients with lower number of metastasis, but associated with OS after adjusting other prognostic factors. We suggested that PTR could be an option for patients with low CEA (<30 ng/mL), old age (≥60), ECOG (≤2), M1a stage, or receiving bevacizumab in this population.
The role of education in adjusting to changes in clinical practice for gastric or gastroesophageal junction adenocarcinomas.
Authors: Ackbarali Tariqa , Janjigian Yelena Y. , Van Cutsem Eric 
Published: January 2023

470 Background: Gastric or gastroesophageal junction (GEJ) adenocarcinomas are difficult to treat and associated with poor prognosis, specifically in advanced disease. Recently approved and investigational immune checkpoint inhibitors (ICIs) and HER2-directed antibody-drug conjugates (ADCs) are changing the treatment landscapes for gastric cancer and GEJ cancer, allowing clinicians to manage difficult-to-treat patients. However, these advances also create knowledge and practice gaps that pose many challenges warranting education to close these gaps and to assess current practices. Methods: PlatformQ Health’s proprietary workflow digital technology was utilized to launch a 4-part CME series online in December 2021 which remains on-demand through December 2022 at OMedLive.com. Each module focused on the following topics: 1) HER2 testing, 2) Current care for HER2+ gastric or GEJ cancer, 3) Treatment for unresectable disease and trastuzumab-resistant disease, and 4) adverse event management. This series was conducted in partnership with the American Gastroenterological Association and accredited by the Postgraduate Institute for Medicine. Clinicians engaging in this educational series were assessed at pre- and immediate post-activity. Practice pattern insights and education impact were assessed post-activity. Results: To date, 2,568 US-based clinicians have participated in the educational series. All 6 questions across the 4 modules in the series showed significant improvements in knowledge and competence related to HER2 testing, defining the standard of care, treatment beyond trastuzumab resistance, treatment for unresectable disease, and managing adverse events. Provider insights evaluated post-series revealed 41% of clinicians will consult with a pulmonologist upon development of interstitial lung disease; 51% identified trastuzumab deruxtecan as a novel HER2-targeted therapy having the greatest potential to improve patient outcomes; and 26% reported not repeating HER2 expression testing following progression on a trastuzumab-containing regimen. Evaluating the impact of the educational series, 88% of clinicians reported a positive impact on patient experience and 94% on clinical practice change following participation. The qualitative data depicting the reported impact will be shared. Conclusions: This serialized education was effective in improving knowledge and competence across four major themes of practice within gastric and GEJ cancer management. Provider insights revealed practice shifts following participation and practice impact assessments demonstrated the rapid application of real-time digital education.
Time to first treatment and optimal adjuvant treatment strategy in patients with resectable gastric cancer pathologically upstaged to lymph node–positive disease.
Authors: Ajay Pranay Shah , Sok Caitlin , Goyal Subir , Switchenko Jeffrey M. , Maegawa Felipe , Gillespie Theresa Wicklin , Paulos Chrystal M , Kooby David A. , Kennedy Timothy , Shah Mihir Maheshkumar 
Published: January 2023

473 Background: Treatment strategies in resectable gastric cancer (GC) patients include perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC). Treatment delay can lead to metastases with unfavorable outcomes. We aim to identify the distribution of patients upstaged to pathologically node positive disease (pLN+) stratified by time and the optimal treatment in this cohort. Methods: We analyzed resected GC patients in the National Cancer Database (2004-2016) with clinically node negative disease (cLN-). Time from diagnosis to first definitive therapy was stratified as ≤2, >2 to ≤4, and >4 weeks. The distribution of patients upstaged from cLN- to pLN+ disease, the concordance between cLN- and pathologically lymph node negative (pLN-) disease based on treatment strategy, and time to first definitive therapy was analyzed. POC and POCR were compared to evaluate their effect on overall survival (OS) in patients with cLN- upstaged to pLN+ disease. Kaplan-Meier test, log-rank test, multivariable Cox proportional hazards analysis (MVA) were performed. Results: Of the 4,828 gastric cancer patients with cLN- disease, 514 (10.65%) patients received PEC and 4,314 (89.35%) patients received upfront surgery followed by POCR/POC. Distribution of patients stratified by time between diagnosis to first definitive treatment - chemotherapy (PEC) or surgery (POC/POCR), for ≤2 weeks was 9.5% vs. 33%, >2 - ≤4 weeks was 28.4% vs. 24.2% and >4weeks was 62% vs 42.7%, respectively. Patients upstaged from cLN- to pLN+ disease in the PEC group was 43.37%(n=206), and 70%(n=2574) in the upfront surgery group (POC/POCR). Of the 206 (43.37%) patients upstaged from cLN- to pLN+ in the PEC cohort, the upstage rate was 7.77% when chemotherapy was started within 2 weeks of diagnosis, compared to 27.67% with >2 to ≤4 weeks, and 64.56% with >4 weeks. Of the 2,574 (70%) patients upstaged in the upfront surgery cohort (POCR/POC), 30.61% were upstaged in ≤2 weeks, 24.95% in >2 to ≤4 weeks, and 44.44% in ≥4 weeks. On MVA, patients with cLN- disease that were pLN- (POCR=766, POC=341) had no significant difference in OS when treated with POCR (HR 1.11, p=0.39) compared to POC. Patients with pLN+ (POCR=2300, POC=907) disease had an association with improved OS when treated with POCR (HR 0.78, p<0.001) compared to POC. Conclusions: When resectable gastric cancer patients undergoing upfront surgery are upstaged from clinically node negative to pathologically node positive disease, postoperative chemoradiation therapy may be the optimal treatment strategy compared to postoperative chemotherapy. Clinical nodal status may not be an optimal predictor of nodal disease.
Racial and ethnic disparities in multinational phase III clinical trials in liver and biliary tract cancer.
Authors: Monge B. M. Cecilia , McGlynn Katherine , Greten Tim F. 
Published: January 2023

