bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1 dose escalation study of a novel coupled CAR T cell therapy, GCC19CART, for patients with metastatic colorectal cancer.
Authors: Schlechter Benjamin L. , Lieu Christopher Hanyoung , Fakih Marwan , Surana Rishi , Chen Dongqi , Lu Lucy , Rowinsky Eric Keith , Lu Victor , Xiao Lei , Ng Kimmie , Keenan Bridget P. 
Published: June 2024

e15572 Background: GCC19CART is a multitargeted CAR-T cell therapy designed to overcome the limitations of conventional CAR-T cells in solid malignancies by pairing a solid tumor targeting CAR with additional CD19-targeting CARs. This addition is meant to amplify proliferation, activation, and persistence of the CAR-T cells with a goal to overcome the inherent resistance of solid tumors to CAR-T cells. Guanylate cyclase-C (GCC) has been reported to be expressed in over 80% of colorectal cancers with normal expression largely restricted to the luminal side of the GI tract, making it an appealing target for CAR-T cell therapy. A Phase 1 investigator-initiated clinical trial in China reported preliminary results with an ORR of 15.4% (2/13), mOS of 13.3 months in dose level 1 (1x106 CAR-T cells/kg) and 50% (4/8), mOS of 26.1 months in dose level 2 (2x106 CAR-T cells/kg). Common adverse events included cytokine release syndrome (CRS), diarrhea/colitis, and immune effector cell-associated neurotoxicity syndrome (ICANS). Methods: A phase 1 study in the United States was initiated in August, 2022, for patients with refractory metastatic colorectal cancer. As of a data cutoff of December 31, 2023, with a prespecified analysis after the DLT window for the first patient treated at dose level 2, 5 subjects have been reinfused: 4 in dose level 1 and 1 in dose level 2. Subjects were screened for GCC expression. Over 95% of participants screened positive, so this requirement was removed. Eligible subjects underwent leukapheresis, lymphodepleting chemotherapy with a single dose of fludarabine 30mg/m2 and cyclophosphamide 300mg/m2, and infusion of GCC19CART. Responses were assessed by RECIST v1.1 by site investigator and an independent third-party imaging review. Results: Five subjects have been treated, 4 in dose level 1 (1x106 cells/kg) and 1 in dose level 2 (2x106 cells/kg), and have completed the 30 day DLT period. The most common CAR-T related adverse events were CRS in 5/5 subjects (grade 1: 2/5 (40%) and grade 2: 3/5 (60%)), diarrhea in 4/5 subjects (grade 1: 1/5 (20%), grade 2: 2/5 (40%), and grade 3: 1/5 (20%)), and ICANS (grade 2: 1/5 (20%)). All adverse events resolved with therapy. The ORR was 40% (2/5) by independent review: 2 subjects demonstrated a partial response however 1 additional subject had partial metabolic response on PET/CT with stable disease. Progressive disease was seen in 2 participants by RECIST 1.1, but 1 has a falling tumor marker suggesting tumor flare. Conclusions: Preliminary results demonstrate that GCC19CART has an acceptable safety profile and meaningful clinical activity in refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented, including from patients treated at dose level 2 (2x106 CAR-T cells/kg). Clinical trial information: NCT05319314 .
Efficacy and safety of neoadjuvant chemoradiotherapy combined with tislelizumab and thymalfasin in the treatment of locally advanced lower rectal cancer.
