bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inequity in emergency room utilization prior to colorectal cancer diagnosis and the opportunity to improve access to colorectal cancer screening.
Authors: Barzi Afsaneh , Zhang Juanjuan , Liu Lihua , Kim Sue 
Published: January 2023

79 Background: The opportunity for early detection of colorectal cancer via screening is not fully realized. Previous efforts to maximize use of screening had targeted patients and primary care providers. Other wildly used healthcare settings may be suitable targets for intervention. We explored emergency room (ER) utilization in patients with colorectal cancer prior to their diagnosis using the linkage between California Cancer Registry (CCR) and OSHPD (Office of Statewide Health Planning and Development). Methods: Patients with diagnosis of colorectal cancer 2010-2015 were identified in the CCR and their records were linked with OSHPD (2009 – 2016) to assess ER utilization. This study aimed to evaluate the patterns of ER utilization (all and nay reason for ER visit) prior to the diagnosis of colorectal cancer. Results: A total of 66,451 colorectal cancer patients were identified, of which 57,876 (87%) were linked with OSHPD data. Among the linked population, 41% (23,890) had at least one ER visit prior to their diagnosis of colon cancer. Of the 23,890 with ER visit, 14% had 3 or more ER visits. The median number of days from first ER visit to diagnosis was 539 days (range: 2551 – 1). A total of 14,372 patients (25%) had an ER visit within one year of their colorectal cancer diagnosis. The median age of patients who had ER visits was younger than those who didn’t have an ER visit, 66 vs. 68 years. There was no difference in the number of ER visits between patients 50 and younger and those older than 50 years. There was no significant difference in the stage at presentation between those with prior ER visit and those without. Patients in high socioeconomic status were less likely to have an ER visit prior to colorectal cancer diagnosis (44%) compared to those with low SES status (36%). Patients with private insurance had a significantly lower likelihood of ER visits compared to those with federal and state funded insurance. Conclusions: A significant percentage of patients with colorectal cancer had ER visit prior to their diagnosis, many within one year of their diagnosis. Inequity in access to care, measured via poor SES and insurance type, was associated with higher chance of ER visit among colorectal cancer patients. Emergency room may be a targetable opportunity to remind and coordinate screening for colorectal cancer.
Identification of risk factors for gastrointestinal irAEs associated with immune checkpoint inhibitors.
Authors: Morikawa Ryo , Nitta Kentaro , Yasuda Shuntaro , Noji Rika , Kano Yoshihito , Sato Shingo , Ikeda Sadakatsu , Nagata Masashi , Mori Takehiko , Suenaga Mitsukuni 
Published: January 2023

791 Background: Immune checkpoint inhibitors (ICIs) are widely used in tumor-agnostic therapy showing remarkable survival benefit in various cancer types. Gastrointestinal (GI) toxicities are common immune-related adverse events (irAEs) with limited reports for risk factors. In this study, we investigated potential risk factors for GI-irAEs in patients receiving immunotherapy. Methods: We retrospectively reviewed medical records of cancer patients treated with ICIs between January 2020 and December 2021 at Tokyo Medical and Dental University hospital, and analyzed the relationship between GI-irAEs and patients’ clinicopathological characteristics, treatment duration or the number of treatment cycles. Results: Among 474 patients, 136 were eligible for analysis. Patient characteristics were as follows: the median age, 68 years (range, 32-92); male/female, 104 (76.5%)/32 (23.5%); and cancer types were mainly GI in 36 (26.5%), head and neck in 33 (24.3%), urinary tract in 35 (25.7%), and others in 32 (23.5%). Details of ICIs were nivolumab in 47 (34.6%), pembrolizumab in 61 (44.9%), atezolizumab in 17 (12.5%), and nivolumab + ipilimumab in 11 (8.1%). GI-irAEs was observed in 29 patients (21.3%), and more frequent in female than male (OR: 3.07, 95% CI: 1.31-7.68, P=0.0146). The median number of treatment cycles to the onset of GI-irAEs from ICIs initiation was 4 (range, 1-70). Female had a shorter event-free survival than male (HR: 2.12, 95% CI: 0.914-4.9, P=0.041). There was no significant difference in gender for the number of treatment cycles to the onset of GI-irAEs from ICIs initiation. Of 17 patients (12.5%) with grade 2≤ GI-irAEs, female had trend toward higher incidence (OR: 2.63, 95% CI: 0.99-7.22, P = 0.122). The outcomes after the GI-irAEs onset were as follows: treatment continuation in 9 patients (52.9%), treatment discontinuation followed by observation in 1 (5.9%) and administration of corticosteroids in 7 patients (41.2%). Of 7 patients receiving corticosteroids, 2 resumed chemotherapy with other drugs, 2 resumed chemotherapy with same drugs, and 3 discontinued chemotherapy. Conclusions: Our results suggest that female is a potential risk factor for GI-irAEs during ICI treatment regardless of cancer types.
Efficacy and tolerability of immune checkpoint inhibitors in elderly patients with MSI/dMMR gastrointestinal cancers and impact of toxicities on efficacy: The immunoMSI cohort.
Authors: Mailly-Giacchetti Leah , Colle Raphael , Lopez-Trabada Ataz Daniel , Duval Alex , Andre Thierry , Cohen Romain 
Published: January 2023