497 Background: Racial and ethnic diversity ensures validity of clinical research and opens novel oncologic treatments to all population groups. Hispanics and non-Hispanic Blacks (NHB) are the largest racial/ethnic groups in the United States after non-Hispanic Whites (NHW). Hispanics accounted for 19%, while NHB accounted for 14% of the population in 2021. From 2012 to 2019 the proportion of hepatocellular carcinomas (HCC) and biliary tract cancers (BTC) occurring in Hispanics was 23.2% and 22.6% respectively; the proportion of HCC and BTC occurring in NHB was 11.1% and 8.3% respectively. We examined the participation of NHB and Hispanics in multinational phase III clinical trials of HCC and BTC in the last ten years. A participant to population ratio (PPR) of 0.8-1.2 reflects adequate ethnic/racial representation; a lower PPR indicates underrepresentation. Methods: A database search was performed in PubMed, Embase and Web of Science: Core Collection (Cl for multinational phase III clinical trials of HCC or BTC, studying first and second line treatments published from August 2012 to August 2022.Trials meeting these criteria were identified and the percentage of NHB and Hispanics included was calculated and compared to the proportion of NHB and Hispanics affected by HCC and BTC as per the National Cancer Institute Surveillance, Epidemiology, and End Results Program. Results: Eighteen multinational phase III clinical trials studying first- and second-line treatments for HCC and BTC were identified. The trials enrolled a total of 12464 patients; 27% (n=5 trials) did not report racial/ethnic characteristics. Of the 9991 patients included in trials for which race/ ethnicity was provided, 11 (0.08%) were Hispanics and 88 (0.7%) were NHB. The participant to population ratio (PPR) in Hispanics for HCC was 0.003 and 0 for BTC, meanwhile the PPR in NHB was 0.6 for HCC and 0 for BTC. Conclusions: NHB and Hispanics are underrepresented in HCC and BTC in multinational phase III trials relative to the U.S population. Most patients included in trials were Asian, consistent with the global incidence of HCC. It may be important for phase III clinical trials seeking FDA approval to require mandatory racial/ethnic diversity that is reflective of the US population.
Incidence and costs associated with clinically significant events in real-world patients with unresectable hepatocellular carcinoma on systemic therapy.
Authors: Healey Marcus , Simmons Daniel , Valerio Stephen J , Sah Janvi , Pierce Debra , Jiang Zhuoxin , Thomas Darren , Levingston Mac Leod Jesica , Lin Yian 
Published: January 2023

514 Background: First-line (1L) treatments for unresectable HCC (uHCC) include atezolizumab plus bevacizumab (ATEZO+BEV), and the tyrosine kinase inhibitors (TKIs) sorafenib (SOR) and lenvatinib (LEN). In clinical trials, these therapies were associated with clinically significant events (CSEs): bleeding, clotting, encephalopathy, and portal hypertension. The objective of this study was to evaluate the real-world incidence of these CSEs and their impact on healthcare resource utilization (HCRU) and costs in patients with uHCC receiving ATEZO+BEV or a TKI. Methods: We conducted a retrospective, observational, cohort study using Clinformatics Data Mart to characterize 1379 US patients diagnosed with uHCC between January 2007 and June 2021 who received treatment with ATEZO+BEV (n=271) or a TKI (SOR, n=891; LEN, n=217). Incidence of the selected CSEs was evaluated as incident cases per 100-person-years (PY) of treatment. Descriptive statistics assessed patient characteristics, HCRU, and medical costs. Results: Mean age at diagnosis was 67.7 years; most patients were male (76.1%), white (52.4%), and had Medicare (74.2%); these characteristics were consistent across treatment groups. While on ATEZO+BEV, SOR or LEN, 147 (54.2%), 481 (54.0%), and 121 (55.8%) patients experienced ≥1 CSEs, respectively. For the ATEZO+BEV group, the most common CSEs were clotting (61.2 cases/100-PY [95% confidence interval {CI}: 45.1, 81.1]) and bleeding (55.4 [40.3, 74.4]). For the SOR group the most common CSEs were encephalopathy (54.5 [46.9, 63.1]) and clotting events (51.3 [44.1, 59.4]), for the LEN group the most common CSEs were clotting events (63.5 [47.4, 83.3]) and encephalopathy (56.7 [42.2, 74.5]). Overall, mean HCRU was high in the outpatient visits, while increases in the cohorts and among events (e.g., for surgery and inpatient visits) were seen in patients with ≥1 CSEs versus those without CSEs. Mean monthly medical costs were also substantially higher with ≥1 CSEs (Table). Conclusions: There were high levels of CSEs in patients receiving ATEZO+BEV or TKIs for 1L uHCC, and the occurrence of these events is associated with an economic burden to the healthcare system. Safety should continue to be monitored for patients treated for uHCC and new therapy options with reduced risks for developing CSEs are needed. [Table: see text]
Trends in incidence, treatments, and clinical outcomes of cholangiocarcinoma diagnosed in British Columbia, Canada, from 2005 through 2019.
Authors: Boutin Mélina , Yang Jenny , Safro Maria , Jafari Helia , Davies Janine Marie , Gill Sharlene 
Published: January 2023