Authors: Yao Hongwei , Gao Jiale , Yang Zhengyang , Sun Liting , Wei Pengyu , Wu Si , Meng Cong , Xu Rui , Chen Guangyong , Wu Guocong , Bai Zhigang , Zhang Zhongtao 
Published: June 2024

e15612 Background: Thymalfasin, as an immunomodulator, can enhance the anti-tumor effects of T cells, NK cells, and macrophages. This study explored the efficacy and safety of a new adjuvant treatment regimen for rectal cancer, combining thymalfasin with chemoradiotherapy and the PD-1 inhibitor tislelizumab, and its impact on the immune microenvironment. Methods: This retrospective study enrolled 26 patients with locally advanced rectal cancer from March 2021 to December 2022. Thirteen patients received long-course concurrent chemoradiotherapy combined with concurrent tislelizumab treatment, and thirteen received thymalfasin combined with long-course chemoradiotherapy and concurrent tislelizumab treatment (radiotherapy: 50 Gy/25 f; capecitabine, 1000mg/m2, bid; tislelizumab: 200mg, every 21 days, 3 cycles; Thymalfasin: 1.6mg, biw). The postoperative pathological complete response rate (ypT0N0M0), tumor regression grade (AJCC 8th Version), and adverse event (CTCAE 4.0) incidence were assessed, along with changes in the immune microenvironment before and after treatment using multiplex immunofluorescence staining. Results: The pathological complete response rates observed postoperatively were 61.5% in the treatment group, compared to 38.5% in the control group. The distribution of tumor regression grades 0, 1, 2, and 3 was 69.2%, 15.4%, 15.4%, 0% in the treatment group respectively, and 38.5%, 38.5%, 7.7%, 15.4%, in the control group respectively. The adverse event rates reached 84.6% in the treatment group and 76.9% in the control group, with all events classified as either grade 1 or 2 according to the CTCAE 4.0. Significant reductions in CD4+PD1+ cell density (p < 0.001), CD8+PD1+ cell density (p = 0.024), CD68+ cell density (p = 0.007), the CD4/CD8 ratio (p < 0.001), and the CD68+CD86+/CD68+CD163+ ratio (p = 0.012) were demonstrated through multiplex immunofluorescence following neoadjuvant treatment. The treatment group exhibited significant decreases in CD8+PD1+ cell density (p = 0.025) and CD68+CD163+ cell density (p = 0.021) when compared to the control group. Conclusions: Thymalfasin combined with chemoradiotherapy and tislelizumab as a neoadjuvant treatment regimen for patients with locally advanced lower rectal cancer has shown favorable efficacy and safety. Neoadjuvant chemoradiotherapy combined with immunotherapy restored T cell function and reduced the proportion of tumor-associated macrophages, but macrophages polarized towards an M2-like phenotype. Thymalfasin may play a role by synergizing with the PD-1 inhibitor to restore cytotoxic T cell function and block macrophage polarization towards M2 cells. Clinical trial information: NCT06024356 .
Adenocarcinoma in multiple adenomatous polyps: An analysis of demographic and socioeconomic factors.
Authors: Johanis Amit , Chin Kat , Zafar Amaan , Robin Rick , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e15619 Background: Adenocarcinoma in multiple adenomatous polyps (AMAP) is a form of gastrointestinal cancer characterized by adenomatous polyps in the gastrointestinal mucosa and distinct lesions found outside the intestines. A rare form of cancer, AMAP can be traced back to mutations in the APC gene, with higher rates of mutation correlating with worse prognosis. There is an association with familial adenomatous polyposis, which can lead to colorectal cancer in patients as young as 15. Examining demographic statistics on AMAP from the National Cancer Database (NCDB) sheds light on this rare form of colorectal cancer, unlocking new possibilities for diagnostics and treatment. Methods: A retrospective cohort analysis identified 193 patients with AMAP from the 2004-2020 NCDB using ICD-O-3 Code 8221 to identify them. Demographic factors such as age, sex, treatment type, and Charles/Deyo score were explored with descriptive statistics. Linear regression analysis was utilized to study incidence trends. Results: A total of 193 cases of histologically confirmed AMAP were retrieved from the 2004-2020 NCDB with a slight decline in incidence rates during this time (R² = 0.39). The majority of patients were male (55%), White (86%), privately insured (46%), and resided in metropolitan areas with a population size of at least one million (60%). Most patients also comprised the top two income quartiles based on median household income (64%). The mean age at diagnosis was 56.5 years (SD = 19.15, range = 15 - 90). The top primary sites affected were the Colon (26%), Sigmoid Colon (16%), and Rectum (11%). Furthermore, most patients were treated surgically (88%) with the average tumor size of 35.3 mm (SD = 20.5, range = 5.0 - 77.0). More patients received chemotherapy (28%) than radiation therapy (10.4%), with few patients receiving hormone therapy (0.5%) and none receiving immunotherapy. Over half (51%) of the patients were categorized as experiencing Stage 0 and Stage 1 cancer according to the NCDB Analytic Stage Group. The vast majority of patients (74%) had no comorbidities (Charlson-Deyo = 0) and did not receive any palliative care (97%). Conclusions: Our NCDB analysis on AMAP is a novel examination that provides insight into various demographics to better understand the disease. The majority of patients were males with adenocarcinoma lesions most commonly diagnosed in the colon and rectal areas, consistent with previous studies on multiple adenomatous polyps. Our analysis revealed that the majority of patients diagnosed with AMAP tend to be White, privately insured, reside in metropolitan areas, and hail from the top two quartiles of median household income. Additional research is required to gain a greater understanding of the demographic and socioeconomic factors that are important for accurate diagnosis, effective treatments, and improved outcomes.