795 Background: Immune checkpoint inhibitors (ICI) are the new standard of care for some MSI/dMMR advanced tumors in first-line setting or after progression under conventional chemotherapy. Frequency of MSI/dMMR increasing with age, the tolerability and efficacy of ICIs in elderly patients, appears as a crucial clinical issue. We aimed to evaluate the tolerability and efficacy of ICIs in ≥ 75 years patients with metastatic MSI/dMMR gastro-intestinal (GI) cancer. Methods: All pts with MSI/dMMR metastatic GI cancer treated by anti-PD1 ± anti-CTLA4 without concomitant chemotherapy at Saint-Antoine hospital and included in our prospective, monocenter cohort, were analyzed. Pts were divided into the elderly (≥75 years) and non-elderly (<75 years) groups. The incidence and evolution of grade ≥ 3 immune-related adverse events (irAE) and grade ≥ 2 endocrine adverse events were evaluated. Secondary objectives were progression-free survival (PFS) and overall survival (OS) regarding age and the occurrence of irAEs. Results: Two hundred and one patients were included: 24 pts≥75 years (75 to 90 years) and 177 pts< 75 years (22 to 74 years). 171 (79%) had mCRC. In the entire population, the incidence of irAEs was 40.5% with anti-PD1 plus anti-CTLA4 and 23% with anti-PD1 monotherapy (p= 0.011). Combination of anti-PD1 and anti-CTLA4 were administered to 29% of the elderly group and 40% of the non-elderly group. There was no statistical difference in the incidence of irAEs between the two populations (37.5% in the elderly group vs 29% in the non-elderly group; p=0.48) neither in their type (12% vs 7% of hepatic cytolysis, 13% vs 16% of endocrine irAEs) or management (17% vs 19% corticosteroid therapy, 21% and 16% of ICI discontinuation). No significant difference was observed between elderly/non elderly for PFS (HR 0.91, 95%CI 0.40-2.06; p=0.83) and OS (HR 1.6, 95%CI 0.65-3.96; p= 0.21). Pts experiencing irAEs had superior survival outcomes than those without irAEs (PFS HR 2.93, 95%CI 1.69-5.09; p=0.02 and OS HR 2.05, 95%CI 1.13-3.74; p=0.045) in the whole cohort (n=201). Conclusions: Tolerability and efficacy of ICIs for pts with MSI/dMMR GI cancers are similar for elderly compare as for non-elderly pts. Pts experiencing irAEs had superior survival outcomes. Further prospective studies with systematic geriatric assessment are required to evaluate the tolerability of ICIs especially for frail elderly pts.
Clinical efficacy and biomarker analysis of pucotenlimab (HX008) in patients with previously treated advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A single-arm, multicenter, phase 2 study.
Authors: Zhang Bo , Song Yan , Luo Suxia , Yin Xianli , Li Enxiao , Wang Hui , He Yifu , Liu Zhihui , Fan Qingxia , Liang Xinjun , Shu Yongqian , Liu Yunpeng , Xu Nong , Zhang Shu , Zhuang Zhixiang , Zhang Jingdong , Kou Xiaoge , Wang Fen , Zhu Xiaodong , Huang Jing 
Published: January 2023