522 Background: While only accounting for 3% of gastrointestinal malignancies, cholangiocarcinoma (CC) has poor prognosis. New targeted therapies are on the horizon and understanding the potential size of the population eligible for such therapies is of importance. Contemporary incidence and outcomes in Canada have not been studied. Methods: Patients diagnosed with CC between 2005-2019 in British Columbia were identified using the BC Cancer Registry. Patient characteristics, treatments received and outcomes were collected and analyzed. Results: A total of 1520 patients were identified. Median age at diagnosis was 69 (interquartile 61-76) and 52% were female, 594 patients presented with localized disease (39%) of whom 416 had disease recurrence. The proportion of intrahepatic CC (ICC) rose from 17% in 2005-2009 to 44% in 2015-2019 while the incidence of extrahepatic (ECC) and gallbladder (GB) cancers followed populational trends. More patients with ICC had stage IV cancer at the time of diagnosis (64% vs 43% for ECC and 45% for GB, p<0.01). Treatments received are shown in the table. Among 1086 patients with recurrent or metastatic disease, 54% and 14% respectively received first- and second-line chemotherapy. Overall survival (OS) was 13.7 months [HR 0.43 (95% CI 0.37-0.49)] with 1 line of treatment and 21.3 months with 2 lines [HR 0.30 (95% CI 0.24-0.37)], compared to 4.8 months with best supportive care. On multivariate analysis, ECOG, first and second-line treatment and liver-directed therapy remained associated with improved outcomes while tumor site or time period did not. Conclusions: The incidence of CC is rising and most patients present with advanced disease. Treatment attrition is high and few patients receive second line therapies. The outcomes of patients receiving first line, second line and liver-directed therapies are significantly better than those receiving supportive care only. Understanding contemporary trends in presentation and treatment patterns is essential as we consider strategies to improve implementation and access of emerging novel therapies in this setting. [Table: see text]
Attitudes toward prevention options in Lynch syndrome (LS): Comparing frameshift peptide vaccination (FSPVAX), colonoscopy (COLO), and aspirin (ASA) chemoprevention.
Authors: Hall Michael J. , Riggs Emma D , Chertock Yana , Daly Mary Beryl 
Published: January 2023

526 Background: LS is among the most common cancer (CA) syndromes affecting 1:280 individuals and portends high lifetime CA risk. Clinical trials are currently evaluating whether FSPVAX could reduce LS CA risk. FSPVAX enhance immune response to diverse FSP neoantigens in MSI-H tumors and have shown promising results in an MSH2-mutant mouse model and metastatic MSI-H CRC. However, negative public attitudes towards vaccination could undermine this novel therapy. Here, we benchmark attitudes towards FSPVAX for CA prevention against intensive colonoscopy, for which uptake is high in LS, and aspirin chemoprevention, where uptake is generally lower. Methods: The PREVENTLynch survey was distributed electronically to participants in the Fox Chase Cancer Center (FCCC) Risk Registry. LS patients were invited to complete the one-time survey after providing informed consent, and received a gift card incentive upon completion. The study was approved by the FCCC IRB (20-8014). Demographic/personal/familial CA history were collected. Attitudes were measured on 9-point scales indicating low vs high agreement with belief statements: e.g.“Colonoscopy is a convenient way to lower my risk of LS-related CA.” Results: Overall 116 out of 220 invited LS patients completed the survey (response rate 53%). 76% were female, and mean age was 52.7 yrs. 72% had personal history of CA. COLO uptake was high (96%), while ASA uptake for prevention was modest (22%). Side effect concerns were higher for FSPVAX compared to both COLO and ASA (both p<0.001). FSPVAX offered patients significantly less reassurance than COLO (p<0.001) and was significantly less likely to be endorsed/pursued as a treatment (p<0.001). Convenience of FSPVAX was similar to COLO but less than ASA (p<0.001). LS patients with (vs w/o) a personal history of CA(p<0.05) and those >50 yrs old (vs<50)(p<0.05) were more likely to participate in a FSPVAX trial. Conclusions: LS patients’ attitudes towards FSPVAX are mixed. Concerns about side effects and efficacy may limit future uptake similar to ASA. [Table: see text]