Disease response of neoadjuvant chemoradiation guiding local excision approach in localized rectal cancer: A systematic review and meta-analysis of prospective data.
Authors: Celso Davi Said Gonçalves , Dos Santos Lima Eduarda , Giuliani Schmitt Luiza , Area Leao Barreto Lucas , Alves Michel Fabiano , Carvalho Rafael 
Published: June 2024

e15639 Background: Total Mesorectal Excision (with or without chemoradiation) has been the established standard of care for the treatment of localized rectal cancer. Neoadjuvant Chemoradiation (nCRT) followed by Local Excision (LE) has been proven as a safe alternative approach for selected patients. This study aims to review the current evidence of this strategy, guided by the disease response from the nCRT. Methods: database research was performed through PubMed, Embase, and Cochrane Central for prospective studies evaluating the use of nCRT followed by LE in localized rectal cancer patients. Our primary outcomes were Local Recurrence Rates (LRR) correlated to patients’ pathological response status. We pooled the proportions of binary outcomes and their 95% confidence intervals. I² analysis was used to assess heterogeneity. We performed statistical analyses using R software version 4.3.1 with a random-effects model. Our analysis was prospectively registered with the number CRD42024499095 (PROSPERO). Results: A pool of 760 citations was initially screened, and 5 prospective trials assessing nCRT following LE in at least one of the arms were selected with a pooled analysis of 438 patients (including CRT-LE single arm, or randomization with CRT followed by total mesorectal excision and short course radiation alone). Neoadjuvant treatment was performed with a radiation dose ranging between 45 - 54Gy and concomitant fluoropyrimidine (5-fluorouracil or Capecitabine) isolated or in combination with Oxaliplatin. The extracted data was subgrouped into favorable responders (FR) (complete or near-complete pathological response) or unfavorable responders (UR). Looking specifically at the nCRT+LE arm, 284 patients were identified, from which 168 were classified as FR (59.1%). The pooled LRR was 0.02 (95% CI 0.00-0.06; I² = 27%) for this group. A total of 116 patients were classified as UR, with a polled LRR of 0.09 (95% CI 0.05-0.16; I² = 0%). Conclusions: Our analysis demonstrate that nCRT + LE is a safe strategy, with data from 5 prospective trials demonstrating very low local recurrence rate, especially in the group of patients who achieved a good response to the neoadjuvant approach. Treatment intensification protocols aiming to achieve a higher response rate can potentially reduce the local recurrence in those patients.
Outcomes of colorectal cancer hospitalization with and without coexisting nutritional anemia: A National Inpatient Sample (NIS) 2016 to 2019 database study.
Authors: Pandey Sagar , Changela Madhav , Manvar Kapilkumar , Patel Dhruvanshu , Basida Sanket , Shah Yash , Karawadia Tejas , Kalavar Madhumati R. 