799 Background: Pucotenlimab is a humanized IgG4 anti-PD-1 monoclonal antibody with an engineered Fc domain. We aim to assess the efficacy and safety of pucotenlimab, and potential predictive biomarkers of response in patients with previously treated advanced microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors. Methods: In this single-arm, multi-center, phase 2 study, eligible patients had locally advanced or metastatic, centrally confirmed MSI-H or dMMR solid tumors treated with at least one prior systemic therapy. Patients received pucotenlimab 200mg every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) assessed by the independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Besides, patients’ PD-L1 expression, blood neutrophil to lymphocyte ratio (NLR), germline HLA-I genotyping, loss of heterozygosity (LOH) of HLA-I genes, tumor mutational burden (TMB), and genetic alterations in the tumor revealed by next-generation sequencing were investigated to identify potential predictors of efficacy. Results: 100 patients with MSI-H or dMMR solid tumors were enrolled. Colorectal cancer (n=71) and gastric cancer (n=10) were the most common cancer types. The median follow-up duration was 22.5 months (range: 0.3-37.4) at data cutoff (December 4, 2021). The ORR was 49.0% (95% CI 38.86%-59.20%), and the 12-month progression-free survival (PFS) rate was 56.1% (95% CI 45.63%-65.24%) based on IRC’s assessment. Both the median PFS and median duration of response were not reached. Pucotenlimab was well tolerated. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 18 patients, most commonly anemia, leukocytopenia, and hypertension. For the biomarker analysis, patients with NLR <4 at the second treatment cycle, TMB≥32.5 muts/Mb (the lower 35th TMB-percentile), or mutations in the KMT2D gene showed significantly higher ORR. Conclusions: Pucotenlimab demonstrated durable antitumor activity and manageable safety for previously treated patients with advanced MSI-H/dMMR solid tumors. KMT2D gene mutation, along with NLR and TMB, warrants further investigation as predictive biomarkers. Clinical trial information: NCT03704246 .
Association of lifestyle-related risk factors with incidence and mortality rates of colorectal cancer among adolescents and young adults (AYA) in the United States.
Authors: Grewal Udhayvir Singh , Aggarwal Manik , Kumar Prabhat , Fei Naomi , Monga Varun , Chandrasekharan Chandrikha 
Published: January 2023

80 Background: Incidence of colorectal cancer (CRC) among adolescents and young adults (AYA) is increasing. A significant proportion of adolescents and young adults (AYA) with colorectal cancer (CRC) lack traceable genetic risk factors. We sought to study the impact of lifestyle-related risk factors on the incidence and mortality of CRC in these patients. Methods: We extracted data on crude incidence and mortality rates of CRC (reported per 100,000 population) for ages 15-39 years in all 50 U.S. states and District of Columbia from the Center for Disease Control (CDC) WONDER database (1999-2018). Data on risk factors such as obesity, physical activity, alcohol and tobacco abuse and nutrition were obtained from the Behavioral Risk Factor Surveillance System (BRFSS, 2020). Correlations were analyzed using Pearson’s co-efficient. p < 0.05 was considered statistically significant. Statistical analysis was performed using VassarStats. Results: Median crude incidence and mortality rates of CRC in AYA in the US from 1999-2018 were 3.8 (IQR 3.2, 4.4) and 0.7 (IQR 0.5,0.9) per 100,000 population respectively. States with higher age-adjusted prevalence of obesity per 100,000 had higher incidence (r = 0.36, p = 0.01) and mortality rates (r = 0.49, p = 0.0002) of CRC in AYA population. States with a higher age-adjusted prevalence of adherence to recommended weekly aerobic activity had lower incidence (r = -0.4515, p = 0.001) and mortality (r = -0.569, p < 0.0001) rates. While states with higher age-adjusted prevalence of tobacco abuse had higher incidence rate of CRC (r = 0.33, p = 0.02), there was no correlation with mortality rates (r = 0.24, p = 0.09). Higher prevalence of alcohol consumption was associated with decreased mortality rate (r = -0.44, p = 0.001), with no impact on incidence rate (r = -0.16, p = 0.26). States with lower daily consumption of fruits had higher incidence (r = 0.37, p = 0.01) and mortality rates (r = 0.59, p < 0.0001). No correlation of daily consumption of vegetables with incidence (r = -0.1516, p = 0.29) and mortality (r = 0.18, p = 0.22) rates was noted. Conclusions: In the current analysis, higher prevalence of obesity, lower rates of aerobic activity and lower daily consumption of fruits were strongly associated with increased incidence and mortality rates. The impact of tobacco abuse and alcohol consumption was more variable. Apart from improving access to genetic testing and counseling, efforts aimed at mitigating the rise of CRC incidence among AYA should also focus on traditional lifestyle-related risk factors.
Prognostic impact of immune-related adverse events on survival outcomes in metastatic gastrointestinal cancer: A single-institutional experience.
Authors: Ogbue Olisaemeka , Unlu Serhan , Sorathia Sharmeen , Nanah Abdel Rahman , Haddad Abdo S. , Daw Hamed 
Published: January 2023