Published: June 2024

e15648 Background: Colorectal carcinoma (CRC) is third most commonly diagnosed cancer in males and second in females. Implications of CRC with coexisting anemia and its outcomes of hospitalization have not been studied. We aim to evaluate the outcomes of CRC hospitalization with and without coexisting nutritional anemia. Methods: A total of 504,515 patients (male: 52.61%, female: 47.39%), aged ≥18 years, admitted from 2016 to 2019 with principal admission diagnosis of CRC were identified using International Classification of Disease 10 (ICD-10) coding for NIS database. Patients were stratified into those with and without nutritional anemia (16.19% vs 83.81%) which included iron, B12, folate deficiency and other nutritional anemia per ICD-10 coding. Mortality was the primary outcome of the study whereas length of stay (LOS), total treatment cost, acute kidney injury (AKI), pulmonary embolism (PE), deep vein thrombosis (DVT), colonoscopy, abdominal surgery and lower gastrointestinal (GI) bleeding were secondary outcomes. Multivariate regression model was used to estimate the outcomes of CRC hospitalization with and without coexisting nutritional anemia after adjusting for confounders like age, sex, race, insurance provider, co-morbidities, median income, hospital region, location, etc. Results: Mean age of patients admitted with CRC with and without anemia was 69.06 and 65.77 years respectively. Among two groups, mortality was significantly lower among patients with nutritional anemia (2.05 % vs 2.64 %). Lower GI bleeding (12.24% vs 4.77%) and colonoscopy during inpatient stay (43.97% vs 23.05%) were significantly higher among CRC cohort with nutritional anemia. Similarly, LOS, cost of inpatient hospitalization, AKI, PE and DVT were also significantly higher among anemia cohort. However, the need for abdominal surgery was significantly higher among CRC patients without nutritional anemia. Table 1 summarizes the results of multivariate regression analysis. Conclusions: Nutritional anemia in CRC patients is associated with longer length of stay, increased cost, higher risk of developing venous thrombosis along with lower GI bleed and colonoscopy. Therefore, it should be corrected to optimize outcomes among CRC patients. [Table: see text]
Impact of breakthrough SARS-CoV-2 infections on vaccinated patients with colorectal cancer: A retrospective cohort study.
Authors: Qasim Hana , Alsakarneh Saqr , Khamees Ibrahim , Sallam Yazan , Adam Mohammad , Jaber Fouad 
Published: June 2024

e15656 Background: Cancer patients are vulnerable to severe SARS-COVID outcomes due to the immunosuppressive effect by both the inherent nature of cancer and its diverse therapeutic interventions. Although COVID-19 vaccines have shown efficacy, their effectiveness appears to decrease among cancer patients. We hypothesize that colorectal cancer (CRC) patients are at a higher risk of breakthrough COVID-19 infection and severe outcomes. Methods: We conducted a retrospective cohort study using TriNetX, a population-based database that sources data from electronic medical records (EHRs) of 61 health care organizations in the US. Using ICD-10 codes, we created two cohorts of patients with COVID-19: with CRC and without CRC. The primary aim was a composite outcome of hospitalization, emergency department (ED) visits, and mortality. Secondary aims of our study included risk of hospitalization, ED visits, critical care admission, intubation, and mortality, individually. We performed propensity score matching (PSM) of 44 variables to control for confounding. Odds ratio (OR) and 95% confidence interval (CI) were used to report associations for the propensity-matched cohorts. Results: In CRC patients, the composite outcome (ED visits, hospitalization, death) was 51.6% with breakthrough infections, higher than 44.3% in matched patients without CRC (aOR = 1.39; [95%CI: 1.17 - 1.53]). CRC patients had a significantly elevated cumulative event probability within 180 days (log-rank test, p < 0.0001). Though mortality and critical care stay were similar, CRC patients had a higher risk of hospitalization (aOR = 1.3; [95%CI: 1.12 – 1.50]) and intubation (aOR = 1.79; [95%CI: 1.06 – 3.03]). In subgroup analysis, CRC patients had a higher composite outcome after 2 doses (aOR = 1.39; [95%CI: 1.17 - 1.53]) and 3 doses (aOR = 1.56; [95%CI: 1.26 - 1.95]). Those with 3 doses faced a higher risk of critical stay (aOR = 1.74; [95%CI: 1.06 – 2.86]). Younger CRC patients (16-64 years) with breakthrough infections were at higher risk of all-cause ED visits (aOR = 2.61; [95%CI: 1.73 - 3.94]). No significant differences were observed based on sex. Conclusions: Our retrospective study provides real-world evidence that CRC patients are at a higher risk of more severe outcomes after breakthrough COVID-19 infections. This may warrant a reevaluation of current preventive measures and the possible need for frequent booster vaccine doses for this patient population. [Table: see text]
Examining the risk factors for trastuzumab-related cardiotoxicity in a predominantly Hispanic South Texas population: A descriptive study.