801 Background: Immune checkpoint inhibitors (ICIs) have several approved indications in the treatment of gastrointestinal (GI) malignancies including metastatic disease. The adverse events related to ICI use or Immune related adverse events (irAEs) are now being more readily recognized. The association between the occurrence of irAEs and survival outcomes is not well understood. Whereas complete tolerability of ICIs with minimal irAEs may be indicative of a lack of response, the development of moderate to severe irAEs could result in significant morbidity and mortality especially in already advanced disease. This dilemma has provided an impetus to present our 5-year single institutional experience wherein we aim to determine the impact of irAEs on survival outcomes in metastatic GI malignancies. Methods: We retrospectively reviewed a cohort of adult patients who received ICIs for metastatic GI malignancies at the Cleveland Clinic foundation between 2017-2022 by utilizing an outpatient oncology pharmacy database. ICIs of interest included atezolizumab, ipilimumab, nivolumab and pembrolizumab. The occurrence of irAEs was as determined by primary oncologist. The primary and secondary outcomes were overall survival (OS) and progression free survival (PFS) in patients based on irAE presence, respectively. Results: There was a total of 151 patients who received ICIs for various metastatic GI malignancies. Among these, 38 unique irAEs were identified constituting 25% of the entire cohort. The table shows their distribution by organ system and type of GI malignancy. We observed hyper progressive disease in 3% of irAE cohort. Grade 3-4 irAEs requiring hospitalization occurred in 32% of all irAEs, median hospital length of stay of 5 (range:1-15) days with 11% resulting in death. 26 % discontinued treatment due to irAEs while 44% had palliative care consultations/hospice transition soon after. The median OS rates in patients who had irAEs vs those who didn’t, respectively, were 10 months [95% confidence interval (CI, 5-NA)] vs. 9 months [95% confidence interval (CI, 6-12)], p=0.85. There was also no statistically significant difference in median PFS between both groups (p=0.76). Conclusions: In our single institution cohort of metastatic gastrointestinal cancer patients, despite significant morbidity from irAEs, the prognosis was similar as previous studies suggesting a better outcome in patients with irAEs compared to those who did not experience irAEs.[Table: see text]
Frequency and outcomes of BRAF alterations identified by liquid biopsy in metastatic non-colorectal gastrointestinal cancers.
Authors: Mahipal Amit , Bucheit Leslie , Zhang Nicole , Jiang Jing , Kiedrowski Lesli A. , Chakrabarti Sakti 
Published: January 2023

808 Background: The impact of BRAF V600E, a known poor prognostic factor in metastatic colorectal cancer (CRC), has not been assessed broadly in non-CRC gastrointestinal (GI) cancers including pancreatic (PC), gastric/gastroesophageal (GC), hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). In view of recent tumor-agnostic approval of a BRAF V600E inhibitor, it is important to determine the prevalence and impact of BRAF alterations on non-CRC GI cancer patients (pts). Methods: Genomic results from pts with PC, GC, HCC, or CCA tested with Guardant360 (G360, Guardant Health) as part of clinical care from June 2019 – June 2022 were retrospectively queried. Prevalence of characterized nonsynonymous BRAF genomic alterations (GA) was analyzed; differences between cancer types was assessed using the Chi-squared test. The GuardantINFORM database with aggregated commercial payer health claims and de-identified records from over 243,000 individuals with G360 results was used to derive real-world overall survival (rwOS), reported in months, calculated from diagnosis of metastatic cancer; differences between cancer types were compared using log-rank tests. Results: 23,069 patients were included: PC:49%; GC:24%; CCA:20%; HCC:6%. Pts were more likely to be male (p<0.01). PC/HCC pts were tested more often at new diagnosis (vs at disease progression) than GC/CCA (p=0.02, p<0.01, respectively). BRAF GAs were identified in 2.9%, comparable to tissue-based datasets (MSK-IMPACT: 2.4%); 21% of BRAF GAs were V600E (0.6% prevalence overall). PC/CCA pts were more likely to have BRAF GAs than the overall cohort (p<0.01); they also had more BRAF V600E GAs (p<0.01). rwOS differed by cancer type and BRAF status (Table). Notably, CCA pts with BRAF V600E had superior rwOS compared to CCA pts without BRAF findings (p=0.02). rwOS is not reported for HCC due to small n. Conclusions: Identification of BRAF GAs and V600E in the non-CRC GI population by liquid biopsy is similar to rates observed in tissue-based testing and may be reliably used to assess BRAF status. BRAF GAs and subtypes have mixed prognostic implications on survival for PC/CCA/GC patients that warrants further exploration. [Table: see text]
Diagnostics and treatment for HER2+ mG&CRC: Learning outcomes of GetSMART.
Authors: Lou Emil , Marshall John , Jacobs Ginny , Fleming Matthew , Coutinho Anelisa Kruschewsky , Yoshino Takayuki , Augustyniak Monica , McFadden Pam 
Published: January 2023

82 Background: Gastric/colorectal cancer (G&CRC) are among the most prevalent cancers. Efforts are ongoing to better assess their clinical/genomic factors. HER2 (human epidermal growth factor receptor 2) testing is strongly recommended in clinical practice to guide treatment. An accredited education program (GetSMART) was launched online (January 2021–April 2022) to equip healthcare providers (HCPs) with knowledge, skills, and confidence to accurately assess/apply molecular testing and therapy options for metastatic G&CRC patients. Methods: A knowledge/confidence-based assessment was embedded in four modules to measure learners’ knowledge mastery (% answering correctly with confidence) pre/post-activity. Self-reported confidence and anticipated performance in clinical practice were measured before/after each module. At the end of program, HCPs were asked about their commitment to change. McNemar’s test was applied to assess statistical significance in pre-post for paired items, and descriptive analysis for non-paired items. Results: Overall, 925 unique HCPs engaged in GetSMART, 31% (n=284) completed all modules, of which 57% (n=163) consented analysis of their data. A statistically significant increase (p<0.05) was measured in percentage of HCPs demonstrating knowledge mastery, confidence, and commitment to change their practice from pre to post across four competencies, except for percentage of HCPs “often”/“always” engaging patients in shared decision-making (SDM) (3, Performance). Largest gains in knowledge mastery/confidence were noted for HCPs’ ability to anticipate/manage adverse events (AE) ( 4A); and for anticipated performance, in HCPs considering appropriate treatment. Post-activity, 66% (98/149) of HCPs intended to change practice based on module content, 83% (70/84) of whom were “highly”/“somewhat” confident to make changes. The activity’s anticipated impact on patients was rated “major”/“moderate” by 69% (103/149) of HCPs. Conclusions: Identification of HER2 aberrations in mG&CRC and its appropriate treatment selection remains challenging in oncology care. This evaluation demonstrated that GetSMART positively impacted HCPs’ knowledge, confidence, and anticipated performance in clinical practice to enhance health outcomes of HER2+ mG&CRC patients. [Table: see text]
Costs of adverse event management associated with first-line cetuximab or panitumumab in patients with metastatic colorectal cancer in Spain.
Authors: Suárez Begoña Graña , Tarazona Noelia , Duran Moran Olga , Fernandez Gonzalez Ana , De los Santos Real Heidi , Pescott Chris P. 
Published: January 2023

83 Background: Patients with RAS wild-type metastatic colorectal cancer (mCRC) in Spain may be treated with an epidermal growth factor receptor inhibitor: cetuximab (cet) or panitumumab (pan), in combination with chemotherapy (CT). Several factors may influence the choice of treatment regimen, including adverse event (AE) management, as cet- and pan-based therapies have distinct individual safety profiles. Patients may experience multiple adverse events during treatment. This study aimed to estimate the associated financial impact on Spain’s National Health System (SNHS). Methods: An economic model was developed to project the mean number of AEs per patient (p-p) and to estimate p-p and population-level costs of AE management (cAEm) associated with first-line cet+CT and pan+CT treatment regimens. Data on common and very common AEs and their severity were sourced from the summaries of product characteristics and a meta-analysis by Petrelli, et al. Categorical values were converted into numerical values using the mean values of the frequencies for each AE. Applicable resource costs were obtained from a Spanish database with health unit costs from official records, and from literature on oncology treatment-related costs. The eligible patient population was determined from published and grey literature, and market research. AEs of grade 1-2 were assumed to be treated in an outpatient setting, and those of grade 3-4 treated in an inpatient setting. The model inputs were validated by clinical oncologists in Spain. Results: An estimated 3,794 (cet+CT) and 2,325 (pan+CT) eligible patients received first-line treatment for mCRC. For patients receiving cet+CT or pan+CT, the average frequency of AEs p-p was estimated to be 7.2 (cet+CT) and 17.2 (pan+CT), with estimated p-p cAEms of €5,655 and €13,571, respectively. Conclusions: The lower rates of AEs for cet+CT may result in a reduced AE burden for eligible patients with mCRC, with estimated savings of €7,917 p-p on average. Although overall costs and clinical outcomes should be considered, treatment with cet+CT could yield annual cAEm savings for the SNHS of 35%. Future studies should consider the impact of AE management in a real-world setting.