Authors: Sharma Aditi , Fierro Maria Elena , Kothare Aishwarya , Governor Samuel B. , Alam Zuha , Liu Karen , Pak Stella , Otchere Prince 
Published: June 2024

e24000 Background: Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), stands as first line treatment for HER2 positive breast cancer. Despite its efficacy, trastuzumab’s association with cardiotoxicity requires monitoring via serial transthoracic echocardiograms (TTEs). We aimed to evaluate the risk factors for trastuzumab related cardiotoxicity in a South Texas population that is uniquely a majority-minority Hispanic population. Methods: A retrospective chart review study was conducted of all female patients with HER2-positive breast cancer who received trastuzumab treatment from 2015-2021. A total of 180 patients were identified. Patients without baseline TTE or a baseline left ventricle ejection fraction (LVEF) less than 53% were excluded. The final sample size included 132 patients. Cardiotoxicity was defined as a decrease in LVEF of more than 10% during the 1-year study period. Results: The mean age at the time of diagnosis in the study population was 54.2 years. The average BMI of the study participants was 30.89. The incidence of cardiotoxicity in this study population was 6%. Among those who developed cardiotoxicity, 50% had hypertension, 25% had hyperlipidemia, 12.5% had type 2 diabetes mellitus, and 12.5% had previous coronary artery bypass surgery (CABG). In terms of cancer treatment, 12.5% of patients had a history of radiation, 25% had a history of anthracycline therapy, and 12.5% had their trastuzumab treatment ended prematurely. Of the cardiotoxicity population, 37.5% patients were former smokers and 25% were former alcohol users. Hispanic/Latino patients composed 58% of the study population and represented 50% of patients who experienced cardiotoxicity. Conclusions: The incidence of trastuzumab-related cardiotoxicity in this Hispanic/Latino majority-minority population was 6%, lower than the 9% observed in a predominantly white population in our previous study. However, further studies are needed to determine the factors contributing to this reduced cardiotoxicity rate in this population.
Cardiovascular events in patients receiving immuno-oncology agents, in phase I clinical trials: CAVIO study.
Authors: Zagami Paola , Nicolò Eleonora , Trapani Dario , Boscolo Bielo Luca , Valenza Carmine , Carnevale Schianca Ambra , Pellizzari Gloria , Castellano Grazia , Gandini Sara , Vignati Silvano , Massaro Maria Angela , Busacca Chiara , Marra Antonio , Taurelli Salimbeni Beatrice , Belli Carmen , Minchella Ida , Locatelli Marzia Adelia , Esposito Angela , Criscitiello Carmen , Curigliano Giuseppe 
Published: June 2024

e24009 Background: Among immunoncology agents (IO), immune checkpoint inhibitors are the most used, demonstrating survival benefit across multiple cancer types. Adverse events are often reported with IO; cardiotoxicity is rare, but potentially fatal. CAVIO study evaluated the occurrence of cardiovascular events (CVE) in patients receiving IO in phase I clinical trials (ph1CT). Methods: We retrospectively reviewed clinical and cardiological data of patients consecutively enrolled, from Jan2016 to Dec2021, in ph1CT with IO alone or in combination. Any type and grade of CVE occurred on treatment, related or not to IO, was evaluated. Fisher’s exact tests were used to compare variables. Cox regression and Kaplan Meier methods were used for multivariable analyses and estimating overall survival (OS). Hazard ratio (HR) and 95% confident interval (CI) were calculated. Results: 211 patients were included; median age was 57 years. The most frequent site of primary tumor was breast (25%). 43 of 211 patients experienced ≥1 CVE of any grade (G) during the treatment, of which < 1% G3 and none ³G4. The most frequent ones were hypertension (n = 20, 9%) and thrombosis (n = 15, 7%), only one myocarditis (2%). Table 1 shows the significant differences observed between patients experiencing CVE or not. The occurrence of CVE was not associated with pre-existing cardiovascular risk factors nor with number of prior therapy lines. The median progression free survival (mPFS) and mOS were 2 and 9 months respectively, regardless the CVE occurrence. Patients using anticoagulant at the end of ph1CT showed worse PFS and OS (1.8 and 5.4m) than those who did not (2.5 and 11.1m), similarly was for PS ECOG 1 vs 0. The result was consistent at the multivariate model adjusted for the primary site of tumor, PS ECOG, previous lines of treatment and age, in which PS ECOG 1 and the use of anticoagulant remained statistically significant associated with negative OS (for PSECOG: HR:1.84, 95% CI 1.31-2.57, p < 0.001; for anticoagulant use: HR: 1.72, 95%CI:1.20-2.47, p:0.003). Conclusions: The occurrence of CVE did not change the outcomes of patients treated with IO in ph1RC. Severe CVE were rare, hypertension being the most frequent. Further data are needed on the correlation of anticoagulant use, IO and patients prognosis. [Table: see text]